Search results for: powerful

Authors: Binder Hans

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Cancer is no longer seen as solely a genetic disease where genetic defects such as mutations and copy number variations affect gene regulation and eventually lead to aberrant cell functioning which can be monitored by transcriptome analysis. It has become obvious that epigenetic alterations represent a further important layer of (de-)regulation of gene activity. For example, aberrant DNA methylation is a hallmark of many cancer types, and methylation patterns were successfully used to subtype cancer heterogeneity. Hence, unraveling the interplay between different omics levels such as genome, transcriptome and epigenome is inevitable for a mechanistic understanding of molecular deregulation causing complex diseases such as cancer. This objective requires powerful downstream integrative bioinformatics methods as an essential prerequisite to discover the whole genome mutational, transcriptome and epigenome landscapes of cancer specimen and to discover cancer genesis, progression and heterogeneity. Basic challenges and tasks arise ‘beyond sequencing’ because of the big size of the data, their complexity, the need to search for hidden structures in the data, for knowledge mining to discover biological function and also systems biology conceptual models to deduce developmental interrelations between different cancer states. These tasks are tightly related to cancer biology as an (epi-)genetic disease giving rise to aberrant genomic regulation under micro-environmental control and clonal evolution which leads to heterogeneous cellular states. Machine learning algorithms such as self organizing maps (SOM) represent one interesting option to tackle these bioinformatics tasks. The SOMmethod enables recognizing complex patterns in large-scale data generated by highthroughput omics technologies. It portrays molecular phenotypes by generating individualized, easy to interpret images of the data landscape in combination with comprehensive analysis options. Our image-based, reductionist machine learning methods provide one interesting perspective how to deal with massive data in the discovery of complex diseases, gliomas, melanomas and colon cancer on molecular level. As an important new challenge, we address the combined portrayal of different omics data such as genome-wide genomic, transcriptomic and methylomic ones. The integrative-omics portrayal approach is based on the joint training of the data and it provides separate personalized data portraits for each patient and data type which can be analyzed by visual inspection as one option. The new method enables an integrative genome-wide view on the omics data types and the underlying regulatory modes. It is applied to high and low-grade gliomas and to melanomas where it disentangles transversal and longitudinal molecular heterogeneity in terms of distinct molecular subtypes and progression paths with prognostic impact.

Keywords: integrative bioinformatics, machine learning, molecular mechanisms of cancer, gliomas and melanomas

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Authors: Laura M. F. Bertens

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There is a long tradition of visually representing the art historical canon, in schematic overviews and diagrams. This is indicative of the desire for scientific, ‘objective’ knowledge of the kind (seemingly) produced in the natural sciences. These diagrams will, however, always retain an element of subjectivity and the modelling methods colour our perception of the represented information. In recent decades visualisations of art historical data, such as hand-drawn diagrams in textbooks, have been extended to include digital, computational tools. These tools significantly increase modelling strength and functionality. As such, they might be used to deconstruct and amend the very problem caused by traditional visualisations of the canon. In this paper, the use of digital tools for modelling the art historical canon is studied, in order to draw attention to the artificial nature of the static models that art historians are presented with in textbooks and lectures, as well as to explore the potential of digital, dynamic tools in creating new models. To study the way diagrams of the canon mediate the represented information, two modelling methods have been used on two case studies of existing diagrams. The tree diagram Stammbaum der neudeutschen Kunst (1823) by Ferdinand Olivier has been translated to a social network using the program Visone, and the famous flow chart Cubism and Abstract Art (1936) by Alfred Barr has been translated to an ontological model using Protégé Ontology Editor. The implications of the modelling decisions have been analysed in an art historical context. The aim of this project has been twofold. On the one hand the translation process makes explicit the design choices in the original diagrams, which reflect hidden assumptions about the Western canon. Ways of organizing data (for instance ordering art according to artist) have come to feel natural and neutral and implicit biases and the historically uneven distribution of power have resulted in underrepresentation of groups of artists. Over the last decades, scholars from fields such as Feminist Studies, Postcolonial Studies and Gender Studies have considered this problem and tried to remedy it. The translation presented here adds to this deconstruction by defamiliarizing the traditional models and analysing the process of reconstructing new models, step by step, taking into account theoretical critiques of the canon, such as the feminist perspective discussed by Griselda Pollock, amongst others. On the other hand, the project has served as a pilot study for the use of digital modelling tools in creating dynamic visualisations of the canon for education and museum purposes. Dynamic computer models introduce functionalities that allow new ways of ordering and visualising the artworks in the canon. As such, they could form a powerful tool in the training of new art historians, introducing a broader and more diverse view on the traditional canon. Although modelling will always imply a simplification and therefore a distortion of reality, new modelling techniques can help us get a better sense of the limitations of earlier models and can provide new perspectives on already established knowledge.

Keywords: canon, ontological modelling, Protege Ontology Editor, social network modelling, Visone

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Authors: Muhammad Karim Ahmadzai

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Floods are natural phenomena and are an integral part of the water cycle. The majority of them are the result of climatic conditions, but are also affected by the geology and geomorphology of the area, topography and hydrology, the water permeability of the soil and the vegetation cover, as well as by all kinds of human activities and structures. However, from the moment that human lives are at risk and significant economic impact is recorded, this natural phenomenon becomes a natural disaster. Flood management is now a key issue at regional and local levels around the world, affecting human lives and activities. The majority of floods are unlikely to be fully predicted, but it is feasible to reduce their risks through appropriate management plans and constructions. The aim of this Case Study is to identify, and map areas of flood risk in the Khinch District of Panjshir Province, Afghanistan specifically in the area of Peshghore, causing numerous damages. The main purpose of this study is to evaluate the contribution of remote sensing technology and Geographic Information Systems (GIS) in assessing the susceptibility of this region to flood events. Panjsher is facing Seasonal floods and human interventions on streams caused floods. The beds of which have been trampled to build houses and hotels or have been converted into roads, are causing flooding after every heavy rainfall. The streams crossing settlements and areas with high touristic development have been intensively modified by humans, as the pressure for real estate development land is growing. In particular, several areas in Khinch are facing a high risk of extensive flood occurrence. This study concentrates on the construction of a flood susceptibility map, of the study area, by combining vulnerability elements, using the Analytical Hierarchy Process/ AHP. The Analytic Hierarchy Process, normally called AHP, is a powerful yet simple method for making decisions. It is commonly used for project prioritization and selection. AHP lets you capture your strategic goals as a set of weighted criteria that you then use to score projects. This method is used to provide weights for each criterion which Contributes to the Flood Event. After processing of a digital elevation model (DEM), important secondary data were extracted, such as the slope map, the flow direction and the flow accumulation. Together with additional thematic information (Landuse and Landcover, topographic wetness index, precipitation, Normalized Difference Vegetation Index, Elevation, River Density, Distance from River, Distance to Road, Slope), these led to the final Flood Risk Map. Finally, according to this map, the Priority Protection Areas and Villages and the structural and nonstructural measures were demonstrated to Minimize the Impacts of Floods on residential and Agricultural areas.

Keywords: flood hazard, flood risk map, flood mitigation measures, AHP analysis

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Authors: Ehsan K. Hazaveh

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This research project explores creative methods of storytelling through photography to portray a vulnerable and marginalised community: former refugees living in Wellington, New Zealand. The project explores photographic representational techniques that can not only empower and give voice to those communities but also challenge dominant stereotypes about refugees and support humanitarian actions. The aims of this study are to develop insights surrounding issues associated with the photographic representation of refugees and to explore the collaborative construction of possible counter-narratives that might lead to the formulation of a practice framework for representing refugees using photography. In other words, the goal of this study is to explore representational and narrative strategies that frame refugees as active community members and as individuals with specific histories and expertise. These counter-narratives will bring the diversity of refugees to the surface by offering personal stories, contextualising their experience, raising awareness about the plight and human rights of the refugee community in New Zealand, evoking empathy and, therefore, facilitating the process of social change. The study has designed a photographic narrative framework by determining effective methods of photo storytelling, framing, and aesthetic techniques, focusing on different ways of taking, selecting, editing and curating photographs. Photo elicitation interviews have been used to ‘explore’, ‘produce’ and ‘co-curate’ the counter-narrative along with participants. Photo elicitation is a qualitative research method that employs images to evoke data in order to find out how other people experience their world - the researcher shows photographs to the participant and asks open-ended questions to get them to talk about their life experiences and the world around them. The qualitative data have been collected and produced through interactions with four former refugees living in Wellington, New Zealand. In this way, this project offers a unique account of their conditions and basic knowledge about their living experience and their stories. The participants of this study have engaged with PhotoVoice, a photo elicitation methodology that employs photography and storytelling, to share activities, emotions, hopes, and aspects of their lived experiences. PhotoVoice was designed to empower members of marginalised populations. It involves a series of meeting sessions, in which participants share photographs they have taken and discuss stories about the photographs to identify, represent, and enhance the issues important to their lives and communities. Finally, the data provide a basis for systematically producing visual counter-narratives that highlight the experiences of former- refugees. By employing these methods, refugees can represent their world as well as interpret it. The process of developing this research framing has enabled the development of powerful counter-narratives that challenge prevailing stereotypical depictions which in turn have the potential to shape improved humanitarian outcomes, shifts in public attitudes and political perspectives in New Zealand.

