Search results for: minimal social networks
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 12393

Search results for: minimal social networks

6783 Women from the Margins: An Exploration of the African Women Marginalization in the South African Context from Postcolonial Feminist Perspective

Authors: Goodness Thandi Ntuli

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As one of the sub-Saharan African countries, South Africa has a majority of women living at the receiving end of all ferocious atrocities, afflictions and social ills such as utter poverty, unemployment, morbidity, sexual exploitation and abuse, gender-based and domestic violence. The response to these social ills that permeate the South African context like wildfire requires postcolonial feminism as a lens which needs to directly address this particular context. In the empirical study that was conducted among the Zulu people about Zulu young women in the South African context, it was found that a postcolonial young woman has a lot of social challenges that militate against her. In her struggle to liberate herself, there are layers of oppression that she has to deal with before attaining emancipation of any kind. These layers of oppression emanate from postcolonial effects on cultural norms that come with patriarchal issues, racial issues as the woman of colour and socio-economic issues as the poverty-stricken marginalised woman. Such layers also render marginalized women voiceless on many occasions, and hence the kind of feminism that needs to be applied in this context has to give them a voice, worth and human dignity that they deserve. From the postcolonial feminist perspective, this paper examines the condition of women from the margins and seeks the ways in which the layers of oppression could be disengaged. In the process of the severed layers of oppression, these women can be uplifted to becoming the women of worth, restored to life-giving dignity from the inferiority complex of racial discrimination and liberation from all forms of patriarchy and its upshots that keep them bound by gender inequality. This requires, in particular, postcolonial feminism that would find profound ways of reaching into the deep-seated socialization and internalization of every kind of prejudice against women. It is the kind of feminism that questions the status core even among those who consider themselves feminists. With the ruination of all postcolonial layers of oppression, women in the margins could find real emancipation that they have always longed for through feminism that will take into consideration their context. This calls for the rethinking of feminism in different contexts because the conditions of the oppressed woman of the South cannot be the same as the conditions of the woman who considers herself oppressed in the North.

Keywords: exploration, feminism, postcolonial, margins, South African, women

Procedia PDF Downloads 216
6782 Coming Closer to Communities of Practice through Situated Learning: The Case Study of Polish-English, English-Polish Undergraduate BA Level Language for Specific Purposes of Translation Class

Authors: Marta Lisowska

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The growing trend of market specialization imposes upon translators the need for proficiency in the working knowledge of specialist discourse. The notion of specialization differs from a broad general category to a highly specialized narrow field. The specialised discourse is used in the channel of communication based upon distinctive features typical for communities of practice whose co-existence is codified and hermetically locked against outsiders. Consequently, any translator deprived of professional discourse competence and social skills is incapable of providing competent translation product from source language into target language. In this paper, we report on research that explores the pedagogical practices aiming to bridge the dichotomy between the professionals and the specialist translators, while accounting for the reality of the world of professional communities entered by undergraduates on two levels: the text-based generic, and the social one. Drawing from the functional social constructivist approach, seen here as situated learning, this paper reports on the case of English-Polish, Polish-English undergraduate BA Level LSP of law translation class run in line with the simulated classroom-based and the reality-based (apprenticeship) approach. This blended method serves the purpose of introducing the young trainees to the professional world. The research provides new insights into how the LSP translation undergraduates become legitimized through discursive and social participation and engagement. The undergraduates, situated peripherally at the outset, experience their own transformation towards becoming members of these professional groups. With subjective evaluation, the trainees take a stance on this dual mode class and development of their skills. Comparing and contrasting their own work done in line with two models of translation teaching: authentic and near-authentic, the undergraduates answer research questions devised by a questionnaire survey The responses take us closer to how students feel about their LSP translation competence development. The major findings show how the trainees perceive the benefits and hardships of their functional translation class. In terms of skills, they related to communication as the most enhanced one; they highly valued the fact of being ‘exposed’ to a variety of texts (cf. multi literalism), team work, learning how to schedule work, IT skills boost and the ability to learn how to work individually. Another finding indicates that students struggled most with specialized language, and co-working with other students. The short-term research shows the momentum when the undergraduate LSP translation trainees entered the path of transformation i.e. gained consciousness of ‘how it is’ to be a participant-translator of real-life communities of practice, gaining pragmatic dint of the social and linguistic skills understood here as discursive competence (text > genre > discourse > professional practice). The undergraduates need to be aware of the work they have to do and challenges they are to face before arriving at the expert level of professional translation competence.

Keywords: communities of practice in LSP translation teaching, learning LSP translation as situated experience, peripheral participation, professional discourse for LSP translation teaching, professional translation competence

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6781 Complementary Child-Care by Grandparents: Comparisons of Zambia and the Netherlands

Authors: Francis Sichimba

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Literature has increasingly acknowledged the important role that grandparents play in child care with evidence highlighting differences in grand-parental investment between countries and cultures. However, there are very few systematic cross cultural studies on grandparents’ participation in child care. Thus, we decided to conduct this study in Zambia and the Netherlands because the two countries differ rather drastically socially and culturally. The objective of this study was to investigate grand-parental involvement in child care in Zambia and the Netherlands. In line with the general objective, four hypotheses were formulated using nationality, family size, social economic status (SES), attachment security as independent variables. The study sample consisted of 411 undergraduate students from the University of Zambia and the University of Leiden. A questionnaire was used to measure grand-parental involvement in child care. Results indicated that grandparent involvement in child care was prevalent in both Zambia and Netherlands. However, as predicted it was found that Zambian grandparents (M = 9.69, SD=2.40) provided more care for their grandchildren compared to their Dutch counterparts (M = 7.80, SD=3.31) even after controlling for parents being alive. Using hierarchical logistic regression analysis the study revealed that nationality and attachment-related avoidance were significant predictors of grand-parental involvement in child care. It was concluded that grand-parental care is a great resource in offering complementary care in both countries.

