Search results for: world social science system
Commenced in January 2007
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Paper Count: 30952

Search results for: world social science system

112 Service Blueprinting: A New Application for Evaluating Service Provision in the Hospice Sector

Authors: L. Sudbury-Riley, P. Hunter-Jones, L. Menzies, M. Pyrah, H. Knight

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Just as manufacturing firms aim for zero defects, service providers strive to avoid service failures where customer expectations are not met. However, because services comprise unique human interactions, service failures are almost inevitable. Consequently, firms focus on service recovery strategies to fix problems and retain their customers for the future. Because a hospice offers care to terminally ill patients, it may not get the opportunity to correct a service failure. This situation makes the identification of what hospice users really need and want, and to ascertain perceptions of the hospice’s service delivery from the user’s perspective, even more important than for other service providers. A well-documented and fundamental barrier to improving end-of-life care is a lack of service quality measurement tools that capture the experiences of user’s from their own perspective. In palliative care, many quantitative measures are used and these focus on issues such as how quickly patients are assessed, whether they receive information leaflets, whether a discussion about their emotional needs is documented, and so on. Consequently, quality of service from the user’s perspective is overlooked. The current study was designed to overcome these limitations by adapting service blueprinting - never before used in the hospice sector - in order to undertake a ‘deep-dive’ to examine the impact of hospice services upon different users. Service blueprinting is a customer-focused approach for service innovation and improvement, where the ‘onstage’ visible service user and provider interactions must be supported by the ‘backstage’ employee actions and support processes. The study was conducted in conjunction with East Cheshire Hospice in England. The Hospice provides specialist palliative care for patients with progressive life-limiting illnesses, offering services to patients, carers and families via inpatient and outpatient units. Using service blueprinting to identify every service touchpoint, in-depth qualitative interviews with 38 in-patients, outpatients, visitors and bereaved families enabled a ‘deep-dive’ to uncover perceptions of the whole service experience among these diverse users. Interviews were recorded and transcribed, and thematic analysis of over 104,000 words of data revealed many excellent aspects of Hospice service. Staff frequently exceed people’s expectations. Striking gratifying comparisons to hospitals emerged. The Hospice makes people feel safe. Nevertheless, the technique uncovered many areas for improvement, including serendipity of referrals processes, the need for better communications with external agencies, improvements amid the daunting arrival and admissions process, a desperate need for more depression counselling, clarity of communication pertaining to actual end of life, and shortcomings in systems dealing with bereaved families. The study reveals that the adapted service blueprinting tool has major advantages of alternative quantitative evaluation techniques, including uncovering the complex nature of service user’s experiences in health-care service systems, highlighting more fully the interconnected configurations within the system and making greater sense of the impact of the service upon different service users. Unlike other tools, this in-depth examination reveals areas for improvement, many of which have already been implemented by the Hospice. The technique has potential to improve experiences of palliative and end-of-life care among patients and their families.

Keywords: hospices, end-of-life-care, service blueprinting, service delivery

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111 The Legal and Regulatory Gaps of Blockchain-Enabled Energy Prosumerism

Authors: Karisma Karisma, Pardis Moslemzadeh Tehrani

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This study aims to conduct a high-level strategic dialogue on the lack of consensus, consistency, and legal certainty regarding blockchain-based energy prosumerism so that appropriate institutional and governance structures can be put in place to address the inadequacies and gaps in the legal and regulatory framework. The drive to achieve national and global decarbonization targets is a driving force behind climate goals and policies under the Paris Agreement. In recent years, efforts to ‘demonopolize’ and ‘decentralize’ energy generation and distribution have driven the energy transition toward decentralized systems, invoking concepts such as ownership, sovereignty, and autonomy of RE sources. The emergence of individual and collective forms of prosumerism and the rapid diffusion of blockchain is expected to play a critical role in the decarbonization and democratization of energy systems. However, there is a ‘regulatory void’ relating to individual and collective forms of prosumerism that could prevent the rapid deployment of blockchain systems and potentially stagnate the operationalization of blockchain-enabled energy sharing and trading activities. The application of broad and facile regulatory fixes may be insufficient to address the major regulatory gaps. First, to the authors’ best knowledge, the concepts and elements circumjacent to individual and collective forms of prosumerism have not been adequately described in the legal frameworks of many countries. Second, there is a lack of legal certainty regarding the creation and adaptation of business models in a highly regulated and centralized energy system, which inhibits the emergence of prosumer-driven niche markets. There are also current and prospective challenges relating to the legal status of blockchain-based platforms for facilitating energy transactions, anticipated with the diffusion of blockchain technology. With the rise of prosumerism in the energy sector, the areas of (a) network charges, (b) energy market access, (c) incentive schemes, (d) taxes and levies, and (e) licensing requirements are still uncharted territories in many countries. The uncertainties emanating from this area pose a significant hurdle to the widespread adoption of blockchain technology, a complementary technology that offers added value and competitive advantages for energy systems. The authors undertake a conceptual and theoretical investigation to elucidate the lack of consensus, consistency, and legal certainty in the study of blockchain-based prosumerism. In addition, the authors set an exploratory tone to the discussion by taking an analytically eclectic approach that builds on multiple sources and theories to delve deeper into this topic. As an interdisciplinary study, this research accounts for the convergence of regulation, technology, and the energy sector. The study primarily adopts desk research, which examines regulatory frameworks and conceptual models for crucial policies at the international level to foster an all-inclusive discussion. With their reflections and insights into the interaction of blockchain and prosumerism in the energy sector, the authors do not aim to develop definitive regulatory models or instrument designs, but to contribute to the theoretical dialogue to navigate seminal issues and explore different nuances and pathways. Given the emergence of blockchain-based energy prosumerism, identifying the challenges, gaps and fragmentation of governance regimes is key to facilitating global regulatory transitions.

Keywords: blockchain technology, energy sector, prosumer, legal and regulatory.

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110 Shared Versus Pooled Automated Vehicles: Exploring Behavioral Intentions Towards On-Demand Automated Vehicles

Authors: Samira Hamiditehrani

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Automated vehicles (AVs) are emerging technologies that could potentially offer a wide range of opportunities and challenges for the transportation sector. The advent of AV technology has also resulted in new business models in shared mobility services where many ride hailing and car sharing companies are developing on-demand AVs including shared automated vehicles (SAVs) and pooled automated vehicles (Pooled AVs). SAVs and Pooled AVs could provide alternative shared mobility services which encourage sustainable transport systems, mitigate traffic congestion, and reduce automobile dependency. However, the success of on-demand AVs in addressing major transportation policy issues depends on whether and how the public adopts them as regular travel modes. To identify conditions under which individuals may adopt on-demand AVs, previous studies have applied human behavior and technology acceptance theories, where Theory of Planned Behavior (TPB) has been validated and is among the most tested in on-demand AV research. In this respect, this study has three objectives: (a) to propose and validate a theoretical model for behavioral intention to use SAVs and Pooled AVs by extending the original TPB model; (b) to identify the characteristics of early adopters of SAVs, who prefer to have a shorter and private ride, versus prospective users of Pooled AVs, who choose more affordable but longer and shared trips; and (c) to investigate Canadians’ intentions to adopt on-demand AVs for regular trips. Toward this end, this study uses data from an online survey (n = 3,622) of workers or adult students (18 to 75 years old) conducted in October and November 2021 for six major Canadian metropolitan areas: Toronto, Vancouver, Ottawa, Montreal, Calgary, and Hamilton. To accomplish the goals of this study, a base bivariate ordered probit model, in which both SAV and Pooled AV adoptions are estimated as ordered dependent variables, alongside a full structural equation modeling (SEM) system are estimated. The findings of this study indicate that affective motivations such as attitude towards AV technology, perceived privacy, and subjective norms, matter more than sociodemographic and travel behavior characteristic in adopting on-demand AVs. Also, the results of second objective provide evidence that although there are a few affective motivations, such as subjective norms and having ample knowledge, that are common between early adopters of SAVs and PooledAVs, many examined motivations differ among SAV and Pooled AV adoption factors. In other words, motivations influencing intention to use on-demand AVs differ among the service types. Likewise, depending on the types of on-demand AVs, the sociodemographic characteristics of early adopters differ significantly. In general, findings paint a complex picture with respect to the application of constructs from common technology adoption models to the study of on-demand AVs. Findings from the final objective suggest that policymakers, planners, the vehicle and technology industries, and the public at large should moderate their expectations that on-demand AVs may suddenly transform the entire transportation sector. Instead, this study suggests that SAVs and Pooled AVs (when they entire the Canadian market) are likely to be adopted as supplementary mobility tools rather than substitutions for current travel modes

Keywords: automated vehicles, Canadian perception, theory of planned behavior, on-demand AVs

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109 Chemicals to Remove and Prevent Biofilm

Authors: Cynthia K. Burzell

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Aequor's Founder, a Marine and Medical Microbiologist, discovered novel, non-toxic chemicals in the ocean that uniquely remove biofilm in minutes and prevent its formation for days. These chemicals and over 70 synthesized analogs that Aequor developed can replace thousands of toxic biocides used in consumer and industrial products and, as new drug candidates, kill biofilm-forming bacteria and fungi Superbugs -the antimicrobial-resistant (AMR) pathogens for which there is no cure. Cynthia Burzell, PhD., is a Marine and Medical Microbiologist studying natural mechanisms that inhibit biofilm formation on surfaces in contact with water. In 2002, she discovered a new genus and several new species of marine microbes that produce small molecules that remove biofilm in minutes and prevent its formation for days. The molecules include new antimicrobials that can replace thousands of toxic biocides used in consumer and industrial products and can be developed into new drug candidates to kill the biofilm-forming bacteria and fungi -- including the antimicrobial-resistant (AMR) Superbugs for which there is no cure. Today, Aequor has over 70 chemicals that are divided into categories: (1) Novel natural chemicals. Lonza validated that the primary natural chemical removed biofilm in minutes and stated: "Nothing else known can do this at non-toxic doses." (2) Specialty chemicals. 25 of these structural analogs are already approved under the U.S. Environmental Protection Agency (EPA)'s Toxic Substances Control Act, certified as "green" and available for immediate sale. These have been validated for the following agro-industrial verticals: (a) Surface cleaners: The U.S. Department of Agriculture validated that low concentrations of Aequor's formulations provide deep cleaning of inert, nano and organic surfaces and materials; (b) Water treatments: NASA validated that one dose of Aequor's treatment in the International Space Station's water reuse/recycling system lasted 15 months without replenishment. DOE validated that our treatments lower energy consumption by over 10% in buildings and industrial processes. Future validations include pilot projects with the EPA to test efficacy in hospital plumbing systems. (c) Algae cultivation and yeast fermentation: The U.S. Department of Energy (DOE) validated that Aequor's treatment boosted biomass of renewable feedstocks by 40% in half the time -- increasing the profitability of biofuels and biobased co-products. DOE also validated increased yields and crop protection of algae under cultivation in open ponds. A private oil and gas company validated decontamination of oilfield water. (3) New structural analogs. These kill Gram-negative and Gram-positive bacteria and fungi alone, in combinations with each other, and in combination with low doses of existing, ineffective antibiotics (including Penicillin), "potentiating" them to kill AMR pathogens at doses too low to trigger resistance. Both the U.S. National Institutes for Health (NIH) and Department of Defense (DOD) has executed contracts with Aequor to provide the pre-clinical trials needed for these new drug candidates to enter the regulatory approval pipelines. Aequor seeks partners/licensees to commercialize its specialty chemicals and support to evaluate the optimal methods to scale-up of several new structural analogs via activity-guided fractionation and/or biosynthesis in order to initiate the NIH and DOD pre-clinical trials.