Keywords: media, photography, refugees, photo-elicitation, storytelling

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Authors: B. K. Kanungo, Monika Thakur, Minati Baral

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8-hydroxyquinoline, (8HQ), experiences a renaissance due to its utility as a building block in metallosupramolecular chemistry and its versatile use of its derivatives in various fields of analytical chemistry, materials science, and pharmaceutics. It forms stable complexes with a variety of metal ions. Assembly of more than one such unit to form a polydentate chelator enhances its coordinating ability and the related properties due to the chelate effect resulting in high stability constant. Keeping in view the above, a nonadentate chelator N-[3,5-bis(8-hydroxyquinoline-2-amido)cyclohexyl]-8-hydroxyquinoline-2-carboxamide, (TACH2OX), containing a central cis,cis-1,3,5-triaminocyclohexane appended to three 8-hydroxyquinoline at 2-position through amide linkage is developed, and its solution thermodynamics, photophysical and Density Functional Theory (DFT) studies were undertaken. The synthesis of TACH2OX was carried out by condensation of cis,cis-1,3,5-triaminocyclohexane, (TACH) with 8‐hydroxyquinoline‐2‐carboxylic acid. The brown colored solid has been fully characterized through melting point, infrared, nuclear magnetic resonance, electrospray ionization mass and electronic spectroscopy. In solution, TACH2OX forms protonated complexes below pH 3.4, which consecutively deprotonates to generate trinegative ion with the rise of pH. Nine protonation constants for the ligand were obtained that ranges between 2.26 to 7.28. The interaction of the chelator with two trivalent metal ion Fe3+ and Al3+ were studied in aqueous solution at 298 K. The metal-ligand formation constants (ML) obtained by potentiometric and spectrophotometric method agree with each other. The protonated and hydrolyzed species were also detected in the system. The in-silico studies of the ligand, as well as the complexes including their protonated and deprotonated species assessed by density functional theory technique, gave an accurate correlation with each observed properties such as the protonation constants, stability constants, infra-red, nmr, electronic absorption and emission spectral bands. The nature of electronic and emission spectral bands in terms of number and type were ascertained from time-dependent density functional theory study and the natural transition orbitals (NTO). The global reactivity indices parameters were used for comparison of the reactivity of the ligand and the complex molecules. The natural bonding orbital (NBO) analysis could successfully describe the structure and bonding of the metal-ligand complexes specifying the percentage of contribution in atomic orbitals in the creation of molecular orbitals. The obtained high value of metal-ligand formation constants indicates that the newly synthesized chelator is a very powerful synthetic chelator. The minimum energy molecular modeling structure of the ligand suggests that the ligand, TACH2OX, in a tripodal fashion firmly coordinates to the metal ion as hexa-coordinated chelate displaying distorted octahedral geometry by binding through three sets of N, O- donor atoms, present in each pendant arm of the central tris-cyclohexaneamine tripod.

Keywords: complexes, DFT, formation constant, TACH2OX

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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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Authors: Joao Ferreira Do Rosario, Maria De Lurdes Calisto, Ana Teresa Machado, Nuno Gustavo, Rui Gonçalves

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The tourism sector is increasingly important to the economic performance of countries and a relevant theme to academic research, increasing the importance of understanding how and why tourists evaluate tourism locations. The city of Lisbon is currently a tourist destination of excellence in the European and world-wide panorama, registering a significant growth of the economic weight of its tourist activities in the Gross Added Value of the region. Although there is research on the feedback of those who visit tourist sites and different methodologies for studying tourist sites have been applied, this research seeks to be innovative in the objective of obtaining insights on the competitiveness in terms of attractiveness of the city of Lisbon as a tourist destination, based the feedback of tourists in the Facebook pages of the most visited museums and monuments of Lisbon, an interpretation that is relevant in the development of strategies of tourist attraction. The intangible dimension of the tourism offer, due to its unique condition of simultaneous production and consumption, makes eWOM particularly relevant. The testimony of consumers is thus a decisive factor in the decision-making and buying process in tourism. Online social networks are one of the most used platforms for tourists to evaluate the attractiveness's points of a tourism destination (e.g. cultural and historical heritage), with this user-generated feedback enabling relevant information about the customer-tourists. This information is related to the tourist experience representing the true voice of the customer. Furthermore, this voice perceived by others as genuine, opposite to marketing messages, may have a powerful word-of-mouth influence on other potential tourists. The relevance of online reviews sharing, however, becomes particularly complex, considering social media users’ different profiles or the possible and different sources of information available, as well as their associated reputation associated with each source. In the light of these trends, our research focuses on the tourists’ feedback on Facebook pages of the most visited museums and monuments of Lisbon that contribute to its attractiveness as a tourism destination. Sentiment Analysis is the methodology selected for this research, using public available information in the online context, which was deemed as an appropriate non-participatory observation method. Data will be collected from two museums (Museu dos Coches and Museu de Arte Antiga) and three monuments ((Mosteiro dos Jerónimos, Torre de Belém and Panteão Nacional) Facebook pages during a period of one year. The research results will help in the evaluation of the considered places by the tourists, their contribution to the city attractiveness and present insights helpful for the management decisions regarding this museums and monuments. The results of this study will also contribute to a better knowledge of the tourism sector, namely the identification of attributes in the evaluation and choice of the city of Lisbon as a tourist destination. Further research will evaluate the Lisbon attraction points for tourists in different categories beyond museums and monuments, will also evaluate the tourist feedback from other sources like TripAdvisor and apply the same methodology in other cities and country regions.

Keywords: Lisbon tourism, opinion mining, sentiment analysis, tourism location attractiveness evaluation

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Authors: Abdalla Ahmed Abdrabou Emam Eldeib

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For more than a century, the Hague Conference has tackled issues in the most challenging areas of private international law, including family law. Its actions in the realm of international child abduction have been remarkable in two ways during the last two decades. First, on October 25, 1980, the Hague Convention on the Civil Aspects of International Child Abduction (the Convention) was promulgated as an unusually inventive and powerful tool. Second, the Convention is rapidly becoming more prominent in the development of international child law. By that time, overseas travel had grown more convenient, and more couples were marrying or travelling across national lines. At the same time, parental separation and divorce have increased, leading to an increase in international child custody battles. The convention they drafted avoids legal quagmires and addresses extra-legal issues well. It literally restores the kid to its place of usual residence by establishing that the youngster was unlawfully abducted from that position or, alternatively, was wrongfully kept abroad after an allowed visit. Legal custody of a child of a contested parent is usually followed by the child's abduction or unlawful relocation to another country by the non-custodial parent or other persons. If a child's custodial parent lives outside of Egypt, the youngster may be kidnapped and brought to Egypt. It's natural to ask what laws should apply and what legal norms should be followed while hearing individual instances. This study comprehensively evaluates and estimates the relevant Hague Child Abduction Convention and the current situation in Egypt and which law is applicable for child custody. In addition, this research emphasis, detail, and focus on the position of Cross-border parental child abductions in Egypt. Moreover, examine the Islamic law compared to the Hague Convention on Child Custody in detail, as well as mentioning the treatment of Islamic countries in this matter in general and Egypt's treatment of this matter in particular, as well as the criticism directed at Egypt regarding the application and implementation of child custody issues. The present research backs up this method by using non-doctrinal techniques, including surveys, interviews, and dialogues. An important objective of this research is to examine the factors that contribute to parental child abduction. In this case, family court attorneys and other interested parties serve as the target audience from whom data is collected. A survey questionnaire was developed and sent to the target population in order to collect data for future empirical testing to validate the identified critical factors on Parental Child Abduction. The main finding in this study is breaking the reservations of many Muslim countries to join the Hague Convention with regard to child custody., Likewise, clarify the problems of implementation in practice in cases of kidnapping a child from one of the parents and traveling with him outside the borders of the country. Finally, this study is to provide suggestions for reforming the current Egyptian Family Law to make it an effective and efficient for all dispute's resolution mechanism and the possibility of joining The Hague Convention.

