Search results for: visual expression

Authors: Marija Vitanovа, Igor Gjorgjiev, Viktor Hristovski, Vlado Micov

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Evaluation of stability is very important in the process of definition of optimal structural measures for maintenance of bridge structures and their strengthening. To define optimal measures for their repair and strengthening, it is necessary to evaluate their static and seismic stability. Presented in this paper are methodologies for evaluation of the seismic stability of existing reinforced concrete bridges designed without consideration of seismic effects and checking of structural justification of newly designed bridge structures. All bridges are located in the territory of the Republic of North Macedonia. A total of 26 existing bridges of different structural systems have been analyzed. Visual inspection has been carried out for all bridges, along with the definition of three main damage categories according to which structures have been categorized in respect to the need for their repair and strengthening. Investigations involving testing the quality of the built-in materials have been carried out, and dynamic tests pointing to the dynamic characteristics of the structures have been conducted by use of non-destructive methods of ambient vibration measurements. The conclusions drawn from the performed measurements and tests have been used for the development of accurate mathematical models that have been analyzed for static and dynamic loads. Based on the geometrical characteristics of the cross-sections and the physical characteristics of the built-in materials, interaction diagrams have been constructed. These diagrams along with the obtained section quantities under seismic effects, have been used to obtain the bearing capacity of the cross-sections. The results obtained from the conducted analyses point to the need for the repair of certain structural parts of the bridge structures. They indicate that the stability of the superstructure elements is not critical during a seismic effect, unlike the elements of the sub-structure, whose strengthening is necessary.

Keywords: existing bridges, newly designed bridges, reinforced concrete bridges, stability assessment

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Authors: Omran M. Kenshel, Alan J. O'Connor

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Estimating the service life of Reinforced Concrete (RC) bridge structures located in corrosive marine environments of a great importance to their owners/engineers. Traditionally, bridge owners/engineers relied more on subjective engineering judgment, e.g. visual inspection, in their estimation approach. However, because financial resources are often limited, rational calculation methods of estimation are needed to aid in making reliable and more accurate predictions for the service life of RC structures. This is in order to direct funds to bridges found to be the most critical. Criticality of the structure can be considered either form the Structural Capacity (i.e. Ultimate Limit State) or from Serviceability viewpoint whichever is adopted. This paper considers the service life of the structure only from the Structural Capacity viewpoint. Considering the great variability associated with the parameters involved in the estimation process, the probabilistic approach is most suited. The probabilistic modelling adopted here used Monte Carlo simulation technique to estimate the Reliability (i.e. Probability of Failure) of the structure under consideration. In this paper the authors used their own experimental data for the Correlation Length (CL) for the most important deterioration parameters. The CL is a parameter of the Correlation Function (CF) by which the spatial fluctuation of a certain deterioration parameter is described. The CL data used here were produced by analyzing 45 chloride profiles obtained from a 30 years old RC bridge located in a marine environment. The service life of the structure were predicted in terms of the load carrying capacity of an RC bridge beam girder. The analysis showed that the influence of SV is only evident if the reliability of the structure is governed by the Flexure failure rather than by the Shear failure.

Keywords: Chloride-induced corrosion, Monte-Carlo simulation, reinforced concrete, spatial variability

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Authors: Leticia Leandro Rade, Amanda Silva de Sousa, Suman Das, Wesley Generoso, Mayara Chagas Ávila, Plinio Salmazo Vieira, Antonio Bonomi, Gabriela Persinoti, Mario Tyago Murakami, Thomas Michael Makris, Leticia Maria Zanphorlin

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Alkenes have an economic appeal, especially in the biofuels field, since they are precursors for drop-in biofuels production, which have similar chemical and physical properties to the conventional fossil fuels, with no oxygen in their composition. After the discovery of the first P450 CYP152 OleTJE in 2011, reported with its unique property of decarboxylating fatty acids (FA), by using hydrogen peroxide as a cofactor and producing 1-alkenes as the main product, the scientific and technological interest in this family of enzymes vastly increased. In this context, the present work presents a new decarboxylase (OleTRN) with low similarity with OleTJE (32%), its biochemical characterization, and structure elucidation. As main results, OleTRN presented a high yield of expression and purity, optimum reaction conditions at 35 °C and pH from 6.5 to 8.0, and higher specificity for oleic acid. Besides that, structure-guided mutations were performed and according to the functional characterizations, it was observed that some mutations presented different specificity and chemoselectivity by varying the chain-length of FA substrates from 12 to 20 carbons. These results are extremely interesting from a biotechnological perspective as those characteristics could diversify the applications and contribute to designing better cytochrome P450 decarboxylases. Considering that peroxygenases have the potential activity of decarboxylating and hydroxylating fatty acids and that the elucidation of the intriguing mechanistic involved in the decarboxylation preferential from OleTJE is still a challenge, the elucidation of OleTRN structure and the functional characterizations of OleTRN and its mutants contribute to new information about CYP152. Besides that, the work also contributed to the discovery of a new decarboxylase with a different selectivity profile from OleTJE, which allows a wide range of applications.