Keywords: biofilm, potentiation, prevention, removal

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108 Comparative Study on the Influence of Different Drugs against Aluminium- Induced Nephrotoxicity and Hepatotoxicity in Rats

Authors: Azza A. Ali, Toqa M. Elnahhas, Abeer I. Abd El-Fattah, Mona M. Kamal, Karema Abu-Elfotuh

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Background: Environmental pollution with the different aluminium (Al) containing compounds especially those in industrial waste water exposes people to higher than normal levels of Al that represents an environmental risk factor. Cosmetics, Al ware, and containers are also sources of Al besides some foods and food additives. In addition to its known neurotoxicity, Al affects other body structures like skeletal system, blood cells, liver and kidney. Accumulation of Al in kidney and liver induces nephrotoxicity and hepatotoxicity. Coenzyme Q10 (CoQ10) is a pseudo-vitamin substance primarily present in the mitochondria. It is a powerful antioxidant and acts as radical scavenger. Wheat grass is a natural product that contains carbohydrates, proteins, vitamins, minerals, enzymes and has antioxidant, anti-inflammatory, anticancer and cardiovascular protection activities. Cocoa is an excellent source of iron, potent antioxidants and can protect against many diseases. Vinpocetine is an antioxidant and anti inflammatory while zinc is an essential trace element involved in cell division and its deficiency is observed in many types of liver disease. Objective: To evaluate and compare the potency of different drugs (CoQ10, wheatgrass, cocoa, vinpocetine and zinc) against nephro- and hepato-toxicity induced by Al in rats. Methods: Rats were divided to seven groups and received daily for three weeks either saline for control group or AlCl3 (70 mg/kg, IP) for Al-toxicity model groups. Five groups of Al-toxicity model (treated groups) were orally received together with Al each of the following; CoQ10 (200mg/kg), wheat grass (100mg/kg), cocoa powder (24mg/kg), vinpocetine (20mg/kg) or zinc (32mg/kg). Biochemical changes in the serum level of Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate deshydrogenase (LDH) as well as total bilirubin, lipids, cholesterol, triglycerides, glucose, proteins, creatinine and urea were measured. Liver and kidney specimens from all groups were also collected for the assessment of hepatic and nephrotic level of inflammatory mediators (TNF-α, IL-6β, nuclear factor kappa B (NF-κB), Caspase-3, oxidative parameters (MDA, SOD, TAC, NO) and DNA fragmentation. Histopathological changes in liver and kidney were also evaluated. Results: Three weeks of AlCl3 (70 mg/kg, IP) exposure induced nephro- and hepato-toxicity in rats. Treatment by the all used drugs showed protection against hazards of AlCl3. The protective effects were indicated by the significant decrease in ALT, AST, ALP, LDH as well as total bilirubin, lipids, cholesterol, triglycerides, glucose, creatinine and urea levels which were increased by Al. Liver and kidney of the treated groups showed decrease in MDA, NO, TNF-α, IL-6β, NF-κB, caspase-3 and DNA fragmentation which were increased by Al, together with significant increase in total proteins, SOD and TAC which were decreased by Al. The protection against both nephro- and hepato-toxicity was more pronounced especially with CoQ10 and wheat grass than the other used drugs. Histopathological examinations confirmed the biochemical results of toxicity and of protection. Conclusion: Protection from nephrotoxicity, hepatotoxicity and the consequent degenerations induced by Al can be achieved by using different drugs as CoQ10, wheatgrass, cocoa, vinpocetine and zinc, but CoQ10 as well as wheat grass possesses the most superior protection.

Keywords: aluminum, nephrotoxicity, hepatotoxicity, coenzyme Q10, wheatgrass, cocoa, vinpocetine, zinc

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107 Exploring Managerial Approaches towards Green Manufacturing: A Thematic Analysis

Authors: Hakimeh Masoudigavgani

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Since manufacturing firms deplete non-renewable resources and pollute air, soil, and water in greatly unsustainable manner, industrial activities or production of products are considered to be a key contributor to adverse environmental impacts. Hence, management strategies and approaches that involve an effective supply chain decision process in a manufacturing sector could be extremely significant to the application of environmental initiatives. Green manufacturing (GM) is one of these strategies which minimises negative effects on the environment through reducing greenhouse gas emissions, waste, and the consumption of energy and natural resources. This paper aims to explore what greening methods and mechanisms could be applied in the manufacturing supply chain and what are the outcomes of adopting these methods in terms of abating environmental burdens? The study is an interpretive research with an exploratory approach, using thematic analysis by coding text, breaking down and grouping the content of collected literature into various themes and categories. It is found that green supply chain could be attained through execution of some pre-production strategies including green building, eco-design, and green procurement as well as a number of in-production and post-production strategies involving green manufacturing and green logistics. To achieve an effective GM, the pre-production strategies are suggested to be employed. This paper defines GM as (1) the analysis of the ecological impacts generated by practices, products, production processes, and operational functions, and (2) the implementation of greening methods to reduce damaging influences of them on the natural environment. Analysis means assessing, monitoring, and auditing of practices in order to measure and pinpoint their harmful impacts. Moreover, greening methods involved within GM (arranged in order from the least to the most level of environmental compliance and techniques) consist of: •product stewardship (e.g. less use of toxic, non-renewable, and hazardous materials in the manufacture of the product; and stewardship of the environmental problems with regard to the product in all production, use, and end-of-life stages); •process stewardship (e.g. controlling carbon emission, energy and resources usage, transportation method, and disposal; reengineering polluting processes; recycling waste materials generated in production); •lean and clean production practices (e.g. elimination of waste, materials replacement, materials reduction, resource-efficient consumption, energy-efficient usage, emission reduction, managerial assessment, waste re-use); •use of eco-industrial parks (e.g. a shared warehouse, shared logistics management system, energy co-generation plant, effluent treatment). However, the focus of this paper is only on methods related to the in-production phase and needs further research on both pre-production and post-production environmental innovations. The outlined methods in this investigation may possibly be taken into account by policy/decision makers. Additionally, the proposed future research direction and identified gaps can be filled by scholars and researchers. The paper compares and contrasts a variety of viewpoints and enhances the body of knowledge by building a definition for GM through synthesising literature and categorising the strategic concept of greening methods, drivers, barriers, and successful implementing tactics.

Keywords: green manufacturing (GM), product stewardship, process stewardship, clean production, eco-industrial parks (EIPs)

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106 Geographic Information System Based Multi-Criteria Subsea Pipeline Route Optimisation

Authors: James Brown, Stella Kortekaas, Ian Finnie, George Zhang, Christine Devine, Neil Healy

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The use of GIS as an analysis tool for engineering decision making is now best practice in the offshore industry. GIS enables multidisciplinary data integration, analysis and visualisation which allows the presentation of large and intricate datasets in a simple map-interface accessible to all project stakeholders. Presenting integrated geoscience and geotechnical data in GIS enables decision makers to be well-informed. This paper is a successful case study of how GIS spatial analysis techniques were applied to help select the most favourable pipeline route. Routing a pipeline through any natural environment has numerous obstacles, whether they be topographical, geological, engineering or financial. Where the pipeline is subjected to external hydrostatic water pressure and is carrying pressurised hydrocarbons, the requirement to safely route the pipeline through hazardous terrain becomes absolutely paramount. This study illustrates how the application of modern, GIS-based pipeline routing techniques enabled the identification of a single most-favourable pipeline route crossing of a challenging seabed terrain. Conventional approaches to pipeline route determination focus on manual avoidance of primary constraints whilst endeavouring to minimise route length. Such an approach is qualitative, subjective and is liable to bias towards the discipline and expertise that is involved in the routing process. For very short routes traversing benign seabed topography in shallow water this approach may be sufficient, but for deepwater geohazardous sites, the need for an automated, multi-criteria, and quantitative approach is essential. This study combined multiple routing constraints using modern least-cost-routing algorithms deployed in GIS, hitherto unachievable with conventional approaches. The least-cost-routing procedure begins with the assignment of geocost across the study area. Geocost is defined as a numerical penalty score representing hazard posed by each routing constraint (e.g. slope angle, rugosity, vulnerability to debris flows) to the pipeline. All geocosted routing constraints are combined to generate a composite geocost map that is used to compute the least geocost route between two defined terminals. The analyses were applied to select the most favourable pipeline route for a potential gas development in deep water. The study area is geologically complex with a series of incised, potentially active, canyons carved into a steep escarpment, with evidence of extensive debris flows. A similar debris flow in the future could cause significant damage to a poorly-placed pipeline. Protruding inter-canyon spurs offer lower-gradient options for ascending an escarpment but the vulnerability of periodic failure of these spurs is not well understood. Close collaboration between geoscientists, pipeline engineers, geotechnical engineers and of course the gas export pipeline operator guided the analyses and assignment of geocosts. Shorter route length, less severe slope angles, and geohazard avoidance were the primary drivers in identifying the most favourable route.