Keywords: egyptian family law, Hague child abduction convention, child custody, cross-border parental child abductions in egypt

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Authors: Sibawu Witness Siyepu

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This study explores the effects of instructional design using blended learning in the learning of radian measures among Engineering students. Blended learning is an education programme that combines online digital media with traditional classroom methods. It requires the physical presence of both lecturer and student in a mathematics computer laboratory. Blended learning provides element of class control over time, place, path or pace. The focus was on the use of Khan Academy to supplement traditional classroom interactions. Khan Academy is a non-profit educational organisation created by educator Salman Khan with a goal of creating an accessible place for students to learn through watching videos in a computer assisted computer. The researcher who is an also lecturer in mathematics support programme collected data through instructing students to watch Khan Academy videos on radian measures, and by supplying students with traditional classroom activities. Classroom activities entails radian measure activities extracted from the Internet. Students were given an opportunity to engage in class discussions, social interactions and collaborations. These activities necessitated students to write formative assessments tests. The purpose of formative assessments tests was to find out about the students’ understanding of radian measures, including errors and misconceptions they displayed in their calculations. Identification of errors and misconceptions serve as pointers of students’ weaknesses and strengths in their learning of radian measures. At the end of data collection, semi-structure interviews were administered to a purposefully sampled group to explore their perceptions and feedback regarding the use of blended learning approach in teaching and learning of radian measures. The study employed Algebraic Insight Framework to analyse data collected. Algebraic Insight Framework is a subset of symbol sense which allows a student to correctly enter expressions into a computer assisted systems efficiently. This study offers students opportunities to enter topics and subtopics on radian measures into a computer through the lens of Khan Academy. Khan academy demonstrates procedures followed to reach solutions of mathematical problems. The researcher performed the task of explaining mathematical concepts and facilitated the process of reinvention of rules and formulae in the learning of radian measures. Lastly, activities that reinforce students’ understanding of radian were distributed. Results showed that this study enthused the students in their learning of radian measures. Learning through videos prompted the students to ask questions which brought about clarity and sense making to the classroom discussions. Data revealed that sense making through reinvention of rules and formulae assisted the students in enhancing their learning of radian measures. This study recommends the use of Khan Academy in blended learning to be introduced as a socialisation programme to all first year students. This will prepare students that are computer illiterate to become conversant with the use of Khan Academy as a powerful tool in the learning of mathematics. Khan Academy is a key technological tool that is pivotal for the development of students’ autonomy in the learning of mathematics and that promotes collaboration with lecturers and peers.

Keywords: algebraic insight framework, blended learning, Khan Academy, radian measures

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Authors: Valentina Dolmova

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What consumers choose to buy and who voters select on election days are two questions that have captivated the interest of both academics and practitioners for many decades. The importance of understanding what influences the behavior of those groups and whether or not we can predict or control it fuels a steady stream of research in a range of fields. By looking only at the past 40 years, more than 70 thousand scientific papers have been published in each field – consumer behavior and political psychology, respectively. From marketing, economics, and the science of persuasion to political and cognitive psychology - we have all remained heavily engaged. The ever-evolving technology, inevitable socio-cultural shifts, global economic conditions, and much more play an important role in choice-equations regardless of context. On one hand, this makes the research efforts always relevant and needed. On the other, the relatively low number of cross-field collaborations, which seem to be picking up only in more in recent years, makes the existing findings isolated into framed bubbles. By performing systematic research across both areas of psychology and building a parallel between theories and factors of influence, however, we find that there is not only a definitive common ground between the behaviors of consumers and voters but that we are moving towards a global model of choice. This means that the lines between contexts are fading which has a direct implication on what we should focus on when predicting or navigating buyers and voters’ behavior. Internal and external factors in four main categories determine the choices we make as consumers and as voters. Together, personal, psychological, social, and cultural create a holistic framework through which all stimuli in relation to a particular product or a political party get filtered. The analogy “consumer-voter” solidifies further. Leading academics suggest that this fundamental parallel is the key to managing successfully political and consumer brands alike. However, we distinguish additional four key stimuli that relate to those factor categories (1/ opportunity costs; 2/the memory of the past; 3/recognisable figures/faces and 4/conflict) arguing that the level of expertise a person has determines the prevalence of factors or specific stimuli. Our efforts take into account global trends such as the establishment of “celebrity politics” and the image of “ethically concerned consumer brands” which bridge the gap between contexts to an even greater extent. Scientists and practitioners are pushed to accept the transformative nature of both fields in social psychology. Existing blind spots as well as the limited number of research conducted outside the American and European societies open up space for more collaborative efforts in this highly demanding and lucrative field. A mixed method of research tests three main hypotheses, the first two of which are focused on the level of irrelevance of context when comparing voting or consumer behavior – both from the factors and stimuli lenses, the third on determining whether or not the level of expertise in any field skews the weight of what prism we are more likely to choose when evaluating options.

Keywords: buyers’ behaviour, decision-making, voters’ behaviour, social psychology

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Authors: V. Giacometti, R. Mirabelli, V. Patera, D. Pinci, A. Sarti, A. Sciubba, G. Traini, M. Marafini

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The particle therapy (PT) is a very modern technique of non invasive radiotherapy mainly devoted to the treatment of tumours untreatable with surgery or conventional radiotherapy, because localised closely to organ at risk (OaR). Nowadays, PT is available in about 55 centres in the word and only the 20\% of them are able to treat with carbon ion beam. However, the efficiency of the ion-beam treatments is so impressive that many new centres are in construction. The interest in this powerful technology lies to the main characteristic of PT: the high irradiation precision and conformity of the dose released to the tumour with the simultaneous preservation of the adjacent healthy tissue. However, the beam interactions with the patient produce a large component of secondary particles whose additional dose has to be taken into account during the definition of the treatment planning. Despite, the largest fraction of the dose is released to the tumour volume, a non-negligible amount is deposed in other body regions, mainly due to the scattering and nuclear interactions of the neutrons within the patient body. One of the main concerns in PT treatments is the possible occurrence of secondary malignant neoplasm (SMN). While SMNs can be developed up to decades after the treatments, their incidence impacts directly life quality of the cancer survivors, in particular in pediatric patients. Dedicated Treatment Planning Systems (TPS) are used to predict the normal tissue toxicity including the risk of late complications induced by the additional dose released by secondary neutrons. However, no precise measurement of secondary neutrons flux is available, as well as their energy and angular distributions: an accurate characterization is needed in order to improve TPS and reduce safety margins. The project MONDO (MOnitor for Neutron Dose in hadrOntherapy) is devoted to the construction of a secondary neutron tracker tailored to the characterization of that secondary neutron component. The detector, based on the tracking of the recoil protons produced in double-elastic scattering interactions, is a matrix of thin scintillating fibres, arranged in layer x-y oriented. The final size of the object is 10 x 10 x 20 cm3 (squared 250µm scint. fibres, double cladding). The readout of the fibres is carried out with a dedicated SPAD Array Sensor (SBAM) realised in CMOS technology by FBK (Fondazione Bruno Kessler). The detector is under development as well as the SBAM sensor and it is expected to be fully constructed for the end of the year. MONDO will make data tacking campaigns at the TIFPA Proton Therapy Center of Trento, at the CNAO (Pavia) and at HIT (Heidelberg) with carbon ion in order to characterize the neutron component and predict the additional dose delivered on the patients with much more precision and to drastically reduce the actual safety margins. Preliminary measurements with charged particles beams and MonteCarlo FLUKA simulation will be presented.

Keywords: secondary neutrons, particle therapy, tracking detector, elastic scattering

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Authors: R. G. Ariyawansa, M. A. N. R. M. Perera

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“House” is a powerful symbol of socio-economic background of individuals and families. In fact, housing provides all types of needs/wants from basic needs to self-actualization needs. This phenomenon can be realized only having analyzed hidden motives of buyers and sellers of the housing market. Hence, the aim of this study is to examine the socio-economic insight of the secondary housing market in Colombo suburbs. This broader aim was achieved via analyzing the general pattern of the secondary housing market, identifying socio-economic motives of sellers of the secondary housing market, and reviewing sellers’ experience of buyer behavior. A purposive sample of 50 sellers from popular residential areas in Colombo such as Maharagama, Kottawa, Piliyandala, Punnipitiya, and Nugegoda was used to collect primary data instead of relevant secondary data from published and unpublished reports. The sample was limited to selling price ranging from Rs15 million to Rs25 million, which apparently falls into middle and upper-middle income houses in the context. Participatory observation and semi-structured interviews were adopted as key data collection tools. Data were descriptively analyzed. This study found that the market is mainly handled by informal agents who are unqualified and unorganized. People such as taxi/tree-wheel drivers, boutique venders, security personals etc. are engaged in housing brokerage as a part time career. Few fulltime and formally organized agents were found but they were also not professionally qualified. As far as housing quality is concerned, it was observed that 90% of houses was poorly maintained and illegally modified. They are situated in poorly maintained neighborhoods as well. Among the observed houses, 2% was moderately maintained and 8% was well maintained and modified. Major socio-economic motives of sellers were “migrating foreign countries for education and employment” (80% and 10% respectively), “family problems” (4%), and “social status” (3%). Other motives were “health” and “environmental/neighborhood problems” (3%). This study further noted that the secondary middle income housing market in the area directly related with the migrants who motivated for education in foreign countries, mainly Australia, UK and USA. As per the literature, families motivated for education tend to migrate Colombo suburbs from remote areas of the country. They are seeking temporary accommodation in lower middle income housing. However, the secondary middle income housing market relates with the migration from Colombo to major global cities. Therefore, final transaction price of this market may depend on migration related dates such as university deadlines, visa and other agreements. Hence, it creates a buyers’ market lowering the selling price. Also it was revealed that the buyers tend to trust more on this market as far as the quality of construction of houses is concerned than brand new houses which are built for selling purpose.

