Search results for: translation rules

Authors: Natsuda Rattamanee

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Like other countries, Thailand continually experiences strong protests against dam and reservoir proposals, especially large-scale projects. The protestors are constantly worried about the potential significant adverse impacts of the projects on the environment and society. Although project proponents are required by laws to assess the environmental and social impacts of the dam proposals by making environmental impact assessment (EIA) reports and finding mitigation measures before implementing the plans, the outcomes of the assessments often do not lessen the affected people and public’s concerns about the potential negative effects of the projects. One of the main reasons is that Thailand does not have a proper and efficient law to regulate project proponents when determining the scope of environmental impact assessments. Scoping is the crucial second stage of the preparation of an EIA report. The appropriate scope of assessments will allow EIA studies to focus only on the significant effects of the proposed project on particular resources, areas, and communities. It will offer crucial and sufficient information to the decision-makers and the public. The decision to implement the dam and reservoir projects considered based on the assessments with a proper scoping will eventually be more widely accepted by the public and reduce community opposition. The research work seeks to identify flaws in the current requirements of scoping steps under Thai laws and regulations and proposes recommendations to improve the legal scheme. The paper explores the well-established United States laws and relevant rules regulating how lead agencies determine the scope of their environmental impact assessments and some guidelines concerning scoping published by dominant institutions. Policymakers and legislature will find the results of studies helpful in improving the scoping-step requirements of EIA for dam and reservoir projects and reducing the level of anti-dam protests in Thailand.

Keywords: dam and reservoir, EIA, environmental impact assessment, law, scoping, Thailand

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Authors: Kevin Kellner, Nga Lao, Orla Coleman, Paula Meleady, Niall Barron

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Chinese Hamster Ovary (CHO) cells are the prominent cell line used in biopharmaceutical production. To improve yields and find beneficial bioprocess phenotypes genetic engineering plays an essential role in recent research. The miR-23 cluster, specifically miR-24 and miR-27, was first identified as differentially expressed during hypothermic conditions suggesting a role in proliferation and productivity in CHO cells. In this study, we used sponge decoy technology to stably deplete the miRNA expression of the cluster. Furthermore, we implemented the CRISPR/Cas9 system to knockdown miRNA expression. Sponge constructs were designed for an imperfect binding of the miRNA target, protecting from RISC mediated cleavage. GuideRNAs for the CRISPR/Cas9 system were designed to target the seed region of the miRNA. The expression of mature miRNA and precursor were confirmed using RT-qPCR. For both approaches stable expressing mixed populations were generated and characterised in batch cultures. It was shown, that CRISPR/Cas9 can be implemented in CHO cells with achieving high knockdown efficacy of every single member of the cluster. Targeting of one miRNA member showed that its genomic paralog is successfully targeted as well. The stable depletion of miR-24 using CRISPR/Cas9 showed increased growth and specific productivity in a CHO-K1 mAb expressing cell line. This phenotype was further characterized using quantitative label-free LC-MS/MS showing 186 proteins differently expressed with 19 involved in proliferation and 26 involved in protein folding/translation. Targeting miR-27 in the same cell line showed increased viability in late stages of the culture compared to the control. To evaluate the phenotype in an industry relevant cell line; the miR-23 cluster, miR-24 and miR-27 were stably depleted in a Fc fusion CHO-S cell line which showed increased batch titers up to 1.5-fold. In this work, we highlighted that the stable depletion of the miR-23 cluster and its members can improve the bioprocess phenotype concerning growth and productivity in two different cell lines. Furthermore, we showed that using CRISPR/Cas9 is comparable to the traditional sponge decoy technology.

Keywords: Chinese Hamster ovary cells, CRISPR/Cas9, microRNAs, sponge decoy technology

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Authors: Steffen Illig, Alexander S. Eggeman, Alessandro Troisi, Stephen G. Yeates, John E. Anthony, Henning Sirringhaus

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Large-amplitude intermolecular vibrations in combination with complex shaped transfer integrals generate a thermally fluctuating energetic landscape. The resulting dynamic disorder and its intrinsic presence in organic semiconductors is one of the most fundamental differences to their inorganic counterparts. Dynamic disorder is believed to govern many of the unique electrical and optical properties of organic systems. However, the low energy nature of these vibrations makes it difficult to access them experimentally and because of this we still lack clear molecular design rules to control and reduce dynamic disorder. Applying a novel technique based on electron diffraction we encountered strong intermolecular, thermal vibrations in every single organic material we studied (14 up to date), indicating that a large degree of dynamic disorder is a universal phenomenon in organic crystals. In this paper a new molecular design strategy will be presented to avoid dynamic disorder. We found that small molecules that have their side chains attached to the long axis of their conjugated core have been found to be less likely to suffer from dynamic disorder effects. In particular, we demonstrate that 2,7-dioctyl[1]benzothieno[3,2-b][1]benzothio-phene (C8-BTBT) and 2,9-di-decyl-dinaphtho-[2,3-b:20,30-f]-thieno-[3,2-b]-thiophene (C10DNTT) exhibit strongly reduced thermal vibrations in comparison to other molecules and relate their outstanding performance to their lower dynamic disorder. We rationalize the low degree of dynamic disorder in C8-BTBT and C10-DNTT with a better encapsulation of the conjugated cores in the crystal structure which helps reduce large amplitude thermal motions. The work presented in this paper provides a general strategy for the design of new classes of very high mobility organic semiconductors with low dynamic disorder.

Keywords: charge transport, C8-BTBT, C10-DNTT, dynamic disorder, organic semiconductors, thermal vibrations

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Authors: Tosin Deborah Akanbi, Adeyemi Oluwaseun Adepoju, Hameed Olusegun Adebambo, Akinloye Fatai Lawal

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Building information modelling (BIM) is a process that starts with the development of a sequential 3D design and encourages data administration, organization, and visualization throughout the life span of a facility (drawings, construction, and supervision). The implementation of building information modelling has been slow in recent years, and this is due to some prominent barriers that hinder its adoption. In this regard, the study aims to examine the significant barriers that influence the adoption of building information modelling in the Lagos state construction industry. Data were gathered through a questionnaire survey with 332 construction professionals in the study area. Three online structured interviews were conducted to support and validate the findings of the quantitative analysis. The results revealed that interest (lack of awareness and understanding of BIM, absence of in-house BIM competent professionals, and unavailability of BIM competent professionals in the labour market), legal (lack of policies and regulations on copyright ownership and lack of enforcement from government agencies and industry leaderships) and professional (people’s inability or refusal to learn new technologies and processes, waste in time and human resource and lack of clarity of professional roles in BIM) barriers are the major barriers influencing the adoption of BIM. The results also revealed that six final themes were generated, namely: finance barriers, industry barriers, interest barriers, leadership barriers, legal barriers, and professional barriers. Thus, there is a need for policymakers to design and implement policies (regulatory, economic, and information) to promote financial schemes to support construction firms and professionals and to reduce financial barriers. It is also important for the government to lay down rules and regulations that must be enforced among the construction professionals and firms in the Lagos state construction industry.