Keywords: geocost, geohazard, pipeline route determination, pipeline route optimisation, spatial analysis

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105 Two Houses in the Arabian Desert: Assessing the Built Work of RCR Architects in the UAE

Authors: Igor Peraza Curiel, Suzanne Strum

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Today, when many foreign architects are receiving commissions in the United Arab Emirates, it is essential to analyze how their designs are influenced by the region's culture, environment, and building traditions. This study examines the approach to siting, geometry, construction methods, and material choices in two private homes for a family in Dubai, a project being constructed on adjacent sites by the acclaimed Spanish team of RCR Architects. Their third project in Dubai, the houses mark a turning point in their design approach to the desert. The Pritzker Prize-winning architects of RCR gained renown for building works deeply responsive to the history, landscape, and customs of their hometown in a volcanic area of the Catalonia region of Spain. Key formative projects and their entry to practice in UAE will be analyzed according to the concepts of place identity, the poetics of construction, and material imagination. The poetics of construction, a theoretical position with a long practical tradition, was revived by the British critic Kenneth Frampton. The idea of architecture as a constructional craft is related to the concepts of material imagination and place identity--phenomenological concerns with the creative engagement with local matter and topography that are at the very essence of RCR's way of designing, detailing, and making. Our study situates RCR within the challenges of building in the region, where western forms and means have largely replaced the ingenious responsiveness of indigenous architecture to the climate and material scarcity. The dwellings, iterations of the same steel and concrete vaulting system, highlight the conceptual framework of RCR's design approach to offer a study in contemporary critical regionalism. The Kama House evokes Bedouin tents, while the Alwah House takes the form of desert dunes in response to the temporality of the winds. Metal mesh screens designed to capture the shifting sands will complete the forms. The original research draws on interviews with the architects and unique documentation provided by them and collected by the authors during on-site visits. By examining the two houses in-depth, this paper foregrounds a series of timely questions: 1) What is the impact of the local climatic, cultural, and material conditions on their project in the UAE? 2) How does this work further their experiences in the region? 3) How has RCR adapted their construction techniques as their work expands beyond familiar settings? The investigation seeks to understand how the design methodology developed for more than 20 years and enmeshed in the regional milieu of their hometown can transform as the architects encounter unique characteristics and values in the Middle East. By focusing on the contemporary interpretation of Arabic geometry and elements, the houses reveal the role of geometry, tectonics, and material specificity in the realization from conceptual sketches to built form. In emphasizing the importance of regional responsiveness, the dynamics of international construction practice, and detailing this study highlights essential issues for professionals and students looking to practice in an increasingly global market.

Keywords: material imagination, regional responsiveness, place identity, poetics of construction

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104 Acoustic Radiation Force Impulse Elastography of the Hepatic Tissue of Canine Brachycephalic Patients

Authors: A. C. Facin, M. C. Maronezi , M. P. Menezes, G. L. Montanhim, L. Pavan, M. A. R. Feliciano, R. P. Nociti, R. A. R. Uscategui, P. C. Moraes

Abstract:

The incidence of brachycephalic syndrome (BS) in the clinical routine of small animals has increased significantly giving the higher proportion of brachycephalic pets in the last years and has been considered as an animal welfare problem. The treatment of BS is surgical and the clinical signs related can be considerably attenuated. Nevertheless, the systemic effects of the BS are still poorly reported and little is known about these when the surgical correction is not performed early. Affected dogs are more likely to develop cardiopulmonary, gastrointestinal and sleep disorders in which the chronic hypoxemia plays a major role. This syndrome is compared with the obstructive sleep apnea (OSA) in humans, both considered as causes of systemic and metabolic dysfunction. Among the several consequences of the BS little is known if the syndrome also affects the hepatic tissue of brachycephalic patients. Elastography is a promising ultrasound technique that evaluates tissue elasticity and has been recently used with the purpose of diagnosis of liver fibrosis. In medicine, it is a growing concern regarding the hepatic injury of patients affected by OSA. This prospective study hypothesizes if there is any consequence of BS in the hepatic parenchyma of brachycephalic dogs that don’t receive any surgical treatment. This study was conducted following the approval of the Animal Ethics and Welfare Committee of the Faculdade de Ciências Agrárias e Veterinárias, UNESP, Campus Jaboticabal, Brazil (protocol no 17944/2017) and funded by Sao Paulo Research Foundation (FAPESP, process no 2017/24809-4). The methodology was based in ARFI elastography using the ACUSON S2000/SIEMENS device, with convex multifrequential transducer and specific software as well as clinical evaluation of the syndrome, in order to determine if they can be used as a prognostic non-invasive tool. On quantitative elastography, it was collected three measures of shear wave velocity (meters per second) and depth in centimeters in the left lateral, left medial, right lateral, right medial and caudate lobe of the liver. The brachycephalic patients, 16 pugs and 30 french bulldogs, were classified using a previously established 4-point functional grading system based on clinical evaluation before and after a 3-minute exercise tolerance test already established and validated. The control group was based on the same features collected in 22 beagles. The software R version 3.3.0 was used for the analysis and the significance level was set at 0.05. The data were analysed for normality of residuals and homogeneity of variances by Shapiro-Wilks test. Comparisons of parametric continuous variables between breeds were performed by using ANOVA with a post hoc test for pair wise comparison. The preliminary results show significant statistic differences between the brachycephalic groups and the control group in all lobes analysed (p ≤ 0,05), with higher values of shear wave velocities in the hepatic tissue of brachycephalic dogs. In this context, the results obtained in this study contributes to the understanding of BS as well as its consequences in our patients, reflecting in evidence that one more systemic consequence of the syndrome may occur in brachycephalic patients, which was not related in the veterinary literature yet.

Keywords: airway obstruction, brachycephalic airway obstructive syndrome, hepatic injury, obstructive sleep apnea

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103 The Stem Cell Transcription Co-factor Znf521 Sustains Mll-af9 Fusion Protein In Acute Myeloid Leukemias By Altering The Gene Expression Landscape

Authors: Emanuela Chiarella, Annamaria Aloisio, Nisticò Clelia, Maria Mesuraca

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ZNF521 is a stem cell-associated transcription co-factor, that plays a crucial role in the homeostatic regulation of the stem cell compartment in the hematopoietic, osteo-adipogenic, and neural system. In normal hematopoiesis, primary human CD34+ hematopoietic stem cells display typically a high expression of ZNF521, while its mRNA levels rapidly decrease when these progenitors progress towards erythroid, granulocytic, or B-lymphoid differentiation. However, most acute myeloid leukemias (AMLs) and leukemia-initiating cells keep high ZNF521 expression. In particular, AMLs are often characterized by chromosomal translocations involving the Mixed Lineage Leukemia (MLL) gene, which MLL gene includes a variety of fusion oncogenes arisen from genes normally required during hematopoietic development; once they are fused, they promote epigenetic and transcription factor dysregulation. The chromosomal translocation t(9;11)(p21-22;q23), fusing the MLL gene with AF9 gene, results in a monocytic immune phenotype with an aggressive course, frequent relapses, and a short survival time. To better understand the dysfunctional transcriptional networks related to genetic aberrations, AML gene expression profile datasets were queried for ZNF521 expression and its correlations with specific gene rearrangements and mutations. The results showed that ZNF521 mRNA levels are associated with specific genetic aberrations: the highest expression levels were observed in AMLs involving t(11q23) MLL rearrangements in two distinct datasets (MILE and den Boer); elevated ZNF521 mRNA expression levels were also revealed in AMLs with t(7;12) or with internal rearrangements of chromosome 16. On the contrary, relatively low ZNF521 expression levels seemed to be associated with the t(8;21) translocation, that in turn is correlated with the AML1-ETO fusion gene or the t(15;17) translocation and in AMLs with FLT3-ITD, NPM1, or CEBPα double mutations. Invitro, we found that the enforced co-expression of ZNF521 in cord blood-derived CD34+ cells induced a significant proliferative advantage, improving MLL-AF9 effects on the induction of proliferation and the expansion of leukemic progenitor cells. Transcriptome profiling of CD34+ cells transduced with either MLL-AF9, ZNF521, or a combination of the two transgenes highlighted specific sets of up- or down-regulated genes that are involved in the leukemic phenotype, including those encoding transcription factors, epigenetic modulators, and cell cycle regulators as well as those engaged in the transport or uptake of nutrients. These data enhance the functional cooperation between ZNF521 and MA9, resulting in the development, maintenance, and clonal expansion of leukemic cells. Finally, silencing of ZNF521 in MLL-AF9-transformed primary CD34+ cells inhibited their proliferation and led to their extinction, as well as ZNF521 silencing in the MLL-AF9+ THP-1 cell line resulted in an impairment of their growth and clonogenicity. Taken together, our data highlight ZNF521 role in the control of self-renewal and in the immature compartment of malignant hematopoiesis, which, by altering the gene expression landscape, contributes to the development and/or maintenance of AML acting in concert with the MLL-AF9 fusion oncogene.

Keywords: AML, human zinc finger protein 521 (hZNF521), mixed lineage leukemia gene (MLL) AF9 (MLLT3 or LTG9), cord blood-derived hematopoietic stem cells (CB-CD34+)

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102 Language Anxiety and Learner Achievement among University Undergraduates in Sri Lanka: A Case Study of University of Sri Jayewardenepura

Authors: Sujeeva Sebastian Pereira

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Language Anxiety (LA) – a distinct psychological construct of self-perceptions and behaviors related to classroom language learning – is perceived as a significant variable highly correlated with Second Language Acquisition (SLA). However, the existing scholarship has inadequately explored the nuances of LA in relation to South Asia, especially in terms of Sri Lankan higher education contexts. Thus, the current study, situated within the broad areas of Psychology of SLA and Applied Linguistics, investigates the impact of competency-based LA and identity-based LA on learner achievement among undergraduates of Sri Lanka. Employing a case study approach to explore the impact of LA, 750 undergraduates of the University of Sri Jayewardenepura, Sri Lanka, thus covering 25% of the student population from all seven faculties of the university, were selected as participants using stratified proportionate sampling in terms of ethnicity, gender, and disciplines. The qualitative and quantitative research inquiry utilized for data collection include a questionnaire consisting a set of structured and unstructured questions, and semi-structured interviews as research instruments. Data analysis includes both descriptive and statistical measures. As per the quantitative measures of data analysis, the study employed Pearson Correlation Coefficient test, Chi-Square test, and Multiple Correspondence Analysis; it used LA as the dependent variable, and two types of independent variables were used: direct and indirect variables. Direct variables encompass the four main language skills- reading, writing, speaking and listening- and test anxiety. These variables were further explored through classroom activities on grammar, vocabulary and individual and group presentations. Indirect variables are identity, gender and cultural stereotypes, discipline, social background, income level, ethnicity, religion and parents’ education level. Learner achievement was measured through final scores the participants have obtained for Compulsory English- a common first-year course unit mandatory for all undergraduates. LA was measured using the FLCAS. In order to increase the validity and reliability of the study, data collected were triangulated through descriptive content analysis. Clearly evident through both the statistical analysis and the qualitative analysis of the results is the significant linear negative correlation between LA and learner achievement, and the significant negative correlation between LA and culturally-operated gender stereotypes which create identity disparities in learners. The study also found that both competency-based LA and identity-based LA are experienced primarily and inescapably due to the apprehensions regarding speaking in English. Most participants who reported high levels of LA were from an urban socio-economic background of lower income families. Findings exemplify the linguistic inequality prevalent in the socio-cultural milieu in Sri Lankan society. This inequality makes learning English a dire need, yet, very much an anxiety provoking process because of many sociolinguistic, cultural and ideological factors related to English as a Second Language (ESL) in Sri Lanka. The findings bring out the intricate interrelatedness of both the dependent variable (LA) and the independent variables stated above, emphasizing that the significant linear negative correlation between LA and learner achievement is connected to the affective, cognitive and sociolinguistic domains of SLA. Thus, the study highlights the promise in linguistic practices such as code-switching, crossing and accommodating hybrid identities as strategies in minimizing LA and maximizing the experience of ESL.