Keywords: informal housing market, hidden motives of buyers and sellers, secondary housing market, socio-economic insight

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Authors: Vaibhav Baliyan, S. S. Parihar

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With the rise in temperature during reproductive phase and moisture stress, winter wheat yields are likely to decrease because of limited plant growth, higher rate of night respiration, higher spikelet sterility or number of grains per spike and restricted embryo development thereby reducing grain number. Crop management practices play a pivotal role in minimizing adverse effects of terminal heat stress on wheat production. Amongst various agronomic management practices, adjusting sowing date, crop cultivars and irrigation scheduling have been realized to be simple yet powerful, implementable and eco-friendly mitigation strategies to sustain yields under elevated temperature conditions. Taking into account, large variability in wheat production in space and time, a study was conducted to identify the suitable wheat varieties under both early and late planting with suitable irrigation schedule for minimizing terminal heat stress effect and thereby improving wheat production. Experiments were conducted at research farms of Indian Agricultural Research Institute, New Delhi, India, separately for timely and late sown conditions with suitable varieties with staggering dates of sowing from 1st November to 30th November in case of timely sown and from 1st December to 31st December for late sown condition. The irrigation schedule followed for both the experiments were 100% of ETc (evapotranspiration of crop), 80% of ETc and 60% of ETc. Results of the timely sown experiment indicated that 1st November sowing resulted in higher grain yield followed by 10th November. However, delay in sowing thereafter resulted in gradual decrease in yield and the maximum reduction was noticed under 30th November sowing. Amongst the varieties, HD3086 produced higher grain yield compared to other varieties. Irrigation applied based on 100% of ETc gave higher yield comparable to 80% of ETc but both were significantly higher than 60% of ETc. It was further observed that even liberal irrigation under 100% of ETc could not compensate the yield under delayed sowing suggesting that rise in temperature beyond January adversely affected the growth and development of crop as well as forced maturity resulting in significant reduction of yield attributing characters due to terminal heat stress. Similar observations were recorded under late sown experiment too. Planting on 1st December along with 100% ETc of irrigation schedule resulted in significantly higher grain yield as compared to other dates and irrigation regimes. Further, it was observed that reduction in yield under late sown conditions was significantly large than the timely sown conditions irrespective of the variety grown and irrigation schedule followed. Delayed sowing resulted in reducing crop growth period and forced maturity in turn led to significant deterioration in all the yield attributing characters and there by reduction in yield suggesting that terminal heat stress had greater impact on yield under late sown crop than timely sown due to temperature rise coinciding with reproductive phase of the crop.

Keywords: climate, irrigation, mitigation, wheat

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Authors: Eleni Karasavvidou

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Social and anthropological research, parallel to Gender Studies, highlighted the relationship between social structures and symbolic forms as an important field of interaction and recording of 'social trends.' Since the study of representations can contribute to the understanding of the social functions and power relations, they encompass. This ‘mirage,’ however, has not only to do with the representations themselves but also with the ways they are received and the film or critical narratives that are established as dominant or alternative. Cinema and the criticism of its cultural products are no exception. Even in the rapidly changing media landscape of the 21st century, movies remain an integral and widespread part of popular culture, making films an extremely powerful means of 'legitimizing' or 'delegitimizing' visions of domination and commonsensical gender stereotypes throughout society. And yet it is film criticism, the 'language per se,' that legitimizes, reinforces, rewards and reproduces (or at least ignores) the stereotypical depictions of female roles that remain common in the realm of film images. This creates the need for this issue to have emerged (also) in academic research questioning gender criteria in film reviews as part of the effort for an inclusive art and society. Qualitative content analysis is used to examine female roles in selected Oscar-nominated films against their reviews from leading websites and newspapers. This method was chosen because of the complex nature of the depictions in the films and the narratives they evoke. The films were divided into basic scenes depicting social functions, such as love and work relationships, positions of power and their function, which were analyzed by content analysis, with borrowings from structuralism (Gennette) and the local/universal images of intercultural philology (Wierlacher). In addition to the measurement of the general ‘representation-time’ by gender, other qualitative characteristics were also analyzed, such as: speaking time, sayings or key actions, overall quality of the character's action in relation to the development of the scenario and social representations in general, as well as quantitatively (insufficient number of female lead roles, fewer key supporting roles, relatively few female directors and people in the production chain and how they might affect screen representations. The quantitative analysis in this study was used to complement the qualitative content analysis. Then the focus shifted to the criteria of film criticism and to the rhetorical narratives that exclude or highlight in relation to gender identities and functions. In the criteria and language of film criticism, stereotypes are often reproduced or allegedly overturned within the framework of apolitical "identity politics," which mainly addresses the surface of a self-referential cultural-consumer product without connecting it more deeply with the material and cultural life. One of the prime examples of this failure is the Bechtel Test, which tracks whether female characters speak in a film regardless of whether women's stories are represented or not in the films analyzed. If perceived unbiased male filmmakers still fail to tell truly feminist stories, the same is the case with the criteria of criticism and the related interventions.

Keywords: representations, context analysis, reviews, sexist stereotypes

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Authors: Rajinder Kumar Gupta, Rajni Kant Agrawal, Jaganniwas

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One of the most frightening phenomena of nature is the occurrence of earthquake as it has terrible and disastrous effects. Many earthquakes occur every day worldwide. There is need to have knowledge regarding the trends in earthquake occurrence worldwide. The recoding and interpretation of data obtained from the establishment of the worldwide system of seismological stations made this possible. From the analysis of recorded earthquake data, the earthquake parameters and source parameters can be computed and the earthquake catalogues can be prepared. These catalogues provide information on origin, time, epicenter locations (in term of latitude and longitudes) focal depths, magnitude and other related details of the recorded earthquakes. Theses catalogues are used for seismic hazard estimation. Manual interpretation and analysis of these data is tedious and time consuming. A geographical information system is a computer based system designed to store, analyzes and display geographic information. The implementation of integrated GIS technology provides an approach which permits rapid evaluation of complex inventor database under a variety of earthquake scenario and allows the user to interactively view results almost immediately. GIS technology provides a powerful tool for displaying outputs and permit to users to see graphical distribution of impacts of different earthquake scenarios and assumptions. An endeavor has been made in present study to compile the earthquake data for the whole world in visual Basic on ARC GIS Plate form so that it can be used easily for further analysis to be carried out by earthquake engineers. The basic data on time of occurrence, location and size of earthquake has been compiled for further querying based on various parameters. A preliminary analysis tool is also provided in the user interface to interpret the earthquake recurrence in region. The user interface also includes the seismic hazard information already worked out under GHSAP program. The seismic hazard in terms of probability of exceedance in definite return periods is provided for the world. The seismic zones of the Indian region are included in the user interface from IS 1893-2002 code on earthquake resistant design of buildings. The City wise satellite images has been inserted in Map and based on actual data the following information could be extracted in real time: • Analysis of soil parameters and its effect • Microzonation information • Seismic hazard and strong ground motion • Soil liquefaction and its effect in surrounding area • Impacts of liquefaction on buildings and infrastructure • Occurrence of earthquake in future and effect on existing soil • Propagation of earth vibration due of occurrence of Earthquake GIS based earthquake information system has been prepared for whole world in Visual Basic on ARC GIS Plate form and further extended micro level based on actual soil parameters. Individual tools has been developed for liquefaction, earthquake frequency etc. All information could be used for development of infrastructure i.e. multi story structure, Irrigation Dam & Its components, Hydro-power etc in real time for present and future.

Keywords: GIS based earthquake information system, microzonation, analysis and real time information about liquefaction, infrastructure development

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Authors: Theophilus Asante, Comfort Nyarko, Daniel Antwi

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Drug-resistant tuberculosis, together with the associated comorbidities like pulmonary fibrosis and silicosis, has been one of the most serious global public health threats that requires immediate action to curb or mitigate it. This prolongs hospital stays, increases the cost of medication, and increases the death toll recorded annually. Crinum asiaticum bulb (CAE) and betulin (BET) are known for their biological and pharmacological effects. Pharmacological effects reported on CAE include antimicrobial, anti-inflammatory, anti-pyretic, anti-analgesic, and anti-cancer effects. Betulin has exhibited a multitude of powerful pharmacological properties ranging from antitumor, anti-inflammatory, anti-parasitic, anti-microbial, and anti-viral activities. This work sought to investigate the anti-tuberculosis and resistant modulatory effects and also assess their effects on mitigating pulmonary fibrosis and silicosis. In the anti-tuberculosis and resistant modulatory effects, both CAE and BET showed strong antimicrobial activities (31.25 ≤ MIC ≤ 500) µg/ml against the studied microorganisms and also produced significant anti-efflux pump and biofilm inhibitory effects (ρ < 0.0001) as well as exhibiting resistance modulatory and synergistic effects when combined with standard antibiotics. Crinum asiaticum bulbs extract and betulin were shown to possess anti-pulmonary fibrosis effects. There was an increased survival rate in the CAE and BET treatment groups compared to the BLM-induced group. There was a marked decrease in the levels of hydroxyproline and collagen I and III in the CAE and BET treatment groups compared to the BLM-treated group. The treatment groups of CAE and BET significantly downregulated the levels of pro-fibrotic and pro-inflammatory cytokine concentrations such as TGF-β1, MMP9, IL-6, IL-1β and TNF-alpha compared to an increase in the BLM-treated groups. The histological findings of the lungs suggested the curative effects of CAE and BET following BLM-induced pulmonary fibrosis in mice. The study showed improved lung functions with a wide focal area of viable alveolar spaces and few collagen fibers deposition on the lungs of the treatment groups. In the anti-silicosis and pulmonoprotective effects of CAE and BET, the levels of NF-κB, TNF-α, IL-1β, IL-6 and hydroxyproline, collagen types I and III were significantly reduced by CAE and BET (ρ < 0.0001). Both CAE and BET significantly (ρ < 0.0001) inhibited the levels of hydroxyproline, collagen I and III when compared with the negative control group. On BALF biomarkers such as macrophages, lymphocytes, monocytes, and neutrophils, CAE and BET were able to reduce their levels significantly (ρ < 0.0001). The CAE and BET were examined for anti-oxidant activity and shown to raise the levels of catalase (CAT) and superoxide dismutase (SOD) while lowering the level of malondialdehyde (MDA). There was an improvement in lung function when lung tissues were examined histologically. Crinum asiaticum bulbs extract and betulin were discovered to exhibit anti-tubercular and resistance-modulatory properties, as well as the capacity to minimize TB comorbidities such as pulmonary fibrosis and silicosis. In addition, CAE and BET may act as protective mechanisms, facilitating the preservation of the lung's physiological integrity. The outcomes of this study might pave the way for the development of leads for producing single medications for the management of drug-resistant tuberculosis and its accompanying comorbidities.

