Search results for: sustainable building environmental model (SBEM)
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 26699

Search results for: sustainable building environmental model (SBEM)

749 Controlling the Release of Cyt C and L- Dopa from pNIPAM-AAc Nanogel Based Systems

Authors: Sulalit Bandyopadhyay, Muhammad Awais Ashfaq Alvi, Anuvansh Sharma, Wilhelm R. Glomm

Abstract:

Release of drugs from nanogels and nanogel-based systems can occur under the influence of external stimuli like temperature, pH, magnetic fields and so on. pNIPAm-AAc nanogels respond to the combined action of both temperature and pH, the former being mostly determined by hydrophilic-to-hydrophobic transitions above the volume phase transition temperature (VPTT), while the latter is controlled by the degree of protonation of the carboxylic acid groups. These nanogels based systems are promising candidates in the field of drug delivery. Combining nanogels with magneto-plasmonic nanoparticles (NPs) introduce imaging and targeting modalities along with stimuli-response in one hybrid system, thereby incorporating multifunctionality. Fe@Au core-shell NPs possess optical signature in the visible spectrum owing to localized surface plasmon resonance (LSPR) of the Au shell, and superparamagnetic properties stemming from the Fe core. Although there exist several synthesis methods to control the size and physico-chemical properties of pNIPAm-AAc nanogels, yet, there is no comprehensive study that highlights the dependence of incorporation of one or more layers of NPs to these nanogels. In addition, effective determination of volume phase transition temperature (VPTT) of the nanogels is a challenge which complicates their uses in biological applications. Here, we have modified the swelling-collapse properties of pNIPAm-AAc nanogels, by combining with Fe@Au NPs using different solution based methods. The hydrophilic-hydrophobic transition of the nanogels above the VPTT has been confirmed to be reversible. Further, an analytical method has been developed to deduce the average VPTT which is found to be 37.3°C for the nanogels and 39.3°C for nanogel coated Fe@Au NPs. An opposite swelling –collapse behaviour is observed for the latter where the Fe@Au NPs act as bridge molecules pulling together the gelling units. Thereafter, Cyt C, a model protein drug and L-Dopa, a drug used in the clinical treatment of Parkinson’s disease were loaded separately into the nanogels and nanogel coated Fe@Au NPs, using a modified breathing-in mechanism. This gave high loading and encapsulation efficiencies (L Dopa: ~9% and 70µg/mg of nanogels, Cyt C: ~30% and 10µg/mg of nanogels respectively for both the drugs. The release kinetics of L-Dopa, monitored using UV-vis spectrophotometry was observed to be rather slow (over several hours) with highest release happening under a combination of high temperature (above VPTT) and acidic conditions. However, the release of L-Dopa from nanogel coated Fe@Au NPs was the fastest, accounting for release of almost 87% of the initially loaded drug in ~30 hours. The chemical structure of the drug, drug incorporation method, location of the drug and presence of Fe@Au NPs largely alter the drug release mechanism and the kinetics of these nanogels and Fe@Au NPs coated with nanogels.

Keywords: controlled release, nanogels, volume phase transition temperature, l-dopa

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748 Gender-Transformative Education: A Pathway to Nourishing and Evolving Gender Equality in the Higher Education of Iran

Authors: Sepideh Mirzaee

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Gender-transformative (G-TE) education is a challenging concept in the field of education and it is a matter of hot debate in the contemporary world. Paulo Freire as the prominent advocate of transformative education considers it as an alternative to conventional banking model of education. Besides, a more inclusive concept has been introduced, namely, G-TE, as an unbiased education fostering an environment of gender justice. As its main tenet, G-TE eliminates obstacles to education and improves social shifts. A plethora of contemporary research indicates that G-TE could completely revolutionize education systems by displacing inequalities and changing gender stereotypes. Despite significant progress in female education and its effects on gender equality in Iran, challenges persist. There are some deficiencies regarding gender disparities in the society and, education, specifically. As an example, the number of women with university degrees is on the rise; thus, there will be an increasing demand for employment in the society by them. Instead, many job opportunities remain occupied by men and it is seen as intolerable for the society to assign such occupations to women. In fact, Iran is regarded as a patriarchal society where educational contexts can play a critical role to assign gender ideology to its learners. Thus, such gender ideologies in the education can become the prevailing ideologies in the entire society. Therefore, improving education in this regard, can lead to a significant change in a society subsequently influencing the status of women not only within their own country but also on a global scale. Notably, higher education plays a vital role in this empowerment and social change. Particularly higher education can have a crucial part in imparting gender neutral ideologies to its learners and bringing about substantial change. It has the potential to alleviate the detrimental effects of gender inequalities. Therefore, this study aims to conceptualize the pivotal role of G-TE and its potential power in developing gender equality within the higher educational system of Iran presented within a theoretical framework. The study emphasizes the necessity of stablishing a theoretical grounding for citizenship, and transformative education while distinguishing gender related issues including gender equality, equity and parity. This theoretical foundation will shed lights on the decisions made by policy-makers, syllabus designers, material developers, and specifically professors and students. By doing so, they will be able to promote and implement gender equality recognizing the determinants, obstacles, and consequences of sustaining gender-transformative approaches in their classes within the Iranian higher education system. The expected outcomes include the eradication of gender inequality, transformation of gender stereotypes and provision of equal opportunities for both males and females in education.

Keywords: citizenship education, gender inequality, higher education, patriarchal society, transformative education

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747 Cross-Validation of the Data Obtained for ω-6 Linoleic and ω-3 α-Linolenic Acids Concentration of Hemp Oil Using Jackknife and Bootstrap Resampling

Authors: Vibha Devi, Shabina Khanam

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Hemp (Cannabis sativa) possesses a rich content of ω-6 linoleic and ω-3 linolenic essential fatty acid in the ratio of 3:1, which is a rare and most desired ratio that enhances the quality of hemp oil. These components are beneficial for the development of cell and body growth, strengthen the immune system, possess anti-inflammatory action, lowering the risk of heart problem owing to its anti-clotting property and a remedy for arthritis and various disorders. The present study employs supercritical fluid extraction (SFE) approach on hemp seed at various conditions of parameters; temperature (40 - 80) °C, pressure (200 - 350) bar, flow rate (5 - 15) g/min, particle size (0.430 - 1.015) mm and amount of co-solvent (0 - 10) % of solvent flow rate through central composite design (CCD). CCD suggested 32 sets of experiments, which was carried out. As SFE process includes large number of variables, the present study recommends the application of resampling techniques for cross-validation of the obtained data. Cross-validation refits the model on each data to achieve the information regarding the error, variability, deviation etc. Bootstrap and jackknife are the most popular resampling techniques, which create a large number of data through resampling from the original dataset and analyze these data to check the validity of the obtained data. Jackknife resampling is based on the eliminating one observation from the original sample of size N without replacement. For jackknife resampling, the sample size is 31 (eliminating one observation), which is repeated by 32 times. Bootstrap is the frequently used statistical approach for estimating the sampling distribution of an estimator by resampling with replacement from the original sample. For bootstrap resampling, the sample size is 32, which was repeated by 100 times. Estimands for these resampling techniques are considered as mean, standard deviation, variation coefficient and standard error of the mean. For ω-6 linoleic acid concentration, mean value was approx. 58.5 for both resampling methods, which is the average (central value) of the sample mean of all data points. Similarly, for ω-3 linoleic acid concentration, mean was observed as 22.5 through both resampling. Variance exhibits the spread out of the data from its mean. Greater value of variance exhibits the large range of output data, which is 18 for ω-6 linoleic acid (ranging from 48.85 to 63.66 %) and 6 for ω-3 linoleic acid (ranging from 16.71 to 26.2 %). Further, low value of standard deviation (approx. 1 %), low standard error of the mean (< 0.8) and low variance coefficient (< 0.2) reflect the accuracy of the sample for prediction. All the estimator value of variance coefficients, standard deviation and standard error of the mean are found within the 95 % of confidence interval.

Keywords: resampling, supercritical fluid extraction, hemp oil, cross-validation

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746 The New Contemporary Cross-Cultural Buddhist Woman and Her Attitude and Perception toward Motherhood

Authors: Szerena Vajkovszki

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Among the relatively large volume of literature, the role and perception of women in Buddhism have been examined from various perspectives such as theology, history, anthropology, and feminism. When Buddhism spread to the West, women had a major role in its adaption and development. The meeting of different cultures and social structures had the fruit of a necessity to change. As Buddhism gained attention in the West, it produced a Buddhist feminist identity across national and ethnic boundaries. So globalization produced a contemporary cross-cultural Buddhist Women. The aim of the research is to find out the new role of such a Buddhist woman in aging societies. More precisely to understand what effect this contemporary Buddhist religion may have, direct or indirect, on fertility. Our worldwide aging society, especially in developed countries, including members of EU, raise sophisticated sociological and economic issues and challenges to be met. As declining fertility has outstanding influence underlying this trend, numerous studies have attempted to identify, describe, measure and interpret contributing factors of the fertility rate, out of which relatively few revealed the impact of religion. Among many religious guidelines, we can separate two major categories: direct and indirect. The aim of this research was to understand what are the most crucial identified (family values, gender related behaviors, religious sentiments) and not yet identified most influential contributing contemporary Buddhist religious factors. Above identifying these direct or indirect factors, it is also important to understand to what extent and how do they influence fertility, which requires a wider (inter-discipline) perspective. As proved by previous studies religion has also an influential role in health, mental state, well-being, working activity and many other components that are also related to fertility rates. All these components are inter-related, hence direct and indirect religious effects can only be well understood, if we figure out all necessary fields and their interaction. With the help of semi-structured opened interviews taking place in different countries, it was showed that indeed Buddhism has significant direct and indirect effect on fertility, hence the initial hypothesis was proved. However, the interviews showed an overall positive effect, the results could only serve for a general understanding about how Buddhism affects fertility. Evolution of Buddhism’s direct and indirect influence may vary in different nations and circumstances according to their specific environmental attributes. According to the local patterns, with special regard to women’s position and role in the society, outstandingly indirect influences could show diversifications. So it is advisory to investigate more for a deeper and clearer understanding of how Buddhism function in different socioeconomic circumstances. For example, in Hungary after the period of secularization more and more people tended to be attracted toward some transcendent values which could be an explanation for the rising number of Buddhists in the country. The present research could serve as a general starting point or a common basis for further specific national investigations how contemporary Buddhism affects fertility.