Keywords: language anxiety, identity-based anxiety, competence-based anxiety, TESL, Sri Lanka

Procedia PDF Downloads 169
101 Representational Issues in Learning Solution Chemistry at Secondary School

Authors: Lam Pham, Peter Hubber, Russell Tytler

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Students’ conceptual understandings of chemistry concepts/phenomena involve capability to coordinate across the three levels of Johnston’s triangle model. This triplet model is based on reasoning about chemical phenomena across macro, sub-micro and symbolic levels. In chemistry education, there is a need for further examining inquiry-based approaches that enhance students’ conceptual learning and problem solving skills. This research adopted a directed inquiry pedagogy based on students constructing and coordinating representations, to investigate senior school students’ capabilities to flexibly move across Johnston’ levels when learning dilution and molar concentration concepts. The participants comprise 50 grade 11 and 20 grade 10 students and 4 chemistry teachers who were selected from 4 secondary schools located in metropolitan Melbourne, Victoria. This research into classroom practices used ethnographic methodology, involved teachers working collaboratively with the research team to develop representational activities and lesson sequences in the instruction of a unit on solution chemistry. The representational activities included challenges (Representational Challenges-RCs) that used ‘representational tools’ to assist students to move across Johnson’s three levels for dilution phenomena. In this report, the ‘representational tool’ called ‘cross and portion’ model was developed and used in teaching and learning the molar concentration concept. Students’ conceptual understanding and problem solving skills when learning with this model are analysed through group case studies of year 10 and 11 chemistry students. In learning dilution concepts, students in both group case studies actively conducted a practical experiment, used their own language and visualisation skills to represent dilution phenomena at macroscopic level (RC1). At the sub-microscopic level, students generated and negotiated representations of the chemical interactions between solute and solvent underpinning the dilution process. At the symbolic level, students demonstrated their understandings about dilution concepts by drawing chemical structures and performing mathematical calculations. When learning molar concentration with a ‘cross and portion’ model (RC2), students coordinated across visual and symbolic representational forms and Johnson’s levels to construct representations. The analysis showed that in RC1, Year 10 students needed more ‘scaffolding’ in inducing to representations to explicit the form and function of sub-microscopic representations. In RC2, Year 11 students showed clarity in using visual representations (drawings) to link to mathematics to solve representational challenges about molar concentration. In contrast, year 10 students struggled to get match up the two systems, symbolic system of mole per litre (‘cross and portion’) and visual representation (drawing). These conceptual problems do not lie in the students’ mathematical calculation capability but rather in students’ capability to align visual representations with the symbolic mathematical formulations. This research also found that students in both group case studies were able to coordinate representations when probed about the use of ‘cross and portion’ model (in RC2) to demonstrate molar concentration of diluted solutions (in RC1). Students mostly succeeded in constructing ‘cross and portion’ models to represent the reduction of molar concentration of the concentration gradients. In conclusion, this research demonstrated how the strategic introduction and coordination of chemical representations across modes and across the macro, sub-micro and symbolic levels, supported student reasoning and problem solving in chemistry.

Keywords: cross and portion, dilution, Johnston's triangle, molar concentration, representations

Procedia PDF Downloads 110
100 Host Preference, Impact of Host Transfer and Insecticide Susceptibility among Aphis gossypii Group (Order: Hemiptera) in Jamaica

Authors: Desireina Delancy, Tannice Hall, Eric Garraway, Dwight Robinson

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Aphis gossypii, as a pest, directly damages its host plant by extracting phloem sap (sucking) and indirectly damages it by the transmission of viruses, ultimately affecting the yield of the host. Due to its polyphagous nature, this species affects a wide range of host plants, some of which may serve as a reservoir for colonisation of important crops. In Jamaica, there have been outbreaks of viral plant pathogens that were transmitted by Aphis gossypii. Three such examples are Citrus tristeza virus, the Watermelon mosaic virus, and Papaya ringspot virus. Aphis gossypii also heavily colonized economically significant host plants, including pepper, eggplant, watermelon, cucumber, and hibiscus. To facilitate integrated pest management, it is imperative to understand the biology of the aphid and its host preference. Preliminary work in Jamaica has indicated differences in biology and host preference, as well as host variety within the species. However, specific details of fecundity, colony growth, host preference, distribution, and insecticide resistance of Aphis gossypii were unknown to the best of our knowledge. The aim was to investigate the following in relation to Aphis gossypii: influence of the host plant on colonization, life span, fecundity, population size, and morphology; the impact of host transfer on fecundity and population size as a measure of host preference and host transfer success and susceptibility to four commonly used insecticides. Fecundity and colony size were documented daily from aphids acclimatized on Capsicum chinense Jacquin 1776, Cucumis sativus Linnaeus 1630, Gossypium hirsutum Linnaeus 1751 and Abelmoschus esculentus (L.) Moench 1794 for three generations. The same measures were used after third instar aphids were transferred among the hosts as a measure of suitability and success. Mortality, and fecundity of survivors, were determined after aphids were exposed to varying concentrations of Actara®, Diazinon™, Karate Zeon®, and Pegasus®. Host preference results indicated that, over a 24-day period, Aphis gossypii reached its largest colony size on G. hirsutum (x̄ 381.80), with January – February being the most fecund period. Host transfer experiments were all significantly different, with the most significant occurring between transfers from C. chinense to C. sativus (p < 0.05). Colony sizes were found to increase significantly every 5 days, which has implications for regimes implemented to monitor and evaluate plots. Insecticides ranked on lethality are Karate Zeon®> Actara®> Pegasus® > Diazinon™. The highest LC50 values were obtained for aphids on G. hirsutum and C. chinense was with Pegasus® and for those on C. sativus with Diazinon™. Survivors of insecticide treatments had colony sizes on average that were 98 % less than untreated aphids. Cotton was preferred both in the field and in the glasshouse. It is on cotton the aphids settled first, had the highest fecundity, and the lowest mortality. Cotton can serve as reservoir for (re)populating other cotton or different host species based on migration due to overcrowding, heavy showers, high wind, or ant attendance. Host transfer success between all three hosts is highly probable within an intercropping system. Survivors of insecticide treatments can successfully repopulate host plants.

Keywords: Aphis gossypii, host-plant preference, colonization sequence, host transfers, insecticide susceptibility

Procedia PDF Downloads 59
99 Multiphysic Coupling Between Hypersonc Reactive Flow and Thermal Structural Analysis with Ablation for TPS of Space Lunchers

Authors: Margarita Dufresne

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This study devoted to development TPS for small space re-usable launchers. We have used SIRIUS design for S1 prototype. Multiphysics coupling for hypersonic reactive flow and thermos-structural analysis with and without ablation is provided by -CCM+ and COMSOL Multiphysics and FASTRAN and ACE+. Flow around hypersonic flight vehicles is the interaction of multiple shocks and the interaction of shocks with boundary layers. These interactions can have a very strong impact on the aeroheating experienced by the flight vehicle. A real gas implies the existence of a gas in equilibrium, non-equilibrium. Mach number ranged from 5 to 10 for first stage flight.The goals of this effort are to provide validation of the iterative coupling of hypersonic physics models in STAR-CCM+ and FASTRAN with COMSOL Multiphysics and ACE+. COMSOL Multiphysics and ACE+ are used for thermal structure analysis to simulate Conjugate Heat Transfer, with Conduction, Free Convection and Radiation to simulate Heat Flux from hypersonic flow. The reactive simulations involve an air chemical model of five species: N, N2, NO, O and O2. Seventeen chemical reactions, involving dissociation and recombination probabilities calculation include in the Dunn/Kang mechanism. Forward reaction rate coefficients based on a modified Arrhenius equation are computed for each reaction. The algorithms employed to solve the reactive equations used the second-order numerical scheme is obtained by a “MUSCL” (Monotone Upstream-cantered Schemes for Conservation Laws) extrapolation process in the structured case. Coupled inviscid flux: AUSM+ flux-vector splitting The MUSCL third-order scheme in STAR-CCM+ provides third-order spatial accuracy, except in the vicinity of strong shocks, where, due to limiting, the spatial accuracy is reduced to second-order and provides improved (i.e., reduced) dissipation compared to the second-order discretization scheme. initial unstructured mesh is refined made using this initial pressure gradient technique for the shock/shock interaction test case. The suggested by NASA turbulence models are the K-Omega SST with a1 = 0.355 and QCR (quadratic) as the constitutive option. Specified k and omega explicitly in initial conditions and in regions – k = 1E-6 *Uinf^2 and omega = 5*Uinf/ (mean aerodynamic chord or characteristic length). We put into practice modelling tips for hypersonic flow as automatic coupled solver, adaptative mesh refinement to capture and refine shock front, using advancing Layer Mesher and larger prism layer thickness to capture shock front on blunt surfaces. The temperature range from 300K to 30 000 K and pressure between 1e-4 and 100 atm. FASTRAN and ACE+ are coupled to provide high-fidelity solution for hot hypersonic reactive flow and Conjugate Heat Transfer. The results of both approaches meet the CIRCA wind tunnel results.