Keywords: P450, decarboxylases, alkenes, biofuels

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Authors: Ritu Karwasra, Surender Singh

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Inflammation is an important physiological response of the body’s self-defense system that helps in eliminating and protecting organism from harmful stimuli and in tissue repair. It is a highly regulated protective response which helps in eliminating the initial cause of cell injury, and initiates the process of repair. The present study was designed to evaluate the ameliorative effect of pomegranate rind extract on pain and inflammation. Hydroalcoholic standardized rind extract of pomegranate at doses 50, 100 and 200 mg/kg and indomethacin (3 mg/kg) was tested against eddy’s hot plate induced thermal algesia, carrageenan (acute inflammation) and Complete Freund’s Adjuvant (chronic inflammation) induced models in Wistar rats. Parameters analyzed were inhibition of paw edema, measurement of joint diameter, levels of GSH, TBARS, SOD, TNF-α, radiographic imaging, tissue histology and synovial expression of pro-inflammatory cytokine receptor (TNF-R1). Radiological and light microscopical analysis were carried out to find out the bone damage in CFA-induced chronic inflammatory model. Findings of the present study revealed that pomegranate rind extract at a dose of 200 mg/kg caused a significant (p<0.05) reduction in paw swelling in both the inflammatory models. Nociceptive threshold was also significantly (p<0.05) improved. Immunohistochemical analysis of TNF-R1 in CFA-induced group showed elevated level, whereas reduction in level of TNF-R1 was observed in pomegranate (200 mg/kg). Henceforth, we might say that pomegranate produced a dose-dependent reduction in inflammation and pain along with the reduction in levels of oxidative stress markers and tissue histology, and the effect was found to be comparable to that of indomethacin. Thus, it can be concluded that pomegranate is a potential therapeutic target in the pathogenesis of inflammation and pain, and punicalagin is the major constituents found in rind extract might be responsible for the activity.

Keywords: carrageenan, inflammation, nociceptive-threshold, pomegranate, histopathology

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Authors: Maryam Parsian, Pelin Mutlu, Ufuk Gunduz

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Two-dimensional cell culture affords simplicity and low cost, but it has serious limitations; lacking cell-cell and cell-matrix interactions that are present in tissues. Cancer cells grown in 3D culture systems have distinct phenotypes of adhesion, growth, migration, invasion as well as profiles of gene and protein expression. These interactions cause the 3D-cultured cells to acquire morphological and cellular characteristics relevant to in vivo tumors. Palbociclib is a chemotherapeutic agent for the treatment of ER-positive and HER-negative metastatic breast cancer. Poly-amidoamine (PAMAM) dendrimer is a well-defined, special three-dimensional structure and has a multivalent surface and internal cavities that can play an essential role in drug delivery systems. In this study, palbociclib is loaded onto the magnetic PAMAM dendrimer. Hanging droplet method was used in order to form 3D spheroids. The possible toxic effects of both free drug and drug loaded nanoparticles were evaluated in 2D and 3D MCF-7, MD-MB-231 and SKBR-3 breast cancer cell culture models by performing MTT cell viability and Alamar Blue assays. MTT analysis was performed with six different doses from 1000 µg/ml to 25 µg/ml. Drug unloaded PAMAM dendrimer did not demonstrate significant toxicity on all breast cancer cell lines. The results showed that 3D spheroids are clearly less sensitive than 2D cell cultures to free palbociclib. Also, palbociclib loaded PAMAM dendrimers showed more toxic effect than free palbociclib in all cell lines at 2D and 3D cultures. The results suggest that the traditional cell culture method (2D) is insufficient for mimicking the actual tumor tissue. The response of the cancer cells to anticancer drugs is different in the 2D and 3D culture conditions. This study showed that breast cancer cells are more resistant to free palbociclib in 3D cultures than in 2D cultures. However, nanoparticle loaded drugs can be more cytotoxic when compared to free drug.