Keywords: contemporary Buddhism, cross-cultural woman, fertility, gender roles, religion

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745 Effect of Toxic Metals Exposure on Rat Behavior and Brain Morphology: Arsenic, Manganese

Authors: Tamar Bikashvili, Tamar Lordkipanidze, Ilia Lazrishvili

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Heavy metals remain one of serious environmental problems due to their toxic effects. The effect of arsenic and manganese compounds on rat behavior and neuromorphology was studied. Wistar rats were assigned to four groups: rats in control group were given regular water, while rats in other groups drank water with final manganese concentration of 10 mg/L (group A), 20 mg/L (group B) and final arsenic concentration 68 mg/L (group C), respectively, for a month. To study exploratory and anxiety behavior and also to evaluate aggressive performance in “home cage” rats were tested in “Open Field” and to estimate learning and memory status multi-branched maze was used. Statistically significant increase of motor and oriental-searching activity in experimental groups was revealed by an open field test, which was expressed in increase of number of lines crossed, rearing and hole reflexes. Obtained results indicated the suppression of fear in rats exposed to manganese. Specifically, this was estimated by the frequency of getting to the central part of the open field. Experiments revealed that 30-day exposure to 10 mg/ml manganese did not stimulate aggressive behavior in rats, while exposure to the higher dose (20 mg/ml), 37% of initially non-aggressive animals manifested aggressive behavior. Furthermore, 25% of rats were extremely aggressive. Obtained data support the hypothesis that excess manganese in the body is one of the immediate causes of enhancement of interspecific predatory aggressive and violent behavior in rats. It was also discovered that manganese intoxication produces non-reversible severe learning disability and insignificant, reversible memory disturbances. Studies of rodents exposed to arsenic also revealed changes in the learning process. As it is known, the distribution of metal ions differs in various brain regions. The principle manganese accumulation was observed in the hippocampus and in the neocortex, while arsenic was predominantly accumulated in nucleus accumbens, striatum, and cortex. These brain regions play an important role in the regulation of emotional state and motor activity. Histopathological analyzes of brain sections illustrated two morphologically distinct altered phenotypes of neurons: (1) shrunk cells with indications of apoptosis - nucleus and cytoplasm were very difficult to be distinguished, the integrity of neuronal cytoplasm was not disturbed; and (2) swollen cells - with indications of necrosis. Pyknotic nucleus, plasma membrane disruption and cytoplasmic vacuoles were observed in swollen neurons and they were surrounded by activated gliocytes. It’s worth to mention that in the cortex the majority of damaged neurons were apoptotic while in subcortical nuclei –neurons were mainly necrotic. Ultrastructural analyses demonstrated that all cell types in the cortex and the nucleus caudatus represent destructed mitochondria, widened neurons’ vacuolar system profiles, increased number of lysosomes and degeneration of axonal endings.

Keywords: arsenic, manganese, behavior, learning, neuron

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744 Upper Jurassic Foraminiferal Assemblages and Palaeoceanographical Changes in the Central Part of the East European Platform

Authors: Clementine Colpaert, Boris L. Nikitenko

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The Upper Jurassic foraminiferal assemblages of the East European Platform have been strongly investigated through the 20th century with biostratigraphical and in smaller degree palaeoecological and palaeobiogeographical purposes. Over the Late Jurassic, the platform was a shallow epicontinental sea that extended from Tethys to the Artic through the Pechora Sea and further toward the northeast in the West Siberian Sea. Foraminiferal assemblages of the Russian Sea were strongly affected by sea-level changes and were controlled by alternated Boreal to Peritethyan influences. The central part of the East European Platform displays very rich and diverse foraminiferal assemblages. Two sections have been analyzed; the Makar'yev Section in the Moscow Depression and the Gorodishi Section in the Yl'yanovsk Depression. Based on the evolution of foraminiferal assemblages, palaeoenvironment has been reconstructed, and sea-level changes have been refined. The aim of this study is to understand palaeoceanographical changes throughout the Oxfordian – Kimmeridgian of the central part of the Russian Sea. The Oxfordian was characterized by a general transgressive event with intermittency of small regressive phases. The platform was connected toward the south with Tethys and Peritethys. During the Middle Oxfordian, opening of a pathway of warmer water from the North-Tethys region to the Boreal Realm favoured the migration of planktonic foraminifera and the appearance of new benthic taxa. It is associated with increased temperature and primary production. During the Late Oxfordian, colder water inputs associated with the microbenthic community crisis may be a response to the closure of this warm-water corridor and the disappearance of planktonic foraminifera. The microbenthic community crisis is probably due to the increased sedimentation rate in the transition from the maximum flooding surface to a second-order regressive event, increasing productivity and inputs of organic matter along with sharp decrease of oxygen into the sediment. It is following during the Early Kimmeridgian by a replacement of foraminiferal assemblages. The almost all Kimmeridgian is characterized by the abundance of many common with Boreal and Subboreal Realm. Connections toward the South began again dominant after a small regressive event recorded during the Late Kimmeridgian and associated with the abundance of many common taxa with Subboreal Realm and Peritethys such as Crimea and Caucasus taxa. Foraminiferal assemblages of the East European Platform are strongly affected by palaeoecological changes and may display a very good model for biofacies typification under Boreal and Subboreal environments. The East European Platform appears to be a key area for the understanding of Upper Jurassic big scale palaeoceanographical changes, being connected with Boreal to Peritethyan basins.

Keywords: foraminifera, palaeoceanography, palaeoecology, upper jurassic

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743 When the Rubber Hits the Road: The Enactment of Well-Intentioned Language Policy in Digital vs. In Situ Spaces on Washington, DC Public Transportation

Authors: Austin Vander Wel, Katherin Vargas Henao

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Washington, DC, is a city in which Spanish, along with several other minority languages, is prevalent not only among tourists but also those living within city limits. In response to this linguistic diversity and DC’s adoption of the Language Access Act in 2004, the Washington Metropolitan Area Transit Authority (WMATA) committed to addressing the need for equal linguistic representation and established a five-step plan to provide the best multilingual information possible for public transportation users. The current study, however, strongly suggests that this de jure policy does not align with the reality of Spanish’s representation on DC public transportation–although perhaps doing so in an unexpected way. In order to investigate Spanish’s de facto representation and how it contrasts with de jure policy, this study implements a linguistic landscapes methodology that takes critical language-policy as its theoretical framework (Tollefson, 2005). Specifically concerning de facto representation, it focuses on the discrepancies between digital spaces and the actual physical spaces through which users travel. These digital vs. in situ conditions are further analyzed by separately addressing aural and visual modalities. In digital spaces, data was collected from WMATA’s website (visual) and their bilingual hotline (aural). For in situ spaces, both bus and metro areas of DC public transportation were explored, with signs comprising the visual modality and recordings, driver announcements, and interactions with metro kiosk workers comprising the aural modality. While digital spaces were considered to successfully fulfill WMATA’s commitment to representing Spanish as outlined in the de jure policy, physical spaces show a large discrepancy between what is said and what is done, particularly regarding the bus system, in addition to the aural modality overall. These discrepancies in situ spaces place Spanish speakers at a clear disadvantage, demanding additional resources and knowledge on the part of residents with limited or no English proficiency in order to have equal access to this public good. Based on our critical language-policy analysis, while Spanish is represented as a right in the de jure policy, its implementation in situ clearly portrays Spanish as a problem since those seeking bilingual information can not expect it to be present when and where they need it most (Ruíz, 1984; Tollefson, 2005). This study concludes with practical, data-based steps to improve the current situation facing DC’s public transportation context and serves as a model for responding to inadequate enactment of de jure policy in other language policy settings.