Keywords: fibrosis, crinum, tuberculosis, antiinflammation, drug resistant

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Authors: Maari Sugawara

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This arts-based research is about "self-torture": the interplay of seemingly opposing elements of pain, pleasure, submission, and power. It asserts that "self-torture" can be considered a nontrivial mediation between the aesthetic and the sociopolitical. It explores what the author calls queered self-torture; "self-torture" marked by an ambivalence that allows the oppressed to resist, and their counter-valorization occasionally functions as therapeutic solutions to the problems they highlight and condense. The research goal is to deconstruct normative self-torture and propose queered self-torture as a fertile ground for considering the complexities of desire that allow the oppressed to practice freedom. While “self-torture” manifests in many societies, this research focuses on cultural and national identity in post-WWII Japan using this lens of self-torture, as masochism functions as the very basis for Japanese cultural and national identity to ensure self-preservation. This masochism is defined as an impulse to realize a sense of pride and construct an identity through the acceptance of subordination, shame, and humiliation in the face of an all-powerful Other; the dominant Euro-America. It could be argued that this self-torture is a result of Japanese cultural annihilation and the trauma of the nation's defeat to the US. This is the definition of "self-torturous thresholds," the author’s post-WWII Japan psycho-historical diagnosis; when this threshold is crossed, the oppressed begin to torture themselves; the oppressors no longer need to do anything to maintain their power. The oppressed are already oppressing themselves. The term "oppressed" here refers to Japanese individuals and residents of Japan who are subjected to oppressive “white” heteropatriarchal supremacist structures and values that serve colonialist interests. There are three stages in "self-torturous thresholds": (1) the oppressors no longer need to oppress because the oppressed voluntarily commit to self-torture; (2) the oppressed find pleasure in self-torture; and (3) the oppressed achieve queered self-torture, to achieve alternative futures. Using the conceptualization of "self-torture," this research examines and critiques pleasure, desire, capital, and power in postwar Japan, which enables the discussion of the data-colonizing “Moonshot Research and Development program”. If the oppressed want to divest from the habits of normative self-torture, which shape what is possible in both our present and future, we need methods to feel and know that the alternative results of self-torture are possible. Phase three will be enacted using Sarah Ahmed's queer methodology to reorient national and cultural identity away from heteronormativity. Through theoretical analysis, textual analysis, archival research, ethnographic interviews, and digital art projects, including experimental documentary as a method to capture the realities of the individuals who are practicing self-torture, this research seeks to reveal how self-torture may become not just a vehicle of pleasure but also a mode of critiquing power and achieving freedom. It seeks to encourage the imaginings of queer Japanese futures, where the marginalized survive Japan’s natural and man-made disasters and Japan’s Imperialist past and present rather than submitting to the country’s continued violence.

Keywords: arts-based research, Japanese studies, interdisciplinary arts, queer studies, cultural studies, popular culture, BDSM, sadomasochism, sexuality, VR, AR, digital art, visual arts, speculative fiction

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Authors: Jade V. Rushby, Tony Loughland, Tracy L. Durksen, Hoa Nguyen, Robert M. Klassen

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This paper reports a study investigating the development and implementation of an online multi-session ‘scenario-based learning’ (SBL) program administered to preservice teachers in Australia. The transition from initial teacher education to the teaching profession can present numerous cognitive and psychological challenges for early career teachers. Therefore, the identification of additional supports, such as scenario-based learning, that can supplement existing teacher education programs may help preservice teachers to feel more confident and prepared for the realities and complexities of teaching. Scenario-based learning is grounded in situated learning theory which holds that learning is most powerful when it is embedded within its authentic context. SBL exposes participants to complex and realistic workplace situations in a supportive environment and has been used extensively to help prepare students in other professions, such as legal and medical education. However, comparatively limited attention has been paid to investigating the effects of SBL in teacher education. In the present study, the SBL intervention provided participants with the opportunity to virtually engage with school-based scenarios, reflect on how they might respond to a series of plausible response options, and receive real-time feedback from experienced educators. The development process involved several stages, including collaboration with experienced educators to determine the scenario content based on ‘critical incidents’ they had encountered during their teaching careers, the establishment of the scoring key, the development of the expert feedback, and an extensive review process to refine the program content. The 4-part SBL program focused on areas that can be challenging in the beginning stages of a teaching career, including managing student behaviour and workload, differentiating the curriculum, and building relationships with colleagues, parents, and the community. Results from prior studies implemented by the research group using a similar 4-part format have shown a statistically significant increase in preservice teachers’ self-efficacy and classroom readiness from the pre-test to the final post-test. In the current research, professional teaching identity - incorporating self-efficacy, motivation, self-image, satisfaction, and commitment to teaching - was measured over six weeks at multiple time points: before, during, and after the 4-part scenario-based learning program. Analyses included latent growth curve modelling to assess the trajectory of change in the outcome variables throughout the intervention. The paper outlines (1) the theoretical underpinnings of SBL, (2) the development of the SBL program and methodology, and (3) the results from the study, including the impact of the SBL program on aspects of participating preservice teachers’ professional identity. The study shows how SBL interventions can be implemented alongside the initial teacher education curriculum to help prepare preservice teachers for the transition from student to teacher.

Keywords: classroom simulations, e-learning, initial teacher education, preservice teachers, professional learning, professional teaching identity, scenario-based learning, teacher development

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Authors: Jothilakshmy Nagammal

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This research paper deals with the different case studies, where the Form-Based Codes are adopted in general and the different implementation methods in particular are discussed to develop a method for formulating a new planning model. The organizing principle of the Form-Based Codes, the transect is used to zone the city into various context specific transects. An approach is adopted to develop the new planning model, city Specific Planning Model (CSPM), as a tool to achieve sustainability for any city in general. A case study comparison method in terms of the planning tools used, the code process adopted and the various control regulations implemented in thirty two different cities are done. The analysis shows that there are a variety of ways to implement form-based zoning concepts: Specific plans, a parallel or optional form-based code, transect-based code /smart code, required form-based standards or design guidelines. The case studies describe the positive and negative results from based zoning, Where it is implemented. From the different case studies on the method of the FBC, it is understood that the scale for formulating the Form-Based Code varies from parts of the city to the whole city. The regulating plan is prepared with the organizing principle as the transect in most of the cases. The various implementation methods adopted in these case studies for the formulation of Form-Based Codes are special districts like the Transit Oriented Development (TOD), traditional Neighbourhood Development (TND), specific plan and Street based. The implementation methods vary from mandatory, integrated and floating. To attain sustainability the research takes the approach of developing a regulating plan, using the transect as the organizing principle for the entire area of the city in general in formulating the Form-Based Codes for the selected Special Districts in the study area in specific, street based. Planning is most powerful when it is embedded in the broader context of systemic change and improvement. Systemic is best thought of as holistic, contextualized and stake holder-owned, While systematic can be thought of more as linear, generalisable, and typically top-down or expert driven. The systemic approach is a process that is based on the system theory and system design principles, which are too often ill understood by the general population and policy makers. The system theory embraces the importance of a global perspective, multiple components, interdependencies and interconnections in any system. In addition, the recognition that a change in one part of a system necessarily alters the rest of the system is a cornerstone of the system theory. The proposed regulating plan taking the transect as an organizing principle and Form-Based Codes to achieve sustainability of the city has to be a hybrid code, which is to be integrated within the existing system - A Systemic Approach with a Systematic Process. This approach of introducing a few form based zones into a conventional code could be effective in the phased replacement of an existing code. It could also be an effective way of responding to the near-term pressure of physical change in “sensitive” areas of the community. With this approach and method the new Context Specific Planning Model is created towards achieving sustainability is explained in detail this research paper.