Keywords: 2D and 3D cell culture, breast cancer, palbociclibe, PAMAM magnetic nanoparticles

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Authors: Graham Hancox, Saydia Razak, Sue Hignett, Jo Barnes, Jyri Silmari, Florian Kading

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In the event of a Chemical, Biological, Radiological and Nuclear (CBRN) incident rapidly gaining, situational awareness is of paramount importance and advanced technologies have an important role to play in improving detection, identification, monitoring (DIM) and patient tracking. Understanding how these advanced technologies can fit into current response systems is essential to ensure they are optimally designed, usable and meet end-users’ needs. For this reason, Human Factors (Ergonomics) methods have been used within an EU Horizon 2020 project (TOXI-Triage) to firstly describe (map) the hierarchical structure in a CBRN response with adapted Accident Map (AcciMap) methodology. Secondly, Hierarchical Task Analysis (HTA) has been used to describe and review the sequence of steps (sub-tasks) in a CBRN scenario response as a task system. HTA methodology was then used to map one advanced technology, ‘Tag and Trace’, which tags an element (people, sample and equipment) with a Near Field Communication (NFC) chip in the Hot Zone to allow tracing of (monitoring), for example casualty progress through the response. This HTA mapping of the Tag and Trace system showed how the provider envisaged the technology being used, allowing for review and fit with the current CBRN response systems. These methodologies have been found to be very effective in promoting and supporting a dialogue between end-users and technology providers. The Human Factors methods have given clear diagrammatic (visual) representations of how providers see their technology being used and how end users would actually use it in the field; allowing for a more user centered approach to the design process. For CBRN events usability is critical as sub-optimum design of technology could add to a responders’ workload in what is already a chaotic, ambiguous and safety critical environment.

Keywords: AcciMap, CBRN, ergonomics, hierarchical task analysis, human factors

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Authors: Ada Yurman

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Using the case of Israeli Atomic Spy Mordechai Vanunu as an example, this study sought to examine social response to political deviance whereby social response can be mobilized in order to achieve social control. Mordechai Vanunu, a junior technician in the Dimona Atomic Research Center, played a normative role in the militaristic discourse while working in the “holy shrine” of the Israeli defense system for many years. At a certain stage, however, Vanunu decided to detach himself from this collective and launched an assault on this top-secret circle. Israeli society in general and the security establishment in particular found this attack intolerable and unforgivable. They presented Vanunu as a ticking time bomb, delegitimized him and portrayed him as “other”. In addition, Israeli enforcement authorities imposed myriad prohibitions and sanctions on Vanunu even after his release from prison – “as will be done to he who desecrates holiness.” Social response to Vanunu at the time of his capture and trial was studied by conducting a content analysis of six contemporary daily newspapers. The analysis focused on use of language and forms of expression. In contrast with traditional content analysis methodology, this study did not just look at frequency of expressions of ideas and terms in the text and covert content; rather, the text was analyzed as a structural whole, and included examination of style, tone and unusual use of imagery, and more, in order to uncover hidden messages within the text. The social response to this case was extraordinarily intense, not only because in this case of political deviance, involving espionage and treason, Vanunu’s actions comprised a real potential threat to the country, but also because of the threat his behavior posed to the symbolic universe of society. Therefore, the response to this instance of political deviance can be seen as being part of a mechanism of social control aiming to protect world view of society as a whole, as well as to punish the criminal.

Keywords: militarism, political deviance, social construction, social control

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Authors: Lubna Azmi, Ila Shukla, Shyam Sundar Gupta, Padam Kant, Ch. V. Rao

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Gastric ulcer is a major global health threat, and it is the leading cause of stomach cancer death worldwide. Helicobacter pylori bacteriumis the most important etiologic factor for gastric ulcer. This infection is highly pervasive in South Asian developing countries, especially in India, Nepal, Srilanka etc. due to diversification in geographic area. Pathophysiology of gastric mucosal damage associated with non-invasive bacterium has not justified in detail, but it leads to change in histopathology, immunochemistry of the gastric and duodenal reason of host. The mechanism responsible for bacteria tissue tropism and mucosal damage in stomach variance during the disease is not clearly described and understood scientifically in treatment and control of pathogenic organisms. Polyphenols are secondary metabolites of plants and are generally involved in defense against aggression by pathogens. 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxychromen-4-one and 1-hydroxy-5,7-dimethoxy-2-naphthalene-carboxaldehyde are polyphenolic compound obtained from popular Indian medicinal plants ghavpatta (ArgeriaspeciosaLinn.f) andBael (Aeglemarmelos) have long been used in traditional Ayurvedic Indian medicine for various diseases. They have promising effects on ulcer, as detailed investigation has made in our laboratory. Therefore, the aim of present study is to explore membrane –dependent morphogenesis of H. pylori and associated apoptosis-mediated cell death. Based on this we analyzed immune gene expression in stomach of experimental animals with H. pylori, using quantitative reverse transcription polymerase chain reaction(q RT-PCR). This revealed rapid induction of prostaglandin, interferon I (INF-I), interferon II (INF-II) and INF-I associated genes in the infected animal. Ultrastructural changes associated with H. pylori will be taken for advanced studies. This investigation shows that the biomarkers eradicate H. pylori bacterium caused gastric ulcer which is a major risk factor for gastric cancer.