Keywords: Urban landscape, language access, critical-language policy, spanish, public transportation

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742 Gamifying Content and Language Integrated Learning: A Study Exploring the Use of Game-Based Resources to Teach Primary Mathematics in a Second Language

Authors: Sarah Lister, Pauline Palmer

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Research findings presented within this paper form part of a larger scale collaboration between academics at Manchester Metropolitan University and a technology company. The overarching aims of this project focus on developing a series of game-based resources to promote the teaching of aspects of mathematics through a second language (L2) in primary schools. This study explores the potential of game-based learning (GBL) as a dynamic way to engage and motivate learners, making learning fun and purposeful. The research examines the capacity of GBL resources to provide a meaningful and purposeful context for CLIL. GBL is a powerful learning environment and acts as an effective vehicle to promote the learning of mathematics through an L2. The fun element of GBL can minimise stress and anxiety associated with mathematics and L2 learning that can create barriers. GBL provides one of the few safe domains where it is acceptable for learners to fail. Games can provide a life-enhancing experience for learners, revolutionizing the routinized ways of learning through fusing learning and play. This study argues that playing games requires learners to think creatively to solve mathematical problems, using the L2 in order to progress, which can be associated with the development of higher-order thinking skills and independent learning. GBL requires learners to engage appropriate cognitive processes with increased speed of processing, sensitivity to environmental inputs, or flexibility in allocating cognitive and perceptual resources. At surface level, GBL resources provide opportunities for learners to learn to do things. Games that fuse subject content and appropriate learning objectives have the potential to make learning academic subjects more learner-centered, promote learner autonomy, easier, more enjoyable, more stimulating and engaging and therefore, more effective. Data includes observations of the children playing the games and follow up group interviews. Given that learning as a cognitive event cannot be directly observed or measured. A Cognitive Discourse Functions (CDF) construct was used to frame the research, to map the development of learners’ conceptual understanding in an L2 context and as a framework to observe the discursive interactions that occur learner to learner and between learner and teacher. Cognitively, the children were required to engage with mathematical content, concepts and language to make decisions quickly, to engage with the gameplay to reason, solve and overcome problems and learn through experimentation. The visual elements of the games supported the learning of new concepts. Children recognised the value of the games to consolidate their mathematical thinking and develop their understanding of new ideas. The games afforded them time to think and reflect. The teachers affirmed that the games provided meaningful opportunities for the learners to practise the language. The findings of this research support the view that using the game-based resources supported children’s grasp of mathematical ideas and their confidence and ability to use the L2. Engaging with the content and language through the games led to deeper learning.

Keywords: CLIL, gaming, language, mathematics

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741 Polycyclic Aromatic Hydrocarbons: Pollution and Ecological Risk Assessment in Surface Soil of the Tezpur Town, on the North Bank of the Brahmaputra River, Assam, India

Authors: Kali Prasad Sarma, Nibedita Baul, Jinu Deka

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In the present study, pollution level of polycyclic aromatic hydrocarbon (PAH) in surface soil of historic Tezpur town located in the north bank of the River Brahmaputra were evaluated. In order to determine the seasonal distribution and concentration level of 16 USEPA priority PAHs surface soil samples were collected from 12 different sampling sites with various land use type. The total concentrations of 16 PAHs (∑16 PAHs) varied from 242.68µgkg-1to 7901.89µgkg-1. Concentration of total probable carcinogenic PAH ranged between 7.285µgkg-1 and 479.184 µgkg-1 in different seasons. However, the concentration of BaP, the most carcinogenic PAH, was found in the range of BDL to 50.01 µgkg-1. The composition profiles of PAHs in 3 different seasons were characterized by following two different types of ring: (1) 4-ring PAHs, contributed to highest percentage of total PAHs (43.75%) (2) while in pre- and post- monsoon season 3- ring compounds dominated the PAH profile, contributing 65.58% and 74.41% respectively. A high PAHs concentration with significant seasonality and high abundance of LMWPAHs was observed in Tezpur town. Soil PAHs toxicity was evaluated taking toxic equivalency factors (TEFs), which quantify the carcinogenic potential of other PAHs relative to BaP and estimate benzo[a]pyrene-equivalent concentration (BaPeq). The calculated BaPeq value signifies considerable risk to contact with soil PAHs. We applied cluster analysis and principal component analysis (PCA) with multivariate linear regression (MLR) to apportion sources of polycyclic aromatic hydrocarbons (PAHs) in surface soil of Tezpur town, based on the measured PAH concentrations. The results indicate that petrogenic and pyrogenic sources are the important sources of PAHs. A combination of chemometric and molecular indices were used to identify the sources of PAHs, which could be attributed to vehicle emissions, a mixed source input, natural gas combustion, wood or biomass burning and coal combustion. Source apportionment using absolute principle component scores–multiple linear regression showed that the main sources of PAHs are 22.3% mix sources comprising of diesel and biomass combustion and petroleum spill,13.55% from vehicle emission, 9.15% from diesel and natural gas burning, 38.05% from wood and biomass burning and 16.95% contribute coal combustion. Pyrogenic input was found to dominate source of PAHs origin with more contribution from vehicular exhaust. PAHs have often been found to co-emit with other environmental pollutants like heavy metals due to similar source of origin. A positive correlation was observed between PAH with Cr and Pb (r2 = 0.54 and 0.55 respectively) in monsoon season and PAH with Cd and Pb (r2 = 0.54 and 0.61 respectively) indicating their common source. Strong correlation was observed between PAH and OC during pre- and post- monsoon (r2=0.46 and r2=0.65 respectively) whereas during monsoon season no significant correlation was observed (r2=0.24).

Keywords: polycyclic aromatic hydrocarbon, Tezpur town, chemometric analysis, ecological risk assessment, pollution

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740 Genetically Informed Precision Drug Repurposing for Rheumatoid Arthritis

Authors: Sahar El Shair, Laura Greco, William Reay, Murray Cairns

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Background: Rheumatoid arthritis (RA) is a chronic, systematic, inflammatory, autoimmune disease that involves damages to joints and erosions to the associated bones and cartilage, resulting in reduced physical function and disability. RA is a multifactorial disorder influenced by heterogenous genetic and environmental factors. Whilst different medications have proven successful in reducing inflammation associated with RA, they often come with significant side effects and limited efficacy. To address this, the novel pharmagenic enrichment score (PES) algorithm was tested in self-reported RA patients from the UK Biobank (UKBB), which is a cohort of predominantly European ancestry, and identified individuals with a high genetic risk in clinically actionable biological pathways to identify novel opportunities for precision interventions and drug repurposing to treat RA. Methods and materials: Genetic association data for rheumatoid arthritis was derived from publicly available genome-wide association studies (GWAS) summary statistics (N=97173). The PES framework exploits competitive gene set enrichment to identify pathways that are associated with RA to explore novel treatment opportunities. This data is then integrated into WebGestalt, Drug Interaction database (DGIdb) and DrugBank databases to identify existing compounds with existing use or potential for repurposed use. The PES for each of these candidates was then profiled in individuals with RA in the UKBB (Ncases = 3,719, Ncontrols = 333,160). Results A total of 209 pathways with known drug targets after multiple testing correction were identified. Several pathways, including interferon gamma signaling and TID pathway (which relates to a chaperone that modulates interferon signaling), were significantly associated with self-reported RA in the UKBB when adjusting for age, sex, assessment centre month and location, RA polygenic risk and 10 principal components. These pathways have a major role in RA pathogenesis, including autoimmune attacks against certain citrullinated proteins, synovial inflammation, and bone loss. Encouragingly, many also relate to the mechanism of action of existing RA medications. The analyses also revealed statistically significant association between RA polygenic scores and self-reported RA with individual PES scorings, highlighting the potential utility of the PES algorithm in uncovering additional genetic insights that could aid in the identification of individuals at risk for RA and provide opportunities for more targeted interventions. Conclusions In this study, pharmacologically annotated genetic risk was explored through the PES framework to overcome inter-individual heterogeneity and enable precision drug repurposing in RA. The results showed a statistically significant association between RA polygenic scores and self-reported RA and individual PES scorings for 3,719 RA patients. Interestingly, several enriched PES pathways were targeted by already approved RA drugs. In addition, the analysis revealed genetically supported drug repurposing opportunities for future treatment of RA with a relatively safe profile.

Keywords: rheumatoid arthritis, precision medicine, drug repurposing, system biology, bioinformatics

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739 Effect of Fuel Type on Design Parameters and Atomization Process for Pressure Swirl Atomizer and Dual Orifice Atomizer for High Bypass Turbofan Engine

Authors: Mohamed K. Khalil, Mohamed S. Ragab

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Atomizers are used in many engineering applications including diesel engines, petrol engines and spray combustion in furnaces as well as gas turbine engines. These atomizers are used to increase the specific surface area of the fuel, which achieve a high rate of fuel mixing and evaporation. In all combustion systems reduction in mean drop size is a challenge which has many advantages since it leads to rapid and easier ignition, higher volumetric heat release rate, wider burning range and lower exhaust concentrations of the pollutant emissions. Pressure atomizers have a different configuration for design such as swirl atomizer (simplex), dual orifice, spill return, plain orifice, duplex and fan spray. Simplex pressure atomizers are the most common type of all. Among all types of atomizers, pressure swirl types resemble a special category since they differ in quality of atomization, the reliability of operation, simplicity of construction and low expenditure of energy. But, the disadvantages of these atomizers are that they require very high injection pressure and have low discharge coefficient owing to the fact that the air core covers the majority of the atomizer orifice. To overcome these problems, dual orifice atomizer was designed. This paper proposes a detailed mathematical model design procedure for both pressure swirl atomizer (Simplex) and dual orifice atomizer, examines the effects of varying fuel type and makes a clear comparison between the two types. Using five types of fuel (JP-5, JA1, JP-4, Diesel and Bio-Diesel) as a case study, reveal the effect of changing fuel type and its properties on atomizers design and spray characteristics. Which effect on combustion process parameters; Sauter Mean Diameter (SMD), spray cone angle and sheet thickness with varying the discharge coefficient from 0.27 to 0.35 during takeoff for high bypass turbofan engines. The spray atomizer performance of the pressure swirl fuel injector was compared to the dual orifice fuel injector at the same differential pressure and discharge coefficient using Excel. The results are analyzed and handled to form the final reliability results for fuel injectors in high bypass turbofan engines. The results show that the Sauter Mean Diameter (SMD) in dual orifice atomizer is larger than Sauter Mean Diameter (SMD) in pressure swirl atomizer, the film thickness (h) in dual orifice atomizer is less than the film thickness (h) in pressure swirl atomizer. The Spray Cone Angle (α) in pressure swirl atomizer is larger than Spray Cone Angle (α) in dual orifice atomizer.

