Search results for: transmission line loading
Commenced in January 2007
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Paper Count: 5905

Search results for: transmission line loading

295 Implementation of Ecological and Energy-Efficient Building Concepts

Authors: Robert Wimmer, Soeren Eikemeier, Michael Berger, Anita Preisler

Abstract:

A relatively large percentage of energy and resource consumption occurs in the building sector. This concerns the production of building materials, the construction of buildings and also the energy consumption during the use phase. Therefore, the overall objective of this EU LIFE project “LIFE Cycle Habitation” (LIFE13 ENV/AT/000741) is to demonstrate innovative building concepts that significantly reduce CO₂emissions, mitigate climate change and contain a minimum of grey energy over their entire life cycle. The project is being realised with the contribution of the LIFE financial instrument of the European Union. The ultimate goal is to design and build prototypes for carbon-neutral and “LIFE cycle”-oriented residential buildings and make energy-efficient settlements the standard of tomorrow in line with the EU 2020 objectives. To this end, a resource and energy-efficient building compound is being built in Böheimkirchen, Lower Austria, which includes 6 living units and a community area as well as 2 single family houses with a total usable floor surface of approximately 740 m². Different innovative straw bale construction types (load bearing and pre-fabricated non loadbearing modules) together with a highly innovative energy-supply system, which is based on the maximum use of thermal energy for thermal energy services, are going to be implemented. Therefore only renewable resources and alternative energies are used to generate thermal as well as electrical energy. This includes the use of solar energy for space heating, hot water and household appliances like dishwasher or washing machine, but also a cooking place for the community area operated with thermal oil as heat transfer medium on a higher temperature level. Solar collectors in combination with a biomass cogeneration unit and photovoltaic panels are used to provide thermal and electric energy for the living units according to the seasonal demand. The building concepts are optimised by support of dynamic simulations. A particular focus is on the production and use of modular prefabricated components and building parts made of regionally available, highly energy-efficient, CO₂-storing renewable materials like straw bales. The building components will be produced in collaboration by local SMEs that are organised in an efficient way. The whole building process and results are monitored and prepared for knowledge transfer and dissemination including a trial living in the residential units to test and monitor the energy supply system and to involve stakeholders into evaluation and dissemination of the applied technologies and building concepts. The realised building concepts should then be used as templates for a further modular extension of the settlement in a second phase.

Keywords: energy-efficiency, green architecture, renewable resources, sustainable building

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294 Investigating Educator Perceptions of Body-Rich Language on Student Self-Image, Body-Consciousness and School Climate

Authors: Evelyn Bilias-Lolis, Emily Louise Winter

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Schools have a responsibility to implement school-wide frameworks that actively prevent, detect, and support all aspects of child development and learning. Such efforts can range from individual or classroom-level supports to school-wide primary prevention practices for the school’s infrastructure or climate. This study assessed the perceptions of educators across a variety of disciplines in Connecticut (i.e., elementary and secondary education, special education, school psychology, and school social work) on the perceived impact of their beliefs, language, and behavior about food and body consciousness on student self-image and school climate. Participants (N=50) completed a short electronic questionnaire measuring perceptions of how their behavior can influence their students’ opinions about themselves, their emerging self-image, and the overall climate of the school community. Secondly, the beliefs that were directly assessed in the first portion of the survey were further measured through the use of applied social vignettes involving students directly or as bystanders. Preliminary findings are intriguing. When asked directly, 100% of the respondents reported that what they say to students directly could influence student opinions about themselves and 98% of participants further agreed that their behavior both to and in front of students could impact a student’s developing self-image. Likewise, 82% of the sample agreed that their personal language and behavior affect the overall climate of a school building. However, when the above beliefs were assessed via applied social vignettes depicting routine social exchanges, results were significantly more widespread (i.e., results were evenly dispersed among levels of agreement and disagreement across participants in all areas). These preliminary findings offer humble but critical implications for informing integrated school wellness frameworks that aim to create body-sensitive school communities. Research indicates that perceptions about body image, attitudes about eating, and the onset of disordered eating practices surface in school-aged years. Schools provide a natural setting for instilling foundations for child wellness as a natural extension of existing school climate reform efforts. These measures do not always need to be expansive or extreme. Rather, educators have a ripe opportunity to become champions for health and wellness through increased self-awareness and subtle shifts in language and behavior. Future psychological research needs to continue to explore this line of inquiry using larger and more varied samples of educators in order to identify needs in teacher training and development that can yield positive and preventative health outcomes for children.

Keywords: body-sensitive schools, integrated school health, school climate reform, teacher awareness

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293 Evaluation of Rheological Properties, Anisotropic Shrinkage, and Heterogeneous Densification of Ceramic Materials during Liquid Phase Sintering by Numerical-Experimental Procedure

Authors: Hamed Yaghoubi, Esmaeil Salahi, Fateme Taati

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The effective shear and bulk viscosity, as well as dynamic viscosity, describe the rheological properties of the ceramic body during the liquid phase sintering process. The rheological parameters depend on the physical and thermomechanical characteristics of the material such as relative density, temperature, grain size, and diffusion coefficient and activation energy. The main goal of this research is to acquire a comprehensive understanding of the response of an incompressible viscose ceramic material during liquid phase sintering process such as stress-strain relations, sintering and hydrostatic stress, the prediction of anisotropic shrinkage and heterogeneous densification as a function of sintering time by including the simultaneous influence of gravity field, and frictional force. After raw materials analysis, the standard hard porcelain mixture as a ceramic body was designed and prepared. Three different experimental configurations were designed including midpoint deflection, sinter bending, and free sintering samples. The numerical method for the ceramic specimens during the liquid phase sintering process are implemented in the CREEP user subroutine code in ABAQUS. The numerical-experimental procedure shows the anisotropic behavior, the complete difference in spatial displacement through three directions, the incompressibility for ceramic samples during the sintering process. The anisotropic shrinkage factor has been proposed to investigate the shrinkage anisotropy. It has been shown that the shrinkage along the normal axis of casting sample is about 1.5 times larger than that of casting direction, the gravitational force in pyroplastic deformation intensifies the shrinkage anisotropy more than the free sintering sample. The lowest and greatest equivalent creep strain occurs at the intermediate zone and around the central line of the midpoint distorted sample, respectively. In the sinter bending test sample, the equivalent creep strain approaches to the maximum near the contact area with refractory support. The inhomogeneity in Von-Misses, pressure, and principal stress intensifies the relative density non-uniformity in all samples, except in free sintering one. The symmetrical distribution of stress around the center of free sintering sample, cause to hinder the pyroplastic deformations. Densification results confirmed that the effective bulk viscosity was well-defined with relative density values. The stress analysis confirmed that the sintering stress is more than the hydrostatic stress from start to end of sintering time so, from both theoretically and experimentally point of view, the sintering process occurs completely.

Keywords: anisotropic shrinkage, ceramic material, liquid phase sintering process, rheological properties, numerical-experimental procedure

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292 Research on Land Use Pattern and Employment-Housing Space of Coastal Industrial Town Based on the Investigation of Liaoning Province, China

Authors: Fei Chen, Wei Lu, Jun Cai

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During the Twelve Five period, China promulgated industrial policies promoting the relocation of energy-intensive industries to coastal areas in order to utilize marine shipping resources. Consequently, some major state-owned steel and gas enterprises have relocated and resulted in a large-scale coastal area development. However, some land may have been over-exploited with seamless coastline projects. To balance between employment and housing, new industrial coastal towns were constructed to support the industrial-led development. In this paper, we adopt a case-study approach to closely examine the development of several new industrial coastal towns of Liaoning Province situated in the Bohai Bay area, which is currently under rapid economic growth. Our investigations reflect the common phenomenon of long distance commuting and a massive amount of vacant residences. More specifically, large plant relocation caused hundreds of kilometers of daily commute and enterprises had to provide housing subsidies and education incentives to motivate employees to relocate to coastal areas. Nonetheless, many employees still refuse to relocate due to job stability, diverse needs of family members and access to convenient services. These employees averaged 4 hours of commute daily and some who lived further had to reside in temporary industrial housing units and subject to long-term family separation. As a result, only a small portion of employees purchase new coastal residences but mostly for investment and retirement purposes, leading to massive vacancy and ghost-town phenomenon. In contrast to the low demand, coastal areas tend to develop large amount of residences prior to industrial relocation, which may be directly related to local government finances. Some local governments have sold residential land to developers to general revenue to support the subsequent industrial development. Subject to the strong preference of ocean-view, residential housing developers tend to select coast-line land to construct new residential towns, which further reduces the access of marine resources for major industrial enterprises. This violates the original intent of developing industrial coastal towns and drastically limits the availability of marine resources. Lastly, we analyze the co-existence of over-exploiting residential areas and massive vacancies in reference to the demand and supply of land, as well as the demand of residential housing units with the choice criteria of enterprise employees.