Keywords: attachment, care, grand-parenting involvement, social economic status

Procedia PDF Downloads 717
6780 Molecular Detection of mRNA bcr-abl and Circulating Leukemic Stem Cells CD34+ in Patients with Acute Lymphoblastic Leukemia and Chronic Myeloid Leukemia and Its Association with Clinical Parameters

Authors: B. Gonzalez-Yebra, H. Barajas, P. Palomares, M. Hernandez, O. Torres, M. Ayala, A. L. González, G. Vazquez-Ortiz, M. L. Guzman

Abstract:

Leukemia arises by molecular alterations of the normal hematopoietic stem cell (HSC) transforming it into a leukemic stem cell (LSC) with high cell proliferation, self-renewal, and cell differentiation. Chronic myeloid leukemia (CML) originates from an LSC-leading to elevated proliferation of myeloid cells and acute lymphoblastic leukemia (ALL) originates from an LSC development leading to elevated proliferation of lymphoid cells. In both cases, LSC can be identified by multicolor flow cytometry using several antibodies. However, to date, LSC levels in peripheral blood (PB) are not established well enough in ALL and CML patients. On the other hand, the detection of the minimal residue disease (MRD) in leukemia is mainly based on the identification of the mRNA bcr-abl gene in CML patients and some other genes in ALL patients. There is no a properly biomarker to detect MDR in both types of leukemia. The objective of this study was to determine mRNA bcr-abl and the percentage of LSC in peripheral blood of patients with CML and ALL and identify a possible association between the amount of LSC in PB and clinical data. We included in this study 19 patients with Leukemia. A PB sample was collected per patient and leukocytes were obtained by Ficoll gradient. The immunophenotype for LSC CD34+ was done by flow cytometry analysis with CD33, CD2, CD14, CD16, CD64, HLA-DR, CD13, CD15, CD19, CD10, CD20, CD34, CD38, CD71, CD90, CD117, CD123 monoclonal antibodies. In addition, to identify the presence of the mRNA bcr-abl by RT-PCR, the RNA was isolated using TRIZOL reagent. Molecular (presence of mRNA bcr-abl and LSC CD34+) and clinical results were analyzed with descriptive statistics and a multiple regression analysis was performed to determine statistically significant association. In total, 19 patients (8 patients with ALL and 11 patients with CML) were analyzed, 9 patients with de novo leukemia (ALL = 6 and CML = 3) and 10 under treatment (ALL = 5 and CML = 5). The overall frequency of mRNA bcr-abl was 31% (6/19), and it was negative in ALL patients and positive in 80% in CML patients. On the other hand, LSC was determined in 16/19 leukemia patients (%LSC= 0.02-17.3). The Novo patients had higher percentage of LSC (0.26 to 17.3%) than patients under treatment (0 to 5.93%). The amount of LSC was significantly associated with the amount of LSC were: absence of treatment, the absence of splenomegaly, and a lower number of leukocytes, negative association for the clinical variables age, sex, blasts, and mRNA bcr-abl. In conclusion, patients with de novo leukemia had a higher percentage of circulating LSC than patients under treatment, and it was associated with clinical parameters as lack of treatment, absence of splenomegaly and a lower number of leukocytes. The mRNA bcr-abl detection was only possible in the series of patients with CML, and molecular detection of LSC could be identified in the peripheral blood of all leukemia patients, we believe the identification of circulating LSC may be used as biomarker for the detection of the MRD in leukemia patients.

Keywords: stem cells, leukemia, biomarkers, flow cytometry

Procedia PDF Downloads 352
6779 ECG Based Reliable User Identification Using Deep Learning

Authors: R. N. Begum, Ambalika Sharma, G. K. Singh

Abstract:

Identity theft has serious ramifications beyond data and personal information loss. This necessitates the implementation of robust and efficient user identification systems. Therefore, automatic biometric recognition systems are the need of the hour, and ECG-based systems are unquestionably the best choice due to their appealing inherent characteristics. The CNNs are the recent state-of-the-art techniques for ECG-based user identification systems. However, the results obtained are significantly below standards, and the situation worsens as the number of users and types of heartbeats in the dataset grows. As a result, this study proposes a highly accurate and resilient ECG-based person identification system using CNN's dense learning framework. The proposed research explores explicitly the calibre of dense CNNs in the field of ECG-based human recognition. The study tests four different configurations of dense CNN which are trained on a dataset of recordings collected from eight popular ECG databases. With the highest FAR of 0.04 percent and the highest FRR of 5%, the best performing network achieved an identification accuracy of 99.94 percent. The best network is also tested with various train/test split ratios. The findings show that DenseNets are not only extremely reliable but also highly efficient. Thus, they might also be implemented in real-time ECG-based human recognition systems.

Keywords: Biometrics, Dense Networks, Identification Rate, Train/Test split ratio

Procedia PDF Downloads 159
6778 An Improved Image Steganography Technique Based on Least Significant Bit Insertion

Authors: Olaiya Folorunsho, Comfort Y. Daramola, Joel N. Ugwu, Lawrence B. Adewole, Olufisayo S. Ekundayo

Abstract:

In today world, there is a tremendous rise in the usage of internet due to the fact that almost all the communication and information sharing is done over the web. Conversely, there is a continuous growth of unauthorized access to confidential data. This has posed a challenge to information security expertise whose major goal is to curtail the menace. One of the approaches to secure the safety delivery of data/information to the rightful destination without any modification is steganography. Steganography is the art of hiding information inside an embedded information. This research paper aimed at designing a secured algorithm with the use of image steganographic technique that makes use of Least Significant Bit (LSB) algorithm for embedding the data into the bit map image (bmp) in order to enhance security and reliability. In the LSB approach, the basic idea is to replace the LSB of the pixels of the cover image with the Bits of the messages to be hidden without destroying the property of the cover image significantly. The system was implemented using C# programming language of Microsoft.NET framework. The performance evaluation of the proposed system was experimented by conducting a benchmarking test for analyzing the parameters like Mean Squared Error (MSE) and Peak Signal to Noise Ratio (PSNR). The result showed that image steganography performed considerably in securing data hiding and information transmission over the networks.

Keywords: steganography, image steganography, least significant bits, bit map image

Procedia PDF Downloads 263
6777 A Three Step Approach Analysis of the Portrayal of Images of Women in Three Ghanaian Newspapers: Newsone, Ebony and the Mirror

Authors: H. K. Bonsu-Owu

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Media portrayal of women in traditional stereotypical roles such as mothers, or seductress has been the norm for years. However, the changing socioeconomic and political environment and advancement of women in today’s society have given rise to questions on the appropriate portrayal of women in the media today. The purpose of the study is to analyze the portrayal of women in Ghanaian newspapers and find women’s perception on the issue. The study uses a three step approach in gathering data for analysis. Using the stratified sampling method, it analyzes front page images of women from 210 issues of the selected newspapers. Further, it administers questionnaires to 100 female students to find out how they relate to the images of women in the selected newspapers. Finally, editors of the newspapers are interviewed to find their rational for portraying women as seen on their front pages. The findings suggest that the newspapers portray women for varied reasons such as promoting sales and influencing the public agenda. Further, the female students claim that in spite of women’s vast contribution to the growth of society, the media continue to marginalize them. They add that such portrayals promote and reinforce social construct, however, refuse to see themselves through the male gaze concept. The study concludes that the stereotyped portrayal of women is likely to continue if the government, regulatory bodies, the media and society do not make a conscious effort to address this problem.