Keywords: gas turbine engines, atomization process, Sauter mean diameter, JP-5

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738 Autophagy in the Midgut Epithelium of Spodoptera exigua Hübner (Lepidoptera: Noctuidae) Larvae Exposed to Various Cadmium Concentration - 6-Generational Exposure

Authors: Magdalena Maria Rost-Roszkowska, Alina Chachulska-Żymełka, Monika Tarnawska, Maria Augustyniak, Alina Kafel, Agnieszka Babczyńska

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Autophagy is a form of cell remodeling in which an internalization of organelles into vacuoles that are called autophagosomes occur. Autophagosomes are the targets of lysosomes, thus causing digestion of cytoplasmic components. Eventually, it can lead to the death of the entire cell. However, in response to several stress factors, e.g., starvation, heavy metals (e.g., cadmium) autophagy can also act as a pro-survival factor, protecting the cell against its death. The main aim of our studies was to check if the process of autophagy, which could appear in the midgut epithelium after Cd treatment, can be fixed during the following generations of insects. As a model animal, we chose the beet armyworm Spodoptera exigua Hübner (Lepidoptera: Noctuidae), a well-known polyphagous pest of many vegetable crops. We analyzed specimens at final larval stage (5th larval stage), due to its hyperfagy, resulting in great amount of cadmium assimilate. The culture consisted of two strains: a control strain (K) fed a standard diet, and a cadmium strain (Cd), fed on standard diet supplemented with cadmium (44 mg Cd per kg of dry weight of food) for 146 generations, both strains. In addition, the control insects were transferred to the Cd supplemented diet (5 mg Cd per kg of dry weight of food, 10 mg Cd per kg of dry weight of food, 20 mg Cd per kg of dry weight of food, 44 mg Cd per kg of dry weight of food). Therefore, we obtained Cd1, Cd2, Cd3 and KCd experimental groups. Autophagy has been examined using transmission electron microscope. During this process, degenerated organelles were surrounded by a membranous phagophore and enclosed in an autophagosome. Eventually, after the autophagosome fused with a lysosome, an autolysosome was formed and the process of the digestion of organelles began. During the 1st year of the experiment, we analyzed specimens of 6 generations in all the lines. The intensity of autophagy depends significantly on the generation, tissue and cadmium concentration in the insect rearing medium. In the Ist, IInd, IIIrd, IVth, Vth and VIth generation the intensity of autophagy in the midguts from cadmium-exposed strains decreased gradually according to the following order of strains: Cd1, Cd2, Cd3 and KCd. The higher amount of cells with autophagy was observed in Cd1 and Cd2. However, it was still higher than the percentage of cells with autophagy in the same tissues of the insects from the control and multigenerational cadmium strain. This may indicate that during 6-generational exposure to various Cd concentration, a preserved tolerance to cadmium was not maintained. The study has been financed by the National Science Centre Poland, grant no 2016/21/B/NZ8/00831.

Keywords: autophagy, cell death, digestive system, ultrastructure

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737 Pickering Dry Emulsion System for Dissolution Enhancement of Poorly Water Soluble Drug (Fenofibrate)

Authors: Nitin Jadhav, Pradeep R. Vavia

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Poor water soluble drugs are difficult to promote for oral drug delivery as they demonstrate poor and variable bioavailability because of its poor solubility and dissolution in GIT fluid. Nowadays lipid based formulations especially self microemulsifying drug delivery system (SMEDDS) is found as the most effective technique. With all the impressive advantages, the need of high amount of surfactant (50% - 80%) is the major drawback of SMEDDS. High concentration of synthetic surfactant is known for irritation in GIT and also interference with the function of intestinal transporters causes changes in drug absorption. Surfactant may also reduce drug activity and subsequently bioavailability due to the enhanced entrapment of drug in micelles. In chronic treatment these issues are very conspicuous due to the long exposure. In addition the liquid self microemulsifying system also suffers from stability issues. Recently one novel approach of solid stabilized micro and nano emulsion (Pickering emulsion) has very admirable properties such as high stability, absence or very less concentration of surfactant and easily converts into the dry form. So here we are exploring pickering dry emulsion system for dissolution enhancement of anti-lipemic, extremely poorly water soluble drug (Fenofibrate). Oil moiety for emulsion preparation was selected mainly on the basis of higher solubility of drug. Captex 300 was showed higher solubility for fenofibrate, hence selected as oil for emulsion. With Silica (solid stabilizer); Span 20 was selected to improve the wetting property of it. Emulsion formed by Silica and Span20 as stabilizer at the ratio 2.5:1 (silica: span 20) was found very stable at the particle size 410 nm. The prepared emulsion was further preceded for spray drying and formed microcapsule evaluated for in-vitro dissolution study, in-vivo pharmacodynamic study and characterized for DSC, XRD, FTIR, SEM, optical microscopy etc. The in vitro study exhibits significant dissolution enhancement of formulation (85 % in 45 minutes) as compared to plain drug (14 % in 45 minutes). In-vivo study (Triton based hyperlipidaemia model) exhibits significant reduction in triglyceride and cholesterol with formulation as compared to plain drug indicating increasing in fenofibrate bioavailability. DSC and XRD study exhibit loss of crystallinity of drug in microcapsule form. FTIR study exhibit chemical stability of fenofibrate. SEM and optical microscopy study exhibit spherical structure of globule coated with solid particles.

Keywords: captex 300, fenofibrate, pickering dry emulsion, silica, span20, stability, surfactant

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736 Strategies for Incorporating Intercultural Intelligence into Higher Education

Authors: Hyoshin Kim

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Most post-secondary educational institutions have offered a wide variety of professional development programs and resources in order to advance the quality of education. Such programs are designed to support faculty members by focusing on topics such as course design, behavioral learning objectives, class discussion, and evaluation methods. These are based on good intentions and might help both new and experienced educators. However, the fundamental flaw is that these ‘effective methods’ are assumed to work regardless of what we teach and whom we teach. This paper is focused on intercultural intelligence and its application to education. It presents a comprehensive literature review on context and cultural diversity in terms of beliefs, values and worldviews. What has worked well with a group of homogeneous local students may not work well with more diverse and international students. It is because students hold different notions of what is means to learn or know something. It is necessary for educators to move away from certain sets of generic teaching skills, which are based on a limited, particular view of teaching and learning. The main objective of the research is to expand our teaching strategies by incorporating what students bring to the course. There have been a growing number of resources and texts on teaching international students. Unfortunately, they tend to be based on the deficiency model, which treats diversity not as strengths, but as problems to be solved. This view is evidenced by the heavy emphasis on assimilationist approaches. For example, cultural difference is negatively evaluated, either implicitly or explicitly. Therefore the pressure is on culturally diverse students. The following questions reflect the underlying assumption of deficiencies: - How can we make them learn better? - How can we bring them into the mainstream academic culture?; and - How can they adapt to Western educational systems? Even though these questions may be well-intended, there seems to be something fundamentally wrong as the assumption of cultural superiority is embedded in this kind of thinking. This paper examines how educators can incorporate intercultural intelligence into the course design by utilizing a variety of tools such as pre-course activities, peer learning and reflective learning journals. The main goal is to explore ways to engage diverse learners in all aspects of learning. This can be achieved by activities designed to understand their prior knowledge, life experiences, and relevant cultural identities. It is crucial to link course material to students’ diverse interests thereby enhancing the relevance of course content and making learning more inclusive. Internationalization of higher education can be successful only when cultural differences are respected and celebrated as essential and positive aspects of teaching and learning.

Keywords: intercultural competence, intercultural intelligence, teaching and learning, post-secondary education

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735 Colocalization Analysis to Understand Yttrium Uptake in Saxifraga paniculata Using Complementary Imaging Technics

Authors: Till Fehlauer, Blanche Collin, Bernard Angeletti, Andrea Somogyi, Claire Lallemand, Perrine Chaurand, Cédric Dentant, Clement Levard, Jerome Rose

Abstract:

Over the last decades, yttrium (Y) has gained importance in high-tech applications. It is an essential part of alloys and compounds used for lasers, displays, or cell phones, for example. Due to its chemical similarities with the lanthanides, Y is often considered a rare earth element (REE). Despite their increased usage, the environmental behavior of REEs remains poorly understood. Especially regarding their interactions with plants, many uncertainties exist. On the one hand, Y is known to have a negative effect on root development and germination, but on the other hand, it appears to promote plant growth at low concentrations. In order to understand these phenomena, a precise knowledge is necessary about how Y is absorbed by the plant and how it is handled once inside the organism. Contradictory studies exist, stating that due to a similar ionic radius, Y and the other REEs might be absorbed through Ca²⁺-channels, while others suspect that Y has a shared pathway with Al³⁺. In this study, laser ablation coupled ICP-MS, and synchrotron-based micro-X-ray fluorescence (µXRF, beamline Nanoscopium, SOLEIL, France) have been used in order to localize Y within the plant tissue and identify associated elements. The plant used in this study is Saxifraga paniculata, a rugged alpine plant that has shown an affinity for Y in previous studies (in prep.). Furthermore, Saxifraga paniculata performs guttation, which means that it possesses phloem sap secreting openings on the leaf surface that serve to regulate root pressure. These so-called hydathodes could provide special insights in elemental transport in plants. The plants have been grown on Y doped soil (500mg/kg DW) for four months. The results showed that Y was mainly concentrated in the roots of Saxifraga paniculata (260 ± 85mg/kg), and only a small amount was translocated to the leaves (10 ± 7.8mg/kg). µXRF analysis indicated that within the root transects, the majority of Y remained in the epidermis and hardly penetrated the stele. Laser ablation coupled ICP-MS confirmed this finding and showed a positive correlation in the roots between Y, Fe, Al, and to a lesser extent Ca. In the stem transect, Y was mainly detected in a hotspot of approximately 40µm in diameter situated in the endodermis area. Within the stem and especially in the hotspot, Y was highly colocalized with Al and Fe. Similar-sized Y hotspots have been detected in/on the leaves. All of them were strongly colocalized with Al and Fe, except for those situated within the hydathodes, which showed no colocalization with any of the measured elements. Accordingly, a relation between Y and Ca during root uptake remains possible, whereas a correlation to Fe and Al appears to be dominant in the aerial parts, suggesting common storage compartments, the formation of complexes, or a shared pathway during translocation.