Keywords: coastal industry town, commuter traffic, employment-housing space, outer suburb industrial area

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291 The 10,000 Fold Effect of Retrograde Neurotransmission, a New Concept for Stroke Revival: Use of Intracarotid Sodium Nitroprusside

Authors: Vinod Kumar

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Background: Tissue Plasminogen Activator (tPA) showed a level 1 benefit in acute stroke (within 3-6 hrs). Intracarotid sodium nitroprusside (ICSNP) has been studied in this context with a wide treatment window, fast recovery and affordability. This work proposes two mechanisms for acute cases and one mechanism for chronic cases, which are interrelated, for physiological recovery. a)Retrograde Neurotransmission (acute cases): 1)Normal excitatory impulse: at the synaptic level, glutamate activates NMDA receptors, with nitric oxide synthetase (NOS) on the postsynaptic membrane, for further propagation by the calcium-calmodulin complex. Nitric oxide (NO, produced by NOS) travels backward across the chemical synapse and binds the axon-terminal NO receptor/sGC of a presynaptic neuron, regulating anterograde neurotransmission (ANT) via retrograde neurotransmission (RNT). Heme is the ligand-binding site of the NO receptor/sGC. Heme exhibits > 10,000-fold higher affinity for NO than for oxygen (the 10,000-fold effect) and is completed in 20 msec. 2)Pathological conditions: normal synaptic activity, including both ANT and RNT, is absent. A NO donor (SNP) releases NO from NOS in the postsynaptic region. NO travels backward across a chemical synapse to bind to the heme of a NO receptor in the axon terminal of a presynaptic neuron, generating an impulse, as under normal conditions. b)Vasospasm: (acute cases) Perforators show vasospastic activity. NO vasodilates the perforators via the NO-cAMP pathway. c)Long-Term Potentıatıon (LTP): (chronic cases) The NO–cGMP-pathway plays a role in LTP at many synapses throughout the CNS and at the neuromuscular junction. LTP has been reviewed both generally and with respect to brain regions specific for memory/learning. Aims/Study Des’gn: The principles of “generation of impulses from the presynaptic region to the postsynaptic region by very potent RNT (10,000-fold effect)” and “vasodilation of arteriolar perforators” are the basis of the authors’ hypothesis to treat stroke cases. Case-control prospective study. Mater’als And Methods: The experimental population included 82 stroke patients (10 patients were given control treatments without superfusion or with 5% dextrose superfusion, and 72 patients comprised the ICSNP group). The mean time for superfusion was 9.5 days post-stroke. Pre- and post-ICSNP status was monitored by NIHSS, MRI and TCD. Results: After 90 seconds in the ICSNP group, the mean change in the NIHSS score was a decrease of 1.44 points, or 6.55%; after 2 h, there was a decrease of 1.16 points; after 24 h, there was an increase of 0.66 points, 2.25%, compared to the control-group increase of 0.7 points, or 3.53%; at 7 days, there was an 8.61-point decrease, 44.58%, compared to the control-group increase of 2.55 points, or 22.37%; at 2 months in ICSNP, there was a 6.94-points decrease, 62.80%, compared to the control-group decrease of 2.77 points, or 8.78%. TCD was documented and improvements were noted. Conclusions: ICSNP is a swift-acting drug in the treatment of stroke, acting within 90 seconds on day 9.5 post-stroke with a small decrease after 24 hours. The drug recovers from this decrease quickly.

Keywords: brain infarcts, intracarotid sodium nitroprusside, perforators, vasodilatıons, retrograde transmission, the 10, 000-fold effect

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290 Developing Sustainable Tourism Practices in Communities Adjacent to Mines: An Exploratory Study in South Africa

Authors: Felicite Ann Fairer-Wessels

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There has always been a disparity between mining and tourism mainly due to the socio-economic and environmental impacts of mines on both the adjacent resident communities and the areas taken up by the mining operation. Although heritage mining tourism has been actively and successfully pursued and developed in the UK, largely Wales, and Scandinavian countries, the debate whether active mining and tourism can have a mutually beneficial relationship remains imminent. This pilot study explores the relationship between the ‘to be developed’ future Nokeng Mine and its adjacent community, the rural community of Moloto, will be investigated in terms of whether sustainable tourism and livelihood activities can potentially be developed with the support of the mine. Concepts such as social entrepreneur, corporate social responsibility, sustainable development and triple bottom line are discussed. Within the South African context as a mineral rich developing country, the government has a statutory obligation to empower disenfranchised communities through social and labour plans and policies. All South African mines must preside over a Social and Labour Plan according to the Mineral and Petroleum Resources Development Act, No 28 of 2002. The ‘social’ component refers to the ‘social upliftment’ of communities within or adjacent to any mine; whereas the ‘labour’ component refers to the mine workers sourced from the specific community. A qualitative methodology is followed using the case study as research instrument for the Nokeng Mine and Moloto community with interviews and focus group discussions. The target population comprised of the Moloto Tribal Council members (8 in-depth interviews), the Moloto community members (17: focus groups); and the Nokeng Mine representatives (4 in-depth interviews). In this pilot study two disparate ‘worlds’ are potentially linked: on the one hand, the mine as social entrepreneur that is searching for feasible and sustainable ideas; and on the other hand, the community adjacent to the mine, with potentially sustainable tourism entrepreneurs that can tap into the resources of the mine should their ideas be feasible to build their businesses. Being an exploratory study the findings are limited but indicate that the possible success of tourism and sustainable livelihood activities lies in the fact that both the Mine and Community are keen to work together – the mine in terms of obtaining labour and profit; and the community in terms of improved and sustainable social and economic conditions; with both parties realizing the importance to mitigate negative environmental impacts. In conclusion, a relationship of trust is imperative between a mine and a community before a long term liaison is possible. However whether tourism is a viable solution for the community to engage in is debatable. The community could initially rather pursue the sustainable livelihoods approach and focus on life-supporting activities such as building, gardening, etc. that once established could feed into possible sustainable tourism activities.

Keywords: community development, mining tourism, sustainability, South Africa

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289 Spatial Accessibility Analysis of Kabul City Public Transport

Authors: Mohammad Idrees Yusofzai, Hirobata Yasuhiro, Matsuo Kojiro

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Kabul is the capital of Afghanistan. It is the focal point of educational, industrial, etc. of Afghanistan. Additionally, the population of Kabul has grown recently and will increase because of return of refugees and shifting of people from other province to Kabul city. However, this increase in population, the issues of urban congestion and other related problems of urban transportation in Kabul city arises. One of the problems is public transport (large buses) service and needs to be modified and enhanced especially large bus routes that are operating in each zone of the 22 zone of Kabul City. To achieve the above mentioned goal of improving public transport, Spatial Accessibility Analysis is one of the important attributes to assess the effectiveness of transportation system and urban transport policy of a city, because accessibility indicator as an alternative tool to support public policy that aims the reinforcement of sustainable urban space. The case study of this research compares the present model (present bus route) and the modified model of public transport. Furthermore, present model, the bus routes in most of the zones are active, however, with having low frequency and unpublished schedule, and accessibility result is analyzed in four cases, based on the variables of accessibility. Whereas in modified model all zones in Kabul is taken into consideration with having specified origin and high frequency. Indeed the number of frequencies is kept high; however, this number is based on the number of buses Millie Bus Enterprise Authority (MBEA) owns. The same approach of cases is applied in modified model to figure out the best accessibility for the modified model. Indeed, the modified model is having a positive impact in congestion level in Kabul city. Besides, analyses of person trip and trip distribution have been also analyzed because how people move in the study area by each mode of transportation. So, the general aims of this research are to assess the present movement of people, identify zones in need of public transport and assess equity level of accessibility in Kabul city. The framework of methodology used in this research is based on gravity analysis model of accessibility; besides, generalized cost (time) of travel and travel mode is calculated. The main data come from person trip survey, socio-economic characteristics, demographic data by Japan International Cooperation Agency, 2008, study of Kabul city and also from the previous researches on travel pattern and the remaining data regarding present bus line and routes have been from MBEA. In conclusion, this research explores zones where public transport accessibility level is high and where it is low. It was found that both models the downtown area or central zones of Kabul city is having high level accessibility. Besides, the present model is the most unfavorable compared with the modified model based on the accessibility analysis.

Keywords: accessibility, bus generalized cost, gravity model, public transportation network

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288 Photoemission Momentum Microscopy of Graphene on Ir (111)

Authors: Anna V. Zaporozhchenko, Dmytro Kutnyakhov, Katherina Medjanik, Christian Tusche, Hans-Joachim Elmers, Olena Fedchenko, Sergey Chernov, Martin Ellguth, Sergej A. Nepijko, Gerd Schoenhense

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Graphene reveals a unique electronic structure that predetermines many intriguing properties such as massless charge carriers, optical transparency and high velocity of fermions at the Fermi level, opening a wide horizon of future applications. Hence, a detailed investigation of the electronic structure of graphene is crucial. The method of choice is angular resolved photoelectron spectroscopy ARPES. Here we present experiments using time-of-flight (ToF) momentum microscopy, being an alternative way of ARPES using full-field imaging of the whole Brillouin zone (BZ) and simultaneous acquisition of up to several 100 energy slices. Unlike conventional ARPES, k-microscopy is not limited in simultaneous k-space access. We have recorded the whole first BZ of graphene on Ir(111) including all six Dirac cones. As excitation source we used synchrotron radiation from BESSY II (Berlin) at the U125-2 NIM, providing linearly polarized (both polarizations p- and s-) VUV radiation. The instrument uses a delay-line detector for single-particle detection up the 5 Mcps range and parallel energy detection via ToF recording. In this way, we gather a 3D data stack I(E,kx,ky) of the full valence electronic structure in approx. 20 mins. Band dispersion stacks were measured in the energy range of 14 eV up to 23 eV with steps of 1 eV. The linearly-dispersing graphene bands for all six K and K’ points were simultaneously recorded. We find clear features of hybridization with the substrate, in particular in the linear dichroism in the angular distribution (LDAD). Recording of the whole Brillouin zone of graphene/Ir(111) revealed new features. First, the intensity differences (i.e. the LDAD) are very sensitive to the interaction of graphene bands with substrate bands. Second, the dark corridors are investigated in detail for both, p- and s- polarized radiation. They appear as local distortions of photoelectron current distribution and are induced by quantum mechanical interference of graphene sublattices. The dark corridors are located in different areas of the 6 Dirac cones and show chirality behaviour with a mirror plane along vertical axis. Moreover, two out of six show an oval shape while the rest are more circular. It clearly indicates orientation dependence with respect to E vector of incident light. Third, a pattern of faint but very sharp lines is visible at energies around 22eV that strongly remind on Kikuchi lines in diffraction. In conclusion, the simultaneous study of all six Dirac cones is crucial for a complete understanding of dichroism phenomena and the dark corridor.