Keywords: context based planning model, form based code, transect, systemic approach

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Authors: Heitor Oliveira, Gabriele De-Waal, Juergen Schmenger, Lynsey Godfrey, Tibor Kovacs

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Rheolaser MASTER™ makes use of multiple scattering of light, caused by scattering objects in a continuous medium (such as droplets and particles in colloids), to characterize the viscoelasticity of soft materials. It offers an alternative to conventional rheometers to characterize viscoelasticity of products such as hair cosmetics. Up to six simultaneous measurements at controlled temperature can be carried out simultaneously (10-15 min), and the method requires only minor sample preparation work. Conversely to conventional rheometer based methods, no mechanical stress is applied to the material during the measurements. Therefore, the properties of the exact same sample can be monitored over time, like in aging and stability studies. We determined the elastic index (EI) of water/emulsion mixtures (1 ≤ fat alcohols (FA) ≤ 5 wt%) and emulsion/gel-network mixtures (8 ≤ FA ≤ 17 wt%) and compared with the elastic/sorage mudulus (G’) for the respective samples using a TA conventional rheometer with flat plates geometry. As expected, it was found that log(EI) vs log(G’) presents a linear behavior. Moreover, log(EI) increased in a linear fashion with solids level in the entire range of compositions (1 ≤ FA ≤ 17 wt%), while rheometer measurements were limited to samples down to 4 wt% solids level. Alternatively, a concentric cilinder geometry would be required for more diluted samples (FA > 4 wt%) and rheometer results from different sample holder geometries are not comparable. The plot of the rheolaser output parameters solid-liquid balance (SLB) vs EI were suitable to monitor product aging processes. These data could quantitatively describe some observations such as formation of lumps over aging time. Moreover, this method allowed to identify that the different specifications of a key raw material (RM < 0.4 wt%) in the respective gel-network (GN) product has minor impact on product viscoelastic properties and it is not consumer perceivable after a short aging time. Broadening of a RM spec range typically has a positive impact on cost savings. Last but not least, the photon path length (λ*)—proportional to droplet size and inversely proportional to volume fraction of scattering objects, accordingly to the Mie theory—and the EI were suitable to characterize product destabilization processes (e.g., coalescence and creaming) and to predict product stability about eight times faster than our standard methods. Using these parameters we could successfully identify formulation and process parameters that resulted in unstable products. In conclusion, Rheolaser allows quick and reliable characterization of viscoelastic properties of hair cosmetics that are related to their performance and stability. It operates in a broad range of product compositions and has applications spanning from the formulation of our hair cosmetics to fast release criteria in our production sites. Last but not least, this powerful tool has positive impact on R&D development time—faster delivery of new products to the market—and consequently on cost savings.

Keywords: colloids, hair cosmetics, light scattering, performance and stability, soft materials, viscoelastic properties

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Authors: Jessica To

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Feedback is one of the powerful levers for enhancing students’ performance. However, some students are under-engaged with feedback because they lack responsibility for feedback uptake. To resolve this conundrum, recent literature proposes feedback partnerships in which students and teachers share the power and responsibilities to co-construct feedback. During feedback co-construction, students express feedback needs to teachers, and teachers respond to individuals’ needs in return. Though this approach can increase students’ feedback ownership, its application is lagging as the field lacks conceptual clarity and implementation guide. This presentation aims to discuss the conceptual framework of feedback partnerships and feedback co-construction strategies. It identifies the components of feedback partnerships and strategies which could facilitate feedback co-construction. A systematic literature review was conducted to answer the questions. The literature search was performed using ERIC, PsycINFO, and Google Scholar with the keywords “assessment partnership”, “student as partner,” and “feedback engagement”. No time limit was set for the search. The inclusion criteria encompassed (i) student-teacher partnerships in feedback, (ii) feedback engagement in higher education, (iii) peer-reviewed publications, and (iv) English as the language of publication. Those without addressing conceptual understanding and implementation strategies were excluded. Finally, 65 publications were identified and analysed using thematic analysis. For the procedure, the texts relating to the questions were first extracted. Then, codes were assigned to summarise the ideas of the texts. Upon subsuming similar codes into themes, four themes emerged: students’ responsibilities, teachers’ responsibilities, conditions for partnerships development, and strategies. Their interrelationships were examined iteratively for framework development. Establishing feedback partnerships required different responsibilities of students and teachers during feedback co-construction. Students needed to self-evaluate performance against task criteria, identify inadequacies and communicate their needs to teachers. During feedback exchanges, they interpreted teachers’ comments, generated self-feedback through reflection, and co-developed improvement plans with teachers. Teachers had to increase students’ understanding of criteria and evaluation skills and create opportunities for students’ expression of feedback needs. In feedback dialogue, teachers responded to students’ needs and advised on the improvement plans. Feedback partnerships would be best grounded in an environment with trust and psychological safety. Four strategies could facilitate feedback co-construction. First, students’ understanding of task criteria could be increased by rubrics explanation and exemplar analysis. Second, students could sharpen evaluation skills if they participated in peer review and received teacher feedback on the quality of peer feedback. Third, provision of self-evaluation checklists and prompts and teacher modeling of self-assessment process could aid students in articulating feedback needs. Fourth, the trust could be fostered when teachers explained the benefits of feedback co-construction, showed empathy, and provided personalised comments in dialogue. Some strategies were applied in interactive cover sheets in which students performed self-evaluation and made feedback requests on a cover sheet during assignment submission, followed by teachers’ response to individuals’ requests. The significance of this presentation lies in unpacking the conceptual framework of feedback partnerships and outlining feedback co-construction strategies. With a solid foundation in theory and practice, researchers and teachers could better enhance students’ engagement with feedback.

Keywords: conceptual framework, feedback co-construction, feedback partnerships, implementation strategies

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Authors: Dhanuj M. Gandikota

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Sensor-derived three-dimensional (3D) point clouds of trees are invaluable in remote sensing analysis for the accurate measurement of key structural metrics, bio-inventory values, spatial planning/visualization, and ecological modeling. Machine learning (ML) holds the potential in addressing the restrictive tradeoffs in cost, spatial coverage, resolution, and information gain that exist in current point cloud sensing methods. Terrestrial laser scanning (TLS) remains the highest fidelity source of both canopy and below-canopy structural features, but usage is limited in both coverage and cost, requiring manual deployment to map out large, forested areas. While aerial laser scanning (ALS) remains a reliable avenue of LIDAR active remote sensing, ALS is also cost-restrictive in deployment methods. Space-borne photogrammetry from high-resolution satellite constellations is an avenue of passive remote sensing with promising viability in research for the accurate construction of vegetation 3-D point clouds. It provides both the lowest comparative cost and the largest spatial coverage across remote sensing methods. However, both space-borne photogrammetry and ALS demonstrate technical limitations in the capture of valuable below-canopy point cloud data. Looking to minimize these tradeoffs, we explored a class of powerful ML algorithms called Deep Learning (DL) that show promise in recent research on 3-D point cloud reconstruction and interpolation. Our research details the efficacy of applying these DL techniques to reconstruct accurate below-canopy point clouds from space-borne and aerial remote sensing through learned patterns of tree species fractal symmetry properties and the supplementation of locally sourced bio-inventory metrics. From our dataset, consisting of tree point clouds obtained from TLS, we deconstructed the point clouds of each tree into those that would be obtained through ALS and satellite photogrammetry of varying resolutions. We fed this ALS/satellite point cloud dataset, along with the simulated local bio-inventory metrics, into the DL point cloud reconstruction architectures to generate the full 3-D tree point clouds (the truth values are denoted by the full TLS tree point clouds containing the below-canopy information). Point cloud reconstruction accuracy was validated both through the measurement of error from the original TLS point clouds as well as the error of extraction of key structural metrics, such as crown base height, diameter above root crown, and leaf/wood volume. The results of this research additionally demonstrate the supplemental performance gain of using minimum locally sourced bio-inventory metric information as an input in ML systems to reach specified accuracy thresholds of tree point cloud reconstruction. This research provides insight into methods for the rapid, cost-effective, and accurate construction of below-canopy tree 3-D point clouds, as well as the supported potential of ML and DL to learn complex, unmodeled patterns of fractal tree growth symmetry.

Keywords: deep learning, machine learning, satellite, photogrammetry, aerial laser scanning, terrestrial laser scanning, point cloud, fractal symmetry

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Authors: Z. Xu

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Immersive virtual reality (VR) has gained momentum in humanitarian communication due to its utopian promises of co-presence, immediacy, and transcendence. These potential benefits have led the United Nations (UN) to tirelessly produce and distribute VR series to evoke global empathy and encourage policymakers, philanthropic business tycoons and citizens around the world to actually do something (i.e. give a donation). However, it is unclear whether or not VR can cultivate cosmopolitans with a sense of social responsibility towards the geographically, socially/culturally and morally mediated misfortune of faraway others. Drawing upon existing works on the mediation of distant suffering, this article constructs an analytical framework to articulate the issue. Applying this framework on a case study of five of the UN’s VR pieces, the article identifies three paradoxes that exist between cyber-utopian and cyber-dystopian narratives. In the “paradox of distance”, VR relies on the notions of “presence” and “storyliving” to implicitly link audiences spatially and temporally to distant suffering, creating global connectivity and reducing perceived distances between audiences and others; yet it also enables audiences to fully occupy the point of view of distant sufferers (creating too close/absolute proximity), which may cause them to feel naive self-righteousness or narcissism with their pleasures and desire, thereby destroying the “proper distance”. In the “paradox of agency”, VR simulates a superficially “real” encounter for visual intimacy, thereby establishing an “audiences–beneficiary” relationship in humanitarian communication; yet in this case the mediated hyperreality is not an authentic reality, and its simulation does not fill the gap between reality and the virtual world. In the “paradox of the hierarchies of human life”, VR enables an audience to experience virtually fundamental “freedom”, epitomizing an attitude of cultural relativism that informs a great deal of contemporary multiculturalism, providing vast possibilities for a more egalitarian representation of distant sufferers; yet it also takes the spectator’s personally empathic feelings as the focus of intervention, rather than structural inequality and political exclusion (an economic and political power relations of viewing). Thus, the audience can potentially remain trapped within the minefield of hegemonic humanitarianism. This study is significant in two respects. First, it advances the turn of digitalization in studies of media and morality in the polymedia milieu; it is motivated by the necessary call for a move beyond traditional technological environments to arrive at a more novel understanding of the asymmetry of power between the safety of spectators and the vulnerability of mediated sufferers. Second, it not only reminds humanitarian journalists and NGOs that they should not rely entirely on the richer news experience or powerful response-ability enabled by VR to gain a “moral bond” with distant sufferers, but also argues that when fully-fledged VR technology is developed, it can serve as a kind of alchemy and should not be underestimated merely as a “bugaboo” of an alarmist philosophical and fictional dystopia.