Keywords: women, newspaper, portrayal, social construct

Procedia PDF Downloads 130
6776 The Role of Emotions in Addressing Social and Environmental Issues in Ethical Decision Making

Authors: Kirsi Snellman, Johannes Gartner, , Katja Upadaya

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A transition towards a future where the economy serves society so that it evolves within the safe operating space of the planet calls for fundamental changes in the way managers think, feel and act, and make decisions that relate to social and environmental issues. Sustainable decision-making in organizations are often challenging tasks characterized by trade-offs between environmental, social and financial aspects, thus often bringing forth ethical concerns. Although there have been significant developments in incorporating uncertainty into environmental decision-making and measuring constructs and dimensions in ethical behavior in organizations, the majority of sustainable decision-making models are rationalist-based. Moreover, research in psychology indicates that one’s readiness to make a decision depends on the individual’s state of mind, the feasibility of the implied change, and the compatibility of strategies and tactics of implementation. Although very informative, most of this extant research is limited in the sense that it often directs attention towards the rational instead of the emotional. Hence, little is known about the role of emotions in sustainable decision making, especially in situations where decision-makers evaluate a variety of options and use their feelings as a source of information in tackling the uncertainty. To fill this lacuna, and to embrace the uncertainty and perceived risk involved in decisions that touch upon social and environmental aspects, it is important to add emotion to the evaluation when aiming to reach the one right and good ethical decision outcome. This analysis builds on recent findings in moral psychology that associate feelings and intuitions with ethical decisions and suggests that emotions can sensitize the manager to evaluate the rightness or wrongness of alternatives if ethical concerns are present in sustainable decision making. Capturing such sensitive evaluation as triggered by intuitions, we suggest that rational justification can be complemented by using emotions as a tool to tune in to what feels right in making sustainable decisions. This analysis integrates ethical decision-making theories with recent advancements in emotion theories. It determines the conditions under which emotions play a role in sustainability decisions by contributing to a personal equilibrium in which intuition and rationality are both activated and in accord. It complements the rationalist ethics view according to which nothing fogs the mind in decision making so thoroughly as emotion, and the concept of cheater’s high that links unethical behavior with positive affect. This analysis contributes to theory with a novel theoretical model that specifies when and why managers, who are more emotional, are, in fact, more likely to make ethical decisions than those managers who are more rational. It also proposes practical advice on how emotions can convert the manager’s preferences into choices that benefit both common good and one’s own good throughout the transition towards a more sustainable future.

Keywords: emotion, ethical decision making, intuition, sustainability

Procedia PDF Downloads 127
6775 Sorption of Charged Organic Dyes from Anionic Hydrogels

Authors: Georgios Linardatos, Miltiadis Zamparas, Vlasoula Bekiari, Georgios Bokias, Georgios Hotos

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Hydrogels are three-dimensional, hydrophilic, polymeric networks composed of homopolymers or copolymers and are insoluble in water due to the presence of chemical or physical cross-links. When hydrogels come in contact with aqueous solutions, they can effectively sorb and retain the dissolved substances, depending on the nature of the monomeric units comprising the hydrogel. For this reason, hydrogels have been proposed in several studies as water purification agents. At the present work anionic hydrogels bearing negatively charged –COO- groups were prepared and investigated. These gels are based on sodium acrylate (ANa), either homopolymerized (poly(sodiumacrylate), PANa) or copolymerized (P(DMAM-co-ANa)) with N,N Dimethylacrylamide (DMAM). The hydrogels were used to extract some model organic dyes from water. It is found that cationic dyes are strongly sorbed and retained by the hydrogels, while sorption of anionic dyes was negligible. In all cases it was found that both maximum sorption capacity and equilibrium binding constant varied from one dye to the other depending on the chemical structure of the dye, the presence of functional chemical groups and the hydrophobic-hydrophilic balance. Finally, the nonionic hydrogel of the homopolymer poly(N,N-dimethylacrylamide), PDMAM, was also used for reasons of comparison.

Keywords: anionic organic hydrogels, sorption, organic dyes, water purification agents

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6774 The Nexus between Wind Energy, Biodiversity Protection and Social Acceptance: Evidence of Good Practices from Greece, Latvia, and Poland

Authors: Christos Bouras, Eirini Stergiou, Charitini Karakostaki, Vasileios Tzanos, Vasileios Kokkinos

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Wind power represents a major pathway to curtailing greenhouse gas emissions and thus reducing the rate of climate change. A wind turbine runs practically emission-free for 20 years, representing one of the most environmentally sustainable sources of energy. Nevertheless, environmental and biodiversity concerns can often slow down or halt the deployment of wind farms due to local public opposition. This opposition is often fueled by poor relationships between wind energy stakeholders and civil society, which in many cases led to conflictual protests and property damage. In this context, addressing these concerns is essential in order to facilitate the proliferation of wind farms in Europe and the phase-out of fossil fuels from the energy mix. The aim of this study is to identify a number of good practices and cases to avoid increasing biodiversity protection at all stages of wind farms’ lifecycle in three participating countries, namely Greece, Latvia, and Poland. The results indicate that although available technological solutions are already being exploited worldwide, in these countries, there is still room for improvement. To address this gap, a set of policy recommendations is proposed to accomplish the wind energy targets in the near future while simultaneously mitigating the pertinent biodiversity risks.

Keywords: biodiversity protection, environmental impact, social acceptance, wind energy

Procedia PDF Downloads 153
6773 Publicizing Peace Intervention and Yoruba Indigenity in Television-Driven Peacemaking in South-West Nigeria

Authors: Temitope Yetunde Bello

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Peacemaking through the television represents a symbiotic relationship between the media and the (Yoruba) society such that the functional role of the media has expanded. Studying the ‘new function’ of the television as it publicizes peacemaking, using Yoruba indigenous means, is yet to be adequately incorporated into academic discourse. Using the Social Responsibility Theory, the paper examines the essence of publicizing peacemaking, the Yoruba indigenous institutions, philosophy and language that are used on the programs as well as the effectiveness of publicity in the television-driven peacemaking. The paper is a qualitative case-study research where five peacemaking television programs from state-owned stations in South-West Nigeria are purposively selected and studied. Findings show that peacemaking publicity facilitates intervention processes as parties’ communication gap is bridged and social justice is attained. Also, Yoruba indigenous peacemaking elements are utilized and projected through the television. The paper concludes by affirming that publicizing culturally-induced interventions in civil conflicts, though with a number of challenges, is effective and that television-driven peacemaking is a modern extension of Yoruba indigenous peacemaking media. It consequently recommends that the programs incorporate the new media to enhance wider audience and faster feedbacks while simultaneously retaining Yoruba indigenous essence of peacebuilding in this modern time.