Keywords: band structure, graphene, momentum microscopy, LDAD

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287 The Application of Patterned Injuries in Reconstruction of Motorcycle Accidents

Authors: Chun-Liang Wu, Kai-Ping Shaw, Cheng-Ping Yu, Wu-Chien Chien, Hsiao-Ting Chen, Shao-Huang Wu

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Objective: This study analyzed three criminal judicial cases. We applied the patterned injuries of the rider to demonstrate the facts of each accident, reconstruct the scenes, and pursue the truth. Methods: Case analysis, a method that collects evidence and reasons the results in judicial procedures, then the importance of the pattern of injury as evidence will be compared and evaluated. The patterned injuries analysis method is to compare the collision situation between an object and human body injuries to determine whether the characteristics can reproduce the unique pattern of injury. Result: Case 1: Two motorcycles, A and B, head-on collided; rider A dead, and rider B was accused. During the prosecutor’s investigation, the defendant learned that rider A had an 80 mm open wound on his neck. During the court trial, the defendant requested copies of the case file and found out that rider A had a large contusion on his chest wall, and the cause of death was traumatic hemothorax and abdominal wall contusion. The defendant compared all the evidence at the scene and determined that the injury was obviously not caused by the collision of the body or the motorcycle of rider B but that rider was out of control and injured himself when he crossed the double yellow line. In this case, the defendant was innocent in the High Court judgment in April 2022. Case 2: Motorcycles C and D head-on crashed, and rider C died of massive abdominal bleeding. The prosecutor decided that rider C was driving under the influence (DUI), but rider D was negligent and sued rider D. The defendant requested the copies’ file and found the special phenomenon that the front wheel of motorcycle C was turned left. The defendant’s injuries were a left facial bone fracture, a left femur fracture, and other injuries on the left side. The injuries were of human-vehicle separation and human-vehicle collision, which proved that rider C suddenly turned left when the two motorcycles approached, knocked down motorcycle D, and the defendant flew forward. Case 3: Motorcycle E and F’s rear end collided, the front rider E was sentenced to 3 months, and the rear rider F sued rider E for more than 7 million N.T. The defendant found in the copies’ file that the injury of rider F was the left tibial platform fracture, etc., and then proved that rider F made the collision with his left knee, causing motorcycle E to fall out of control. This evidence was accepted by the court and is still on trial. Conclusion: The application of patterned injuries in the reconstruction of a motorcycle accident could discover the truth and provide the basis for judicial justice. The cases and methods could be the reference for the policy of preventing traffic accident casualties.

Keywords: judicial evidence, patterned injuries analysis, accident reconstruction, fatal motorcycle injuries

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286 Tales of Two Cities: 'Motor City' Detroit and 'King Cotton' Manchester: Transatlantic Transmissions and Transformations, Flows of Communications, Commercial and Cultural Connections

Authors: Dominic Sagar

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Manchester ‘King Cotton’, the first truly industrial city of the nineteenth century, passing on the baton to Detroit ‘Motor City’, is the first truly modern city. We are exploring the tales of the two cities, their rise and fall and subsequent post-industrial decline, their transitions and transformations, whilst alongside paralleling their corresponding, commercial, cultural, industrial and even agricultural, artistic and musical transactions and connections. The paper will briefly contextualize how technologies of the industrial age and modern age have been instrumental in the development of these cities and other similar cities including New York. However, the main focus of the study will be the present and more importantly the future, how globalisation and the advancements of digital technologies and industries have shaped the cities developments from AlanTuring and the making of the first programmable computer to the effect of digitalisation and digital initiatives. Manchester now has a thriving creative digital infrastructure of Digilabs, FabLabs, MadLabs and hubs, the study will reference the Smart Project and the Manchester Digital Development Association whilst paralleling similar digital and creative industrial initiatives now starting to happen in Detroit. The paper will explore other topics including the need to allow for zones of experimentation, areas to play, think and create in order develop and instigate new initiatives and ideas of production, carrying on the tradition of influential inventions throughout the history of these key cities. Other topics will be briefly touched on, such as urban farming, citing the Biospheric foundation in Manchester and other similar projects in Detroit. However, the main thread will focus on the music industries and how they are contributing to the regeneration of cities. Musically and artistically, Manchester and Detroit have been closely connected by the flow and transmission of information and transfer of ideas via ‘cars and trains and boats and planes’ through to the new ‘super highway’. From Detroit to Manchester often via New York and Liverpool and back again, these musical and artistic connections and flows have greatly affected and influenced both cities and the advancement of technology are still connecting the cities. In summary two hugely important industrial cities, subsequently both experienced massive decline in fortunes, having had their large industrial hearts ripped out, ravaged leaving dying industrial carcasses and car crashes of despair, dereliction, desolation and post-industrial wastelands vacated by a massive exodus of the cities’ inhabitants. To examine the affinity, similarity and differences between Manchester & Detroit, from their industrial importance to their post-industrial decline and their current transmutations, transformations, transient transgressions, cities in transition; contrasting how they have dealt with these problems and how they can learn from each other. With a view to framing these topics with regard to how various communities have shaped these cities and the creative industries and design [the new cotton/car manufacturing industries] are reinventing post-industrial cities, to speculate on future development of these themes in relation to Globalisation, digitalisation and how cities can function to develop solutions to communal living in cities of the future.

Keywords: cultural capital, digital developments, musical initiatives, zones of experimentation

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285 Sustainable Production of Pharmaceutical Compounds Using Plant Cell Culture

Authors: David A. Ullisch, Yantree D. Sankar-Thomas, Stefan Wilke, Thomas Selge, Matthias Pump, Thomas Leibold, Kai Schütte, Gilbert Gorr

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Plants have been considered as a source of natural substances for ages. Secondary metabolites from plants are utilized especially in medical applications but are more and more interesting as cosmetical ingredients and in the field of nutraceuticals. However, supply of compounds from natural harvest can be limited by numerous factors i.e. endangered species, low product content, climate impacts and cost intensive extraction. Especially in the pharmaceutical industry the ability to provide sufficient amounts of product and high quality are additional requirements which in some cases are difficult to fulfill by plant harvest. Whereas in many cases the complexity of secondary metabolites precludes chemical synthesis on a reasonable commercial basis, plant cells contain the biosynthetic pathway – a natural chemical factory – for a given compound. A promising approach for the sustainable production of natural products can be plant cell fermentation (PCF®). A thoroughly accomplished development process comprises the identification of a high producing cell line, optimization of growth and production conditions, the development of a robust and reliable production process and its scale-up. In order to address persistent, long lasting production, development of cryopreservation protocols and generation of working cell banks is another important requirement to be considered. So far the most prominent example using a PCF® process is the production of the anticancer compound paclitaxel. To demonstrate the power of plant suspension cultures here we present three case studies: 1) For more than 17 years Phyton produces paclitaxel at industrial scale i.e. up to 75,000 L in scale. With 60 g/kg dw this fully controlled process which is applied according to GMP results in outstanding high yields. 2) Thapsigargin is another anticancer compound which is currently isolated from seeds of Thapsia garganica. Thapsigargin is a powerful cytotoxin – a SERCA inhibitor – and the precursor for the derivative ADT, the key ingredient of the investigational prodrug Mipsagargin (G-202) which is in several clinical trials. Phyton successfully generated plant cell lines capable to express this compound. Here we present data about the screening for high producing cell lines. 3) The third case study covers ingenol-3-mebutate. This compound is found in the milky sap of the intact plants of the Euphorbiacae family at very low concentrations. Ingenol-3-mebutate is used in Picato® which is approved against actinic keratosis. Generation of cell lines expressing significant amounts of ingenol-3-mebutate is another example underlining the strength of plant cell culture. The authors gratefully acknowledge Inspyr Therapeutics for funding.

Keywords: Ingenol-3-mebutate, plant cell culture, sustainability, thapsigargin

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284 Comparative Study for Neonatal Outcome and Umbilical Cord Blood Gas Parameters in Balanced and Inhalant Anesthesia for Elective Cesarean Section in Dogs

Authors: Agnieszka Antończyk, MałGorzata Ochota, Wojciech Niżański, ZdzisłAw Kiełbowicz

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The goal of the cesarean section (CS) is the delivery of healthy, vigorous pups with the provision of surgical plane anesthesia, appropriate analgesia, and rapid recovery of the dam. In human medicine, spinal or epidural anesthesia is preferred for a cesarean section as associated with a lower risk of neonatal asphyxia and the need for resuscitation. Nevertheless, the specificity of veterinary patients makes the application of regional anesthesia as a sole technique impractical, thus to obtain patient compliance the general anesthesia is required. This study aimed to compare the influence of balanced (inhalant with epidural) and inhalant anesthesia on neonatal umbilical cord blood gas (UCBG) parameters and vitality (modified Apgar scoring). The bitches (31) undergoing elective CS were enrolled in this study. All females received a single dose of 0.2 mg/kg s.c. Meloxicam. Females were randomly assigned into two groups: Gr I (Isoflurane, n=16) and Gr IE (Isoflurane plus Epidural, n=15). Anesthesia was induced with propofol at 4-6 mg/kg to effect, and maintained with isoflurane in oxygen; in IE group epidural anesthesia was also done using lidocaine (3-4 mg/kg) into the lumbosacral space. CSs were performed using a standard mid-line approach. Directly after the puppy extraction, the umbilical cord was double clamped before the placenta detachment. The vessels were gently stretched between forceps to allow blood sampling. At least 100 mcl of mixed umbilical cord blood was collected into a heparinized syringe for further analysis. The modified Apgar scoring system (AS) was used to objectively score neonatal health and vitality immediately after birth (before first aid or neonatal care was instituted), at 5 and 20 min after birth. The neonates were scored as normal (AS 7-10), weak (AS 4-6), or critical (AS 0-3). During surgery, the IE group required a lower isoflurane concentration compared to the females in group I (MAC 1.05±0.2 and 1.4±0.13, respectively, p<0.01). All investigated UCBG parameters were not statistically different between groups. All pups had mild acidosis (pH 7.21±0.08 and 7.21±0.09 in Gr I and IE, respectively) with moderately elevated pCO2 (Gr I 57.18±11.48, Gr IE 58.74±15.07), HCO3- on the lower border (Gr I 22.58±3.24, Gr IE 22.83±3.6), lowered BE (Gr I -6.1±3.57, Gr IE -5.6±4.19) and mildly elevated level of lactates (Gr I 2.58±1.48, Gr IE2.53±1.03). The glucose levels were above the reference limits in both groups of puppies (74.50±25.32 in Gr I, 79.50±29.73 in Gr IE). The initial Apgar score results were similar in I and IE groups. However, the subsequent measurements of AS revealed significant differences between both groups. Puppies from the IE group received better AS scores at 5 and 20 min compared to the I group (6.86±2.23 and 8.06±2.06 vs 5.11±2.40 and 7.83±2.05, respectively). The obtained results demonstrated that administration of epidural anesthesia reduced the requirement for isoflurane in dams undergoing cesarean section and did not affect the neonatal umbilical blood gas results. Moreover, newborns from the epidural anesthesia group were scored significantly higher in AS at 5 and 20 min, indicating their better vitality and quicker improvement post-surgery.