Keywords: hypersonic, first stage, high speed compressible flow, shock wave, aerodynamic heating, conugate heat transfer, conduction, free convection, radiation, fastran, ace+, comsol multiphysics, star-ccm+, thermal protection system (tps), space launcher, wind tunnel

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98 Structural Geology along the Jhakri-Wangtu Road (Jutogh Section) Himachal Pradesh, NW Higher Himalaya, India

Authors: Rajkumar Ghosh

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The paper presents a comprehensive study of the structural analysis of the Chaura Thrust in Himachal Pradesh, India. The research focuses on several key aspects, including the activation timing of the Main Central Thrust (MCT) and the South Tibetan Detachment System (STDS), the identification and characterization of mylonitised zones through microscopic examination, and the understanding of box fold characteristics and their implications in the regional geology of the Himachal Himalaya. The primary objective of the study is to provide field documentation of the Chaura Thrust, which was previously considered a blind thrust with limited field evidence. Additionally, the research aims to characterize box folds and their signatures within the broader geological context of the Himachal Himalaya, document the temperature range associated with grain boundary migration (GBM), and explore the overprinting structures related to multiple sets of Higher Himalayan Out-of-Sequence Thrusts (OOSTs). The research methodology employed geological field observations and microscopic studies. Samples were collected along the Jhakri-Chaura transect at regular intervals of approximately 1 km to conduct strain analysis. Microstructural studies at the grain scale along the Jhakri-Wangtu transect were used to document the GBM-associated temperature range. The study reveals that the MCT activated in two parts, as did the STDS, and provides insights into the activation ages of the Main Boundary Thrust (MBT) and the Main Frontal Thrust (MFT). Under microscopic examination, the study identifies two mylonitised zones characterized by S-C fabric, and it documents dynamic and bulging recrystallization, as well as sub-grain formation. Various types of crenulated schistosity are observed in photomicrographs, including a rare occurrence where crenulation cleavage and sigmoid Muscovite are found juxtaposed. The study also notes the presence of S/SE-verging meso- and micro-scale box folds around Chaura, which may indicate structural upliftment. Kink folds near Chaura are visible, while asymmetric shear sense indicators in augen mylonite are predominantly observed under microscopic examination. Moreover, the research highlights the documentation of the Higher Himalayan Out-of-Sequence Thrust (OOST) in Himachal Pradesh, which activated the MCT and occurred within a zone south of the Main Central Thrust Upper (MCTU). The presence of multiple sets of OOSTs suggests a zigzag pattern of strain accumulation in the area. The study emphasizes the significance of understanding the overprinting structures associated with OOSTs. Overall, this study contributes to the understanding of the structural analysis of the Chaura Thrust and its implications in the regional geology of the Himachal Himalaya. The research underscores the importance of microscopic studies in identifying mylonitised zones and various types of crenulated schistosity. Additionally, the study documents the GBM-associated temperature range and provides insights into the activation of the Higher Himalayan Out-of-Sequence Thrust (OOST) in Himachal Pradesh. The findings of the study were obtained through geological field observations, microscopic studies, and strain analysis, offering valuable insights into the activation timing, mylonitization characteristics, and overprinting structures related to the Chaura Thrust and the broader tectonic framework of the region.

Keywords: Main Central Thrust, Jhakri Thrust, Chaura Thrust, Higher Himalaya, Out-of-Sequence Thrust, Sarahan Thrust

Procedia PDF Downloads 71
97 Gene Expression Meta-Analysis of Potential Shared and Unique Pathways Between Autoimmune Diseases Under anti-TNFα Therapy

Authors: Charalabos Antonatos, Mariza Panoutsopoulou, Georgios K. Georgakilas, Evangelos Evangelou, Yiannis Vasilopoulos

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The extended tissue damage and severe clinical outcomes of autoimmune diseases, accompanied by the high annual costs to the overall health care system, highlight the need for an efficient therapy. Increasing knowledge over the pathophysiology of specific chronic inflammatory diseases, namely Psoriasis (PsO), Inflammatory Bowel Diseases (IBD) consisting of Crohn’s disease (CD) and Ulcerative colitis (UC), and Rheumatoid Arthritis (RA), has provided insights into the underlying mechanisms that lead to the maintenance of the inflammation, such as Tumor Necrosis Factor alpha (TNF-α). Hence, the anti-TNFα biological agents pose as an ideal therapeutic approach. Despite the efficacy of anti-TNFα agents, several clinical trials have shown that 20-40% of patients do not respond to treatment. Nowadays, high-throughput technologies have been recruited in order to elucidate the complex interactions in multifactorial phenotypes, with the most ubiquitous ones referring to transcriptome quantification analyses. In this context, a random effects meta-analysis of available gene expression cDNA microarray datasets was performed between responders and non-responders to anti-TNFα therapy in patients with IBD, PsO, and RA. Publicly available datasets were systematically searched from inception to 10th of November 2020 and selected for further analysis if they assessed the response to anti-TNFα therapy with clinical score indexes from inflamed biopsies. Specifically, 4 IBD (79 responders/72 non-responders), 3 PsO (40 responders/11 non-responders) and 2 RA (16 responders/6 non-responders) datasetswere selected. After the separate pre-processing of each dataset, 4 separate meta-analyses were conducted; three disease-specific and a single combined meta-analysis on the disease-specific results. The MetaVolcano R package (v.1.8.0) was utilized for a random-effects meta-analysis through theRestricted Maximum Likelihood (RELM) method. The top 1% of the most consistently perturbed genes in the included datasets was highlighted through the TopConfects approach while maintaining a 5% False Discovery Rate (FDR). Genes were considered as Differentialy Expressed (DEGs) as those with P ≤ 0.05, |log2(FC)| ≥ log2(1.25) and perturbed in at least 75% of the included datasets. Over-representation analysis was performed using Gene Ontology and Reactome Pathways for both up- and down-regulated genes in all 4 performed meta-analyses. Protein-Protein interaction networks were also incorporated in the subsequentanalyses with STRING v11.5 and Cytoscape v3.9. Disease-specific meta-analyses detected multiple distinct pro-inflammatory and immune-related down-regulated genes for each disease, such asNFKBIA, IL36, and IRAK1, respectively. Pathway analyses revealed unique and shared pathways between each disease, such as Neutrophil Degranulation and Signaling by Interleukins. The combined meta-analysis unveiled 436 DEGs, 86 out of which were up- and 350 down-regulated, confirming the aforementioned shared pathways and genes, as well as uncovering genes that participate in anti-inflammatory pathways, namely IL-10 signaling. The identification of key biological pathways and regulatory elements is imperative for the accurate prediction of the patient’s response to biological drugs. Meta-analysis of such gene expression data could aid the challenging approach to unravel the complex interactions implicated in the response to anti-TNFα therapy in patients with PsO, IBD, and RA, as well as distinguish gene clusters and pathways that are altered through this heterogeneous phenotype.

Keywords: anti-TNFα, autoimmune, meta-analysis, microarrays

Procedia PDF Downloads 148
96 Surface Plasmon Resonance Imaging-Based Epigenetic Assay for Blood DNA Post-Traumatic Stress Disorder Biomarkers

Authors: Judy M. Obliosca, Olivia Vest, Sandra Poulos, Kelsi Smith, Tammy Ferguson, Abigail Powers Lott, Alicia K. Smith, Yang Xu, Christopher K. Tison

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Post-Traumatic Stress Disorder (PTSD) is a mental health problem that people may develop after experiencing traumatic events such as combat, natural disasters, and major emotional challenges. Tragically, the number of military personnel with PTSD correlates directly with the number of veterans who attempt suicide, with the highest rate in the Army. Research has shown epigenetic risks in those who are prone to several psychiatric dysfunctions, particularly PTSD. Once initiated in response to trauma, epigenetic alterations in particular, the DNA methylation in the form of 5-methylcytosine (5mC) alters chromatin structure and represses gene expression. Current methods to detect DNA methylation, such as bisulfite-based genomic sequencing techniques, are laborious and have massive analysis workflow while still having high error rates. A faster and simpler detection method of high sensitivity and precision would be useful in a clinical setting to confirm potential PTSD etiologies, prevent other psychiatric disorders, and improve military health. A nano-enhanced Surface Plasmon Resonance imaging (SPRi)-based assay that simultaneously detects site-specific 5mC base (termed as PTSD base) in methylated genes related to PTSD is being developed. The arrays on a sensing chip were first constructed for parallel detection of PTSD bases using synthetic and genomic DNA (gDNA) samples. For the gDNA sample extracted from the whole blood of a PTSD patient, the sample was first digested using specific restriction enzymes, and fragments were denatured to obtain single-stranded methylated target genes (ssDNA). The resulting mixture of ssDNA was then injected into the assay platform, where targets were captured by specific DNA aptamer probes previously immobilized on the surface of a sensing chip. The PTSD bases in targets were detected by anti-5-methylcytosine antibody (anti-5mC), and the resulting signals were then enhanced by the universal nanoenhancer. Preliminary results showed successful detection of a PTSD base in a gDNA sample. Brighter spot images and higher delta values (control-subtracted reflectivity signal) relative to those of the control were observed. We also implemented the in-house surface activation system for detection and developed SPRi disposable chips. Multiplexed PTSD base detection of target methylated genes in blood DNA from PTSD patients of severity conditions (asymptomatic and severe) was conducted. This diagnostic capability being developed is a platform technology, and upon successful implementation for PTSD, it could be reconfigured for the study of a wide variety of neurological disorders such as traumatic brain injury, Alzheimer’s disease, schizophrenia, and Huntington's disease and can be extended to the analyses of other sample matrices such as urine and saliva.

Keywords: epigenetic assay, DNA methylation, PTSD, whole blood, multiplexing

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95 Design Aspects for Developing a Microfluidics Diagnostics Device Used for Low-Cost Water Quality Monitoring

Authors: Wenyu Guo, Malachy O’Rourke, Mark Bowkett, Michael Gilchrist

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Many devices for real-time monitoring of surface water have been developed in the past few years to provide early warning of pollutions and so to decrease the risk of environmental pollution efficiently. One of the most common methodologies used in the detection system is a colorimetric process, in which a container with fixed volume is filled with target ions and reagents to combine a colorimetric dye. The colorimetric ions can sensitively absorb a specific-wavelength radiation beam, and its absorbance rate is proportional to the concentration of the fully developed product, indicating the concentration of target nutrients in the pre-mixed water samples. In order to achieve precise and rapid detection effect, channels with dimensions in the order of micrometers, i.e., microfluidic systems have been developed and introduced into these diagnostics studies. Microfluidics technology largely reduces the surface to volume ratios and decrease the samples/reagents consumption significantly. However, species transport in such miniaturized channels is limited by the low Reynolds numbers in the regimes. Thus, the flow is extremely laminar state, and diffusion is the dominant mass transport process all over the regimes of the microfluidic channels. The objective of this present work has been to analyse the mixing effect and chemistry kinetics in a stop-flow microfluidic device measuring Nitride concentrations in fresh water samples. In order to improve the temporal resolution of the Nitride microfluidic sensor, we have used computational fluid dynamics to investigate the influence that the effectiveness of the mixing process between the sample and reagent within a microfluidic device exerts on the time to completion of the resulting chemical reaction. This computational approach has been complemented by physical experiments. The kinetics of the Griess reaction involving the conversion of sulphanilic acid to a diazonium salt by reaction with nitrite in acidic solution is set in the Laminar Finite-rate chemical reaction in the model. Initially, a methodology was developed to assess the degree of mixing of the sample and reagent within the device. This enabled different designs of the mixing channel to be compared, such as straight, square wave and serpentine geometries. Thereafter, the time to completion of the Griess reaction within a straight mixing channel device was modeled and the reaction time validated with experimental data. Further simulations have been done to compare the reaction time to effective mixing within straight, square wave and serpentine geometries. Results show that square wave channels can significantly improve the mixing effect and provides a low standard deviations of the concentrations of nitride and reagent, while for straight channel microfluidic patterns the corresponding values are 2-3 orders of magnitude greater, and consequently are less efficiently mixed. This has allowed us to design novel channel patterns of micro-mixers with more effective mixing that can be used to detect and monitor levels of nutrients present in water samples, in particular, Nitride. Future generations of water quality monitoring and diagnostic devices will easily exploit this technology.