Keywords: peace intervention publicity, television, television-driven peacemaking, yoruba indigenous elements

Procedia PDF Downloads 158
6772 Detailed Quantum Circuit Design and Evaluation of Grover's Algorithm for the Bounded Degree Traveling Salesman Problem Using the Q# Language

Authors: Wenjun Hou, Marek Perkowski

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The Traveling Salesman problem is famous in computing and graph theory. In short, it asks for the Hamiltonian cycle of the least total weight in a given graph with N nodes. All variations on this problem, such as those with K-bounded-degree nodes, are classified as NP-complete in classical computing. Although several papers propose theoretical high-level designs of quantum algorithms for the Traveling Salesman Problem, no quantum circuit implementation of these algorithms has been created up to our best knowledge. In contrast to previous papers, the goal of this paper is not to optimize some abstract complexity measures based on the number of oracle iterations, but to be able to evaluate the real circuit and time costs of the quantum computer. Using the emerging quantum programming language Q# developed by Microsoft, which runs quantum circuits in a quantum computer simulation, an implementation of the bounded-degree problem and its respective quantum circuit were created. To apply Grover’s algorithm to this problem, a quantum oracle was designed, evaluating the cost of a particular set of edges in the graph as well as its validity as a Hamiltonian cycle. Repeating the Grover algorithm with an oracle that finds successively lower cost each time allows to transform the decision problem to an optimization problem, finding the minimum cost of Hamiltonian cycles. N log₂ K qubits are put into an equiprobablistic superposition by applying the Hadamard gate on each qubit. Within these N log₂ K qubits, the method uses an encoding in which every node is mapped to a set of its encoded edges. The oracle consists of several blocks of circuits: a custom-written edge weight adder, node index calculator, uniqueness checker, and comparator, which were all created using only quantum Toffoli gates, including its special forms, which are Feynman and Pauli X. The oracle begins by using the edge encodings specified by the qubits to calculate each node that this path visits and adding up the edge weights along the way. Next, the oracle uses the calculated nodes from the previous step and check that all the nodes are unique. Finally, the oracle checks that the calculated cost is less than the previously-calculated cost. By performing the oracle an optimal number of times, a correct answer can be generated with very high probability. The oracle of the Grover Algorithm is modified using the recalculated minimum cost value, and this procedure is repeated until the cost cannot be further reduced. This algorithm and circuit design have been verified, using several datasets, to generate correct outputs.

Keywords: quantum computing, quantum circuit optimization, quantum algorithms, hybrid quantum algorithms, quantum programming, Grover’s algorithm, traveling salesman problem, bounded-degree TSP, minimal cost, Q# language

Procedia PDF Downloads 187
6771 Research on the Updating Strategy of Public Space in Small Towns in Zhejiang Province under the Background of New-Style Urbanization

Authors: Chen Yao, Wang Ke

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Small towns are the most basic administrative institutions in our country, which are connected with cities and rural areas. Small towns play an important role in promoting local urban and rural economic development, providing the main public services and maintaining social stability in social governance. With the vigorous development of small towns and the transformation of industrial structure, the changes of social structure, spatial structure, and lifestyle are lagging behind, causing that the spatial form and landscape style do not belong to both cities and rural areas, and seriously affecting the quality of people’s life space and environment. The rural economy in Zhejiang Province has started, the society and the population are also developing in relative stability. In September 2016, Zhejiang Province set out the 'Technical Guidelines for Comprehensive Environmental Remediation of Small Towns in Zhejiang Province,' so as to comprehensively implement the small town comprehensive environmental remediation with the main content of strengthening the plan and design leading, regulating environmental sanitation, urban order and town appearance. In November 2016, Huzhou City started the comprehensive environmental improvement of small towns, strived to use three years to significantly improve the 115 small towns, as well as to create a number of high quality, distinctive and beautiful towns with features of 'clean and livable, rational layout, industrial development, poetry and painting style'. This paper takes Meixi Town, Zhangwu Town and Sanchuan Village in Huzhou City as the empirical cases, analyzes the small town public space by applying the relative theory of actor-network and space syntax. This paper also analyzes the spatial composition in actor and social structure elements, as well as explores the relationship of actor’s spatial practice and public open space by combining with actor-network theory. This paper introduces the relevant theories and methods of spatial syntax, carries out research analysis and design planning analysis of small town spaces from the perspective of quantitative analysis. And then, this paper proposes the effective updating strategy for the existing problems in public space. Through the planning and design in the building level, the dissonant factors produced by various spatial combination of factors and between landscape design and urban texture during small town development will be solved, inhabitant quality of life will be promoted, and town development vitality will be increased.

Keywords: small towns, urbanization, public space, updating

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6770 Top-Down, Middle-Out, Bottom-Up: A Design Approach to Transforming Prison

Authors: Roland F. Karthaus, Rachel S. O'Brien

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Over the past decade, the authors have undertaken applied research aimed at enabling transformation within the prison service to improve conditions and outcomes for those living, working and visiting in prisons in the UK and the communities they serve. The research has taken place against a context of reducing resources and public discontent at increasing levels of violence, deteriorating conditions and persistently high levels of re-offending. Top-down governmental policies have mainly been ineffectual and in some cases counter-productive. The prison service is characterised by hierarchical organisation, and the research has applied design thinking at multiple levels to challenge and precipitate change: top-down, middle-out and bottom-up. The research employs three distinct but related approaches, system design (top-down): working at the national policy level to analyse the changing policy context, identifying opportunities and challenges; engaging with the Ministry of Justice commissioners and sector organisations to facilitate debate, introducing new evidence and provoking creative thinking, place-based design (middle-out): working with individual prison establishments as pilots to illustrate and test the potential for local empowerment, creative change, and improved architecture within place-specific contexts and organisational hierarchies, everyday design (bottom-up): working with individuals in the system to explore the potential for localised, significant, demonstrator changes; including collaborative design, capacity building and empowerment in skills, employment, communication, training, and other activities. The research spans a series of projects, through which the methodological approach has developed responsively. The projects include a place-based model for the re-purposing of Ministry of Justice land assets for the purposes of rehabilitation; an evidence-based guide to improve prison design for health and well-being; capacity-based employment, skills and self-build project as a template for future open prisons. The overarching research has enabled knowledge to be developed and disseminated through policy and academic networks. Whilst the research remains live and continuing; key findings are emerging as a basis for a new methodological approach to effecting change in the UK prison service. An interdisciplinary approach is necessary to overcome the barriers between distinct areas of the prison service. Sometimes referred to as total environments, prisons encompass entire social and physical environments which themselves are orchestrated by institutional arms of government, resulting in complex systems that cannot be meaningfully engaged through narrow disciplinary lenses. A scalar approach is necessary to connect strategic policies with individual experiences and potential, through the medium of individual prison establishments, operating as discrete entities within the system. A reflexive process is necessary to connect research with action in a responsive mode, learning to adapt as the system itself is changing. The role of individuals in the system, their latent knowledge and experience and their ability to engage and become agents of change are essential. Whilst the specific characteristics of the UK prison system are unique, the approach is internationally applicable.