Keywords: apgar scoring, balanced anesthesia, cesarean section, umbilical blood gas

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283 A Demonstration of How to Employ and Interpret Binary IRT Models Using the New IRT Procedure in SAS 9.4

Authors: Ryan A. Black, Stacey A. McCaffrey

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Over the past few decades, great strides have been made towards improving the science in the measurement of psychological constructs. Item Response Theory (IRT) has been the foundation upon which statistical models have been derived to increase both precision and accuracy in psychological measurement. These models are now being used widely to develop and refine tests intended to measure an individual's level of academic achievement, aptitude, and intelligence. Recently, the field of clinical psychology has adopted IRT models to measure psychopathological phenomena such as depression, anxiety, and addiction. Because advances in IRT measurement models are being made so rapidly across various fields, it has become quite challenging for psychologists and other behavioral scientists to keep abreast of the most recent developments, much less learn how to employ and decide which models are the most appropriate to use in their line of work. In the same vein, IRT measurement models vary greatly in complexity in several interrelated ways including but not limited to the number of item-specific parameters estimated in a given model, the function which links the expected response and the predictor, response option formats, as well as dimensionality. As a result, inferior methods (a.k.a. Classical Test Theory methods) continue to be employed in efforts to measure psychological constructs, despite evidence showing that IRT methods yield more precise and accurate measurement. To increase the use of IRT methods, this study endeavors to provide a comprehensive overview of binary IRT models; that is, measurement models employed on test data consisting of binary response options (e.g., correct/incorrect, true/false, agree/disagree). Specifically, this study will cover the most basic binary IRT model, known as the 1-parameter logistic (1-PL) model dating back to over 50 years ago, up until the most recent complex, 4-parameter logistic (4-PL) model. Binary IRT models will be defined mathematically and the interpretation of each parameter will be provided. Next, all four binary IRT models will be employed on two sets of data: 1. Simulated data of N=500,000 subjects who responded to four dichotomous items and 2. A pilot analysis of real-world data collected from a sample of approximately 770 subjects who responded to four self-report dichotomous items pertaining to emotional consequences to alcohol use. Real-world data were based on responses collected on items administered to subjects as part of a scale-development study (NIDA Grant No. R44 DA023322). IRT analyses conducted on both the simulated data and analyses of real-world pilot will provide a clear demonstration of how to construct, evaluate, and compare binary IRT measurement models. All analyses will be performed using the new IRT procedure in SAS 9.4. SAS code to generate simulated data and analyses will be available upon request to allow for replication of results.

Keywords: instrument development, item response theory, latent trait theory, psychometrics

Procedia PDF Downloads 358
282 Valorization of Banana Peels for Mercury Removal in Environmental Realist Conditions

Authors: E. Fabre, C. Vale, E. Pereira, C. M. Silva

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Introduction: Mercury is one of the most troublesome toxic metals responsible for the contamination of the aquatic systems due to its accumulation and bioamplification along the food chain. The 2030 agenda for sustainable development of United Nations promotes the improving of water quality by reducing water pollution and foments an enhance in wastewater treatment, encouraging their recycling and safe water reuse globally. Sorption processes are widely used in wastewater treatments due to their many advantages such as high efficiency and low operational costs. In these processes the target contaminant is removed from the solution by a solid sorbent. The more selective and low cost is the biosorbent the more attractive becomes the process. Agricultural wastes are especially attractive approaches for sorption. They are largely available, have no commercial value and require little or no processing. In this work, banana peels were tested for mercury removal from low concentrated solutions. In order to investigate the applicability of this solid, six water matrices were used increasing the complexity from natural waters to a real wastewater. Studies of kinetics and equilibrium were also performed using the most known models to evaluate the viability of the process In line with the concept of circular economy, this study adds value to this by-product as well as contributes to liquid waste management. Experimental: The solutions were prepared with Hg(II) initial concentration of 50 µg L-1 in natural waters, at 22 ± 1 ºC, pH 6, magnetically stirring at 650 rpm and biosorbent mass of 0.5 g L-1. NaCl was added to obtain the salt solutions, seawater was collected from the Portuguese coast and the real wastewater was kindly provided by ISQ - Instituto de Soldadura e qualidade (Welding and Quality Institute) and diluted until the same concentration of 50 µg L-1. Banana peels were previously freeze-drying, milled, sieved and the particles < 1 mm were used. Results: Banana peels removed more than 90% of Hg(II) from all the synthetic solutions studied. In these cases, the enhance in the complexity of the water type promoted a higher mercury removal. In salt waters, the biosorbent showed removals of 96%, 95% and 98 % for 3, 15 and 30 g L-1 of NaCl, respectively. The residual concentration of Hg(II) in solution achieved the level of drinking water regulation (1 µg L-1). For real matrices, the lower Hg(II) elimination (93 % for seawater and 81 % for the real wastewaters), can be explained by the competition between the Hg(II) ions and the other elements present in these solutions for the sorption sites. Regarding the equilibrium study, the experimental data are better described by the Freundlich isotherm (R ^ 2=0.991). The Elovich equation provided the best fit to the kinetic points. Conclusions: The results exhibited the great ability of the banana peels to remove mercury. The environmental realist conditions studied in this work, highlight their potential usage as biosorbents in water remediation processes.

Keywords: banana peels, mercury removal, sorption, water treatment

Procedia PDF Downloads 156
281 Teaching Children about Their Brains: Evaluating the Role of Neuroscience Undergraduates in Primary School Education

Authors: Clea Southall

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Many children leave primary school having formed preconceptions about their relationship with science. Thus, primary school represents a critical window for stimulating scientific interest in younger children. Engagement relies on the provision of hands-on activities coupled with an ability to capture a child’s innate curiosity. This requires children to perceive science topics as interesting and relevant to their everyday life. Teachers and pupils alike have suggested the school curriculum be tailored to help stimulate scientific interest. Young children are naturally inquisitive about the human body; the brain is one topic which frequently engages pupils, although it is not currently included in the UK primary curriculum. Teaching children about the brain could have wider societal impacts such as increasing knowledge of neurological disorders. However, many primary school teachers do not receive formal neuroscience training and may feel apprehensive about delivering lessons on the nervous system. This is exacerbated by a lack of educational neuroscience resources. One solution is for undergraduates to form partnerships with schools - delivering engaging lessons and supplementing teacher knowledge. The aim of this project was to evaluate the success of a short lesson on the brain delivered by an undergraduate neuroscientist to primary school pupils. Prior to entering schools, semi-structured online interviews were conducted with teachers to gain pedagogical advice and relevant websites were searched for neuroscience resources. Subsequently, a single lesson plan was created comprising of four hands-on activities. The activities were devised in a top-down manner, beginning with learning about the brain as an entity, before focusing on individual neurons. Students were asked to label a ‘brain map’ to assess prior knowledge of brain structure and function. They viewed animal brains and created ‘pipe-cleaner neurons’ which were later used to depict electrical transmission. The same session was delivered by an undergraduate student to 570 key stage 2 (KS2) pupils across five schools in Leeds, UK. Post-session surveys, designed for teachers and pupils respectively, were used to evaluate the session. Children in all year groups had relatively poor knowledge of brain structure and function at the beginning of the session. When asked to label four brain regions with their respective functions, older pupils labeled a mean of 1.5 (± 1.0) brain regions compared to 0.8 (± 0.96) for younger pupils (p=0.002). However, by the end of the session, 95% of pupils felt their knowledge of the brain had increased. Hands-on activities were rated most popular by pupils and were considered the most successful aspect of the session by teachers. Although only half the teachers were aware of neuroscience educational resources, nearly all (95%) felt they would have more confidence in teaching a similar session in the future. All teachers felt the session was engaging and that the content could be linked to the current curriculum. Thus, a short fifty-minute session can successfully enhance pupils’ knowledge of a new topic: the brain. Partnerships with an undergraduate student can provide an alternative method for supplementing teacher knowledge, increasing their confidence in delivering future lessons on the nervous system.