Keywords: audience, cosmopolitan, distant suffering, virtual reality, humanitarian communication

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Authors: Yi Li, Rui Lu, Lianjun Wang

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With the rapid development of chemical industry, the consumption of volatile organic compounds (VOCs) has increased extensively. In the process of VOCs production and application, plenty of them have been transferred to environment. As a result, it has led to pollution problems not only in soil and ground water but also to human beings. Thus, it is important to develop a sensitive and cost-effective analytical method for trace VOCs detection in environment. Surface-enhanced Raman Spectroscopy (SERS), as one of the most sensitive optical analytical technique with rapid response, pinpoint accuracy and noninvasive detection, has been widely used for ultratrace analysis. Based on the plasmon resonance on the nanoscale metallic surface, SERS technology can even detect single molecule due to abundant nanogaps (i.e. 'hot spots') on the nanosubstrate. In this work, a self-supported flexible silver nitrate (AgNO3)/ethylene-propylene copolymer (EPM) hybrid nanofibers was fabricated by electrospinning. After an in-situ chemical reduction using ice-cold sodium borohydride as reduction agent, numerous silver nanoparticles were formed on the nanofiber surface. By adjusting the reduction time and AgNO3 content, the morphology and dimension of silver nanoparticles could be controlled. According to the principles of solid-phase extraction, the hydrophobic substance is more likely to partition into the hydrophobic EPM membrane in an aqueous environment while water and other polar components are excluded from the analytes. By the enrichment of EPM fibers, the number of hydrophobic molecules located on the 'hot spots' generated from criss-crossed nanofibers is greatly increased, which further enhances SERS signal intensity. The as-prepared Ag/EPM hybrid nanofibers were first employed to detect common SERS probe molecule (p-aminothiophenol) with the detection limit down to 10-12 M, which demonstrated an excellent SERS performance. To further study the application of the fabricated substrate for monitoring hydrophobic substance in water, several typical VOCs, such as benzene, toluene and p-xylene, were selected as model compounds. The results showed that the characteristic peaks of these target analytes in the mixed aqueous solution could be distinguished even at a concentration of 10-6 M after multi-peaks gaussian fitting process, including C-H bending (850 cm-1), C-C ring stretching (1581 cm-1, 1600 cm-1) of benzene, C-H bending (844 cm-1 ,1151 cm-1), C-C ring stretching (1001 cm-1), CH3 bending vibration (1377 cm-1) of toluene, C-H bending (829 cm-1), C-C stretching (1614 cm-1) of p-xylene. The SERS substrate has remarkable advantages which combine the enrichment capacity from EPM and the Raman enhancement of Ag nanoparticles. Meanwhile, the huge specific surface area resulted from electrospinning is benificial to increase the number of adsoption sites and promotes 'hot spots' formation. In summary, this work provides powerful potential in rapid, on-site and accurate detection of trace VOCs using a portable Raman.

Keywords: electrospinning, ethylene-propylene copolymer, silver nanoparticles, SERS, VOCs

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Authors: Neha Adsul, Rohit Shah

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Background: The global history of nursing is exclusively a history of deep contradictions as it seeks to negotiate inclusion in an already gendered world. Although a powerful 'clinical gaze exists, nurses have toiled to re-negotiate and subvert the 'medical gaze' by practicing the 'therapeutic gaze' to tether back 'care into nursing practice.' This helps address the duality of the 'body' and 'mind' wherein the patient is not just limited to being an object of medical inquiry. Nevertheless, there has been a consistent effort to fit 'nursing' into being an art or an emerging science over the years. Especially with advances in hospital-based techno-centric medical practices, the boundaries between technology and nursing practices are becoming more blurred as the technical process becomes synonymous with nursing, eroding the essence of nursing care. Aim: This paper examines the history of nursing and offers insights into how gendered relations and the ideological belief of 'nursing as gendered work' have propagated to the subjugation of the nursing profession. It further aims to provide insights into the patriarchally imbibed techno-centrism that negates the gendered caregiving which lies at the crux of a nurse's work. Method: A literature search was carried out using Google Scholar, Web of Science and PubMed databases. Search words included: technology and nursing, medical technology and nursing, history of nursing, sociology and nursing and nursing care. The history of nursing is presented in a discussion that weaves together the historical events of the 'Birth of the Clinic' and the shift from 'bed-side medicine' to 'hospital-based medicine' that legitimizes exploitation of the bodies of patients to the 'medical gaze while the emergence of nursing as acquiescent to instrumental, technical, positivist and dominant views of medicine. The resultant power asymmetries, wherein in contemporary nursing, the constant struggle of nurses to juggle between being the physicians "operational right arm" to harboring that subjective understanding of the patients to refrain from de-humanizing nursing-care. Findings: The nursing profession suffers from being rendered invisible due to gendered relations having patrifocal societal roots. This perpetuates a notion rooted in the idea that emphasizes empiricism and has resulted in theoretical and epistemological fragmentation of the understanding of body and mind as separate entities. Nurses operate within this structure while constantly being at the brink of being pushed beyond the legitimate professional boundaries while being labeled as being 'unscientific' as the work does not always corroborate and align with the existing dominant positivist lines of inquiries. Conclusion: When understood in this broader context of how nursing as a practice has evolved over the years, it provides a particularly crucial testbed for understanding contemporary gender relations. Not because nurses like to live in a gendered work trap but because the gendered relations at work are written in a covert narcissistic patriarchal milieu that fails to recognize the value of intangible yet utmost necessary 'caring work in nursing. This research urges and calls for preserving and revering the humane aspect of nursing care alongside the emerging tech-savvy expectations from nursing work.

Keywords: nursing history, technocentric, power relations, scientific duality

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

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

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

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Authors: Azza A. Ali, Doaa M. Abd El-Latif, Amany M. Gad, Yasser M. A. Elnahas, Karema Abu-Elfotuh

Abstract:

Background: Exposure to Aluminium (Al) has been increased recently. It is found in food products, food additives, drinking water, cosmetics and medicines. Chronic consumption of Al causes oxidative stress and has been implicated in several chronic disorders. Liver is considered as the major site for detoxification while kidney is involved in the elimination of toxic substances and is a target organ of metal toxicity. Social isolation (SI) or protein malnutrition (PM) also causes oxidative stress and has negative impact on Al-induced nephrotoxicity as well as hepatotoxicity. Coenzyme Q10 (CoQ10) is a powerful intracellular antioxidant with mitochondrial membrane stabilizing ability while wheat grass is a natural product with antioxidant, anti-inflammatory and different protective activities, cocoa is also potent antioxidants and can protect against many diseases. They provide different degrees of protection from the impact of oxidative stress. Objective: To study the impact of social isolation together with Protein malnutrition on nephro- and hepato-toxicity induced by chronic Al exposure in rats as well as to investigate the postulated protection using a combination of Co Q10, wheat grass and cocoa. Methods: Eight groups of rats were used; four served as protected groups and four as un-protected. Each of them received daily for five weeks AlCl3 (70 mg/kg, IP) for Al-toxicity model groups except one group served as control. Al-toxicity model groups were divided to Al-toxicity alone, SI- associated PM (10% casein diet) and Al- associated SI&PM groups. Protection was induced by oral co-administration of CoQ10 (200mg/kg), wheat grass (100mg/kg) and cocoa powder (24mg/kg) combination together with Al. Biochemical changes in total bilirubin, lipids, cholesterol, triglycerides, glucose, proteins, creatinine and urea as well as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate deshydrogenase (LDH) were measured in serum of all groups. Specimens of kidney and liver were used for assessment of oxidative parameters (MDA, SOD, TAC, NO), inflammatory mediators (TNF-α, IL-6β, nuclear factor kappa B (NF-κB), Caspase-3) and DNA fragmentation in addition to evaluation of histopathological changes. Results: SI together with PM severely enhanced nephro- and hepato-toxicity induced by chronic Al exposure. Co Q10, wheat grass and cocoa combination showed clear protection against hazards of Al exposure either alone or when associated with SI&PM. Their protection were indicated by the significant decrease in Al-induced elevations in total bilirubin, lipids, cholesterol, triglycerides, glucose, creatinine and urea levels as well as ALT, AST, ALP, LDH. Liver and kidney of the treated groups also showed significant decrease in MDA, NO, TNF-α, IL-6β, NF-κB, caspase-3 and DNA fragmentation, together with significant increase in total proteins, SOD and TAC. Biochemical results were confirmed by the histopathological examinations. Conclusion: SI together with PM represents a risk factor in enhancing nephro- and hepato-toxicity induced by Al in rats. CoQ10, wheat grass and cocoa combination provide clear protection against nephro- and hepatotoxicity as well as the consequent degenerations induced by chronic Al-exposure even when associated with the risk of SI together with PM.