Keywords: architecture, design, policy, prison, system, transformation

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6769 Computational Fluid Dynamics Simulation to Study the Effect of Ambient Temperature on the Ventilation in a Metro Tunnel

Authors: Yousef Almutairi, Yajue Wu

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Various large-scale trends have characterized the current century thus far, including increasing shifts towards urbanization and greater movement. It is predicted that there will be 9.3 billion people on Earth in 2050 and that over two-thirds of this population will be city dwellers. Moreover, in larger cities worldwide, mass transportation systems, including underground systems, have grown to account for the majority of travel in those settings. Underground networks are vulnerable to fires, however, endangering travellers’ safety, with various examples of fire outbreaks in this setting. This study aims to increase knowledge of the impacts of extreme climatic conditions on fires, including the role of the high ambient temperatures experienced in Middle Eastern countries and specifically in Saudi Arabia. This is an element that is not always included when assessments of fire safety are made (considering visibility, temperatures, and flows of smoke). This paper focuses on a tunnel within Riyadh’s underground system as a case study and includes simulations based on computational fluid dynamics using ANSYS Fluent, which investigates the impact of various ventilation systems while identifying smoke density, speed, pressure and temperatures within this tunnel.

Keywords: fire, subway tunnel, CFD, mechanical ventilation, smoke, temperature, harsh weather

Procedia PDF Downloads 124
6768 Intellectual Telepathy between Arabs and Pashtuns; Study of Their Proverbs as a Model

Authors: Shams Ul Hussain Zaheer, Bibi Alia, Shehla Shams

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With the creation of human beings, almost all of them are blessed with the award of the power of expression, and this series starts from the life of Adam (A.S) in Paradise when he was blesses with language and knowledge and given priority upon the Angels. Later on, when the population spread and many other languages came into being, the method of the different people of different regions remained various. And when the Arabic was formed as a language after Ismail (A.S) and his sons spread in the gulf area, the words adopted from other gulf languages also became a part of this new language with it immense. Beside this, the tone of expression in other areas of the word was different, but the incidents, norms of bad and good, parameters for like and dislike, thinking styles, and rules of good and bad governance with social values remained round about the same. People practiced their lives according to the set norms everywhere in the world. Especially the two built, i.e., Hijaz and Khurasan, wherein Arabs and Pashtun accordingly were dwelling; it seems that their social values were much closed to each other. These norms reflect in various kinds of literature of both of the nations, but this article deals in with their proverbs specifically. This article discusses the intellectual telepathic between them in a research way. And put the defined similarities and dissimilarities between both in the proverb. And it also draws a sketch in front of readers that how the thinking and expression styles remains same in humans. As it belongs to a comparative analysis of the proverbs so, the same methodology has been adopted in the articles.

Keywords: intellectual telepathy, hijaz, arab, khurasan, pashtun, proverbs, comparison

Procedia PDF Downloads 86
6767 An Improved Convolution Deep Learning Model for Predicting Trip Mode Scheduling

Authors: Amin Nezarat, Naeime Seifadini

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Trip mode selection is a behavioral characteristic of passengers with immense importance for travel demand analysis, transportation planning, and traffic management. Identification of trip mode distribution will allow transportation authorities to adopt appropriate strategies to reduce travel time, traffic and air pollution. The majority of existing trip mode inference models operate based on human selected features and traditional machine learning algorithms. However, human selected features are sensitive to changes in traffic and environmental conditions and susceptible to personal biases, which can make them inefficient. One way to overcome these problems is to use neural networks capable of extracting high-level features from raw input. In this study, the convolutional neural network (CNN) architecture is used to predict the trip mode distribution based on raw GPS trajectory data. The key innovation of this paper is the design of the layout of the input layer of CNN as well as normalization operation, in a way that is not only compatible with the CNN architecture but can also represent the fundamental features of motion including speed, acceleration, jerk, and Bearing rate. The highest prediction accuracy achieved with the proposed configuration for the convolutional neural network with batch normalization is 85.26%.

Keywords: predicting, deep learning, neural network, urban trip

Procedia PDF Downloads 133
6766 The Determinants of the Operational Performance in Airline Industry: A Case of a Turkish Airline Company

Authors: Mustafa K. Yilmaz, Ahmet Kaplan, Murat Guven, Vildan Kesici

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Aviation industry influences the social and economic growth across the countries. Further, airline companies are highly affected by social, political, and financial crises and show a high degree of cyclicity in operational performance. Hence, this paper investigates the effects of available seat kilometers (ASK), revenue per kilometer (RPK), passenger load factor (PLF) as well as socio-political crisis on the number of passengers carried (PC) by Turkish Airlines company over the period of 2010M1-2018M12. To conduct the analysis, we employ fully modified ordinary least squares (FMOLS), dynamic ordinary least squares (DOLS), and canonical cointegration regression (CCR) techniques using monthly data. We use ASK, RPK, PLF as independent variables to identify the determinants of the PC, as a dependent variable. We also test the effect of the socio-political crisis. The results reveal that there is a significant and negative relationship between ASK and PC, while the relationship between RPK and PC is positive and significant. We also find that there is an insignificant relationship between PLF and PC. Further, we also find a negative effect of the crisis on the PC. These findings show although the crisis had an immediate effect on the operational performance of Turkish Airlines, the company recovered from the crisis and cope with the situation very promptly. Thus, this proves the resilience and agile management ability of the company.

Keywords: airline industry, operational performance, air traffic, socio-political crisis

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6765 Woman, House, Identity: The Study of the Role of House in Constructing the Contemporary Dong Minority Woman’s Identity

Authors: Sze Wai Veera Fung, Peter W. Ferretto

Abstract:

Similar to most ethnic groups in China, men of the Dong minority hold the primary position in policymaking, moral authority, social values, and the control of the property. As the spatial embodiment of the patriarchal ideals, the house plays a significant role in producing and reproducing the distinctive gender status within the Dong society. Nevertheless, Dong women do not see their home as a cage of confinement, nor do they see themselves as a victim of oppression. For these women with reference to their productive identity, a house is a dwelling place with manifold meanings, including a proof of identity, an economic instrument, and a public resource operating on the community level. This paper examines the role of the house as a central site for identity construction and maintenance for the southern dialect Dong minority women in Hunan, China. Drawing on recent interviews with the Dong women, this study argues that women as productive individuals have a strong influence on the form of their house and the immediate environment, regardless of the male-dominated social construct of the Dong society. The aim of this study is not to produce a definitive relationship between women, house, and identity. Rather, it seeks to offer an alternative lens into the complexity and diversity of gender dynamics operating in and beyond the boundary of the house in the context of contemporary rural China.