Keywords: BIM barriers, BIM adoption characteristics, construction industry, Lagos State Nigeria

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Authors: C. Catalina Zapata, Z. Claudia Montoya

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Transplant from hematopoietic parents (THP) or medulla (MT) is a procedure used to replace the medulla that does not work as part of a disease or when it is destroyed either by a treatment of high medication doses against cancer or by radiation. The transplant process has three stages, a stage prior to transplant, during and after the transplant. It is held with the help of an interdisciplinary team, including nursing, carrying out mainly educative procedures to warrant the adhesion and the changes in lifestyles needed to whom will undergo this procedure. The aim of the study was to assess the results of an educative procedure by nursing, on adult patients subjected to a transplant from hematopoietic parents at a high complexity institution of Medellin city, Colombia. This study had an observational longitudinal design. According to the rules of protocol, the educative activity must be held on all patients joining the procedure. Four instruments were designed in order to collect all the information. One of them to measure the sociodemographic variables, another one to measure self-care practices, another one to measure transplant knowledge and its cares and the other one to measure the 30-day post-transplant complications. The last three instruments were applied before and after the educative procedure. A univaried analysis was carried out but the bivaried analysis was not carried out since there were not statistically meaningful differences before and after. Within the results, ten patients were evaluated. The average age was 38.2 (13.38 SD – standard deviation), 8/10 were men. Some self-care practices such us having pets and plants and consuming some specific food as well as little use of UV protection are all present in this type of patients and are not modified after the procedure. In measuring the knowledge, something stands out among the answers. It is the fact that some patients do not know what the medulla is, the nature of separating wastes at home and the need to consult about vomit and nausea. The most frequent complications during the first thirty days were: nausea, vomit, fever, and rash. They are considered to be expected within this period. Patients do not exhibit differences in their level of knowledge before and after the educative procedure by nursing. The patients’ self-care practices do not involve all the necessary ones to avoid complications. During the first 30 days, most of the complications are typical of the transplant process from hematopoietic parents.

Keywords: bone marrow transplant, education, family, nursing, patients, Transplantation of hematopoietic progenitors

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Authors: Ambra Giovannelli, Erika Maria Archilei

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The electrical power consumption related to refrigeration systems is evaluated to be in the order of 15% of the total electricity consumption worldwide. For this reason, in the last years several energy saving techniques have been suggested to reduce the power demand of refrigeration and air conditioning plants. The research work deals with the development of an innovative internal power recovery system for industrial cryogenic cooling plants. Such system is based on a Compressor-Expander Group (CEG). Both the expander and the compressor have been designed starting from automotive turbocharging components, strongly modified to take refrigerant fluid properties and specific system requirements into consideration. A preliminary choice of the machines (radial compressors and expanders) among existing components available on the market was realised according to the rules of the similarity theory. Once the expander was selected, it was strongly modified and performance verified by means of steady-state 3D CFD simulations. This paper focuses the attention on the development of the second CEG main component: the compressor. Once the preliminary selection has been done, the compressor geometry has been modified to take the new boundary conditions into account. In particular, the impeller has been machined to address the required total enthalpy increase. Such evaluation has been carried out by means of a simplified 1D model. Moreover, a vaneless diffuser has been added, modifying the shape of casing rear and front disks. To verify the performance of the modified compressor geometry and suggest improvements, a numerical fluid dynamic model has been set up and the commercial Ansys-CFX software has been used to perform steady-state 3D simulations. In this work, all the numerical results will be shown, highlighting critical aspects and suggesting further developments to increase compressor performance and flexibility.

Keywords: vapour compression systems, energy saving, refrigeration plant, organic fluids, centrifugal compressor

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Authors: Samane Eftekhari Ranjbar

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Diabetes mellitus, a metabolic disorder characterized by elevated blood glucose levels, ranks among the leading causes of adult mortality. This study investigates the impact of an eight-week high-intensity interval training (HIIT) program combined with sodium nitrite supplementation on TNF- α, MURF1, and PI3K in a type 2 diabetes rodent model. Elevated TNF-α levels have been associated with insulin resistance, while MURF1 and PI3K play roles in muscle atrophy and insulin signaling pathways, respectively. In this experimental study, 15 eight-week-old rats from the Sara Laboratory Center in Tabriz were assigned to one of five groups: healthy control, diabetic control, diabetic with sodium nitrite supplementation, diabetic with eight weeks of intermittent exercise, and diabetic with eight weeks of interval training plus sodium nitrite supplementation. The HIIT protocol was designed to span eight weeks, with five weekly sessions at specified intensities and durations. Sodium nitrite, known for its vasodilatory and cytoprotective properties, was administered via injection. The findings revealed that the HIIT program and sodium nitrite supplementation influenced the examined biomarkers. ANOVA test outcomes indicated statistically significant differences in TNF- α (P=0.001), MURF1 (P=0.001), and PI3K (P=0.001) concentrations among the various groups. The healthy control group exhibited substantially decreased TNF- α, and MURF1 levels, as well as elevated PI3K levels compared to the diabetic control group. The exercise group, in conjunction with sodium nitrite supplementation, demonstrated a significant rise in PI3K levels (P=0.001) and a decline in TNF- α levels (P=0.018) relative to the diabetic control group. These results suggest that the combined intervention may help improve insulin sensitivity and reduce inflammation. However, MURF1 levels, which are related to muscle atrophy, showed no significant difference (P=0.24). In conclusion, in type 2 diabetic rats, an eight-week high-intensity interval training program with sodium nitrite supplementation does not affect MURF1 levels but does influence PI3K and TNF- α levels. This combination may hold potential for improving insulin sensitivity and reducing inflammation in type 2 diabetes patients, warranting further investigation and potential translation to human clinical trials.