Keywords: nitride detection, computational fluid dynamics, chemical kinetics, mixing effect

Procedia PDF Downloads 180
94 The Optimization of Topical Antineoplastic Therapy Using Controlled Release Systems Based on Amino-functionalized Mesoporous Silica

Authors: Lacramioara Ochiuz, Aurelia Vasile, Iulian Stoleriu, Cristina Ghiciuc, Maria Ignat

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Topical administration of chemotherapeutic agents (eg. carmustine, bexarotene, mechlorethamine etc.) in local treatment of cutaneous T-cell lymphoma (CTCL) is accompanied by multiple side effects, such as contact hypersensitivity, pruritus, skin atrophy or even secondary malignancies. A known method of reducing the side effects of anticancer agent is the development of modified drug release systems using drug incapsulation in biocompatible nanoporous inorganic matrices, such as mesoporous MCM-41 silica. Mesoporous MCM-41 silica is characterized by large specific surface, high pore volume, uniform porosity, and stable dispersion in aqueous medium, excellent biocompatibility, in vivo biodegradability and capacity to be functionalized with different organic groups. Therefore, MCM-41 is an attractive candidate for a wide range of biomedical applications, such as controlled drug release, bone regeneration, protein immobilization, enzymes, etc. The main advantage of this material lies in its ability to host a large amount of the active substance in uniform pore system with adjustable size in a mesoscopic range. Silanol groups allow surface controlled functionalization leading to control of drug loading and release. This study shows (I) the amino-grafting optimization of mesoporous MCM-41 silica matrix by means of co-condensation during synthesis and post-synthesis using APTES (3-aminopropyltriethoxysilane); (ii) loading the therapeutic agent (carmustine) obtaining a modified drug release systems; (iii) determining the profile of in vitro carmustine release from these systems; (iv) assessment of carmustine release kinetics by fitting on four mathematical models. Obtained powders have been described in terms of structure, texture, morphology thermogravimetric analysis. The concentration of the therapeutic agent in the dissolution medium has been determined by HPLC method. In vitro dissolution tests have been done using cell Enhancer in a 12 hours interval. Analysis of carmustine release kinetics from mesoporous systems was made by fitting to zero-order model, first-order model Higuchi model and Korsmeyer-Peppas model, respectively. Results showed that both types of highly ordered mesoporous silica (amino grafted by co-condensation process or post-synthesis) are thermally stable in aqueous medium. In what regards the degree of loading and efficiency of loading with the therapeutic agent, there has been noticed an increase of around 10% in case of co-condensation method application. This result shows that direct co-condensation leads to even distribution of amino groups on the pore walls while in case of post-synthesis grafting many amino groups are concentrated near the pore opening and/or on external surface. In vitro dissolution tests showed an extended carmustine release (more than 86% m/m) both from systems based on silica functionalized directly by co-condensation and after synthesis. Assessment of carmustine release kinetics revealed a release through diffusion from all studied systems as a result of fitting to Higuchi model. The results of this study proved that amino-functionalized mesoporous silica may be used as a matrix for optimizing the anti-cancer topical therapy by loading carmustine and developing prolonged-release systems.

Keywords: carmustine, silica, controlled, release

Procedia PDF Downloads 231
93 Poly(Trimethylene Carbonate)/Poly(ε-Caprolactone) Phase-Separated Triblock Copolymers with Advanced Properties

Authors: Nikola Toshikj, Michel Ramonda, Sylvain Catrouillet, Jean-Jacques Robin, Sebastien Blanquer

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Biodegradable and biocompatible block copolymers have risen as the golden materials in both medical and environmental applications. Moreover, if their architecture is of controlled manner, higher applications can be foreseen. In the meantime, organocatalytic ROP has been promoted as more rapid and immaculate route, compared to the traditional organometallic catalysis, towards efficient synthesis of block copolymer architectures. Therefore, herein we report novel organocatalytic pathway with guanidine molecules (TBD) for supported synthesis of trimethylene carbonate initiated by poly(caprolactone) as pre-polymer. Pristine PTMC-b-PCL-b-PTMC block copolymer structure, without any residual products and clear desired block proportions, was achieved under 1.5 hours at room temperature and verified by NMR spectroscopies and size-exclusion chromatography. Besides, when elaborating block copolymer films, further stability and amelioration of mechanical properties can be achieved via additional reticulation step of precedently methacrylated block copolymers. Subsequently, stimulated by the insufficient studies on the phase-separation/crystallinity relationship in these semi-crystalline block copolymer systems, their intrinsic thermal and morphology properties were investigated by differential scanning calorimetry and atomic force microscopy. Firstly, by DSC measurements, the block copolymers with χABN values superior to 20 presented two distinct glass transition temperatures, close to the ones of the respecting homopolymers, demonstrating an initial indication of a phase-separated system. In the interim, the existence of the crystalline phase was supported by the presence of melting temperature. As expected, the crystallinity driven phase-separated morphology predominated in the AFM analysis of the block copolymers. Neither crosslinking at melted state, hence creation of a dense polymer network, disturbed the crystallinity phenomena. However, the later revealed as sensible to rapid liquid nitrogen quenching directly from the melted state. Therefore, AFM analysis of liquid nitrogen quenched and crosslinked block copolymer films demonstrated a thermodynamically driven phase-separation clearly predominating over the originally crystalline one. These AFM films remained stable with their morphology unchanged even after 4 months at room temperature. However, as demonstrated by DSC analysis once rising the temperature above the melting temperature of the PCL block, neither the crosslinking nor the liquid nitrogen quenching shattered the semi-crystalline network, while the access to thermodynamical phase-separated structures was possible for temperatures under the poly (caprolactone) melting point. Precisely this coexistence of dual crosslinked/crystalline networks in the same copolymer structure allowed us to establish, for the first time, the shape-memory properties in such materials, as verified by thermomechanical analysis. Moreover, the response temperature to the material original shape depended on the block copolymer emplacement, hence PTMC or PCL as end-block. Therefore, it has been possible to reach a block copolymer with transition temperature around 40°C thus opening potential real-life medical applications. In conclusion, the initial study of phase-separation/crystallinity relationship in PTMC-b-PCL-b-PTMC block copolymers lead to the discovery of novel shape memory materials with superior properties, widely demanded in modern-life applications.

Keywords: biodegradable block copolymers, organocatalytic ROP, self-assembly, shape-memory

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92 Gis Based Flash Flood Runoff Simulation Model of Upper Teesta River Besin - Using Aster Dem and Meteorological Data

Authors: Abhisek Chakrabarty, Subhraprakash Mandal

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Flash flood is one of the catastrophic natural hazards in the mountainous region of India. The recent flood in the Mandakini River in Kedarnath (14-17th June, 2013) is a classic example of flash floods that devastated Uttarakhand by killing thousands of people.The disaster was an integrated effect of high intensityrainfall, sudden breach of Chorabari Lake and very steep topography. Every year in Himalayan Region flash flood occur due to intense rainfall over a short period of time, cloud burst, glacial lake outburst and collapse of artificial check dam that cause high flow of river water. In Sikkim-Derjeeling Himalaya one of the probable flash flood occurrence zone is Teesta Watershed. The Teesta River is a right tributary of the Brahmaputra with draining mountain area of approximately 8600 Sq. km. It originates in the Pauhunri massif (7127 m). The total length of the mountain section of the river amounts to 182 km. The Teesta is characterized by a complex hydrological regime. The river is fed not only by precipitation, but also by melting glaciers and snow as well as groundwater. The present study describes an attempt to model surface runoff in upper Teesta basin, which is directly related to catastrophic flood events, by creating a system based on GIS technology. The main object was to construct a direct unit hydrograph for an excess rainfall by estimating the stream flow response at the outlet of a watershed. Specifically, the methodology was based on the creation of a spatial database in GIS environment and on data editing. Moreover, rainfall time-series data collected from Indian Meteorological Department and they were processed in order to calculate flow time and the runoff volume. Apart from the meteorological data, background data such as topography, drainage network, land cover and geological data were also collected. Clipping the watershed from the entire area and the streamline generation for Teesta watershed were done and cross-sectional profiles plotted across the river at various locations from Aster DEM data using the ERDAS IMAGINE 9.0 and Arc GIS 10.0 software. The analysis of different hydraulic model to detect flash flood probability ware done using HEC-RAS, Flow-2D, HEC-HMS Software, which were of great importance in order to achieve the final result. With an input rainfall intensity above 400 mm per day for three days the flood runoff simulation models shows outbursts of lakes and check dam individually or in combination with run-off causing severe damage to the downstream settlements. Model output shows that 313 Sq. km area were found to be most vulnerable to flash flood includes Melli, Jourthang, Chungthang, and Lachung and 655sq. km. as moderately vulnerable includes Rangpo,Yathang, Dambung,Bardang, Singtam, Teesta Bazarand Thangu Valley. The model was validated by inserting the rain fall data of a flood event took place in August 1968, and 78% of the actual area flooded reflected in the output of the model. Lastly preventive and curative measures were suggested to reduce the losses by probable flash flood event.