Keywords: conception of home, Dong minority, house, rural China, woman’s identity

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6764 An Investigation into the Social Determinants of Crowdfunding Effectiveness in developing, non-Western contexts: Some Evidence from Thailand

Authors: Khin Thi Htun, James Jain, Tim Andrews

Abstract:

This study examines the under-researched phenomenon of crowdfunding use and effectiveness in developing non-western markets. More precisely, using an institutional theoretical lens, the research explores the attitudes, motivations, and practice surrounding the initiation, development, and receipt of crowdfunding campaignsin a business context symptomatic of widely dissimilar regulatory, normative cognitive institutional ‘pillars’ to those studied – and utilized in practice - to date. As, in essence, a form of alternative finance, crowdfunding is used primarily to fund a wide range of projects through the securement of small amounts of money from a large pool of investors/participants. Being tied almost inextricably to e-commerce channels, the practice of crowdfunding typically sources its means and communicates the purpose of each venture mainly, though not exclusively, online. The wide range of projects supported to date span social entrepreneurship, community benefits initiatives, creative and artistic endeavors, assistance to disadvantaged social cohorts, and small business start-ups. Adopting a longitudinal, comparative approach, the study reported here embodies an investigation centered on six case start-up campaigns within the Thai societal context, covering a range of fundings calls and cause choices. Data was sourced from a variety of respondents using semi-structured interviews, observation (direct and participant), and company information. Results suggest that the motives and effectiveness of crowdfunding campaigns differ significantly in non-western consumer contexts from the norms that have evolved to date in mature Western contexts(particularly the US and UK). Specifically, whereas data on the different regulatory pressures showed relatively insignificant variation, the results regarding cognitive and, especially, normative dissimilarities between the Thai and US/UK institutional profiles surfaced potentially important differences with far-reaching implications. Particular issuesto emerge from our data concerned consumer motivation in terms of support and engagement with different types of campaigns. This was found to stem from social norms symptomatic of ‘collectivist’ and ‘relations based/particularist’ cultural assistance behavior, in turn, linked to deeply-held societal values regarding interpersonal network (‘in group’) reciprocity. This research serves to refine and extend the limited body of knowledge to date on crowdfunding by exploring the phenomenon in a non-western, non-developed country contextswhere social norms and values differ. This was achieved through uncovering and explicating the effects of cultural dissimilarity on motivation, decision-making, construed ethics, and general engagement with crowdfunding ideas. Implications for theory into e-marketing and cross-cultural marketing, as well as for practitioners seeking to develop effective crowdfunding campaigns in a Southeast Asian cultural environment, are discussed to conclude the paper.

Keywords: crowdfunding, national culture, e-marketing, cross-cultural business

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6763 The Impact of Information and Communication Technology on the Re-Engineering Process of Small and Medium Enterprises

Authors: Hiba Mezaache

Abstract:

The current study aimed to know the impact of using information and communication technology on the process of re-engineering small and medium enterprises, as the world witnessed the speed development of the latter in its field of work and the diversity of its objectives and programs, that also made its process important for the growth and development of the institution and also gaining the flexibility to face the changes that may occur in the environment of work, so in order to know the impact of information and communication technology on the success of this process, we prepared an electronic questionnaire that included (70) items, and we also used the SPSS statistical calendar to analyze the data obtained. In the end of our study, our conclusion was that there was a positive correlation between the four dimensions of information and communication technology, i.e., hardware and equipment, software, communication networks, databases, and the re-engineering process, in addition to the fact that the studied institutions attach great importance to formal communication, for its positive advantages that it achieves in reducing time and effort and costs in performing the business. We could also say that communication technology contributes to the process of formulating objectives related to the re-engineering strategy. Finally, we recommend the necessity of empowering workers to use information technology and communication more in enterprises, and to integrate them more into the activity of the enterprise by involving them in the decision-making process, and also to keep pace with the development in the field of software, hardware, and technological equipment.

Keywords: information and communication technology, re-engineering, small and medium enterprises, the impact

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6762 The Theory and Practice of Translanguaging: Scope, Potential and Limitations in a Multilingual Urban Context

Authors: Luzia Dominguez

Abstract:

This paper explores the concept of ‘translanguaging’ and the relevance of its pedagogical application in the context of foreign language education in a multilingual urban environment. We review relevant literature discussing this theoretical concept, its scope, potential, and limitations when applied to the teaching of foreign languages. We then discuss its possible practical application in Welsh secondary schools, particularly in the most diverse areas of the Welsh capital, Cardiff (United Kingdom). The concept of translanguaging has evolved in scope, from its initial application in the teaching of Welsh and English in the Welsh bilingual context to finding a relevant space not only in the international arena of Sociolinguistics and language pedagogy but also being present in current Welsh educational policies and, presumably, practices. However, it is important to consider the actual pedagogical relevance of incorporating this concept into these policies, particularly in the teaching of Modern Foreign Languages. Additionally, it is important to examine any social factors that may influence the effectiveness of its application in the social context, in our case, a multilingual, ethnically diverse urban context. By analyzing these issues, we aim to explore possible teaching practices that could be pedagogically effective in applying the concept in Cardiff secondary schools.

Keywords: pedagogy, modern foreign languages, applied linguistics, sociolinguistics

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6761 Affective Robots: Evaluation of Automatic Emotion Recognition Approaches on a Humanoid Robot towards Emotionally Intelligent Machines

Authors: Silvia Santano Guillén, Luigi Lo Iacono, Christian Meder

Abstract:

One of the main aims of current social robotic research is to improve the robots’ abilities to interact with humans. In order to achieve an interaction similar to that among humans, robots should be able to communicate in an intuitive and natural way and appropriately interpret human affects during social interactions. Similarly to how humans are able to recognize emotions in other humans, machines are capable of extracting information from the various ways humans convey emotions—including facial expression, speech, gesture or text—and using this information for improved human computer interaction. This can be described as Affective Computing, an interdisciplinary field that expands into otherwise unrelated fields like psychology and cognitive science and involves the research and development of systems that can recognize and interpret human affects. To leverage these emotional capabilities by embedding them in humanoid robots is the foundation of the concept Affective Robots, which has the objective of making robots capable of sensing the user’s current mood and personality traits and adapt their behavior in the most appropriate manner based on that. In this paper, the emotion recognition capabilities of the humanoid robot Pepper are experimentally explored, based on the facial expressions for the so-called basic emotions, as well as how it performs in contrast to other state-of-the-art approaches with both expression databases compiled in academic environments and real subjects showing posed expressions as well as spontaneous emotional reactions. The experiments’ results show that the detection accuracy amongst the evaluated approaches differs substantially. The introduced experiments offer a general structure and approach for conducting such experimental evaluations. The paper further suggests that the most meaningful results are obtained by conducting experiments with real subjects expressing the emotions as spontaneous reactions.