Keywords: education, neuroscience, primary school, undergraduate

Procedia PDF Downloads 212
280 Potential of Polyphenols from Tamarix Gallica towards Common Pathological Features of Diabetes and Alzheimer’s Diseases

Authors: Asma Ben Hmidene, Mizuho Hanaki, Kazuma Murakami, Kazuhiro Irie, Hiroko Isoda, Hideyuki Shigemori

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Type 2 diabetes mellitus (T2DM) and Alzheimer’s disease (AD) are characterized as a peripheral metabolic disorder and a degenerative disease of the central nervous system, respectively. It is now widely recognized that T2DM and AD share many pathophysiological features including glucose metabolism, increased oxidative stress and amyloid aggregation. Amyloid beta (Aβ) is the components of the amyloid deposits in the AD brain and while the component of the amyloidogenic peptide deposit in the pancreatic islets of Langerhans is identified as human islet amyloid polypeptide (hIAPP). These two proteins are originated from the amyloid precursor protein and have a high sequence similarity. Although the amino acid sequences of amyloidogenic proteins are diverse, they all adopt a similar structure in aggregates called cross-beta-spine. Add at that, extensive studies in the past years have found that like Aβ1-42, IAPP forms early intermediate assemblies as spherical oligomers, implicating that these oligomers possess a common folding pattern or conformation. These similarities can be used in the search for effective pharmacotherapy for DM, since potent therapeutic agents such as antioxidants with a catechol moiety, proved to inhibit Aβ aggregation, may play a key role in the inhibit the aggregation of hIAPP treatment of patients with DM. Tamarix gallica is one of the halophyte species having a powerful antioxidant system. Although it was traditionally used for the treatment of various liver metabolic disorders, there is no report about the use of this plant for the treatment or prevention of T2DM and AD. Therefore, the aim of this work is to investigate their protective effect towards T2DM and AD by isolation and identification of α-glucosidase inhibitors, with antioxidant potential, that play an important role in the glucose metabolism in diabetic patient, as well as, the polymerization of hIAPP and Aβ aggregation inhibitors. Structure-activity relationship study was conducted for both assays. And as for α-glucosidase inhibitors, their mechanism of action and their synergistic potential when applied with a very low concentration of acarbose were also suggesting that they can be used not only as α-glucosidase inhibitors but also be combined with established α-glucosidase inhibitors to reduce their adverse effect. The antioxidant potential of the purified substances was evaluated by DPPH and SOD assays. Th-T assay using 42-mer amyloid β-protein (Aβ42) for AD and hIAPP which is a 37-residue peptide secreted by the pancreatic β –cells for T2DM and Transmission electronic microscopy (TEM) were conducted to evaluate the amyloid aggragation of the actives substances. For α-glucosidase, p-NPG and glucose oxidase assays were performed for determining the inhibition potential and structure-activity relationship study. The Enzyme kinetic protocol was used to study the mechanism of action. From this research, it was concluded that polyphenols playing a role in the glucose metabolism and oxidative stress can also inhibit the amyloid aggregation, and that substances with a catechol and glucuronide moieties inhibiting amyloid-β aggregation, might be used to inhibit the aggregation of hIAPP.

Keywords: α-glucosidase inhibitors, amyloid aggregation inhibition, mechanism of action, polyphenols, structure activity relationship, synergistic potential, tamarix gallica

Procedia PDF Downloads 280
279 Characterizing the Spatially Distributed Differences in the Operational Performance of Solar Power Plants Considering Input Volatility: Evidence from China

Authors: Bai-Chen Xie, Xian-Peng Chen

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China has become the world's largest energy producer and consumer, and its development of renewable energy is of great significance to global energy governance and the fight against climate change. The rapid growth of solar power in China could help achieve its ambitious carbon peak and carbon neutrality targets early. However, the non-technical costs of solar power in China are much higher than at international levels, meaning that inefficiencies are rooted in poor management and improper policy design and that efficiency distortions have become a serious challenge to the sustainable development of the renewable energy industry. Unlike fossil energy generation technologies, the output of solar power is closely related to the volatile solar resource, and the spatial unevenness of solar resource distribution leads to potential efficiency spatial distribution differences. It is necessary to develop an efficiency evaluation method that considers the volatility of solar resources and explores the mechanism of the influence of natural geography and social environment on the spatially varying characteristics of efficiency distribution to uncover the root causes of managing inefficiencies. The study sets solar resources as stochastic inputs, introduces a chance-constrained data envelopment analysis model combined with the directional distance function, and measures the solar resource utilization efficiency of 222 solar power plants in representative photovoltaic bases in northwestern China. By the meta-frontier analysis, we measured the characteristics of different power plant clusters and compared the differences among groups, discussed the mechanism of environmental factors influencing inefficiencies, and performed statistical tests through the system generalized method of moments. Rational localization of power plants is a systematic project that requires careful consideration of the full utilization of solar resources, low transmission costs, and power consumption guarantee. Suitable temperature, precipitation, and wind speed can improve the working performance of photovoltaic modules, reasonable terrain inclination can reduce land cost, and the proximity to cities strongly guarantees the consumption of electricity. The density of electricity demand and high-tech industries is more important than resource abundance because they trigger the clustering of power plants to result in a good demonstration and competitive effect. To ensure renewable energy consumption, increased support for rural grids and encouraging direct trading between generators and neighboring users will provide solutions. The study will provide proposals for improving the full life-cycle operational activities of solar power plants in China to reduce high non-technical costs and improve competitiveness against fossil energy sources.

Keywords: solar power plants, environmental factors, data envelopment analysis, efficiency evaluation

Procedia PDF Downloads 92
278 Characteristics of Bio-hybrid Hydrogel Materials with Prolonged Release of the Model Active Substance as Potential Wound Dressings

Authors: Katarzyna Bialik-Wąs, Klaudia Pluta, Dagmara Malina, Małgorzata Miastkowska

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In recent years, biocompatible hydrogels have been used more and more in medical applications, especially as modern dressings and drug delivery systems. The main goal of this research was the characteristics of bio-hybrid hydrogel materials incorporated with the nanocarrier-drug system, which enable the release in a gradual and prolonged manner, up to 7 days. Therefore, the use of such a combination will provide protection against mechanical damage and adequate hydration. The proposed bio-hybrid hydrogels are characterized by: transparency, biocompatibility, good mechanical strength, and the dual release system, which allows for gradual delivery of the active substance, even up to 7 days. Bio-hybrid hydrogels based on sodium alginate (SA), poly(vinyl alcohol) (PVA), glycerine, and Aloe vera solution (AV) were obtained through the chemical crosslinking method using poly(ethylene glycol) diacrylate as a crosslinking agent. Additionally, a nanocarrier-drug system was incorporated into SA/PVA/AV hydrogel matrix. Here, studies were focused on the release profiles of active substances from bio-hybrid hydrogels using the USP4 method (DZF II Flow-Through System, Erweka GmbH, Langen, Germany). The equipment incorporated seven in-line flow-through diffusion cells. The membrane was placed over support with an orifice of 1,5 cm in diameter (diffusional area, 1.766 cm²). All the cells were placed in a cell warmer connected with the Erweka heater DH 2000i and the Erweka piston pump HKP 720. The piston pump transports the receptor fluid via seven channels to the flow-through cells and automatically adapts the setting of the flow rate. All volumes were measured by gravimetric methods by filling the chambers with Milli-Q water and assuming a density of 1 g/ml. All the determinations were made in triplicate for each cell. The release study of the model active substance was carried out using a regenerated cellulose membrane Spectra/Por®Dialysis Membrane MWCO 6-8,000 Carl Roth® Company. These tests were conducted in buffer solutions – PBS at pH 7.4. A flow rate of receptor fluid of about 4 ml /1 min was selected. The experiments were carried out for 7 days at a temperature of 37°C. The released concentration of the model drug in the receptor solution was analyzed using UV-Vis spectroscopy (Perkin Elmer Company). Additionally, the following properties of the modified materials were studied: physicochemical, structural (FT-IR analysis), morphological (SEM analysis). Finally, the cytotoxicity tests using in vitro method were conducted. The obtained results exhibited that the dual release system allows for the gradual and prolonged delivery of the active substances, even up to 7 days.

Keywords: wound dressings, SA/PVA hydrogels, nanocarrier-drug system, USP4 method

Procedia PDF Downloads 148
277 Chemical vs Visual Perception in Food Choice Ability of Octopus vulgaris (Cuvier, 1797)

Authors: Al Sayed Al Soudy, Valeria Maselli, Gianluca Polese, Anna Di Cosmo

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Cephalopods are considered as a model organism with a rich behavioral repertoire. Sophisticated behaviors were widely studied and described in different species such as Octopus vulgaris, who has evolved the largest and more complex nervous system among invertebrates. In O. vulgaris, cognitive abilities in problem-solving tasks and learning abilities are associated with long-term memory and spatial memory, mediated by highly developed sensory organs. They are equipped with sophisticated eyes, able to discriminate colors even with a single photoreceptor type, vestibular system, ‘lateral line analogue’, primitive ‘hearing’ system and olfactory organs. They can recognize chemical cues either through direct contact with odors sources using suckers or by distance through the olfactory organs. Cephalopods are able to detect widespread waterborne molecules by the olfactory organs. However, many volatile odorant molecules are insoluble or have a very low solubility in water, and must be perceived by direct contact. O. vulgaris, equipped with many chemosensory neurons located in their suckers, exhibits a peculiar behavior that can be provocatively described as 'smell by touch'. The aim of this study is to establish the priority given to chemical vs. visual perception in food choice. Materials and methods: Three different types of food (anchovies, clams, and mussels) were used, and all sessions were recorded with a digital camera. During the acclimatization period, Octopuses were exposed to the three types of food to test their natural food preferences. Later, to verify if food preference is maintained, food was provided in transparent screw-jars with pierced lids to allow both visual and chemical recognition of the food inside. Subsequently, we tested alternatively octopuses with food in sealed transparent screw-jars and food in blind screw-jars with pierced lids. As a control, we used blind sealed jars with the same lid color to verify a random choice among food types. Results and discussion: During the acclimatization period, O. vulgaris shows a higher preference for anchovies (60%) followed by clams (30%), then mussels (10%). After acclimatization, using the transparent and pierced screw jars octopus’s food choices resulted in 50-50 between anchovies and clams, avoiding mussels. Later, guided by just visual sense, with transparent but not pierced jars, their food preferences resulted in 100% anchovies. With pierced but not transparent jars their food preference resulted in 100% anchovies as first food choice, the clams as a second food choice result (33.3%). With no possibility to select food, neither by vision nor by chemoreception, the results were 20% anchovies, 20% clams, and 60% mussels. We conclude that O. vulgaris uses both chemical and visual senses in an integrative way in food choice, but if we exclude one of them, it appears clear that its food preference relies on chemical sense more than on visual perception.