Keywords: laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS), Phytoaccumulation, Rare earth elements, Saxifraga paniculata, Synchrotron-based micro-X-ray fluorescence, Yttrium

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734 Prediction of Coronary Artery Stenosis Severity Based on Machine Learning Algorithms

Authors: Yu-Jia Jian, Emily Chia-Yu Su, Hui-Ling Hsu, Jian-Jhih Chen

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Coronary artery is the major supplier of myocardial blood flow. When fat and cholesterol are deposit in the coronary arterial wall, narrowing and stenosis of the artery occurs, which may lead to myocardial ischemia and eventually infarction. According to the World Health Organization (WHO), estimated 740 million people have died of coronary heart disease in 2015. According to Statistics from Ministry of Health and Welfare in Taiwan, heart disease (except for hypertensive diseases) ranked the second among the top 10 causes of death from 2013 to 2016, and it still shows a growing trend. According to American Heart Association (AHA), the risk factors for coronary heart disease including: age (> 65 years), sex (men to women with 2:1 ratio), obesity, diabetes, hypertension, hyperlipidemia, smoking, family history, lack of exercise and more. We have collected a dataset of 421 patients from a hospital located in northern Taiwan who received coronary computed tomography (CT) angiography. There were 300 males (71.26%) and 121 females (28.74%), with age ranging from 24 to 92 years, and a mean age of 56.3 years. Prior to coronary CT angiography, basic data of the patients, including age, gender, obesity index (BMI), diastolic blood pressure, systolic blood pressure, diabetes, hypertension, hyperlipidemia, smoking, family history of coronary heart disease and exercise habits, were collected and used as input variables. The output variable of the prediction module is the degree of coronary artery stenosis. The output variable of the prediction module is the narrow constriction of the coronary artery. In this study, the dataset was randomly divided into 80% as training set and 20% as test set. Four machine learning algorithms, including logistic regression, stepwise regression, neural network and decision tree, were incorporated to generate prediction results. We used area under curve (AUC) / accuracy (Acc.) to compare the four models, the best model is neural network, followed by stepwise logistic regression, decision tree, and logistic regression, with 0.68 / 79 %, 0.68 / 74%, 0.65 / 78%, and 0.65 / 74%, respectively. Sensitivity of neural network was 27.3%, specificity was 90.8%, stepwise Logistic regression sensitivity was 18.2%, specificity was 92.3%, decision tree sensitivity was 13.6%, specificity was 100%, logistic regression sensitivity was 27.3%, specificity 89.2%. From the result of this study, we hope to improve the accuracy by improving the module parameters or other methods in the future and we hope to solve the problem of low sensitivity by adjusting the imbalanced proportion of positive and negative data.

Keywords: decision support, computed tomography, coronary artery, machine learning

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733 The Current Home Hemodialysis Practices and Patients’ Safety Related Factors: A Case Study from Germany

Authors: Ilyas Khan. Liliane Pintelon, Harry Martin, Michael Shömig

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The increasing costs of healthcare on one hand, and the rise in aging population and associated chronic disease, on the other hand, are putting increasing burden on the current health care system in many Western countries. For instance, chronic kidney disease (CKD) is a common disease and in Europe, the cost of renal replacement therapy (RRT) is very significant to the total health care cost. However, the recent advancement in healthcare technology, provide the opportunity to treat patients at home in their own comfort. It is evident that home healthcare offers numerous advantages apparently, low costs and high patients’ quality of life. Despite these advantages, the intake of home hemodialysis (HHD) therapy is still low in particular in Germany. Many factors are accounted for the low number of HHD intake. However, this paper is focusing on patients’ safety-related factors of current HHD practices in Germany. The aim of this paper is to analyze the current HHD practices in Germany and to identify risks related factors if any exist. A case study has been conducted in a dialysis center which consists of four dialysis centers in the south of Germany. In total, these dialysis centers have 350 chronic dialysis patients, of which, four patients are on HHD. The centers have 126 staff which includes six nephrologists and 120 other staff i.e. nurses and administration. The results of the study revealed several risk-related factors. Most importantly, these centers do not offer allied health services at the pre-dialysis stage, the HHD training did not have an established curriculum; however, they have just recently developed the first version. Only a soft copy of the machine manual is offered to patients. Surprisingly, the management was not aware of any standard available for home assessment and installation. The home assessment is done by a third party (i.e. the machines and equipment provider) and they may not consider the hygienic quality of the patient’s home. The type of machine provided to patients at home is similar to the one in the center. The model may not be suitable at home because of its size and complexity. Even though portable hemodialysis machines, which are specially designed for home use, are available in the market such as the NxStage series. Besides the type of machine, no assistance is offered for space management at home in particular for placing the machine. Moreover, the centers do not offer remote assistance to patients and their carer at home. However, telephonic assistance is available. Furthermore, no alternative is offered if a carer is not available. In addition, the centers are lacking medical staff including nephrologists and renal nurses.

Keywords: home hemodialysis, home hemodialysis practices, patients’ related risks in the current home hemodialysis practices, patient safety in home hemodialysis

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732 Advanced Palliative Aquatics Care Multi-Device AuBento for Symptom and Pain Management by Sensorial Integration and Electromagnetic Fields: A Preliminary Design Study

Authors: J. F. Pollo Gaspary, F. Peron Gaspary, E. M. Simão, R. Concatto Beltrame, G. Orengo de Oliveira, M. S. Ristow Ferreira, J.C. Mairesse Siluk, I. F. Minello, F. dos Santos de Oliveira

Abstract:

Background: Although palliative care policies and services have been developed, research in this area continues to lag. An integrated model of palliative care is suggested, which includes complementary and alternative services aimed at improving the well-being of patients and their families. The palliative aquatics care multi-device (AuBento) uses several electromagnetic techniques to decrease pain and promote well-being through relaxation and interaction among patients, specialists, and family members. Aim: The scope of this paper is to present a preliminary design study of a device capable of exploring the various existing theories on the biomedical application of magnetic fields. This will be achieved by standardizing clinical data collection with sensory integration, and adding new therapeutic options to develop an advanced palliative aquatics care, innovating in symptom and pain management. Methods: The research methodology was based on the Work Package Methodology for the development of projects, separating the activities into seven different Work Packages. The theoretical basis was carried out through an integrative literature review according to the specific objectives of each Work Package and provided a broad analysis, which, together with the multiplicity of proposals and the interdisciplinarity of the research team involved, generated consistent and understandable complex concepts in the biomedical application of magnetic fields for palliative care. Results: Aubento ambience was idealized with restricted electromagnetic exposure (avoiding data collection bias) and sensory integration (allowing relaxation associated with hydrotherapy, music therapy, and chromotherapy or like floating tank). This device has a multipurpose configuration enabling classic or exploratory options on the use of the biomedical application of magnetic fields at the researcher's discretion. Conclusions: Several patients in diverse therapeutic contexts may benefit from the use of magnetic fields or fluids, thus validating the stimuli to clinical research in this area. A device in controlled and multipurpose environments may contribute to standardizing research and exploring new theories. Future research may demonstrate the possible benefits of the aquatics care multi-device AuBento to improve the well-being and symptom control in palliative care patients and their families.

Keywords: advanced palliative aquatics care, magnetic field therapy, medical device, research design

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731 Role of Artificial Intelligence in Nano Proteomics

Authors: Mehrnaz Mostafavi

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Recent advances in single-molecule protein identification (ID) and quantification techniques are poised to revolutionize proteomics, enabling researchers to delve into single-cell proteomics and identify low-abundance proteins crucial for biomedical and clinical research. This paper introduces a different approach to single-molecule protein ID and quantification using tri-color amino acid tags and a plasmonic nanopore device. A comprehensive simulator incorporating various physical phenomena was designed to predict and model the device's behavior under diverse experimental conditions, providing insights into its feasibility and limitations. The study employs a whole-proteome single-molecule identification algorithm based on convolutional neural networks, achieving high accuracies (>90%), particularly in challenging conditions (95–97%). To address potential challenges in clinical samples, where post-translational modifications affecting labeling efficiency, the paper evaluates protein identification accuracy under partial labeling conditions. Solid-state nanopores, capable of processing tens of individual proteins per second, are explored as a platform for this method. Unlike techniques relying solely on ion-current measurements, this approach enables parallel readout using high-density nanopore arrays and multi-pixel single-photon sensors. Convolutional neural networks contribute to the method's versatility and robustness, simplifying calibration procedures and potentially allowing protein ID based on partial reads. The study also discusses the efficacy of the approach in real experimental conditions, resolving functionally similar proteins. The theoretical analysis, protein labeler program, finite difference time domain calculation of plasmonic fields, and simulation of nanopore-based optical sensing are detailed in the methods section. The study anticipates further exploration of temporal distributions of protein translocation dwell-times and the impact on convolutional neural network identification accuracy. Overall, the research presents a promising avenue for advancing single-molecule protein identification and quantification with broad applications in proteomics research. The contributions made in methodology, accuracy, robustness, and technological exploration collectively position this work at the forefront of transformative developments in the field.