Keywords: affective computing, emotion recognition, humanoid robot, human-robot-interaction (HRI), social robots

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6760 Contesting Blind Obedience in Islam within the Malay-Language Media: Case Study of 'I Want to Touch a Dog' Event

Authors: Aisya Zaharin

Abstract:

The reporting of Islam in the Malaysian government-controlled press is complicated and occurs almost daily. This is due to the Islamisation process that has been heavily politicized in recent years. This article analyses media representations of Islam in the Malaysian media through the social responsibility theory. A provocative case study of media reporting on the “I want to touch a dog” event was analysed since dog’s saliva is ritually considered unhygienic by Muslims. This paper will not question the Islamic ruling on the dog’s issue. Instead, it calls for discussions in relation to openness and maturity in religious discourse with respect to the dog’s saliva dialogue in 1937. It applies Hage’s “minor and major reality” to explain the increasing percentage of Muslim who define their own understandings of Islam vs the government’s dogmatic versions. This paper employs Alatas’s method of “sociological investigation in Southeast Asia” by using ethnographic examination on selected mass media. Through Asiacentricity approach, this paper revisited the local framework of Alatas’s New Man encouraging Muslims to engage in knowledge and to appreciate diversities in Islamic jurisprudences. Despite government’s control, findings showed that non-Malay languages and online media are more comprehensive in reporting the news about Islam. Clearly, there has to be a re-conceptualization of Islamic discourses in the Malay-language media.

Keywords: dog, Fiqh, Islamic jurisprudence, Malaysian media, New Man, social responsibility

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6759 Indium-Gallium-Zinc Oxide Photosynaptic Device with Alkylated Graphene Oxide for Optoelectronic Spike Processing

Authors: Seyong Oh, Jin-Hong Park

Abstract:

Recently, neuromorphic computing based on brain-inspired artificial neural networks (ANNs) has attracted huge amount of research interests due to the technological abilities to facilitate massively parallel, low-energy consuming, and event-driven computing. In particular, research on artificial synapse that imitate biological synapses responsible for human information processing and memory is in the spotlight. Here, we demonstrate a photosynaptic device, wherein a synaptic weight is governed by a mixed spike consisting of voltage and light spikes. Compared to the device operated only by the voltage spike, ∆G in the proposed photosynaptic device significantly increased from -2.32nS to 5.95nS with no degradation of nonlinearity (NL) (potentiation/depression values were changed from 4.24/8 to 5/8). Furthermore, the Modified National Institute of Standards and Technology (MNIST) digit pattern recognition rates improved from 36% and 49% to 50% and 62% in ANNs consisting of the synaptic devices with 20 and 100 weight states, respectively. We expect that the photosynaptic device technology processed by optoelectronic spike will play an important role in implementing the neuromorphic computing systems in the future.

Keywords: optoelectronic synapse, IGZO (Indium-Gallium-Zinc Oxide) photosynaptic device, optoelectronic spiking process, neuromorphic computing

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6758 Novel EGFR Ectodomain Mutations and Resistance to Anti-EGFR and Radiation Therapy in H&N Cancer

Authors: Markus Bredel, Sindhu Nair, Hoa Q. Trummell, Rajani Rajbhandari, Christopher D. Willey, Lewis Z. Shi, Zhuo Zhang, William J. Placzek, James A. Bonner

Abstract:

Purpose: EGFR-targeted monoclonal antibodies (mAbs) provide clinical benefit in some patients with H&N squamous cell carcinoma (HNSCC), but others progress with minimal response. Missense mutations in the EGFR ectodomain (ECD) can be acquired under mAb therapy by mimicking the effect of large deletions on receptor untethering and activation. Little is known about the contribution of EGFR ECD mutations to EGFR activation and anti-EGFR response in HNSCC. Methods: We selected patient-derived HNSCC cells (UM-SCC-1) for resistance to mAb Cetuximab (CTX) by repeated, stepwise exposure to mimic what may occur clinically and identified two concurrent EGFR ECD mutations (UM-SCC-1R). We examined the competence of the mutants to bind EGF ligand or CTX. We assessed the potential impact of the mutations through visual analysis of space-filling models of the native sidechains in the original structures vs. their respective side-chain mutations. We performed CRISPR in combination with site-directed mutagenesis to test for the effect of the mutants on ligand-independent EGFR activation and sorting. We determined the effects on receptor internalization, endocytosis, downstream signaling, and radiation sensitivity. Results: UM-SCC-1R cells carried two non-synonymous missense mutations (G33S and N56K) mapping to domain I in or near the EGF binding pocket of the EGFR ECD. Structural modeling predicted that these mutants restrict the adoption of a tethered, inactive EGFR conformation while not permitting association of EGFR with the EGF ligand or CTX. Binding studies confirmed that the mutant, untethered receptor displayed a reduced affinity for both EGF and CTX but demonstrated sustained activation and presence at the cell surface with diminished internalization and sorting for endosomal degradation. Single and double-mutant models demonstrated that the G33S mutant is dominant over the N56K mutant in its effect on EGFR activation and EGF binding. CTX-resistant UM-SCC-1R cells demonstrated cross-resistance to mAb Panitumuab but, paradoxically, remained sensitive to the reversible receptor tyrosine kinase inhibitor Erlotinib. Conclusions: HNSCC cells can select for EGFR ECD mutations under EGFR mAb exposure that converge to trap the receptor in an open, constitutively activated state. These mutants impede the receptor’s competence to bind mAbs and EGF ligand and alter its endosomal trafficking, possibly explaining certain cases of clinical mAb and radiation resistance.