Keywords: high-intensity interval training, sodium nitrate supplementation, type 2 diabetes, tumor necrosis factor-alpha, phosphatidylinositol-3-kinase, muscle RING-finger protein-1

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Authors: Maria Ashitko

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The Constitution of the Republic of Belarus is based on the principle of the unity of rights and obligations, including those of the child. The constitutional status of the child is aspecific system of constitutional elements established and guaranteed by the state through the current legislation and regulatory acts that ensure the special legal status of the child, his or her constitutional legal capacity, implementation of the principles of the constitutional and legal status of the child, constitutional rights of the child and their safeguards. Under the principles of the constitutional status of the child, we consider the general, normative, social-volitional rules of behavior established by the Constitution of the Republic of Belarus, laws and other regulatory acts that determine the content and social purpose of the legal status of the child. The constitutional and legal status of the child is characterized by the following special principles, which form a feature of the state legal system:1) Ensuring the interests of the child means providing for the child in accordance with his or her age, state of health, characteristics of development, life experience, family life, cultural traditions, ethnicity. 2) The principle of equal responsibility of both parents or their substitutes characterized by caring for the next generation as one of the priority tasks of the state and society, and all issues related to the implementation of children’s rights should be addressed at the constitutional level. 3) We would like to highlight such a special principle as the subprinciple of safeguards, which is the principle of ensuring the safety of the child. It is also worth noting that in legal studies, there is no relationship between safety and constitutional rights as general safeguards of individual rights and freedoms, and as special safeguards for the right to life. 4) The principle of justice is expressed by the fact that in modern conditions, the quality of life is determined not only by material wealth but also by the ability of the state to ensure the harmonization of social relations and social harmony on the basis of humanism and justice. Thus, the specificity of the constitutional status of the child is the age boundary between adulthood and minority; therefore, we propose to highlight the age characteristics of the child as an additional element. It is advisable to highlight such a special principle as the subprinciple of safeguards, which is the principle of ensuring the safety of the child.

Keywords: children’s rights, constitutional status, constitutional principles, constitutional rights

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Authors: Bikram Jung Kunwar

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Forests have central roles in climate change. The conservation of forests sequestrates the carbon from the atmosphere and also regulates the carbon cycle. However, knowingly and unknowingly the world’s forests were deforested and degraded annually at the rate of 0.18% and emitted the carbon to the atmosphere. The IPCC reports claimed that the deforestation and forest degradation accounts 1/5th of total carbon emission, which is second position after fossil fuels. Since 1.6 billion people depend on varying degree on forests for their daily livelihood, not all deforestation are undesirable. Therefore, to conserve the forests and find the livelihood opportunities for forest surrounding people is prerequisites to address the climate change problems especially in developing countries, and also a growing concern to the forestry sector researchers, planners and policy makers. The study examines the role of community based forest management in carbon mitigation and adaptation taking the examples of Nepal’s community forestry program. In the program, the government hands over a part of national forests to the local communities with sole forest management authorities. However, the government itself retained the ownership rights of forestland. Local communities organized through a local institution called Community Forest User Group (CFUG) managed the forests. They also formed an operational plan with technical prescriptions and a constitution with forest management rules and regulations. The implementation results showed that the CFUGs are not only found effective to organize the local people and construct a local institution to forest conservation and management activities, but also they are able to collect a community fund from the sale of forest products and carried out various community development activities. These development activities have decisive roles to improve the livelihood of forest surrounding people and eventually to address the climate change problems.

Keywords: climate change, community forestry, local institution, Nepal

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Authors: Maximo Cozzetti

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The aim is to evaluate the capability of the 'Siberian Husky' (FCI-Standard Nº 270) breed of the common dog (Canis lupus familiaris) to detect terminally-ill human patients undergoing palliative care. A total of 49 such patients that fulfill the 'National Scientific and Technical Research Council–Ethical Principles for the Behavior of the Scientific and Technical Investigator' policy, (mainly affected with Stage IV Hodgkin lymphoma or Stage IV Carcinoma, though various other terminal diseases were present) and 49 controls were enrolled. A total of 13 specimens of Siberian Huskies (Canis lupus familiaris FCI – Standard Nº 270) were selected. After a conditioning training regime in which the canines were rewarded when identifying terminally ill patients and excluding the control subjects, a double-blind experiment was conducted in which the canines were presented with a previously unknown patient through an olfactory-proof plexiglass window for 2-minute intervals. The test subjects correctly identified 89.80% of the humans as either ‘ill’ or ‘healthy’. It is important to note that both groups of humans were selected considering and preventing confounding and self-identifying factors such as age, ethnicity, clothing, posture, skin color, alopecia (chemotherapy-induced or otherwise), etc. The olfactory-proofing of the test area rules out the use of the sense of smell to detect distinctive drugs or bodily odors that may be associated with terminal diseases. Thus, the Siberian Husky breed of the common dog shows the visual capability to detect and identify terminally ill patients undergoing palliative care regardless of age, posture, and quantity of hair. Though the capability of the breed of dog to detect terminally-ill patients was observed thoroughly during the course of the experiments, the exact process by which the canines identify the test subjects remains unknown and further research is encouraged.

Keywords: Canis lupus familiaris, Siberian Husky, visual identification of terminall illness, FCI-Standard Nº270

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Authors: Angela Maria Fenu

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The aim of this study was to better characterize the nature of word association responses in people with aphasia. The participants selected for the experimental group were 4 individuals with mild Broca’s aphasia. The control group consisted of 51 cognitively intact age- and gender-matched individuals. The participants were asked to perform a word association task in which they had to say the first word they thought of when hearing each cue. The cue words (n= 16) were the translation in Italian of the set of English cue words of a published study. The participants from the experimental group were administered the word association test every two weeks for a period of two months when they received speech-language therapy A combination of analytical approaches to measure the data was used. To analyse different patterns of word association responses in both groups, the nature of the relationship between the cue and the response was examined: responses were divided into five categories of association. To investigate the similarity between aphasic and non-aphasic subjects, the stereotypy of responses was examined.While certain stimulus words (nouns, adjectives) elicited responses from Broca’s aphasics that tended to resemble those made by non-aphasic subjects; others (adverbs, verbs) showed the tendency to elicit responses different from the ones given by normal subjects. This suggests that some mechanisms underlying certain types of associations are degraded in aphasics individuals, while others display little evidence of disruption. The high number of paradigmatic associations given in response to a noun or an adjective might imply that the mechanisms, largely semantic, underlying paradigmatic associations are relatively preserved in Broca’s aphasia, but it might also mean that some words are more easily processed depending on their grammatical class (nouns, adjectives). The most significant variation was noticed when the grammatical class of the cue word was an adverb. Unlike the normal individuals, the experimental subjects gave the most idiosyncratic associations, which are often produced when the attempt to give a paradigmatic response fails. In turn, the failure to retrieve paradigmatic responses when the cue is an adverb might suggest that Broca’s aphasics are more sensitive to this grammatical class.The findings from this study suggest that, from research on word associations in people with aphasia, important data can arise concerning the specific lexical retrieval impairments that characterize the different types of aphasia and the various treatments that might positively influence the kinds of word association responses affected by language disruption.