Keywords: nano proteomics, nanopore-based optical sensing, deep learning, artificial intelligence

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730 Effects of Abiotic Stress on the Phytochemical Content and Bioactivity of Pistacia lentiscus L.

Authors: S. Mamoucha, N. Tsafantakis, Α. Ioannidis, S. Chatzipanagiotou, C. Nikolaou, L. Skaltsounis, N. Fokialakis, N. Christodoulakis

Abstract:

Introduction: Plant secondary metabolites (SM) can be grouped into three chemically distinct groups: terpenes, phenolics, and nitrogen-containing compounds. For many years the adaptive significance of SM was unknown. They were thought to be functionless end-products. Currently it is accepted that many secondary metabolites (also known as natural products) have important ecological roles in plants. For instance, they serve as attractants (odor, color, taste) for pollinators and seed-dispersing animals. Moreover, they protect plants from herbivores, microbial pathogens and from environmental stress (high and low temperatures, drought, alkalinity, salinity, radiation etc). It is well known that both biotic and abiotic stress often increase the accumulation of SM. The local climatic conditions, seasonal changes, external factors such as light, temperature, humidity affect the biosynthesis and composition of secondary metabolites. A well known dioecious evergreen plant, Pistacia lentiscus L. (mastic tree), was selected in order to study the metabolic variations occur in response to the different climate conditions, due to the seasonal variation and its effect on the biosynthesis of bioactive compounds. Materials-methods: Young and mature leaves were collected in January and July 2014, dried and extracted by accelerated solvent extraction (Dionex ASE™ 350) using solvents of increased polarity (DCM, MeOH, and H2O). GC-MS and UHPLC-HRMS analysis were carried out in order to define the nature and the relative abundance of SM. The antibacterial activity was evaluated by using the Agar Disc Diffusion Assay against ATCC and clinical isolates strains: Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Candida albicans, Streptococcus mutans and Klebsiella pneumoniae. All tests were carried out in duplicate and the average radii of the inhibition zones were calculated for each extract. Results: According to the phytochemical profile obtained from each extract, the biosynthesis of SM varied both qualitatively and quantitatively under the two different types of seasonal stress. With exception of the biologically inactive nonpolar DCM extract of July, all extracts inhibited the growth of most of the investigated microorganisms. A clear positive correlation has been observed between the relative abundance of SM and the bioactivity of the DCM extracts of January and July. Observed changes during phytochemical analysis were mainly focused on the triterpenoid content. On the other hand, the bioactivity of the polar extracts (MeOH and H2O) of January and July resulted practically invariable against most of the microorganisms, besides the significant variation of the SM content due to the seasonal variation. Conclusion: Our results clearly confirmed the hypothesis of abiotic stress as an important regulating factor that significantly affects the biosynthesis of secondary metabolites and thus the presence of bioactive compounds. Acknowledgment: This work was supported by IKY - State Scholarship Foundation, Athens, Greece.

Keywords: antibacterial screening, phytochemical profile, Pistacia lentiscus, abiotic stress

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729 The Two Question Challenge: Embedding the Serious Illness Conversation in Acute Care Workflows

Authors: D. M. Lewis, L. Frisby, U. Stead

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Objective: Many patients are receiving invasive treatments in acute care or are dying in hospital without having had comprehensive goals of care conversations. Some of these treatments may not align with the patient’s wishes, may be futile, and may cause unnecessary suffering. While many staff may recognize the benefits of engaging patients and families in Serious Illness Conversations (a goal of care framework developed by Ariadne Labs in Boston), few staff feel confident and/or competent in having these conversations in acute care. Another barrier to having these conversations may be due to a lack of incorporation in the current workflow. An educational exercise, titled the Two Question Challenge, was initiated on four medical units across two Vancouver Coastal Health (VCH) hospitals in attempt to engage the entire interdisciplinary team in asking patients and families questions around goals of care and to improve the documentation of these expressed wishes and preferences. Methods: Four acute care units across two separate hospitals participated in the Two Question Challenge. On each unit, over the course of two eight-hour shifts, all members of the interdisciplinary team were asked to select at least two questions from a selection of nine goals of care questions. They were asked to pose these questions of a patient or family member throughout their shift and then asked to document their conversations in a centralized Advance Care Planning/Goals of Care discussion record in the patient’s chart. A visual representation of conversation outcomes was created to demonstrate to staff and patients the breadth of conversations that took place throughout the challenge. Staff and patients were interviewed about their experiences throughout the challenge. Two palliative approach leads remained present on the units throughout the challenge to support, guide, or role model these conversations. Results: Across four acute care medical units, 47 interdisciplinary staff participated in the Two Question Challenge, including nursing, allied health, and a physician. A total of 88 questions were asked of patients, or their families around goals of care and 50 newly documented goals of care conversations were charted. Two code statuses were changed as a result of the conversations. Patients voiced an appreciation for these conversations and staff were able to successfully incorporate these questions into their daily care. Conclusion: The Two Question Challenge proved to be an effective way of having teams explore the goals of care of patients and families in an acute care setting. Staff felt that they gained confidence and competence. Both staff and patients found these conversations to be meaningful and impactful and felt they were notably different from their usual interactions. Documentation of these conversations in a centralized location that is easily accessible to all care providers increased significantly. Application of the Two Question Challenge in non-medical units or other care settings, such as long-term care facilities or community health units, should be explored in the future.

Keywords: advance care planning, goals of care, interdisciplinary, palliative approach, serious illness conversations

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728 Compromising Quality of Life in Low Income Settlement's: The Case of Ashrayan Prakalpa, Khulna

Authors: Salma Akter, Md. Kamal Uddin

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This study aims to demonstrate how top-down shelter policy and its resultant dwelling environment leads to ‘everyday compromise’ by the grassroots according to subjective (satisfaction) and objective (physical design elements and physical environmental elements) indicators, which are measured across three levels of the settlement; macro (Community), meso (Neighborhood or shelter/built environment) and micro (family). Ashrayan Prakalpa is a resettlement /housing project of Government of Bangladesh for providing shelters and human resources development activities like education, microcredit, and training programme to landless, homeless and rootless people. Despite the integrated nature of the shelter policies (comprises poverty alleviation, employment opportunity, secured tenure, and livelihood training), the ‘quality of life’ issue at the different levels of settlements becomes questionable. As dwellers of shelter units (although formally termed as ‘barracks’ rather shelter or housing) remain on the receiving end of government’s resettlement policies, they often involve with spatial-physical and socio-economic negotiation and assume curious forms of spatial practice, which often upholds contradiction with policy planning. Thus, policy based shelter force dwellers to persistently compromise with their provided built environments both in overtly and covertly. Compromising with prescribed designed space and facilities across living places articulated their negotiation with the quality of allocated space, built form and infrastructures, which in turn exert as less quality of life. The top-down shelter project, Dakshin Chandani Mahal Ashrayan Prakalpa at Dighalia Upazila, the study area located at the Eastern fringe area of Khulna, Bangladesh, is still in progress to resettle internally displaced and homeless people. In terms of methodology, this research is primarily exploratory and adopts a case study method, and an analytical framework is developed through the deductive approach for evaluating the quality of life. Secondary data have been obtained from housing policy analysis and relevant literature review, while key informant interview, focus group discussion, necessary drawings and photographs and participant observation across dwelling, neighborhood, and community level have also been administered as primary data collection methodology. Findings have revealed that various shortages, inadequacies, and negligence of policymakers force to compromise with allocated designed space, physical infrastructure and economic opportunities across dwelling, neighborhood and mostly community level. Thus, the outcome of this study can be beneficial for a global-level understating of the compromising the ‘quality of life’ under top-down shelter policy. Locally, for instance, in the context of Bangladesh, it can help policymakers and concerned authorities to formulate the shelter policies and take initiatives to improve the well-being of marginalized.