Keywords: head and neck cancer, EGFR mutation, resistance, cetuximab

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6757 Activation-TV® to Reduce Elderly Loneliness and Insecurity

Authors: Hannele Laaksonen, Seija Nyqvist, Kari Nurmes

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Objectives: In the year 2011 the City of Vaasa started to develop know-how in the technology and the introduction of services for aging people in cooperation with the Polytechnic Novia University of Applied Sciences and VAMK, University of Applied Sciences. The project´s targets included: to help elderly people to maintain their ability to function, to provide them social and physical activities, to prevent their social exclusion, to decrease their feelings of loneliness and insecurity and to develop their technical know-how. Methods: The project was built based on open source code, tailor-made service system and user interface for the elderly living at home and their families, based on the users´ expectations and experiences of services. Activation-TV®-project vas carried out 1.4.2011-31.3.2014. A pilot group of eight elderly persons, who were living at home, were selected to the project. All necessary technical means as well as guidance and teaching equipment were provided to the pilot group. The students of University of Applied Sciences (VAMK, Novia) and employees of Center of Ageing were made all programs to the Activation-TV®. The project group were interviewed after and before intervention. The data were evaluated both qualitatively and quantitatively. Results: The built service includes a video library, a group room for interactive programs and a personal room for bilateral meetings and direct shipment. The program is bilingual and produced in both national languages. The Activation TV® reduced elderly peoples´ (n=8) feelings of emptiness, added mental well-being and quality of life with social contacts. Relatives felt, that they were able to get in to older peoples´ everyday life with Activation TV®. Discussion: The built application was tailored to the model that has not been developed elsewhere in Finland. This model can be copied from one server to another and thus transferred to other municipalities but the program requires its own personnel system management and maintenance as well as program production cooperation between the different actors. This service can be used for the elderly who are living at home without dementia.

Keywords: mental well-being, quality of life, elderly people, Finland

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6756 Hybrid Transformer and Neural Network Configuration for Protein Classification Using Amino Acids

Authors: Nathan Labiosa, Aryan Kohli

Abstract:

This study introduces a hybrid machine learning model for classifying proteins, developed to address the complexities of protein sequence and structural analysis. Utilizing an architecture that combines a lightweight transformer with a concurrent neural network, the hybrid model leverages both sequential and intrinsic physical properties of proteins. Trained on a comprehensive dataset from the Research Collaboratory for Structural Bioinformatics Protein Data Bank, the model demonstrates a classification accuracy of 95%, outperforming existing methods by at least 15%. The high accuracy achieved demonstrates the potential of this approach to innovate protein classification, facilitating advancements in drug discovery and the development of personalized medicine. By enabling precise protein function prediction, the hybrid model allows for specialized strategies in therapeutic targeting and the exploration of protein dynamics in biological systems. Future work will focus on enhancing the model’s generalizability across diverse datasets and exploring the integration of more machine learning techniques to refine predictive capabilities further. The implications of this research offer potential breakthroughs in biomedical research and the broader field of protein engineering.

Keywords: amino acids, deep learning, enzymes, neural networks, protein classification, proteins, transformers

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6755 A Comparative Evaluation of the SIR and SEIZ Epidemiological Models to Describe the Diffusion Characteristics of COVID-19 Polarizing Viewpoints on Online

Authors: Maryam Maleki, Esther Mead, Mohammad Arani, Nitin Agarwal

Abstract:

This study is conducted to examine how opposing viewpoints related to COVID-19 were diffused on Twitter. To accomplish this, six datasets using two epidemiological models, SIR (Susceptible, Infected, Recovered) and SEIZ (Susceptible, Exposed, Infected, Skeptics), were analyzed. The six datasets were chosen because they represent opposing viewpoints on the COVID-19 pandemic. Three of the datasets contain anti-subject hashtags, while the other three contain pro-subject hashtags. The time frame for all datasets is three years, starting from January 2020 to December 2022. The findings revealed that while both models were effective in evaluating the propagation trends of these polarizing viewpoints, the SEIZ model was more accurate with a relatively lower error rate (6.7%) compared to the SIR model (17.3%). Additionally, the relative error for both models was lower for anti-subject hashtags compared to pro-subject hashtags. By leveraging epidemiological models, insights into the propagation trends of polarizing viewpoints on Twitter were gained. This study paves the way for the development of methods to prevent the spread of ideas that lack scientific evidence while promoting the dissemination of scientifically backed ideas.

Keywords: mathematical modeling, epidemiological model, seiz model, sir model, covid-19, twitter, social network analysis, social contagion

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6754 Combination Therapies Targeting Apoptosis Pathways in Pediatric Acute Myeloid Leukemia (AML)

Authors: Ahlam Ali, Katrina Lappin, Jaine Blayney, Ken Mills

Abstract:

Leukaemia is the most frequently (30%) occurring type of paediatric cancer. Of these, approximately 80% are acute lymphoblastic leukaemia (ALL) with acute myeloid leukaemia (AML) cases making up the remaining 20% alongside other leukaemias. Unfortunately, children with AML do not have promising prognosis with only 60% surviving 5 years or longer. It has been highlighted recently the need for age-specific therapies for AML patients, with paediatric AML cases having a different mutational landscape compared with AML diagnosed in adult patients. Drug Repurposing is a recognized strategy in drug discovery and development where an already approved drug is used for diseases other than originally indicated. We aim to identify novel combination therapies with the promise of providing alternative more effective and less toxic induction therapy options. Our in-silico analysis highlighted ‘cell death and survival’ as an aberrant, potentially targetable pathway in paediatric AML patients. On this basis, 83 apoptotic inducing compounds were screened. A preliminary single agent screen was also performed to eliminate potentially toxic chemicals, then drugs were constructed into a pooled library with 10 drugs per well over 160 wells, with 45 possible pairs and 120 triples in each well. Seven cell lines were used during this study to represent the clonality of AML in paediatric patients (Kasumi-1, CMK, CMS, MV11-14, PL21, THP1, MOLM-13). Cytotoxicity was assessed up to 72 hours using CellTox™ Green reagent. Fluorescence readings were normalized to a DMSO control. Z-Score was assigned to each well based on the mean and standard deviation of all the data. Combinations with a Z-Score <2 were eliminated and the remaining wells were taken forward for further analysis. A well was considered ‘successful’ if each drug individually demonstrated a Z-Score <2, while the combination exhibited a Z-Score >2. Each of the ten compounds in one well (155) had minimal or no effect as single agents on cell viability however, a combination of two or more of the compounds resulted in a substantial increase in cell death, therefore the ten compounds were de-convoluted to identify a possible synergistic pair/triple combinations. The screen identified two possible ‘novel’ drug pairing, with BCL2 inhibitor ABT-737, combined with either a CDK inhibitor Purvalanol A, or AKT/ PI3K inhibitor LY294002. (ABT-737- 100 nM+ Purvalanol A- 1 µM) (ABT-737- 100 nM+ LY294002- 2 µM). Three possible triple combinations were identified (LY2409881+Akti-1/2+Purvalanol A, SU9516+Akti-1/2+Purvalanol A, and ABT-737+LY2409881+Purvalanol A), which will be taken forward for examining their efficacy at varying concentrations and dosing schedules, across multiple paediatric AML cell lines for optimisation of maximum synergy. We believe that our combination screening approach has potential for future use with a larger cohort of drugs including FDA approved compounds and patient material.

Keywords: AML, drug repurposing, ABT-737, apoptosis

Procedia PDF Downloads 200