Keywords: food choice, Octopus vulgaris, olfaction, sensory organs, visual sense

Procedia PDF Downloads 221
276 A Comprehensive Key Performance Indicators Dashboard for Emergency Medical Services

Authors: Giada Feletti, Daniela Tedesco, Paolo Trucco

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The present study aims to develop a dashboard of Key Performance Indicators (KPI) to enhance information and predictive capabilities in Emergency Medical Services (EMS) systems, supporting both operational and strategic decisions of different actors. The employed research methodology consists of the first phase of revision of the technical-scientific literature concerning the indicators currently used for the performance measurement of EMS systems. From this literature analysis, it emerged that current studies focus on two distinct perspectives: the ambulance service, a fundamental component of pre-hospital health treatment, and the patient care in the Emergency Department (ED). The perspective proposed by this study is to consider an integrated view of the ambulance service process and the ED process, both essential to ensure high quality of care and patient safety. Thus, the proposal focuses on the entire healthcare service process and, as such, allows considering the interconnection between the two EMS processes, the pre-hospital and hospital ones, connected by the assignment of the patient to a specific ED. In this way, it is possible to optimize the entire patient management. Therefore, attention is paid to the dependency of decisions that in current EMS management models tend to be neglected or underestimated. In particular, the integration of the two processes enables the evaluation of the advantage of an ED selection decision having visibility on EDs’ saturation status and therefore considering the distance, the available resources and the expected waiting times. Starting from a critical review of the KPIs proposed in the extant literature, the design of the dashboard was carried out: the high number of analyzed KPIs was reduced by eliminating the ones firstly not in line with the aim of the study and then the ones supporting a similar functionality. The KPIs finally selected were tested on a realistic dataset, which draws us to exclude additional indicators due to the unavailability of data required for their computation. The final dashboard, which was discussed and validated by experts in the field, includes a variety of KPIs able to support operational and planning decisions, early warning, and citizens’ awareness of EDs accessibility in real-time. By associating each KPI to the EMS phase it refers to, it was also possible to design a well-balanced dashboard covering both efficiency and effective performance of the entire EMS process. Indeed, just the initial phases related to the interconnection between ambulance service and patient’s care are covered by traditional KPIs compared to the subsequent phases taking place in the hospital ED. This could be taken into consideration for the potential future development of the dashboard. Moreover, the research could proceed by building a multi-layer dashboard composed of the first level with a minimal set of KPIs to measure the basic performance of the EMS system at an aggregate level and further levels with KPIs that can bring additional and more detailed information.

Keywords: dashboard, decision support, emergency medical services, key performance indicators

Procedia PDF Downloads 113
275 The 10,000 Fold Effect of Retrograde Neurotransmission: A New Concept for Cerebral Palsy Revival by the Use of Nitric Oxide Donars

Authors: V. K. Tewari, M. Hussain, H. K. D. Gupta

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Background: Nitric Oxide Donars (NODs) (intrathecal sodium nitroprusside (ITSNP) and oral tadalafil 20mg post ITSNP) has been studied in this context in cerebral palsy patients for fast recovery. This work proposes two mechanisms for acute cases and one mechanism for chronic cases, which are interrelated, for physiological recovery. a) Retrograde Neurotransmission (acute cases): 1) Normal excitatory impulse: at the synaptic level, glutamate activates NMDA receptors, with nitric oxide synthetase (NOS) on the postsynaptic membrane, for further propagation by the calcium-calmodulin complex. Nitric oxide (NO, produced by NOS) travels backward across the chemical synapse and binds the axon-terminal NO receptor/sGC of a presynaptic neuron, regulating anterograde neurotransmission (ANT) via retrograde neurotransmission (RNT). Heme is the ligand-binding site of the NO receptor/sGC. Heme exhibits > 10,000-fold higher affinity for NO than for oxygen (the 10,000-fold effect) and is completed in 20 msec. 2) Pathological conditions: normal synaptic activity, including both ANT and RNT, is absent. A NO donor (SNP) releases NO from NOS in the postsynaptic region. NO travels backward across a chemical synapse to bind to the heme of a NO receptor in the axon terminal of a presynaptic neuron, generating an impulse, as under normal conditions. b) Vasopasm: (acute cases) Perforators show vasospastic activity. NO vasodilates the perforators via the NO-cAMP pathway. c) Long-Term Potentiation (LTP): (chronic cases) The NO–cGMP-pathway plays a role in LTP at many synapses throughout the CNS and at the neuromuscular junction. LTP has been reviewed both generally and with respect to brain regions specific for memory/learning. Aims/Study Design: The principles of “generation of impulses from the presynaptic region to the postsynaptic region by very potent RNT (10,000-fold effect)” and “vasodilation of arteriolar perforators” are the basis of the authors’ hypothesis to treat cerebral palsy cases. Case-control prospective study. Materials and Methods: The experimental population included 82 cerebral palsy patients (10 patients were given control treatments without NOD or with 5% dextrose superfusion, and 72 patients comprised the NOD group). The mean time for superfusion was 5 months post-cerebral palsy. Pre- and post-NOD status was monitored by Gross Motor Function Classification System for Cerebral Palsy (GMFCS), MRI, and TCD studies. Results: After 7 days in the NOD group, the mean change in the GMFCS score was an increase of 1.2 points mean; after 3 months, there was an increase of 3.4 points mean, compared to the control-group increase of 0.1 points at 3 months. MRI and TCD documented the improvements. Conclusions: NOD (ITSNP boosts up the recovery and oral tadalafil maintains the recovery to a well-desired level) acts swiftly in the treatment of CP, acting within 7 days on 5 months post-cerebral palsy either of the three mechanisms.

Keywords: cerebral palsy, intrathecal sodium nitroprusside, oral tadalafil, perforators, vasodilations, retrograde transmission, the 10, 000-fold effect, long-term potantiation

Procedia PDF Downloads 363
274 Hybrid Living: Emerging Out of the Crises and Divisions

Authors: Yiorgos Hadjichristou

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The paper will focus on the hybrid living typologies which are brought about due to the Global Crisis. Mixing of the generations and the groups of people, mingling the functions of living with working and socializing, merging the act of living in synergy with the urban realm and its constituent elements will be the springboard of proposing an essential sustainable housing approach and the respective urban development. The thematic will be based on methodologies developed both on the academic, educational environment including participation of students’ research and on the practical aspect of architecture including case studies executed by the author in the island of Cyprus. Both paths of the research will deal with the explorative understanding of the hybrid ways of living, testing the limits of its autonomy. The evolution of the living typologies into substantial hybrid entities, will deal with the understanding of new ways of living which include among others: re-introduction of natural phenomena, accommodation of the activity of work and services in the living realm, interchange of public and private, injections of communal events into the individual living territories. The issues and the binary questions raised by what is natural and artificial, what is private and what public, what is ephemeral and what permanent and all the in-between conditions are eloquently traced in the everyday life in the island. Additionally, given the situation of Cyprus with the eminent scar of the dividing ‘Green line’ and the waiting of the ‘ghost city’ of Famagusta to be resurrected, the conventional way of understanding the limits and the definitions of the properties is irreversibly shaken. The situation is further aggravated by the unprecedented phenomenon of the crisis on the island. All these observations set the premises of reexamining the urban development and the respective sustainable housing in a synergy where their characteristics start exchanging positions, merge into each other, contemporarily emerge and vanish, changing from permanent to ephemeral. This fluidity of conditions will attempt to render a future of the built- and unbuilt realm where the main focusing point will be redirected to the human and the social. Weather and social ritual scenographies together with ‘spontaneous urban landscapes’ of ‘momentary relationships’ will suggest a recipe for emerging urban environments and sustainable living. Thus, the paper will aim at opening a discourse on the future of the sustainable living merged in a sustainable urban development in relation to the imminent solution of the division of island, where the issue of property became the main obstacle to be overcome. At the same time, it will attempt to link this approach to the global need for a sustainable evolution of the urban and living realms.