Keywords: aphasia therapy, clinical linguistics, word-association behaviour, mental lexicon

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Authors: Shih-Chieh Liao, Cheng-Yan Shuai

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"Party game" is a game mode that enables players to maintain a good social and interactive experience. The common game modes include Teamwork, Team competitive, Independent competitive, Battle Royale. Party games are defined as a game with easy rules, easy to play, quickly spice up a party, and support four to six players. It also needs to let the player feel satisfied no matter victory or defeat. However, players may feel negative or angry when the game is imbalanced, especially when they play with teammates. Some players care about winning or losing, and they will blame it on the game mechanics. What is more serious is that the player will cause the argument, which is unnecessary. These behaviors that trigger quarrels and negative emotions often originate from the player's determination of the victory and the ratio of victory during the competition. In view of this, our research invited a group of subjects to the experiment, which is going to inspect player’s emotions by Electromyography (EMG) and Electrodermal Activity (EDA) when they are playing party games with others. When a player wins or loses, the negative and positive feeling will be recorded from the game beginning to the end. At the same time, physiologic and emotional reactions are also being recorded in each part of the game. The game will be designed as telling the interaction when players are in the quest of a party game. The experiment content includes the emotional changes affected by the physiological values of game victory and defeat between “player against friend” and “player against stranger.” Through this experiment, the balance between winners and losers lies in the basis of good game interaction and game interaction in the game and explore the emotional positive and negative effects caused by the result of the party game. The result shows that “player against friend” has a significant negative emotion and significant positive emotion at “player against stranger.” According to the result, the player's experience will be affected with winning rate or form when they play the party game. We suggest the developer balance the game with our experiment method to let players get a better experience.

Keywords: party games, biofeedback, emotional responses, user experience, game design

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Authors: Vera Wilden, Benno Hoffmeister, Markus Feldmann

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Glued laminated timber (glulam) is a preferred choice for long span girders, e.g., for gyms or storage halls. While the material provides sufficient strength to resist the bending moments, large spans lead to increased slenderness of such members and to a higher susceptibility to stability issues, in particular to lateral torsional buckling (LTB). Rules for the determination of the ultimate LTB resistance are provided by Eurocode 5. The verifications of the resistance may be performed using the so called equivalent member method or by means of theory 2nd order calculations (direct method), considering equivalent imperfections. Both methods have significant limitations concerning their applicability; the equivalent member method is limited to rather simple cases; the direct method is missing detailed provisions regarding imperfections and requirements for numerical modeling. In this paper, the results of a test series on slender glulam beams in three- and four-point bending are presented. The tests were performed in an innovative, newly developed testing rig, allowing for a very precise definition of loading and boundary conditions. The load was introduced by a hydraulic jack, which follows the lateral deformation of the beam by means of a servo-controller, coupled with the tested member and keeping the load direction vertically. The deformation-controlled tests allowed for the identification of the ultimate limit state (governed by elastic stability) and the corresponding deformations. Prior to the tests, the structural and geometrical imperfections were determined and used later in the numerical models. After the stability tests, the nearly undamaged members were tested again in pure bending until reaching the ultimate moment resistance of the cross-section. These results, accompanied by numerical studies, were compared to resistance values obtained using both methods according to Eurocode 5.

Keywords: experimental tests, glued laminated timber, lateral torsional buckling, numerical simulation

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Authors: Safaa H. Sindi, Michael Roe

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This project divides supply chain (SC) models into seven Eras, according to the evolution of the market’s needs throughout time. The five earliest Eras describe the emergence of supply chains, while the last two Eras are to be created. Research objectives: The aim is to generate the two latest Eras with their respective models that focus on the consumable goods. Era Six contains the Optimal Multidimensional Matrix (OMM) that incorporates most characteristics of the SC and allocates them into four quarters (Agile, Lean, Leagile, and Basic SC). This will help companies, especially (SMEs) plan their optimal SC route. Era Seven creates an Automated Multidimensional Model (AMM) which upgrades the matrix of Era six, as it accounts for all the supply chain factors (i.e. Offshoring, sourcing, risk) into an interactive system with Heuristic Learning that helps larger companies and industries to select the best SC model for their market. Methodologies: The data collection is based on a Fuzzy-Delphi study that analyses statements using Fuzzy Logic. The first round of Delphi study will contain statements (fuzzy rules) about the matrix of Era six. The second round of Delphi contains the feedback given from the first round and so on. Preliminary findings: both models are applicable, Matrix of Era six reduces the complexity of choosing the best SC model for SMEs by helping them identify the best strategy of Basic SC, Lean, Agile and Leagile SC; that’s tailored to their needs. The interactive heuristic learning in the AMM of Era seven will help mitigate error and aid large companies to identify and re-strategize the best SC model and distribution system for their market and commodity, hence increasing efficiency. Potential contributions to the literature: The problematic issue facing many companies is to decide which SC model or strategy to incorporate, due to the many models and definitions developed over the years. This research simplifies this by putting most definition in a template and most models in the Matrix of era six. This research is original as the division of SC into Eras, the Matrix of Era six (OMM) with Fuzzy-Delphi and Heuristic Learning in the AMM of Era seven provides a synergy of tools that were not combined before in the area of SC. Additionally the OMM of Era six is unique as it combines most characteristics of the SC, which is an original concept in itself.

Keywords: Leagile, automation, heuristic learning, supply chain models

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Authors: Marijana Ivanov, Roman Šubić

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The single rulebook together with the Single Supervisory Mechanism and the Single Resolution Mechanism - as two main pillars of the banking union, represent important steps towards completing the Economic and Monetary Union. It should provide a consistent application of common rules and administrative standards for supervision, recovery and resolution of banks – with the final aim that a former practice of the bail-out is replaced with the bail-in system through which bank failures will be resolved by their own funds, i.e. with minimal costs for taxpayers and real economy. It has to reduce the financial fragmentation recorded in the years of crisis as the result of divergent behaviors in risk premium, lending activities, and interest rates between the core and the periphery. In addition, it should strengthen the effectiveness of monetary transmission channels, in particular the credit channels and overflows of liquidity on the single interbank money market. However, contrary to all the positive expectations related to the future functioning of the banking union, low and unbalanced economic growth rates remain a challenge for the maintenance of financial stability in the euro area, and this problem cannot be resolved just by a single supervision. In many countries bank assets exceed their GDP by several times, and large banks are still a matter of concern because of their systemic importance for individual countries and the euro zone as a whole. The creation of the SSM and the SRM should increase transparency of the banking system in the euro area and restore confidence that have been disturbed during the depression. It would provide a new opportunity to strengthen economic and financial systems in the peripheral countries. On the other hand, there is a potential threat that future focus of the ECB, resolution mechanism and other relevant institutions will be extremely oriented to the large and significant banks (whereby one half of them operate in the core and most important euro area countries), while it is questionable to what extent the common resolution funds will be used for rescue of less important institutions.