Keywords: flash flood, GIS, runoff, simulation model, Teesta river basin

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91 Development of Peptide Inhibitors against Dengue Virus Infection by in Silico Design

Authors: Aussara Panya, Nunghathai Sawasdee, Mutita Junking, Chatchawan Srisawat, Kiattawee Choowongkomon, Pa-Thai Yenchitsomanus

Abstract:

Dengue virus (DENV) infection is a global public health problem with approximately 100 million infected cases a year. Presently, there is no approved vaccine or effective drug available; therefore, the development of anti-DENV drug is urgently needed. The clinical reports revealing the positive association between the disease severity and viral titer has been reported previously suggesting that the anti-DENV drug therapy can possibly ameliorate the disease severity. Although several anti-DENV agents showed inhibitory activities against DENV infection, to date none of them accomplishes clinical use in the patients. The surface envelope (E) protein of DENV is critical for the viral entry step, which includes attachment and membrane fusion; thus, the blocking of envelope protein is an attractive strategy for anti-DENV drug development. To search the safe anti-DENV agent, this study aimed to search for novel peptide inhibitors to counter DENV infection through the targeting of E protein using a structure-based in silico design. Two selected strategies has been used including to identify the peptide inhibitor which interfere the membrane fusion process whereby the hydrophobic pocket on the E protein was the target, the destabilization of virion structure organization through the disruption of the interaction between the envelope and membrane proteins, respectively. The molecular docking technique has been used in the first strategy to search for the peptide inhibitors that specifically bind to the hydrophobic pocket. The second strategy, the peptide inhibitor has been designed to mimic the ectodomain portion of membrane protein to disrupt the protein-protein interaction. The designed peptides were tested for the effects on cell viability to measure the toxic to peptide to the cells and their inhibitory assay to inhibit the DENV infection in Vero cells. Furthermore, their antiviral effects on viral replication, intracellular protein level and viral production have been observed by using the qPCR, cell-based flavivirus immunodetection and immunofluorescence assay. None of tested peptides showed the significant effect on cell viability. The small peptide inhibitors achieved from molecular docking, Glu-Phe (EF), effectively inhibited DENV infection in cell culture system. Its most potential effect was observed for DENV2 with a half maximal inhibition concentration (IC50) of 96 μM, but it partially inhibited other serotypes. Treatment of EF at 200 µM on infected cells also significantly reduced the viral genome and protein to 83.47% and 84.15%, respectively, corresponding to the reduction of infected cell numbers. An additional approach was carried out by using peptide mimicking membrane (M) protein, namely MLH40. Treatment of MLH40 caused the reduction of foci formation in four individual DENV serotype (DENV1-4) with IC50 of 24-31 μM. Further characterization suggested that the MLH40 specifically blocked viral attachment to host membrane, and treatment with 100 μM could diminish 80% of viral attachment. In summary, targeting the hydrophobic pocket and M-binding site on the E protein by using the peptide inhibitors could inhibit DENV infection. The results provide proof of-concept for the development of antiviral therapeutic peptide inhibitors to counter DENV infection through the use of a structure-based design targeting conserved viral protein.

Keywords: dengue virus, dengue virus infection, drug design, peptide inhibitor

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90 Membrane Permeability of Middle Molecules: A Computational Chemistry Approach

Authors: Sundaram Arulmozhiraja, Kanade Shimizu, Yuta Yamamoto, Satoshi Ichikawa, Maenaka Katsumi, Hiroaki Tokiwa

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Drug discovery is shifting from small molecule based drugs targeting local active site to middle molecules (MM) targeting large, flat, and groove-shaped binding sites, for example, protein-protein interface because at least half of all targets assumed to be involved in human disease have been classified as “difficult to drug” with traditional small molecules. Hence, MMs such as peptides, natural products, glycans, nucleic acids with various high potent bioactivities become important targets for drug discovery programs in the recent years as they could be used for ‘undruggable” intracellular targets. Cell membrane permeability is one of the key properties of pharmacodynamically active MM drug compounds and so evaluating this property for the potential MMs is crucial. Computational prediction for cell membrane permeability of molecules is very challenging; however, recent advancement in the molecular dynamics simulations help to solve this issue partially. It is expected that MMs with high membrane permeability will enable drug discovery research to expand its borders towards intracellular targets. Further to understand the chemistry behind the permeability of MMs, it is necessary to investigate their conformational changes during the permeation through membrane and for that their interactions with the membrane field should be studied reliably because these interactions involve various non-bonding interactions such as hydrogen bonding, -stacking, charge-transfer, polarization dispersion, and non-classical weak hydrogen bonding. Therefore, parameters-based classical mechanics calculations are hardly sufficient to investigate these interactions rather, quantum mechanical (QM) calculations are essential. Fragment molecular orbital (FMO) method could be used for such purpose as it performs ab initio QM calculations by dividing the system into fragments. The present work is aimed to study the cell permeability of middle molecules using molecular dynamics simulations and FMO-QM calculations. For this purpose, a natural compound syringolin and its analogues were considered in this study. Molecular simulations were performed using NAMD and Gromacs programs with CHARMM force field. FMO calculations were performed using the PAICS program at the correlated Resolution-of-Identity second-order Moller Plesset (RI-MP2) level with the cc-pVDZ basis set. The simulations clearly show that while syringolin could not permeate the membrane, its selected analogues go through the medium in nano second scale. These correlates well with the existing experimental evidences that these syringolin analogues are membrane-permeable compounds. Further analyses indicate that intramolecular -stacking interactions in the syringolin analogues influenced their permeability positively. These intramolecular interactions reduce the polarity of these analogues so that they could permeate the lipophilic cell membrane. Conclusively, the cell membrane permeability of various middle molecules with potent bioactivities is efficiently studied using molecular dynamics simulations. Insight of this behavior is thoroughly investigated using FMO-QM calculations. Results obtained in the present study indicate that non-bonding intramolecular interactions such as hydrogen-bonding and -stacking along with the conformational flexibility of MMs are essential for amicable membrane permeation. These results are interesting and are nice example for this theoretical calculation approach that could be used to study the permeability of other middle molecules. This work was supported by Japan Agency for Medical Research and Development (AMED) under Grant Number 18ae0101047.

Keywords: fragment molecular orbital theory, membrane permeability, middle molecules, molecular dynamics simulation

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

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

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

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

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88 A Multi-Model Approach to Assess Atlantic Bonito (Sarda Sarda, Bloch 1793) in the Eastern Atlantic Ocean: A Case Study of the Senegalese Exclusive Economic Zone

Authors: Ousmane Sarr

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The Senegalese coasts have high productivity of fishery resources due to the frequency of intense up-welling system that occurs along its coast, caused by the maritime trade winds making its waters nutrients rich. Fishing plays a primordial role in Senegal's socioeconomic plans and food security. However, a global diagnosis of the Senegalese maritime fishing sector has highlighted the challenges this sector encounters. Among these concerns, some significant stocks, a priority target for artisanal fishing, need further assessment. If no efforts are made in this direction, most stock will be overexploited or even in decline. It is in this context that this research was initiated. This investigation aimed to apply a multi-modal approach (LBB, Catch-only-based CMSY model and its most recent version (CMSY++); JABBA, and JABBA-Select) to assess the stock of Atlantic bonito, Sarda sarda (Bloch, 1793) in the Senegalese Exclusive Economic Zone (SEEZ). Available catch, effort, and size data from Atlantic bonito over 15 years (2004-2018) were used to calculate the nominal and standardized CPUE, size-frequency distribution, and length at retentions (50 % and 95 % selectivity) of the species. These relevant results were employed as input parameters for stock assessment models mentioned above to define the stock status of this species in this region of the Atlantic Ocean. The LBB model indicated an Atlantic bonito healthy stock status with B/BMSY values ranging from 1.3 to 1.6 and B/B0 values varying from 0.47 to 0.61 of the main scenarios performed (BON_AFG_CL, BON_GN_Length, and BON_PS_Length). The results estimated by LBB are consistent with those obtained by CMSY. The CMSY model results demonstrate that the SEEZ Atlantic bonito stock is in a sound condition in the final year of the main scenarios analyzed (BON, BON-bt, BON-GN-bt, and BON-PS-bt) with sustainable relative stock biomass (B2018/BMSY = 1.13 to 1.3) and fishing pressure levels (F2018/FMSY= 0.52 to 1.43). The B/BMSY and F/FMSY results for the JABBA model ranged between 2.01 to 2.14 and 0.47 to 0.33, respectively. In contrast, The estimated B/BMSY and F/FMSY for JABBA-Select ranged from 1.91 to 1.92 and 0.52 to 0.54. The Kobe plots results of the base case scenarios ranged from 75% to 89% probability in the green area, indicating sustainable fishing pressure and an Atlantic bonito healthy stock size capable of producing high yields close to the MSY. Based on the stock assessment results, this study highlighted scientific advice for temporary management measures. This study suggests an improvement of the selectivity parameters of longlines and purse seines and a temporary prohibition of the use of sleeping nets in the fishery for the Atlantic bonito stock in the SEEZ based on the results of the length-base models. Although these actions are temporary, they can be essential to reduce or avoid intense pressure on the Atlantic bonito stock in the SEEZ. However, it is necessary to establish harvest control rules to provide coherent and solid scientific information that leads to appropriate decision-making for rational and sustainable exploitation of Atlantic bonito in the SEEZ and the Eastern Atlantic Ocean.

Keywords: multi-model approach, stock assessment, atlantic bonito, healthy stock, sustainable, SEEZ, temporary management measures

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87 Socio-Sensorial Assessment of Nursing Homes in Singapore: Towards Integrated Enabling Design

Authors: Zdravko Trivic, John Chye Fung, Ruzica Bozovic-Stamenovic

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Within the context of rapidly ageing population in Singapore and the pressing demands on both caregivers and care providers, an integrated approach to ageing-friendly and ability-sensitive enabling environment becomes an imperative. This particularly applies to nursing home environments and their immediate surroundings, as they are becoming one of the main available options of long-term care for many senior adults who are unable to age at home. Yet, despite the considerable efforts to break the still predominant clinical approach to eldercare and to introduce more home-like design and person-centric care model, nursing homes keep being stigmatised and perceived as not so desirable environments to grow old in. The challenges are further emphasised by the associated physical, sensorial, psychological and cognitive declines that are the common consequences of ageing. Such declines have an immense impact on almost all aspects of older adults’ daily functioning, including problems with mobility and spatial orientation, difficulties in communication, withdrawal from social interaction, higher level of depression and decreased sense of independence and autonomy. However, typical nursing home designs tend to neglect the full capacities of balanced and carefully integrated multisensory stimuli as active component of care and ability building. This paper outlines part of a larger multi-disciplinary study of six nursing homes in Singapore, with overarching objectives to create new models of supportive nursing home environments that go beyond the clinical care model and encourage community integration with the nursing home settings. The paper focuses on the largely neglected aspects of sensorial comfort and multi-sensorial properties of nursing homes, including both indoor and immediate outdoor spaces (boundaries). The objective was to investigate the sensory rhythms and explore their role in nursing home users’ daily routine and therapeutic capacities. Socio-sensory rhythms were captured and analysed through a combination of on-site sensory recordings of “objective” quantitative sensory data (air temperature and humidity, sound level and luminance) using multi-function environment meter, perceived experienced data, spatial mapping, first-person observations of nursing home users’ activity patterns, and interviews. This was done in addition to employment of available assessment tools, such as Wisconsin Person Directed Care assessment tool, Dementia Quality of Life [DQoL] instrument, and Resident Environment Impact Scale [REIS], as these tools address the issues of sensorial experience insufficiently and selectively. Key findings indicate varied levels of sensory comfort, as well as diversity, intensity, and customisation of multi-sensory conditions within different nursing home spaces. Sensory stimulation is typically concentrated in communal living areas of the nursing homes or in the areas that often provide controlled or limited access, including specifically designed sensory rooms and outdoor green spaces (gardens and terraces). Opportunities for sensory stimulation are particularly limited for bed-bound senior residents and within more functional areas, such as corridors. This suggests that the capacities of nursing home designs to provide more diverse and better integrated pleasant sensory conditions as integrated “therapeutic devices” to build nursing home residents’ physical and mental abilities, encourage activity and improve wellbeing are far from exhausted.