Keywords: social ritual scenographies, spontaneous urban landscapes, substantial hybrid entities, re-introduction of natural phenomena

Procedia PDF Downloads 264
273 Predictive Maintenance: Machine Condition Real-Time Monitoring and Failure Prediction

Authors: Yan Zhang

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Predictive maintenance is a technique to predict when an in-service machine will fail so that maintenance can be planned in advance. Analytics-driven predictive maintenance is gaining increasing attention in many industries such as manufacturing, utilities, aerospace, etc., along with the emerging demand of Internet of Things (IoT) applications and the maturity of technologies that support Big Data storage and processing. This study aims to build an end-to-end analytics solution that includes both real-time machine condition monitoring and machine learning based predictive analytics capabilities. The goal is to showcase a general predictive maintenance solution architecture, which suggests how the data generated from field machines can be collected, transmitted, stored, and analyzed. We use a publicly available aircraft engine run-to-failure dataset to illustrate the streaming analytics component and the batch failure prediction component. We outline the contributions of this study from four aspects. First, we compare the predictive maintenance problems from the view of the traditional reliability centered maintenance field, and from the view of the IoT applications. When evolving to the IoT era, predictive maintenance has shifted its focus from ensuring reliable machine operations to improve production/maintenance efficiency via any maintenance related tasks. It covers a variety of topics, including but not limited to: failure prediction, fault forecasting, failure detection and diagnosis, and recommendation of maintenance actions after failure. Second, we review the state-of-art technologies that enable a machine/device to transmit data all the way through the Cloud for storage and advanced analytics. These technologies vary drastically mainly based on the power source and functionality of the devices. For example, a consumer machine such as an elevator uses completely different data transmission protocols comparing to the sensor units in an environmental sensor network. The former may transfer data into the Cloud via WiFi directly. The latter usually uses radio communication inherent the network, and the data is stored in a staging data node before it can be transmitted into the Cloud when necessary. Third, we illustrate show to formulate a machine learning problem to predict machine fault/failures. By showing a step-by-step process of data labeling, feature engineering, model construction and evaluation, we share following experiences: (1) what are the specific data quality issues that have crucial impact on predictive maintenance use cases; (2) how to train and evaluate a model when training data contains inter-dependent records. Four, we review the tools available to build such a data pipeline that digests the data and produce insights. We show the tools we use including data injection, streaming data processing, machine learning model training, and the tool that coordinates/schedules different jobs. In addition, we show the visualization tool that creates rich data visualizations for both real-time insights and prediction results. To conclude, there are two key takeaways from this study. (1) It summarizes the landscape and challenges of predictive maintenance applications. (2) It takes an example in aerospace with publicly available data to illustrate each component in the proposed data pipeline and showcases how the solution can be deployed as a live demo.

Keywords: Internet of Things, machine learning, predictive maintenance, streaming data

Procedia PDF Downloads 387
272 Hampering The 'Right to Know': Consequences of the Excessive Interpretation of the Notion of Exemption from the Right to Information

Authors: Tomasz Lewinski

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The right to know becomes gradually recognised as an increasing number of states adopts national legislations regarding access to state-held information. Laws differ from each other in the scope of the right to information (hereinafter: RTI). In all regimes of RTI, there are exceptions from the general notion of the right. States’ authorities too often use exceptions to justify refusals to requests for state-held information. This paper sets out how states hamper RTI basing on the notion of exception and by not providing an effective procedure that could redress unlawful denials. This paper bases on two selected examples of RTI incorporation into the national legal regime, United Kingdom, and South Africa. It succinctly outlines the international standard given in Article 19 of the International Covenant on Civil and Political Rights (hereinafter: ICCPR) and its influence on the RTI in selected countries. It shortly demonstrates as a background to further analysis the Human Rights Committee’s jurisprudence and standards articulated by successive Special Rapporteurs on freedom of opinion and expression. Subsequently, it presents a brief comparison of these standards with the regional standards, namely the African Charter on Human and Peoples' Rights and the European Convention on Human Rights. It critically discusses the regimes of exceptions in RTI legislations in respective national laws. It shows how excessive these regimes are, what implications they have for the transparency in general. Also, the objective is to divide exceptions enumerated in legislations of selected states in relation to exceptions provided in Article 19 of the ICCPR. Basing on the established division of exceptions by its natures, it compares both regimes of exceptions related to the principle of national security. That is to compare jurisprudence of domestic courts, and overview practices of states’ authorities applied to RTI requests. The paper evaluates remedies available in legislations, including contexts of the length and costs of the subsequent proceedings. This provides a general assessment of the given mechanisms and present potential risks of its ineffectiveness. The paper relies on examination of the national legislations, comments of the credible non-governmental organisations (e.g. The Public's Right to Know Principles on Freedom of Information Legislation by the Article 19, The Tshwane Principles on National Security and the Right to Information), academics and also the research of the relevant judgements delivered by domestic and international courts. Conclusion assesses whether selected countries’ legislations go in line with international law and trends, whether the jurisprudence of the regional courts provide appropriate benchmarks for national courts to address RTI issues effectively. Furthermore, it identifies the largest disadvantages of current legislations and to what outcomes it leads in domestic courts jurisprudences. In the end, it provides recommendations and policy arguments for states to improve transparency and support local organisations in their endeavours to establish more transparent states and societies.

Keywords: access to information, freedom of information, national security, right to know, transparency

Procedia PDF Downloads 214
271 Using Computer Vision and Machine Learning to Improve Facility Design for Healthcare Facility Worker Safety

Authors: Hengameh Hosseini

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Design of large healthcare facilities – such as hospitals, multi-service line clinics, and nursing facilities - that can accommodate patients with wide-ranging disabilities is a challenging endeavor and one that is poorly understood among healthcare facility managers, administrators, and executives. An even less-understood extension of this problem is the implications of weakly or insufficiently accommodative design of facilities for healthcare workers in physically-intensive jobs who may also suffer from a range of disabilities and who are therefore at increased risk of workplace accident and injury. Combine this reality with the vast range of facility types, ages, and designs, and the problem of universal accommodation becomes even more daunting and complex. In this study, we focus on the implication of facility design for healthcare workers suffering with low vision who also have physically active jobs. The points of difficulty are myriad and could span health service infrastructure, the equipment used in health facilities, and transport to and from appointments and other services can all pose a barrier to health care if they are inaccessible, less accessible, or even simply less comfortable for people with various disabilities. We conduct a series of surveys and interviews with employees and administrators of 7 facilities of a range of sizes and ownership models in the Northeastern United States and combine that corpus with in-facility observations and data collection to identify five major points of failure common to all the facilities that we concluded could pose safety threats to employees with vision impairments, ranging from very minor to severe. We determine that lack of design empathy is a major commonality among facility management and ownership. We subsequently propose three methods for remedying this lack of empathy-informed design, to remedy the dangers posed to employees: the use of an existing open-sourced Augmented Reality application to simulate the low-vision experience for designers and managers; the use of a machine learning model we develop to automatically infer facility shortcomings from large datasets of recorded patient and employee reviews and feedback; and the use of a computer vision model fine tuned on images of each facility to infer and predict facility features, locations, and workflows, that could again pose meaningful dangers to visually impaired employees of each facility. After conducting a series of real-world comparative experiments with each of these approaches, we conclude that each of these are viable solutions under particular sets of conditions, and finally characterize the range of facility types, workforce composition profiles, and work conditions under which each of these methods would be most apt and successful.

Keywords: artificial intelligence, healthcare workers, facility design, disability, visually impaired, workplace safety

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270 Exploring the Role of Hydrogen to Achieve the Italian Decarbonization Targets using an OpenScience Energy System Optimization Model

Authors: Alessandro Balbo, Gianvito Colucci, Matteo Nicoli, Laura Savoldi

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Hydrogen is expected to become an undisputed player in the ecological transition throughout the next decades. The decarbonization potential offered by this energy vector provides various opportunities for the so-called “hard-to-abate” sectors, including industrial production of iron and steel, glass, refineries and the heavy-duty transport. In this regard, Italy, in the framework of decarbonization plans for the whole European Union, has been considering a wider use of hydrogen to provide an alternative to fossil fuels in hard-to-abate sectors. This work aims to assess and compare different options concerning the pathway to be followed in the development of the future Italian energy system in order to meet decarbonization targets as established by the Paris Agreement and by the European Green Deal, and to infer a techno-economic analysis of the required asset alternatives to be used in that perspective. To accomplish this objective, the Energy System Optimization Model TEMOA-Italy is used, based on the open-source platform TEMOA and developed at PoliTo as a tool to be used for technology assessment and energy scenario analysis. The adopted assessment strategy includes two different scenarios to be compared with a business-as-usual one, which considers the application of current policies in a time horizon up to 2050. The studied scenarios are based on the up-to-date hydrogen-related targets and planned investments included in the National Hydrogen Strategy and in the Italian National Recovery and Resilience Plan, with the purpose of providing a critical assessment of what they propose. One scenario imposes decarbonization objectives for the years 2030, 2040 and 2050, without any other specific target. The second one (inspired to the national objectives on the development of the sector) promotes the deployment of the hydrogen value-chain. These scenarios provide feedback about the applications hydrogen could have in the Italian energy system, including transport, industry and synfuels production. Furthermore, the decarbonization scenario where hydrogen production is not imposed, will make use of this energy vector as well, showing the necessity of its exploitation in order to meet pledged targets by 2050. The distance of the planned policies from the optimal conditions for the achievement of Italian objectives is be clarified, revealing possible improvements of various steps of the decarbonization pathway, which seems to have as a fundamental element Carbon Capture and Utilization technologies for its accomplishment. In line with the European Commission open science guidelines, the transparency and the robustness of the presented results is ensured by the adoption of the open-source open-data model such as the TEMOA-Italy.