Keywords: banking union, financial integration, single supervision mechanism (SSM)

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Authors: M. Vlahovic

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This paper presents a model of public finances, which combines three concepts: participatory budgeting, crowdfunding and blockchain technology. Participatory budgeting is defined as a process in which community members decide how to spend a part of community’s budget. Crowdfunding is a practice of funding a project by collecting small monetary contributions from a large number of people via an Internet platform. Blockchain technology is a distributed ledger that enables efficient and reliable transactions that are secure and transparent. In this hypothetical model, the government or authorities on local/regional level would set up a platform where they would propose public projects to citizens. Citizens would browse through projects and support or vote for those which they consider justified and necessary. In return, they would be entitled to a tax relief in the amount of their monetary contribution. Since the blockchain technology enables tracking of transactions, it can be used to mitigate corruption, money laundering and lack of transparency in public finances. Models of its application have already been created for e-voting, health records or land registries. By presenting a model of application of blockchain technology in public finances, this paper takes into consideration the potential of blockchain technology to disrupt governments and make processes more democratic, secure, transparent and efficient. The framework for this paper consists of multiple streams of research, including key concepts of direct democracy, public finance (especially the voluntary theory of public finance), information and communication technology, especially blockchain technology and crowdfunding. The framework defines rules of the game, basic conditions for the implementation of the model, benefits, potential problems and development perspectives. As an oversimplified map of a new form of public finances, the proposed model identifies primary factors, that influence the possibility of implementation of the model, and that could be tracked, measured and controlled in case of experimentation with the model.

Keywords: blockchain technology, distributed ledger, participatory budgeting, crowdfunding, direct democracy, internet platform, e-government, public finance

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Authors: J. Izan, E.I. Tengku Azmina, F. Pey Thing

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Sustainability has been introduced globally since the emerging of the advancement of technology and product development in various aspects. This concept is regarded highly, listed among the seventeenth elements in Sustainable Development Goals (SDG), especially by developed countries in any of their development plans and being considered in the development of the developing countries. It is such as the concept of sustainability can undeniably provide a medium where the cost used by energy consumption and pollution problems can be greatly reduced. In Malaysia, many rules and policies had been advocated to achieve sustainability; however, the practice and implementation as well the enforcement to ensure its implementation are still not great. University, as an educational institution, shall practice and implement sustainability concepts in as much aspect as possible as a positive example for a wider community. University Malaysia Terengganu (UMT) has already published a blueprint guide in 2015, aims to introduce and implement sustainable practice in the university, and solid waste is one of the key elements highlighted. This study was conducted to determine the status of solid waste management practice among the university community associated with several factors that facilitate the room for sustainable management, as drawn in the established blueprint document. The quantitative analysis was carried out via survey conducted online, acquired the questions on green campus concept and implementation in general and solid waste in particular. The results showed that community UMT showed a high level of awareness and knowledge on sustainable solid waste; however, low percentage in managing solid waste in a sustainable manner. Respondents suggested that stringent guidelines and the establishment of policy greatly help in the realization and enforcement of sustainable solid waste handling and management. Facilities such as waste collection centre with separation and segregation containers will motivate the community to practice 3Rs on a daily basis. This will eventually reduce the generation of waste need to be sent to landfill hence reduce the disposal cost. Prolong, and continuous campaign on sustainable solid waste management need to be carried out more frequently.

Keywords: management, solid waste, sustainability, university

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Authors: M. Vassou, A. Karasimos

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A primary concern in the field of Second Language Acquisition (SLA) research is to determine the innate mechanisms of second language learning and acquisition through the systematic study of a learner's interlanguage. Errors emerge while a learner attempts to communicate using the target-language and can be seen either as the observable linguistic product of the latent cognitive and language process of mental representations or as an indispensable learning mechanism. Therefore, the study of the learner’s erroneous forms may depict the various strategies and mechanisms that take place during the language acquisition process resulting in deviations from the target-language norms and difficulties in communication. Mapping the erroneous utterances of a late adult learner in the process of acquiring Greek as a second language constitutes one of the main aims of this study. For our research purposes, we created an error-tagged learner corpus composed of the participant’s written texts produced throughout a period of a 4- year instructed language acquisition. Error analysis and interlanguage theory constitute the methodological and theoretical framework, respectively. The research questions pertain to the learner's most frequent errors per linguistic category and per year as well as his choices concerning the Greek Article System. According to the quantitative analysis of the data, the most frequent errors are observed in the categories of the stress system and syntax, whereas a significant fluctuation and/or gradual reduction throughout the 4 years of instructed acquisition indicate the emergence of developmental stages. The findings with regard to the article usage bespeak fossilization of erroneous structures in certain contexts. In general, our results point towards the existence and further development of an established learner’s (inter-) language system governed not only by mother- tongue and target-language influences but also by the learner’s assumptions and set of rules as the result of a complex cognitive process. It is expected that this study will contribute not only to the knowledge in the field of Greek as a second language and SLA generally, but it will also provide an insight into the cognitive mechanisms and strategies developed by multilingual learners of late adulthood.

Keywords: Greek as a second language, error analysis, interlanguage, late adult learner

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Authors: Abhisek Dash

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This study had three neural networks, one for number segmentation, one for number detection and one for number recognition all of which are coupled to one another. All networks were trained on the MNIST dataset and were convolutional. It was assumed that the images had lighter background and darker foreground. The segmentation network took 28x28 images as input and had sixteen outputs. Segmentation training starts when a dark pixel is encountered. Taking a window(7x7) over that pixel as focus, the eight neighborhood of the focus was checked for further dark pixels. The segmentation network was then trained to move in those directions which had dark pixels. To this end the segmentation network had 16 outputs. They were arranged as “go east”, ”don’t go east ”, “go south east”, “don’t go south east”, “go south”, “don’t go south” and so on w.r.t focus window. The focus window was resized into a 28x28 image and the network was trained to consider those neighborhoods which had dark pixels. The neighborhoods which had dark pixels were pushed into a queue in a particular order. The neighborhoods were then popped one at a time stitched to the existing partial image of the number one at a time and trained on which neighborhoods to consider when the new partial image was presented. The above process was repeated until the image was fully covered by the 7x7 neighborhoods and there were no more uncovered black pixels. During testing the network scans and looks for the first dark pixel. From here on the network predicts which neighborhoods to consider and segments the image. After this step the group of neighborhoods are passed into the detection network. The detection network took 28x28 images as input and had two outputs denoting whether a number was detected or not. Since the ground truth of the bounds of a number was known during training the detection network outputted in favor of number not found until the bounds were not met and vice versa. The recognition network was a standard CNN that also took 28x28 images and had 10 outputs for recognition of numbers from 0 to 9. This network was activated only when the detection network votes in favor of number detected. The above methodology could segment connected and overlapping numbers. Additionally the recognition unit was only invoked when a number was detected which minimized false positives. It also eliminated the need for rules of thumb as segmentation is learned. The strategy can also be extended to other characters as well.