Keywords: Ashrayan Prakalpa, compromise, displaced people, quality of life

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727 Through Additive Manufacturing. A New Perspective for the Mass Production of Made in Italy Products

Authors: Elisabetta Cianfanelli, Paolo Pupparo, Maria Claudia Coppola

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The recent evolutions in the innovation processes and in the intrinsic tendencies of the product development process, lead to new considerations on the design flow. The instability and complexity that contemporary life describes, defines new problems in the production of products, stimulating at the same time the adoption of new solutions across the entire design process. The advent of Additive Manufacturing, but also of IOT and AI technologies, continuously puts us in front of new paradigms regarding design as a social activity. The totality of these technologies from the point of view of application describes a whole series of problems and considerations immanent to design thinking. Addressing these problems may require some initial intuition and the use of some provisional set of rules or plausible strategies, i.e., heuristic reasoning. At the same time, however, the evolution of digital technology and the computational speed of new design tools describe a new and contrary design framework in which to operate. It is therefore interesting to understand the opportunities and boundaries of the new man-algorithm relationship. The contribution investigates the man-algorithm relationship starting from the state of the art of the Made in Italy model, the most known fields of application are described and then focus on specific cases in which the mutual relationship between man and AI becomes a new driving force of innovation for entire production chains. On the other hand, the use of algorithms could engulf many design phases, such as the definition of shape, dimensions, proportions, materials, static verifications, and simulations. Operating in this context, therefore, becomes a strategic action, capable of defining fundamental choices for the design of product systems in the near future. If there is a human-algorithm combination within a new integrated system, quantitative values can be controlled in relation to qualitative and material values. The trajectory that is described therefore becomes a new design horizon in which to operate, where it is interesting to highlight the good practices that already exist. In this context, the designer developing new forms can experiment with ways still unexpressed in the project and can define a new synthesis and simplification of algorithms, so that each artifact has a signature in order to define in all its parts, emotional and structural. This signature of the designer, a combination of values and design culture, will be internal to the algorithms and able to relate to digital technologies, creating a generative dialogue for design purposes. The result that is envisaged indicates a new vision of digital technologies, no longer understood only as of the custodians of vast quantities of information, but also as a valid integrated tool in close relationship with the design culture.

Keywords: decision making, design euristics, product design, product design process, design paradigms

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726 Childhood Adversity and Delinquency in Youth: Self-Esteem and Depression as Mediators

Authors: Yuhui Liu, Lydia Speyer, Jasmin Wertz, Ingrid Obsuth

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Childhood adversities refer to situations where a child's basic needs for safety and support are compromised, leading to substantial disruptions in their emotional, cognitive, social, or neurobiological development. Given the prevalence of adversities (8%-39%), their impact on developmental outcomes is challenging to completely avoid. Delinquency is an important consequence of childhood adversities, given its potential causing violence and other forms of victimisation, influencing victims, delinquents, their families, and the whole of society. Studying mediators helps explain the link between childhood adversity and delinquency, which aids in designing effective intervention programs that target explanatory variables to disrupt the path and mitigate the effects of childhood adversities on delinquency. The Dimensional Model of Adversity and Psychopathology suggests that threat-based adversities influence outcomes through emotion processing, while deprivation-based adversities do so through cognitive mechanisms. Thus, considering a wide range of threat-based and deprivation-based adversities and their co-occurrence and their associations with delinquency through cognitive and emotional mechanisms is essential. This study employs the Millennium Cohort Study, tracking the development of approximately 19,000 individuals born across England, Scotland, Wales and Northern Ireland, representing a nationally representative sample. Parallel mediation models compare the mediating roles of self-esteem (cognitive) and depression (affective) in the associations between childhood adversities and delinquency. Eleven types of childhood adversities were assessed both individually and through latent class analysis, considering adversity experiences from birth to early adolescence. This approach aimed to capture how threat-based, deprived-based, or combined threat and deprived-based adversities are associated with delinquency. Eight latent classes were identified: three classes (low adversity, especially direct and indirect violence; low childhood and moderate adolescent adversities; and persistent poverty with declining bullying victimisation) were negatively associated with delinquency. In contrast, three classes (high parental alcohol misuse, overall high adversities, especially regarding household instability, and high adversity) were positively associated with delinquency. When mediators were included, all classes showed a significant association with delinquency through depression, but not through self-esteem. Among the eleven single adversities, seven were positively associated with delinquency, with five linked through depression and none through self-esteem. The results imply the importance of affective variables, not just for threat-based but also deprivation-based adversities. Academically, this suggests exploring other mechanisms linking adversities and delinquency since some adversities are linked through neither depression nor self-esteem. Clinically, intervention programs should focus on affective variables like depression to mitigate the effects of childhood adversities on delinquency.

Keywords: childhood adversity, delinquency, depression, self-esteem

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725 Biofuels from Hybrid Poplar: Using Biochemicals and Wastewater Treatment as Opportunities for Early Adoption

Authors: Kevin W. Zobrist, Patricia A. Townsend, Nora M. Haider

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Advanced Hardwood Biofuels Northwest (AHB) is a consortium funded by the United States Department of Agriculture (USDA) to research the potential for a system to produce advanced biofuels (jet fuel, diesel, and gasoline) from hybrid poplar in the Pacific Northwest region of the U.S. An Extension team was established as part of the project to examine community readiness and willingness to adopt hybrid as a purpose-grown bioenergy crop. The Extension team surveyed key stakeholder groups, including growers, Extension professionals, policy makers, and environmental groups, to examine attitudes and concerns about growing hybrid poplar for biofuels. The surveys found broad skepticism about the viability of such a system. The top concern for most stakeholder groups was economic viability and the availability of predictable markets. Growers had additional concerns stemming from negative past experience with hybrid poplar as an unprofitable endeavor for pulp and paper production. Additional barriers identified included overall land availability and the availability of water and water rights for irrigation in dry areas of the region. Since the beginning of the project, oil and natural gas prices have plummeted due to rapid increases in domestic production. This has exacerbated the problem with economic viability by making biofuels even less competitive than fossil fuels. However, the AHB project has identified intermediate market opportunities to use poplar as a renewable source for other biochemicals produced by petroleum refineries, such as acetic acid, ethyl acetate, ethanol, and ethylene. These chemicals can be produced at a lower cost with higher yields and higher, more-stable prices. Despite these promising market opportunities, the survey results suggest that it will still be challenging to induce growers to adopt hybrid poplar. Early adopters will be needed to establish an initial feedstock supply for a budding industry. Through demonstration sites and outreach events to various stakeholder groups, the project attracted interest from wastewater treatment facilities, since these facilities are already growing hybrid poplar plantations for applying biosolids and treated wastewater for further purification, clarification, and nutrient control through hybrid poplar’s phytoremediation capabilities. Since these facilities are already using hybrid poplar, selling the wood as feedstock for a biorefinery would be an added bonus rather than something requiring a high rate of return to compete with other crops and land uses. By holding regional workshops and conferences with wastewater professionals, AHB Extension has found strong interest from wastewater treatment operators. In conclusion, there are several significant barriers to developing a successful system for producing biofuels from hybrid poplar, with the largest barrier being economic viability. However, there is potential for wastewater treatment facilities to serve as early adopters for hybrid poplar production for intermediate biochemicals and eventually biofuels.

Keywords: hybrid poplar, biofuels, biochemicals, wastewater treatment

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724 Safety Validation of Black-Box Autonomous Systems: A Multi-Fidelity Reinforcement Learning Approach

Authors: Jared Beard, Ali Baheri

Abstract:

As autonomous systems become more prominent in society, ensuring their safe application becomes increasingly important. This is clearly demonstrated with autonomous cars traveling through a crowded city or robots traversing a warehouse with heavy equipment. Human environments can be complex, having high dimensional state and action spaces. This gives rise to two problems. One being that analytic solutions may not be possible. The other is that in simulation based approaches, searching the entirety of the problem space could be computationally intractable, ruling out formal methods. To overcome this, approximate solutions may seek to find failures or estimate their likelihood of occurrence. One such approach is adaptive stress testing (AST) which uses reinforcement learning to induce failures in the system. The premise of which is that a learned model can be used to help find new failure scenarios, making better use of simulations. In spite of these failures AST fails to find particularly sparse failures and can be inclined to find similar solutions to those found previously. To help overcome this, multi-fidelity learning can be used to alleviate this overuse of information. That is, information in lower fidelity can simulations can be used to build up samples less expensively, and more effectively cover the solution space to find a broader set of failures. Recent work in multi-fidelity learning has passed information bidirectionally using “knows what it knows” (KWIK) reinforcement learners to minimize the number of samples in high fidelity simulators (thereby reducing computation time and load). The contribution of this work, then, is development of the bidirectional multi-fidelity AST framework. Such an algorithm, uses multi-fidelity KWIK learners in an adversarial context to find failure modes. Thus far, a KWIK learner has been used to train an adversary in a grid world to prevent an agent from reaching its goal; thus demonstrating the utility of KWIK learners in an AST framework. The next step is implementation of the bidirectional multi-fidelity AST framework described. Testing will be conducted in a grid world containing an agent attempting to reach a goal position and adversary tasked with intercepting the agent as demonstrated previously. Fidelities will be modified by adjusting the size of a time-step, with higher-fidelity effectively allowing for more responsive closed loop feedback. Results will compare the single KWIK AST learner with the multi-fidelity algorithm with respect to number of samples, distinct failure modes found, and relative effect of learning after a number of trials.