Keywords: aluminum, nephrotoxicity, hepatotoxicity, isolation and protein malnutrition, coenzyme Q10, wheatgrass, cocoa, nutrients combinations

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Authors: Shpetim Rezniqi

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Financial Policies in the process of global crisis the current crisis has swept the world with special emphasis, most developed countries, those countries which have most gross -product world and you have a high level of living.Even those who are not experts can describe the consequences of the crisis to see the reality that is seen, but how far will it go this crisis is impossible to predict. Even the biggest experts have conjecture and large divergence, but agree on one thing: - The devastating effects of this crisis will be more severe than ever before and can not be predicted.Long time, the world was dominated economic theory of free market laws. With the belief that the market is the regulator of all economic problems. The market, as river water will flow to find the best and will find the necessary solution best. Therefore much less state market barriers, less state intervention and market itself is an economic self-regulation. Free market economy became the model of global economic development and progress, it transcends national barriers and became the law of the development of the entire world economy. Globalization and global market freedom were principles of development and international cooperation. All international organizations like the World Bank, states powerful economic, development and cooperation principles laid free market economy and the elimination of state intervention. The less state intervention much more freedom of action was this market- leading international principle. We live in an era of financial tragic. Financial markets and banking in particular economies are in a state of thy good, US stock markets fell about 40%, in other words, this time, was one of the darkest moments 5 since 1920. Prior to her rank can only "collapse" of the stock of Wall Street in 1929, technological collapse of 2000, the crisis of 1973 after the Yom Kippur war, while the price of oil quadrupled and famous collapse of 1937 / '38, when Europe was beginning World war II In 2000, even though it seems like the end of the world was the corner, the world economy survived almost intact. Of course, that was small recessions in the United States, Europe, or Japan. Much more difficult the situation was at crisis 30s, or 70s, however, succeeded the world. Regarding the recent financial crisis, it has all the signs to be much sharper and with more consequences. The decline in stock prices is more a byproduct of what is really happening. Financial markets began dance of death with the credit crisis, which came as a result of the large increase in real estate prices and household debt. It is these last two phenomena can be matched very well with the gains of the '20s, a period during which people spent fists as if there was no tomorrow. All is not away from the mouth of the word recession, that fact no longer a sudden and abrupt. But as much as the financial markets melt, the greater is the risk of a problematic economy for years to come. Thus, for example, the banking crisis in Japan proved to be much more severe than initially expected, partly because the assets which were based more loans had, especially the land that falling in value. The price of land in Japan is about 15 years that continues to fall. (ADRI Nurellari-Published in the newspaper "Classifieds"). At this moment, it is still difficult to çmosh to what extent the crisis has affected the economy and what would be the consequences of the crisis. What we know is that many banks will need more time to reduce the award of credit, but banks have this primary function, this means huge loss.

Keywords: globalisation, finance, crisis, recomandation, bank, credits

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Authors: Massimiliano Biagini, Marco Spinsanti, Gabriella De Angelis, Sara Tomei, Ilaria Ferlenghi, Maria Scarselli, Alessia Biolchi, Alessandro Muzzi, Brunella Brunelli, Silvana Savino, Marzia M. Giuliani, Isabel Delany, Paolo Costantino, Rino Rappuoli, Vega Masignani, Nathalie Norais

Abstract:

The gram-negative bacterium Neisseria meningitidis serogroup B (MenB) is an exclusively human pathogen representing the major cause of meningitides and severe sepsis in infants and children but also in young adults. This pathogen is usually present in the 30% of healthy population that act as a reservoir, spreading it through saliva and respiratory fluids during coughing, sneezing, kissing. Among surface-exposed protein components of this diplococcus, factor H binding protein is a lipoprotein proved to be a protective antigen used as a component of the recently licensed Bexsero vaccine. fHbp is a highly variable meningococcal protein: to reflect its remarkable sequence variability, it has been classified in three variants (or two subfamilies), and with poor cross-protection among the different variants. Furthermore, the level of fHbp expression varies significantly among strains, and this has also been considered an important factor for predicting MenB strain susceptibility to anti-fHbp antisera. Different methods have been used to assess fHbp expression on meningococcal strains, however, all these methods use anti-fHbp antibodies, and for this reason, the results are affected by the different affinity that antibodies can have to different antigenic variants. To overcome the limitations of an antibody-based quantification, we developed a quantitative Mass Spectrometry (MS) approach. Selected Reaction Monitoring (SRM) recently emerged as a powerful MS tool for detecting and quantifying proteins in complex mixtures. SRM is based on the targeted detection of ProteoTypicPeptides (PTPs), which are unique signatures of a protein that can be easily detected and quantified by MS. This approach, proven to be highly sensitive, quantitatively accurate and highly reproducible, was used to quantify the absolute amount of fHbp antigen in total extracts derived from 105 clinical isolates, evenly distributed among the three main variant groups and selected to be representative of the fHbp circulating subvariants around the world. We extended the study at the genetic level investigating the correlation between the differential level of expression and polymorphisms present within the genes and their promoter sequences. The implications of fHbp expression on the susceptibility of the strain to killing by anti-fHbp antisera are also presented. To date this is the first comprehensive fHbp expression profiling in a large panel of Neisseria meningitidis clinical isolates driven by an antibody-independent MS-based methodology, opening the door to new applications in vaccine coverage prediction and reinforcing the molecular understanding of released vaccines.

Keywords: quantitative mass spectrometry, Neisseria meningitidis, vaccines, bexsero, molecular epidemiology

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Authors: Mohamad F. Jamiluddin, Emeline Sarry, Ana Bejanariu, Cécile Bauche

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Introduction: Over 360 million people are chronically infected with hepatitis B virus (HBV), of whom 1 million die each year from HBV-associated liver cirrhosis or hepatocellular carcinoma. Current treatment options for chronic hepatitis B depend on interferon-α (IFNα) or nucleos(t)ide analogs, which control virus replication but rarely eliminate the virus. Treatment with PEG-IFNα leads to a sustained antiviral response in only one third of patients. After withdrawal of the drugs, the rebound of viremia is observed in the majority of patients. Furthermore, the long-term treatment is subsequently associated with the appearance of drug resistant HBV strains that is often the cause of the therapy failure. Among the new therapeutic avenues being developed, therapeutic vaccine aimed at inducing immune responses similar to those found in resolvers is of growing interest. The high prevalence of chronic hepatitis B necessitates the design of better vaccination strategies capable of eliciting broad-spectrum of cell-mediated immunity(CMI) and humoral immune response that can control chronic hepatitis B. Induction of HBV-specific T cells and B cells by therapeutic vaccination may be an innovative strategy to overcome virus persistence. Lentiviral vectors developed and optimized by THERAVECTYS, due to their ability to transduce non-dividing cells, including dendritic cells, and induce CMI response, have demonstrated their effectiveness as vaccination tools. Method: To develop a HBV therapeutic vaccine that can induce a broad but specific immune response, we generated recombinant lentiviral vector carrying IRES(Internal Ribosome Entry Site)-containing bicistronic constructs which allow the coexpression of two vaccine products, namely HBV T- cell epitope vaccine and HBV virus like particle (VLP) vaccine. HBV T-cell epitope vaccine consists of immunodominant cluster of CD4 and CD8 epitopes with spacer in between them and epitopes are derived from HBV surface protein, HBV core, HBV X and polymerase. While HBV VLP vaccine is a HBV core protein based chimeric VLP with surface protein B-cell epitopes displayed. In order to evaluate the immunogenicity, mice were immunized with lentiviral constructs by intramuscular injection. The T cell and antibody immune responses of the two vaccine products were analyzed using IFN-γ ELISpot assay and ELISA respectively to quantify the adaptive response to HBV antigens. Results: Following a single administration in mice, lentiviral construct elicited robust antigen-specific IFN-γ responses to the encoded antigens. The HBV T- cell epitope vaccine demonstrated significantly higher T cell immunogenicity than HBV VLP vaccine. Importantly, we demonstrated by ELISA that antibodies are induced against both HBV surface protein and HBV core protein when mice injected with vaccine construct (p < 0.05). Conclusion: Our results highlight that THERAVECTYS lentiviral vectors may represent a powerful platform for immunization strategy against chronic hepatitis B. Our data suggests the likely importance of Lentiviral vector based novel bicistronic construct for further study, in combination with drugs or as standalone antigens, as a therapeutic lentiviral based HBV vaccines. THERAVECTYS bicistronic HBV vaccine will be further evaluated in animal efficacy studies.

Keywords: chronic hepatitis B, lentiviral vectors, therapeutic vaccine, virus-like particle

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