Keywords: convolutional neural networks, OCR, text detection, text segmentation

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Authors: Khan Md. Abdus Subhan, Rabeya Bushra

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Bangladesh has already seen significant growth in Islamic banking and finance, contributing to the rapid expansion of this sector in the global banking and finance industry. The objective of this study is to analyse the Islamic finance and banking industry's ability to contribute to sustainable development in Bangladesh. It aims to assess the current state, potential, and limitations of Islamic banking and finance in the country. Bangladesh has significant growth potential for Islamic banking and finance. However, addressing several challenges is imperative. These challenges include the absence of a well-developed infrastructure for Islamic banking and finance, a lack of a solid legal framework, limited attention from the central bank, the absence of an Islamic capital market, and a shortage of experts in Sharia law as well as public awareness. Bangladesh, a nation characterized by a primarily Muslim populace, has acknowledged the importance of Islamic finance and banking in promoting sustainable development. Islamic banking principles advocate for ethical practices, risk sharing, and the avoidance of interest-based transactions. This article examines the impact of Islamic finance and banking on promoting sustainable development in Bangladesh and emphasizes its capacity to tackle socio-economic difficulties. The Islamic banking sector, as a trailblazer in funding sustainable development, has the potential to play a significant role in facilitating the shift toward a circular economy. According to Shari'ah rules and the Sustainable Development Goals (SDGs), Islamic finance principles will help change the linear economy into a circular one. They will also provide a strong framework and a lot of funding sources. This study aims to offer crucial recommendations and techniques for the successful implementation of Islamic finance institutions in Bangladesh. The study will use quantitative research methodology, collecting data from secondary sources. This research offers a thorough understanding of the reasoning for the payment of Zakat and its socio-economic importance. Furthermore, the study provides significant insights that could assist Bangladeshi policymakers and governments in implementing Islamic financing systems.

Keywords: sustainable development, Islamic fintech, Islamic banking, Bangladesh

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Authors: Sarthak Kumar Jena, Chandra Sekhar Mishra, Prabina Rajib

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Purpose: This paper aims to derive undervaluation signal from the insiders trading of Indian companies where the ownership is complex and concentrated, investors protection is weak, and the insider rules and regulations are not stringent like developed country. This study examines the relationship between insider trading with short term and long term abnormal return. The study also examines the relationship between insider trading and the actual share repurchase by the firm. Methodology: A sample of 78 companies over the period 2008-2013 are analyzed in the study due to not availability of insider data in Indian context. For preliminary analysis T-test and Wilcoxon rank sum test is used to find the difference between the insider trading before and after the share repurchase announcement. Tobit model is used to find out whether insider trading influence shares repurchase decisions or not. Return on the basis of market model and buy hold are calculated in the previous year and the following year of share repurchase announcement. Findings: The paper finds that insider trading around share repurchase is more than control firms and there is positive and significant difference in insider buying between the previous year of share buyback announcement and the following year of buyback announcement. Insider buying before share repurchase announcement has a positive influence on share repurchase decisions. We find insider buying has a positive and significant relationship with announcement return, whereas insider selling has a negative significant relationship with announcement return. Actual share repurchase and program completion also depend on insider trading before share repurchase. Research limitation: The study is constrained by the small sample size, so the results should be viewed by keeping this limitation in mind. Originality: The paper is to our best knowledge the first study based on Indian context to extend the insider trading literature to share repurchase event and examine insider trading to find out undervaluation signal associated with insider buying.

Keywords: insider trading, buyback, open market share repurchase, signalling

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Authors: Pavel Borodkin, Nikolay Khrennikov, Azamat Gazetdinov

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The problem of ensuring of VVER type reactor equipment integrity is now most actual in connection with justification of safety of the NPP Units and extension of their service life to 60 years and more. First of all, it concerns old units with VVER-440 and VVER-1000. The justification of the VVER equipment integrity depends on the reliability of estimation of the degree of the equipment damage. One of the mandatory requirements, providing the reliability of such estimation, and also evaluation of VVER equipment lifetime, is the monitoring of equipment radiation loading parameters. In this connection, there is a problem of justification of such normative parameters, used for an estimation of the pressure vessel metal embrittlement, as the fluence and fluence rate (FR) of fast neutrons above 0.5 MeV. From the point of view of regulatory practice, a comparison of displacement per atom (DPA) and fast neutron fluence (FNF) above 0.5 MeV has a practical concern. In accordance with the Russian regulatory rules, neutron fluence F(E > 0.5 MeV) is a radiation exposure parameter used in steel embrittlement prediction under neutron irradiation. However, the DPA parameter is a more physically legitimate quantity of neutron damage of Fe based materials. If DPA distribution in reactor structures is more conservative as neutron fluence, this case should attract the attention of the regulatory authority. The purpose of this work was to show what radiation load parameters (fluence, DPA) on all VVER equipment should be under control, and give the reasonable estimations of such parameters in the volume of all equipment. The second task is to give the conservative estimation of each parameter including its uncertainty. Results of recently received investigations allow to test the conservatism of calculational predictions, and, as it has been shown in the paper, combination of ex-vessel measured data with calculated ones allows to assess unpredicted uncertainties which are results of specific unique features of individual equipment for VVER reactor. Some results of calculational-experimental investigations are presented in this paper.

Keywords: equipment integrity, fluence, displacement per atom, nuclear power plant, neutron activation measurements, neutron transport calculations

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Authors: Dahiru Jafaru Usman

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Nigerian courts have been sanctioned by a plethora of authorities to always employ the literal rule in interpreting statutes where the language of the statute is clear and unambiguous. This cardinal rule of interpretation appears not to be employed on Shari'ah issues in Nigeria. This is more pronounced in the interpretation of the jurisdiction of the Shari'ah Court of Appeal (hereinafter the court). The paper doctrinally assesses the judicial attitude of Nigerian appellate courts towards the construction of Section 277 of the 1999 Constitution as amended and other relevant statutory enactments by the State Houses of Assembly. The paper argues that a careful examination of the wordings of the constitution on the jurisdiction of the court literally reveals the intention of the constitutional drafters empowering the National Assembly and States' House of Assemblies to add to the itemised jurisdictional areas of the court other matters not mentioned. The paper found that the appellate courts failed in their construction of the constitutional provisions to accord the words and phrases used in the establishment, jurisdiction, and quorum sections of the court their ordinary and grammatical meaning. This results in consistent limitation of the jurisdiction of the court to matters of Islamic personal law. This remains so even when Decree No. 26 of 1986 was in force suspending and amending the provisions of the 1979 Constitution deleting the word 'personal' in the suspended Nigerian Constitutions. In order not to render section 277 futile, the paper recommends that appellate courts in Nigeria should as required by rules of statutory interpretation adopt literal and ordinary grammatical meaning in interpreting constitutional provisions on the jurisdiction of the court. It is further recommended that appellate courts must interpret the provisions of the 1999 constitution in a manner not to frustrate the several decades' yearnings of the Muslims for a court that would hear all their appellate criminal and civil matters on the path of Shari'ah from the lowest court to the highest. This is a duty the Nigerian Supreme Court placed on their shoulders.