Keywords: multi-fidelity reinforcement learning, multi-fidelity simulation, safety validation, falsification

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723 Assessing the Severity of Traffic Related Air Pollution in South-East London to School Pupils

Authors: Ho Yin Wickson Cheung, Liora Malki-Epshtein

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Outdoor air pollution presents a significant challenge for public health globally, especially in urban areas, with road traffic acting as the primary contributor to air pollution. Several studies have documented the antagonistic relation between traffic-related air pollution (TRAP) and the impact on health, especially to the vulnerable group of population, particularly young pupils. Generally, TRAP could cause damage to their brain, restricting the ability of children to learn and, more importantly, causing detrimental respiratory issues in later life. Butlittle is known about the specific exposure of children at school during the school day and the impact this may have on their overall exposure to pollution at a crucial time in their development. This project has set out to examine the air quality across primary schools in South-East London and assesses the variability of data found based on their geographic location and surroundings. Nitrogen dioxide, PM contaminants, and carbon dioxide were collected with diffusion tubes and portable monitoring equipment for eight schools across three local areas, that are Greenwich, Lewisham, and Tower Hamlets. This study first examines the geographical features of the schools surrounding (E.g., coverage of urban road structure and green infrastructure), then utilize three different methods to capture pollutants data. Moreover, comparing the obtained results with existing data from monitoring stations to understand the differences in air quality before and during the pandemic. Furthermore, most studies in this field have unfortunately neglected human exposure to pollutants and calculated based on values from fixed monitoring stations. Therefore, this paper introduces an alternative approach by calculating human exposure to air pollution from real-time data obtained when commuting within related areas (Driving routes and field walking). It is found that schools located highly close to motorways are generally not suffering from the most air pollution contaminants. Instead, one with the worst traffic congested routes nearby might also result in poor air quality. Monitored results also indicate that the annual air pollution values have slightly decreased during the pandemic. However, the majority of the data is currently still exceeding the WHO guidelines. Finally, the total human exposures for NO2 during commuting in the two selected routes were calculated. Results illustrated the total exposure for route 1 were 21,730 μm/m3 and 28,378.32 μm/m3, and for route 2 were 30,672 μm/m3 and 16,473 μm/m3. The variance that occurred might be due to the difference in traffic volume that requires further research. Exposure for NO2 during commuting was plotted with detailed timesteps that have shown their peak usually occurred while commuting. These have consolidated the initial assumption to the extremeness of TRAP. To conclude, this paper has yielded significant benefits to understanding air quality across schools in London with the new approach of capturing human exposure (Driving routes). Confirming the severity of air pollution and promoting the necessity of considering environmental sustainability for policymakers during decision making to protect society's future pillars.

Keywords: air pollution, schools, pupils, congestion

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722 In vitro and in vivo Effects of 'Sonneratia alba' Extract against the Fish Pathogen 'Aphanomyces invadans'

Authors: S. F. Afzali, W. L. Wong

Abstract:

The epizootic ulcerative syndrome (EUS) causes by the oomycete fungus, Aphanomyces invadans; known to be one of the infectious fish diseases for farmed and wild fishes in fresh and brackish-water from the Asia-pacific region, America and Africa. Although, EUS had been documented by the Office International des Epizooties (OIE) since 1995, hitherto, there is neither standard chemical agents that can be used for successful treatment of this destructive infection in the time of outbreak; nor available vaccine for prevention. Plant-based remedies in controlling fish diseases are gaining much attention recently as an alternative to chemical treatments, which possess negative effects to the environment and human. In present study, Sonneratia alba, a mangrove plant belongs to the Sonneratiaceae family, was screened in vitro and in vivo for its antifungal activity against A. invadans mycelium growth and its effects on fish innate immune system and disease resistant. The in vitro tests was performed using the disc diffusion methods with measurements of minimum inhibitory concentration (MIC) and inhibition zone. For in vivo study, the S. alba extract supplemented diets were administrated at 0.0, 1.0%, 3.0%, and 5.0% on healthy goldfish, Carassius auratus, which challenged with A. invadans zoospores (100 spores/ml). To compare the significant differences in the hematological and immunological parameters obtained from the experiments, the data were analysed using the SPSS. The methanol extract of S. alba effectively inhibited the mycelial growth of A. invadans at a minimum concentration of 1000 ppm for agar and filter paper diffusion experiments. In the agar diffusion test, 500 ppm of the extract inhibited the fungus mycelial growth up to 96 hours after exposure. The mycelial growth from the edge of the pre-inoculated A. invadans agar discs treated with S. alba extracts at concentrations of 100, 500 and 1000 ppm were 15, 8 and 0 mm respectively. The results of the filter paper disc test showed that the S. alba extract at its minimal inhibitory concentration (1000 ppm) has similar qualitative inhibitory effect as malachite green at 1 ppm and formalin at 250 ppm. According to the in vivo tests findings, in the infected fish fed with 3.0% and 5.0% supplementation diet, the numbers of white blood cell and myeloperoxidase activity significantly increased after the second week of treatment. Whilst the numbers of red blood cell significantly decreased in the infected fish fed with 0.0 and 1.0% supplementation diet. After the third week of feeding, significant increases in the total protein, albumin level, lysozyme activity were recorded in the infected fish fed with 3.0% and 5.0% supplementation diet. Also, the enriched diets increased the survival rate as compared to the untreated group that suffered from 90% mortality. The present study indicated that S. alba extract may inhibit the mycelial growth of A. invadans effectively, suggesting an alternative to other chemotherapeutic agents, which brought much environmental and health concerns to the public, for EUS treatment.

Keywords: fungal pathogen, goldfish, organic extract, treatment

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721 No-Par Shares Working in European LLCs

Authors: Agnieszka P. Regiec

Abstract:

Capital companies are based on monetary capital. In the traditional model, the capital is the sum of the nominal values of all shares issued. For a few years within the European countries, the limited liability companies’ (LLC) regulations are leaning towards liberalization of the capital structure in order to provide higher degree of autonomy regarding the intra-corporate governance. Reforms were based primarily on the legal system of the USA. In the USA, the tradition of no-par shares is well-established. Thus, as a point of reference, the American legal system is being chosen. Regulations of Germany, Great Britain, France, Netherlands, Finland, Poland and the USA will be taken into consideration. The analysis of the share capital is important for the development of science not only because the capital structure of the corporation has significant impact on the shareholders’ rights, but also it reflects on relationships between creditors of the company and the company itself. Multi-level comparative approach towards the problem will allow to present a wide range of the possible outcomes stemming from the novelization. The dogmatic method was applied. The analysis was based on the statutes, secondary sources and judicial awards. Both the substantive and the procedural aspects of the capital structure were considered. In Germany, as a result of the regulatory competition, typical for the EU, the structure of LLCs was reshaped. New LLC – Unternehmergesellschaft, which does not require a minimum share capital, was introduced. The minimum share capital for Gesellschaft mit beschrankter Haftung was lowered from 25 000 to 10 000 euro. In France the capital structure of corporations was also altered. In 2003, the minimum share capital of société à responsabilité limitée (S.A.R.L.) was repealed. In 2009, the minimum share capital of société par actions simplifiée – in the “simple” version of S.A.R.L. was also changed – there is no minimum share capital required by a statute. The company has to, however, indicate a share capital without the legislator imposing the minimum value of said capital. In Netherlands the reform of the Besloten Vennootschap met beperkte aansprakelijkheid (B.V.) was planned with the following change: repeal of the minimum share capital as the answer to the need for higher degree of autonomy for shareholders. It, however, preserved shares with nominal value. In Finland the novelization of yksityinen osakeyhtiö took place in 2006 and as a result the no-par shares were introduced. Despite the fact that the statute allows shares without face value, it still requires the minimum share capital in the amount of 2 500 euro. In Poland the proposal for the restructuration of the capital structure of the LLC has been introduced. The proposal provides among others: devaluation of the capital to 1 PLN or complete liquidation of the minimum share capital, allowing the no-par shares to be issued. In conclusion: American solutions, in particular, balance sheet test and solvency test provide better protection for creditors; European no-par shares are not the same as American and the existence of share capital in Poland is crucial.

Keywords: balance sheet test, limited liability company, nominal value of shares, no-par shares, share capital, solvency test

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720 Enhance Concurrent Design Approach through a Design Methodology Based on an Artificial Intelligence Framework: Guiding Group Decision Making to Balanced Preliminary Design Solution

Authors: Loris Franchi, Daniele Calvi, Sabrina Corpino

Abstract:

This paper presents a design methodology in which stakeholders are assisted with the exploration of a so-called negotiation space, aiming to the maximization of both group social welfare and single stakeholder’s perceived utility. The outcome results in less design iterations needed for design convergence while obtaining a higher solution effectiveness. During the early stage of a space project, not only the knowledge about the system but also the decision outcomes often are unknown. The scenario is exacerbated by the fact that decisions taken in this stage imply delayed costs associated with them. Hence, it is necessary to have a clear definition of the problem under analysis, especially in the initial definition. This can be obtained thanks to a robust generation and exploration of design alternatives. This process must consider that design usually involves various individuals, who take decisions affecting one another. An effective coordination among these decision-makers is critical. Finding mutual agreement solution will reduce the iterations involved in the design process. To handle this scenario, the paper proposes a design methodology which, aims to speed-up the process of pushing the mission’s concept maturity level. This push up is obtained thanks to a guided negotiation space exploration, which involves autonomously exploration and optimization of trade opportunities among stakeholders via Artificial Intelligence algorithms. The negotiation space is generated via a multidisciplinary collaborative optimization method, infused by game theory and multi-attribute utility theory. In particular, game theory is able to model the negotiation process to reach the equilibria among stakeholder needs. Because of the huge dimension of the negotiation space, a collaborative optimization framework with evolutionary algorithm has been integrated in order to guide the game process to efficiently and rapidly searching for the Pareto equilibria among stakeholders. At last, the concept of utility constituted the mechanism to bridge the language barrier between experts of different backgrounds and differing needs, using the elicited and modeled needs to evaluate a multitude of alternatives. To highlight the benefits of the proposed methodology, the paper presents the design of a CubeSat mission for the observation of lunar radiation environment. The derived solution results able to balance all stakeholders needs and guaranteeing the effectiveness of the selection mission concept thanks to its robustness in valuable changeability. The benefits provided by the proposed design methodology are highlighted, and further development proposed.

Keywords: concurrent engineering, artificial intelligence, negotiation in engineering design, multidisciplinary optimization

Procedia PDF Downloads 128