Keywords: ageing-supportive environment, enabling design, multi-sensory assessment, nursing home environment

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86 La0.80Ag0.15MnO3 Magnetic Nanoparticles for Self-Controlled Magnetic Fluid Hyperthermia

Authors: Marian Mihalik, Kornel Csach, Martin Kovalik, Matúš Mihalik, Martina Kubovčíková, Maria Zentková, Martin Vavra, Vladimír Girman, Jaroslav Briančin, Marija Perovic, Marija Boškovic, Magdalena Fitta, Robert Pelka

Abstract:

Current nanomaterials for use in biomedicine are based mainly on iron oxides and on present knowledge on magnetic nanostructures. Manganites can represent another material which can be used optionally. Manganites and their unique electronic properties have been extensively studied in the last decades not only due to fundamental interest but to possible applications of colossal magnetoresistance, magnetocaloric effect, and ferroelectric properties. It was found that the oxygen-reduction reaction on perovskite oxide is intimately connected with metal ion e.g., orbital occupation. The effect of oxygen deviation from the stoichiometric composition on crystal structure was studied very carefully by many authors on LaMnO₃. Depending on oxygen content, the crystal structure changes from orthorhombic one to rhombohedric for oxygen content 3.1. In the case of hole-doped manganites, the change from the orthorhombic crystal structure, which is typical for La1-xCaxMnO3 based manganites, to the rhombohedric crystal structure (La1-xMxMnO₃ where M = K, Ag, and Sr based materials) results in an enormous increase of the Curie temperature. In our paper, we study the effect of oxygen content on crystal structure, thermal, and magnetic properties (including magnetocaloric effect) of La1-xAgxMnO₃nano particle system. The content of oxygen in samples was tuned by heat treatment in different thermal regimes and in various environment (air, oxygen, argon). Water nanosuspensions based on La0.80Ag0.15MnO₃ magnetic particles with the Curie temperature of about 43oC were prepared by two different approaches. First, by using a laboratory circulation mill for milling of powder in the presence of sodium dodecyl sulphate (SDS) and subsequent centrifugation. Second nanosuspension was prepared using an agate bowl, etching in citric acid and HNO3, ultrasound homogeniser, centrifugation, and dextran 40 kDA or 15 kDA as surfactant. Electrostatic stabilisation obtained by the first approach did not offer long term kinetic and aggregation colloidal stability and was unable to compensate for attractive forces between particles under a magnetic field. By the second approach, we prepared suspension oversaturated by dextran 40 kDA for steric stabilisation, with evidence of the presence of superparamagnetic behaviour. Low concentration of nanoparticles and not ideal coverage of nanoparticles impacting the stability of ferrofluids was the disadvantage of this approach. Strong steric stabilisation was observable at alcaic conditions under pH = ~10. Application of dextran 15 kDA leads to relatively stable ferrofluid with pH around physiological conditions, but desegregation of powder by HNO₃ was not effective enough, and the average size of fragments was to large of about 150 nm, and we did not see any signature of superparamagnetic behaviour. The prepared ferrofluids were characterised by scanning and transition microscope method, thermogravimetry, magnetization, and AC susceptibility measurements. Specific Absorption Rate measurements were undertaken on powder as well on ferrofluids in order to estimate the potential application of La₀.₈₀Ag₀.₁₅MnO₃ magnetic particles based ferrofluid for hyperthermia. Our complex study contains an investigation of biocompatibility and potential biohazard of this material.

Keywords: manganites, magnetic nanoparticles, oxygen content, magnetic phase transition, magnetocaloric effect, ferrofluid, hyperthermia

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85 Complete Genome Sequence Analysis of Pasteurella multocida Subspecies multocida Serotype A Strain PMTB2.1

Authors: Shagufta Jabeen, Faez J. Firdaus Abdullah, Zunita Zakaria, Nurulfiza M. Isa, Yung C. Tan, Wai Y. Yee, Abdul R. Omar

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Pasteurella multocida (PM) is an important veterinary opportunistic pathogen particularly associated with septicemic pasteurellosis, pneumonic pasteurellosis and hemorrhagic septicemia in cattle and buffaloes. P. multocida serotype A has been reported to cause fatal pneumonia and septicemia. Pasteurella multocida subspecies multocida of serotype A Malaysian isolate PMTB2.1 was first isolated from buffaloes died of septicemia. In this study, the genome of P. multocida strain PMTB2.1 was sequenced using third-generation sequencing technology, PacBio RS2 system and analyzed bioinformatically via de novo analysis followed by in-depth analysis based on comparative genomics. Bioinformatics analysis based on de novo assembly of PacBio raw reads generated 3 contigs followed by gap filling of aligned contigs with PCR sequencing, generated a single contiguous circular chromosome with a genomic size of 2,315,138 bp and a GC content of approximately 40.32% (Accession number CP007205). The PMTB2.1 genome comprised of 2,176 protein-coding sequences, 6 rRNA operons and 56 tRNA and 4 ncRNAs sequences. The comparative genome sequence analysis of PMTB2.1 with nine complete genomes which include Actinobacillus pleuropneumoniae, Haemophilus parasuis, Escherichia coli and five P. multocida complete genome sequences including, PM70, PM36950, PMHN06, PM3480, PMHB01 and PMTB2.1 was carried out based on OrthoMCL analysis and Venn diagram. The analysis showed that 282 CDs (13%) are unique to PMTB2.1and 1,125 CDs with orthologs in all. This reflects overall close relationship of these bacteria and supports the classification in the Gamma subdivision of the Proteobacteria. In addition, genomic distance analysis among all nine genomes indicated that PMTB2.1 is closely related with other five Pasteurella species with genomic distance less than 0.13. Synteny analysis shows subtle differences in genetic structures among different P.multocida indicating the dynamics of frequent gene transfer events among different P. multocida strains. However, PM3480 and PM70 exhibited exceptionally large structural variation since they were swine and chicken isolates. Furthermore, genomic structure of PMTB2.1 is more resembling that of PM36950 with a genomic size difference of approximately 34,380 kb (smaller than PM36950) and strain-specific Integrative and Conjugative Elements (ICE) which was found only in PM36950 is absent in PMTB2.1. Meanwhile, two intact prophages sequences of approximately 62 kb were found to be present only in PMTB2.1. One of phage is similar to transposable phage SfMu. The phylogenomic tree was constructed and rooted with E. coli, A. pleuropneumoniae and H. parasuis based on OrthoMCL analysis. The genomes of P. multocida strain PMTB2.1 were clustered with bovine isolates of P. multocida strain PM36950 and PMHB01 and were separated from avian isolate PM70 and swine isolates PM3480 and PMHN06 and are distant from Actinobacillus and Haemophilus. Previous studies based on Single Nucleotide Polymorphism (SNPs) and Multilocus Sequence Typing (MLST) unable to show a clear phylogenetic relatedness between Pasteurella multocida and the different host. In conclusion, this study has provided insight on the genomic structure of PMTB2.1 in terms of potential genes that can function as virulence factors for future study in elucidating the mechanisms behind the ability of the bacteria in causing diseases in susceptible animals.

Keywords: comparative genomics, DNA sequencing, phage, phylogenomics

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84 Dynamic Facades: A Literature Review on Double-Skin Façade with Lightweight Materials

Authors: Victor Mantilla, Romeu Vicente, António Figueiredo, Victor Ferreira, Sandra Sorte

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Integrating dynamic facades into contemporary building design is shaping a new era of energy efficiency and user comfort. These innovative facades, often constructed using lightweight construction systems and materials, offer an opportunity to have a responsive and adaptive nature to the dynamic behavior of the outdoor climate. Therefore, in regions characterized by high fluctuations in daily temperatures, the ability to adapt to environmental changes is of paramount importance and a challenge. This paper presents a thorough review of the state of the art on double-skin facades (DSF), focusing on lightweight solutions for the external envelope. Dynamic facades featuring elements like movable shading devices, phase change materials, and advanced control systems have revolutionized the built environment. They offer a promising path for reducing energy consumption while enhancing occupant well-being. Lightweight construction systems are increasingly becoming the choice for the constitution of these facade solutions, offering benefits such as reduced structural loads and reduced construction waste, improving overall sustainability. However, the performance of dynamic facades based on low thermal inertia solutions in climatic contexts with high thermal amplitude is still in need of research since their ability to adapt is traduced in variability/manipulation of the thermal transmittance coefficient (U-value). Emerging technologies can enable such a dynamic thermal behavior through innovative materials, changes in geometry and control to optimize the facade performance. These innovations will allow a facade system to respond to shifting outdoor temperature, relative humidity, wind, and solar radiation conditions, ensuring that energy efficiency and occupant comfort are both met/coupled. This review addresses the potential configuration of double-skin facades, particularly concerning their responsiveness to seasonal variations in temperature, with a specific focus on addressing the challenges posed by winter and summer conditions. Notably, the design of a dynamic facade is significantly shaped by several pivotal factors, including the choice of materials, geometric considerations, and the implementation of effective monitoring systems. Within the realm of double skin facades, various configurations are explored, encompassing exhaust air, supply air, and thermal buffering mechanisms. According to the review places a specific emphasis on the thermal dynamics at play, closely examining the impact of factors such as the color of the facade, the slat angle's dimensions, and the positioning and type of shading devices employed in these innovative architectural structures.This paper will synthesize the current research trends in this field, with the presentation of case studies and technological innovations with a comprehensive understanding of the cutting-edge solutions propelling the evolution of building envelopes in the face of climate change, namely focusing on double-skin lightweight solutions to create sustainable, adaptable, and responsive building envelopes. As indicated in the review, flexible and lightweight systems have broad applicability across all building sectors, and there is a growing recognition that retrofitting existing buildings may emerge as the predominant approach.

Keywords: adaptive, control systems, dynamic facades, energy efficiency, responsive, thermal comfort, thermal transmittance

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83 Optimized Electron Diffraction Detection and Data Acquisition in Diffraction Tomography: A Complete Solution by Gatan

Authors: Saleh Gorji, Sahil Gulati, Ana Pakzad

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

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

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