Keywords: interpretation of statutes, jurisdiction, literal rule, Nigeria, Shari'ah Court of Appeal, 1999 Constitution

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Authors: Oscar E. Cariceo, Claudia V. Casal

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Machine learning offers a set of techniques to promote social work interventions and can lead to support decisions of practitioners in order to predict new behaviors based on data produced by the organizations, services agencies, users, clients or individuals. Machine learning techniques include a set of generalizable algorithms that are data-driven, which means that rules and solutions are derived by examining data, based on the patterns that are present within any data set. In other words, the goal of machine learning is teaching computers through 'examples', by training data to test specifics hypothesis and predict what would be a certain outcome, based on a current scenario and improve that experience. Machine learning can be classified into two general categories depending on the nature of the problem that this technique needs to tackle. First, supervised learning involves a dataset that is already known in terms of their output. Supervising learning problems are categorized, into regression problems, which involve a prediction from quantitative variables, using a continuous function; and classification problems, which seek predict results from discrete qualitative variables. For social work research, machine learning generates predictions as a key element to improving social interventions on complex social issues by providing better inference from data and establishing more precise estimated effects, for example in services that seek to improve their outcomes. This paper exposes the results of a classification algorithm to predict cyberbullying among adolescents. Data were retrieved from the National Polyvictimization Survey conducted by the government of Chile in 2017. A logistic regression model was created to predict if an adolescent would experience cyberbullying based on the interaction and behavior of gender, age, grade, type of school, and self-esteem sentiments. The model can predict with an accuracy of 59.8% if an adolescent will suffer cyberbullying. These results can help to promote programs to avoid cyberbullying at schools and improve evidence based practice.

Keywords: cyberbullying, evidence based practice, machine learning, social work research

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Authors: James Barmby

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Canada’s westernmost provinces of British Columbia and Alberta are similar in many respects as they are both reliant on volatile natural resources for major portions of their economies. The two provinces have banded together to develop mutually beneficial trade, investment and labour market mobility rules, but in terms of developing systems of higher education, the two provinces are attempting to align higher education programs to economic development objectives by means that are quite different. In British Columbia, the recently announced initiative, B.C’s Skills for Jobs Blueprint will “make sure education and training programs are aligned with the demands of the labor market.” Meanwhile in Alberta, the province’s institutions of higher education are enjoying the tenth year of their membership in the Campus Alberta Quality Council, which makes recommendations to government on issues related to post-secondary education, including the approval of new programs. In B.C., public institutions of higher education are encouraged to comply with government objectives, and are rewarded with targeted funds for their efforts. In Alberta, the institutions as a system tell the government what programs they want to offer and government can agree or not agree to fund these programs through a ministerial approval process. In comparing the two higher education systems, the question emerges as to which one is more beneficial to the province: the one where change is directed primarily by financial incentives to achieve economic objectives or the one that makes recommendations to the government for changes in programs to achieve institutional objectives? How is institutional autonomy affected in each strategy? Does institutional autonomy matter anymore? In recent years, much has been written in regard to academic freedom, but less about institutional autonomy, which is seen by many as essential to protecting academic freedom. However, while institutional autonomy means freedom from government control, it does not necessarily mean self-government. In this study, a comparison of the two higher education systems is made using recent government policy initiatives in both provinces, and responses to those actions by the higher education institutions. The findings indicate that the economic needs in both provinces take precedence over issues of institutional autonomy.

Keywords: alberta, British Columbia, institutional autonomy, funding

Procedia PDF Downloads 701

Authors: Rima A. Ajlouni

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The discovery of quasi-periodic structures in material science is revealing an exciting new class of symmetries, which has never been explored before. Due to their unique structural and visual properties, these symmetries are drawing interest from many scientific and design disciplines. Especially, in art and architecture, these symmetries can provide a rich source of geometry for exploring new patterns, forms, systems, and structures. However, the structural systems of these complicated symmetries are still posing a perplexing challenge. While much of their local order has been explored, the global governing system is still unresolved. Understanding their unique global long-range order is essential to their generation and application. The recent discovery of dodecagonal quasi-periodic patterns in historical Islamic architecture is generating a renewed interest into understanding the mathematical principles of traditional Islamic geometry. Astonishingly, many centuries before its description in the modern science, ancient artists, by using the most primitive tools (a compass and a straight edge), were able to construct patterns with quasi-periodic formations. These ancient patterns can be found all over the ancient Islamic world, many of which exhibit formations with 5, 8, 10 and 12 quasi-periodic symmetries. Based on the examination of these historical patterns and derived from the generating principles of Islamic geometry, a global multi-level structural model is presented that is able to describe the global long-range order of dodecagonal quasi-periodic formations in Islamic Architecture. Furthermore, this method is used to construct new quasi-periodic tiling systems as well as generating their deflation and inflation rules. This method can be used as a general guiding principle for constructing infinite patches of dodecagon-based quasi-periodic formations, without the need for local strategies (tiling, matching, grid, substitution, etc.) or complicated mathematics; providing an easy tool for scientists, mathematicians, teachers, designers and artists, to generate and study a wide range of dodecagonal quasi-periodic formations.

Keywords: dodecagonal, Islamic architecture, long-range order, quasi-periodi

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Authors: Calogero Lo Destro

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Numerous nations around the world are facing exceptional challenges in employing measures to stop the spread of COVID-19. Following the recommendations of the World Health Organization, a series of preventive measures have been adopted. However, individuals must comply with these rules and recommendations in order to make these measures effective. While COVID-19 was climaxing, it seemed of crucial importance to analyze which psychosocial factors contribute to the acceptance of such preventive behavior, thus favoring the management of COVID-19 worldwide health crisis. In particular, the identification of aspects related to obstacles and facilitation of adherence to social distancing has been considered crucial in the containment of the virus spread. Since the virus was firstly detected in China, Asian people could be considered a relevant outgroup targeted for exclusion. We also hypothesized social distance could be influenced by characteristics of the target, such as smiling or coughing. 260 participants participated in this research on a voluntary basis. They filled a survey designed to explore a series of COVID-19 measures (such as exposure to virus and fear of infection). We also assessed participants state and trait anxiety. The dependent variable was social distance, based on a measure of seating distance designed ad hoc for the present work. Our hypothesis that participants could report greater distance in response to Asian people was not confirmed. On the other hand, significantly lower distance in response to smiling compared to coughing targets was reported. Adopting a regression analysis model, we found that participants' social distance, in response to both coughing and smiling targets, was predicted by fear of infection and by the perception COVID-19 could become a pandemic. Social distance in response to the coughing target was also significantly and positively predicted by age and state anxiety. In summary, the present work has sought to identify a set of psychological variables, which may still be predictive of social distancing.