Keywords: decarbonization, energy system optimization models, hydrogen, open-source modeling, TEMOA

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269 A Clinical Audit on Screening Women with Subfertility Using Transvaginal Scan and Hysterosalpingo Contrast Sonography

Authors: Aarti M. Shetty, Estela Davoodi, Subrata Gangooly, Anita Rao-Coppisetty

Abstract:

Background: Testing Patency of Fallopian Tubes is among one of the several protocols for investigating Subfertile Couples. Both, Hysterosalpingogram (HSG) and Laparoscopy and dye test have been used as Tubal patency test for several years, with well-known limitation. Hysterosalpingo Contrast Sonography (HyCoSy) can be used as an alternative tool to HSG, to screen patency of Fallopian tubes, with an advantage of being non-ionising, and also, use of transvaginal scan to diagnose pelvic pathology. Aim: To determine the indication and analyse the performance of transvaginal scan and HyCoSy in Broomfield Hospital. Methods: We retrospectively analysed fertility workup of 282 women, who attended HyCoSy clinic at our institution from January 2015 to June 2016. An Audit proforma was designed, to aid data collection. Data was collected from patient notes and electronic records, which included patient demographics; age, parity, type of subfertility (primary or secondary), duration of subfertility, past medical history and base line investigation (hormone profile and semen analysis). Findings of the transvaginal scan, HyCoSy and Laparoscopy were also noted. Results: The most common indication for referral were as a part of primary fertility workup on couples who had failure to conceive despite intercourse for a year, other indication for referral were recurrent miscarriage, history of ectopic pregnancy, post reversal of sterilization(vasectomy and tuboplasty), Post Gynaecology surgery(Loop excision, cone biopsy) and amenorrhea. Basic Fertility workup showed 34% men had abnormal semen analysis. HyCoSy was successfully completed in 270 (95%) women using ExEm foam and Transvaginal Scan. Of the 270 patients, 535 tubes were examined in total. 495/535 (93%) tubes were reported as patent, 40/535 (7.5%) tubes were reported as blocked. A total of 17 (6.3%) patients required laparoscopy and dye test after HyCoSy. In these 17 patients, 32 tubes were examined under laparoscopy, and 21 tubes had findings similar to HyCoSy, with a concordance rate of 65%. In addition to this, 41 patients had some form of pelvic pathology (endometrial polyp, fibroid, cervical polyp, fibroid, bicornuate uterus) detected during transvaginal scan, who referred to corrective surgeries after attending HyCoSy Clinic. Conclusion: Our audit shows that HyCoSy and Transvaginal scan can be a reliable screening test for low risk women. Furthermore, it has competitive diagnostic accuracy to HSG in identifying tubal patency, with an additional advantage of screening for pelvic pathology. With addition of 3D Scan, pulse Doppler and other non-invasive imaging modality, HyCoSy may potentially replace Laparoscopy and chromopertubation in near future.

Keywords: hysterosalpingo contrast sonography (HyCoSy), transvaginal scan, tubal infertility, tubal patency test

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268 Analyzing the Effects of Bio-fibers on the Stiffness and Strength of Adhesively Bonded Thermoplastic Bio-fiber Reinforced Composites by a Mixed Experimental-Numerical Approach

Authors: Sofie Verstraete, Stijn Debruyne, Frederik Desplentere

Abstract:

Considering environmental issues, the interest to apply sustainable materials in industry increases. Specifically for composites, there is an emerging need for suitable materials and bonding techniques. As an alternative to traditional composites, short bio-fiber (cellulose-based flax) reinforced Polylactic Acid (PLA) is gaining popularity. However, these thermoplastic based composites show issues in adhesive bonding. This research focusses on analyzing the effects of the fibers near the bonding interphase. The research applies injection molded plate structures. A first important parameter concerns the fiber volume fraction, which directly affects adhesion characteristics of the surface. This parameter is varied between 0 (pure PLA) and 30%. Next to fiber volume fraction, the orientation of fibers near the bonding surface governs the adhesion characteristics of the injection molded parts. This parameter is not directly controlled in this work, but its effects are analyzed. Surface roughness also greatly determines surface wettability, thus adhesion. Therefore, this research work considers three different roughness conditions. Different mechanical treatments yield values up to 0.5 mm. In this preliminary research, only one adhesive type is considered. This is a two-part epoxy which is cured at 23 °C for 48 hours. In order to assure a dedicated parametric study, simple and reproduceable adhesive bonds are manufactured. Both single lap (substrate width 25 mm, thickness 3 mm, overlap length 10 mm) and double lap tests are considered since these are well documented and quite straightforward to conduct. These tests are conducted for the different substrate and surface conditions. Dog bone tensile testing is applied to retrieve the stiffness and strength characteristics of the substrates (with different fiber volume fractions). Numerical modelling (non-linear FEA) relates the effects of the considered parameters on the stiffness and strength of the different joints, obtained through the abovementioned tests. Ongoing work deals with developing dedicated numerical models, incorporating the different considered adhesion parameters. Although this work is the start of an extensive research project on the bonding characteristics of thermoplastic bio-fiber reinforced composites, some interesting results are already prominent. Firstly, a clear correlation between the surface roughness and the wettability of the substrates is observed. Given the adhesive type (and viscosity), it is noticed that an increase in surface energy is proportional to the surface roughness, to some extent. This becomes more pronounced when fiber volume fraction increases. Secondly, ultimate bond strength (single lap) also increases with increasing fiber volume fraction. On a macroscopic level, this confirms the positive effect of fibers near the adhesive bond line.

Keywords: adhesive bonding, bio-fiber reinforced composite, flax fibers, lap joint

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267 Fuzzy Availability Analysis of a Battery Production System

Authors: Merve Uzuner Sahin, Kumru D. Atalay, Berna Dengiz

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In today’s competitive market, there are many alternative products that can be used in similar manner and purpose. Therefore, the utility of the product is an important issue for the preferability of the brand. This utility could be measured in terms of its functionality, durability, reliability. These all are affected by the system capabilities. Reliability is an important system design criteria for the manufacturers to be able to have high availability. Availability is the probability that a system (or a component) is operating properly to its function at a specific point in time or a specific period of times. System availability provides valuable input to estimate the production rate for the company to realize the production plan. When considering only the corrective maintenance downtime of the system, mean time between failure (MTBF) and mean time to repair (MTTR) are used to obtain system availability. Also, the MTBF and MTTR values are important measures to improve system performance by adopting suitable maintenance strategies for reliability engineers and practitioners working in a system. Failure and repair time probability distributions of each component in the system should be known for the conventional availability analysis. However, generally, companies do not have statistics or quality control departments to store such a large amount of data. Real events or situations are defined deterministically instead of using stochastic data for the complete description of real systems. A fuzzy set is an alternative theory which is used to analyze the uncertainty and vagueness in real systems. The aim of this study is to present a novel approach to compute system availability using representation of MTBF and MTTR in fuzzy numbers. Based on the experience in the system, it is decided to choose 3 different spread of MTBF and MTTR such as 15%, 20% and 25% to obtain lower and upper limits of the fuzzy numbers. To the best of our knowledge, the proposed method is the first application that is used fuzzy MTBF and fuzzy MTTR for fuzzy system availability estimation. This method is easy to apply in any repairable production system by practitioners working in industry. It is provided that the reliability engineers/managers/practitioners could analyze the system performance in a more consistent and logical manner based on fuzzy availability. This paper presents a real case study of a repairable multi-stage production line in lead-acid battery production factory in Turkey. The following is focusing on the considered wet-charging battery process which has a higher production level than the other types of battery. In this system, system components could exist only in two states, working or failed, and it is assumed that when a component in the system fails, it becomes as good as new after repair. Instead of classical methods, using fuzzy set theory and obtaining intervals for these measures would be very useful for system managers, practitioners to analyze system qualifications to find better results for their working conditions. Thus, much more detailed information about system characteristics is obtained.

Keywords: availability analysis, battery production system, fuzzy sets, triangular fuzzy numbers (TFNs)

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266 Mesenchymal Stem Cells (MSC)-Derived Exosomes Could Alleviate Neuronal Damage and Neuroinflammation in Alzheimer’s Disease (AD) as Potential Therapy-Carrier Dual Roles

Authors: Huan Peng, Chenye Zeng, Zhao Wang

Abstract:

Alzheimer’s disease (AD) is an age-related neurodegenerative disease that is a leading cause of dementia syndromes and has become a huge burden on society and families. The main pathological features of AD involve excessive deposition of β-amyloid (Aβ) and Tau proteins in the brain, resulting in loss of neurons, expansion of neuroinflammation, and cognitive dysfunction in patients. Researchers have found effective drugs to clear the brain of error-accumulating proteins or to slow the loss of neurons, but their direct administration has key bottlenecks such as single-drug limitation, rapid blood clearance rate, impenetrable blood-brain barrier (BBB), and poor ability to target tissues and cells. Therefore, we are committed to seeking a suitable and efficient delivery system. Inspired by the possibility that exosomes may be involved in the secretion and transport mechanism of many signaling molecules or proteins in the brain, exosomes have attracted extensive attention as natural nanoscale drug carriers. We selected exosomes derived from bone marrow mesenchymal stem cells (MSC-EXO) with low immunogenicity and exosomes derived from hippocampal neurons (HT22-EXO) that may have excellent homing ability to overcome the deficiencies of oral or injectable pathways and bypass the BBB through nasal administration and evaluated their delivery ability and effect on AD. First, MSC-EXO and HT22 cells were isolated and cultured, and MSCs were identified by microimaging and flow cytometry. Then MSC-EXO and HT22-EXO were obtained by gradient centrifugation and qEV SEC separation column, and a series of physicochemical characterization were performed by transmission electron microscope, western blot, nanoparticle tracking analysis and dynamic light scattering. Next, exosomes labeled with lipophilic fluorescent dye were administered to WT mice and APP/PS1 mice to obtain fluorescence images of various organs at different times. Finally, APP/PS1 mice were administered intranasally with two exosomes 20 times over 40 days and 20 μL each time. Behavioral analysis and pathological section analysis of the hippocampus were performed after the experiment. The results showed that MSC-EXO and HT22-EXO were successfully isolated and characterized, and they had good biocompatibility. MSC-EXO showed excellent brain enrichment in APP/PS1 mice after intranasal administration, could improve the neuronal damage and reduce inflammation levels in the hippocampus of APP/PS1 mice, and the improvement effect was significantly better than HT22-EXO. However, intranasal administration of the two exosomes did not cause depression and anxious-like phenotypes in APP/PS1 mice, nor significantly improved the short-term or spatial learning and memory ability of APP/PS1 mice, and had no significant effect on the content of Aβ plaques in the hippocampus, which also meant that MSC-EXO could use their own advantages in combination with other drugs to clear Aβ plaques. The possibility of realizing highly effective non-invasive synergistic treatment for AD provides new strategies and ideas for clinical research.

Keywords: Alzheimer’s disease, exosomes derived from mesenchymal stem cell, intranasal administration, therapy-carrier dual roles

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