Keywords: COVID-19, social distancing, health, preventive behaviors, risk of infection

Procedia PDF Downloads 124

Authors: Urbánek Jiří J., Krahulec Josef, Urbánek Jiří F., Johanidesová Jitka

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These Computational assistance for the research and modelling of critical infrastructure subjects continuity deal with this paper. It enables us the using of prevailing operation system MS Office (SmartArt...) for mathematical models, using DYVELOP (Dynamic Vector Logistics of Processes) method. It serves for crisis situations investigation and modelling within the organizations of critical infrastructure. In the first part of the paper, it will be introduced entities, operators and actors of DYVELOP method. It uses just three operators of Boolean algebra and four types of the entities: the Environments, the Process Systems, the Cases and the Controlling. The Process Systems (PrS) have five “brothers”: Management PrS, Transformation PrS, Logistic PrS, Event PrS and Operation PrS. The Cases have three “sisters”: Process Cell Case, Use Case and Activity Case. They all need for the controlling of their functions special Ctrl actors, except ENV – it can do without Ctrl. Model´s maps are named the Blazons and they are able mathematically - graphically express the relationships among entities, actors and processes. In the second part of this paper, the rich blazons of DYVELOP method will be used for the discovering and modelling of the cycling cases and their phases. The blazons need live PowerPoint presentation for better comprehension of this paper mission. The crisis management of energetic crisis infrastructure organization is obliged to use the cycles for successful coping of crisis situations. Several times cycling of these cases is a necessary condition for the encompassment of the both the emergency event and the mitigation of organization´s damages. Uninterrupted and continuous cycling process bring for crisis management fruitfulness and it is a good indicator and controlling actor of organizational continuity and its sustainable development advanced possibilities. The research reliable rules are derived for the safety and reliable continuity of energetic critical infrastructure organization in the crisis situation.

Keywords: blazons, computational assistance, DYVELOP method, critical infrastructure

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Authors: Reza Safdari, Goli Arji, Robab Abdolkhani Maryam zahmatkeshan

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Background and purpose: Cardiovascular diseases are among the most common diseases in all societies. The most important step in minimizing myocardial infarction and its complications is to minimize its risk factors. The amount of medical data is increasingly growing. Medical data mining has a great potential for transforming these data into information. Using data mining techniques to generate predictive models for identifying those at risk for reducing the effects of the disease is very helpful. The present study aimed to collect data related to risk factors of heart infarction from patients’ medical record and developed predicting models using data mining algorithm. Methods: The present work was an analytical study conducted on a database containing 350 records. Data were related to patients admitted to Shahid Rajaei specialized cardiovascular hospital, Iran, in 2011. Data were collected using a four-sectioned data collection form. Data analysis was performed using SPSS and Clementine version 12. Seven predictive algorithms and one algorithm-based model for predicting association rules were applied to the data. Accuracy, precision, sensitivity, specificity, as well as positive and negative predictive values were determined and the final model was obtained. Results: five parameters, including hypertension, DLP, tobacco smoking, diabetes, and A+ blood group, were the most critical risk factors of myocardial infarction. Among the models, the neural network model was found to have the highest sensitivity, indicating its ability to successfully diagnose the disease. Conclusion: Risk prediction models have great potentials in facilitating the management of a patient with a specific disease. Therefore, health interventions or change in their life style can be conducted based on these models for improving the health conditions of the individuals at risk.

Keywords: decision trees, neural network, myocardial infarction, Data Mining

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Authors: Jae-Hyeon Kim, Michael Lee

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Intrinsic and acquired resistance limits the therapeutic benefits of oncogenic BRAF inhibitors in melanoma. MicroRNAs (miRNA) regulate the expression of target mRNAs by repressing their translation. Thus, we investigated miRNA expression patterns in melanoma cell lines to identify candidate biomarkers for acquired resistance to BRAF inhibitor. Here, we used Affymetrix miRNA V3.0 microarray profiling platform to compare miRNA expression levels in three cell lines containing BRAF inhibitor-sensitive A375P BRAF V600E cells, their BRAF inhibitor-resistant counterparts (A375P/Mdr), and SK-MEL-2 BRAF-WT cells with intrinsic resistance to BRAF inhibitor. The miRNAs with at least a two-fold change in expression between BRAF inhibitor-sensitive and –resistant cell lines, were identified as differentially expressed. Averaged intensity measurements identified 138 and 217 miRNAs that were differentially expressed by 2 fold or more between: 1) A375P and A375P/Mdr; 2) A375P and SK-MEL-2, respectively. The hierarchical clustering revealed differences in miRNA expression profiles between BRAF inhibitor-sensitive and –resistant cell lines for miRNAs involved in intrinsic and acquired resistance to BRAF inhibitor. In particular, 43 miRNAs were identified whose expression was consistently altered in two BRAF inhibitor-resistant cell lines, regardless of intrinsic and acquired resistance. Twenty five miRNAs were consistently upregulated and 18 downregulated more than 2-fold. Although some discrepancies were detected when miRNA microarray data were compared with qPCR-measured expression levels, qRT-PCR for five miRNAs (miR-3617, miR-92a1, miR-1246, miR-1936-3p, and miR-17-3p) results showed excellent agreement with microarray experiments. To further investigate cellular functions of miRNAs, we examined effects on cell proliferation. Synthetic oligonucleotide miRNA mimics were transfected into three cell lines, and proliferation was quantified using a colorimetric assay. Of the 5 miRNAs tested, only miR-1246 altered cell proliferation of A375P/Mdr cells. The transfection of miR-1246 mimic strongly conferred PLX-4720 resistance to A375P/Mdr cells, implying that miR-1246 upregulation confers acquired resistance to BRAF inhibition. We also found that PLX-4720 caused much greater G2/M arrest in A375P/Mdr cells transfected with miR-1246mimic than that seen in scrambled RNA-transfected cells. Additionally, miR-1246 mimic partially caused a resistance to autophagy induction by PLX-4720. These results indicate that autophagy does play an essential death-promoting role inPLX-4720-induced cell death. Taken together, these results suggest that miRNA expression profiling in melanoma cells can provide valuable information for a network of BRAF inhibitor resistance-associated miRNAs.

Keywords: microRNA, BRAF inhibitor, drug resistance, autophagy

Procedia PDF Downloads 325