Keywords: gastric ulcer, Helicobacter pylori, immunochemistry, polyphenols

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Authors: Hyeon Sop Baek

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This paper will briefly investigate Jeong Do-jeon’s political philosophy. Jeong Do-jeon was a Korean Confucian philosopher and politician during the turbulent 14th Century who revolted against the old order, founded Joseon Dynasty, and significantly impacted the development of Korean culture. Jeong’s vision of an ideal state involved a polity that has its roots in the people -that is, an ideal government prioritizes caring for the welfare of the people, respecting and attending to the diverse opinions and concerns of the people, and relies on the genuine, voluntary support of the people. With the neo-Confucian worldview in mind -that every human being has the equal potential to become a moral person- Jeong sought to create a world suitable for everybody to contribute to the decision-making procedure and be able to realize their potential fully. This paper will first examine his works and present a quick overview of his vision of the ideal government. Then, it will examine the Confucian virtues of ren (仁) and yi (義) and how they formulate the basis of his philosophy, and then discuss the central features of his vision of government: popular mandate, equity of wealth, promoting freedom of expression and political participation, and elevating caring disposition as the paramount quality of the political leaders. Furthermore, this paper aims to analyze the element of care inherent within his political philosophy, namely his view on the dynamics of power, nurturing the people, and noncoercive justice. Finally, a discussion on why his philosophy is still relevant in the contemporary context will be provided. Jeong’s view aimed at building a sustainable model of government, by proposing that the people should be the foundation of a state and that they need to be carefully nurtured so they can realize their inborn potential and continue to contribute to the sustenance of the world, is the focal point of Jeong’s philosophy. Just as he sought to rebuild his world following the turmoils of the 14th Century, his philosophy still has a substantial implication on how we should strive to rebuild our society today.

Keywords: Korea, Confucianism, Jeong Do-jeon, Joseon, Korean philosophy, political philosophy

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Authors: Shanakr Bhattarai, V. S. Tiwari, Barak Akabayov

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The plummeting number of infections and death is due to the development of drug-resistant bacteria. In addition, the number of approved antibiotic drugs by the Food and Drug Administration (FDA) is insufficient. Therefore, developing new drugs and finding novel targets for central metabolic pathways in bacteria is urgently needed. One of the promising targets is DNA replication machinery which consists of many essential proteins and enzymes. DnaG primase is an essential enzyme and a central part of the DNA replication machinery. DnaG primase synthesizes short RNA primers that initiate the Okazaki fragments by the lagging strand DNA polymerase. Therefore, it is reasonable to assume that inhibition of primase activity will stall DNA replication and prevent bacterial proliferation. We did the expression and purification of eight different bacterial DnaGs (Mycobacterium tuberculosis(Mtb), Bacillus anthracis (Ba), Mycobacterium smegmatis (Msmeg), Francisella tularencis (Ft), Vibrio cholerae (Vc) and Yersinia pestis (Yp), Staphylococcus aureus(Saureus), Escherichia coli(Ecoli)) followed by the radioactive activity assay. After obtaining the pure and active protein DnaG, we synthesized the inhibitors for them. The inhibitors were divided into five different groups, each containing five molecules, and the cocktail inhibition assay was performed against each DnaGs. The groups of molecules inhibiting the DnaGs were further tested with individual molecules belonging to inhibiting groups. Each molecule showing inhibition was titrated against the corresponding DnaGs to find IC50. We got a molecule(VS167) that acted as broad inhibitors, inhibiting all eight DnaGs. Molecules VS180 and VS186 inhibited seven DnaGs (except Saureus). Similarly, two molecules(VS 173, VS176) inhibited five DnaGs (Mtb, Ba, Ft, Yp, Ecoli). VS261 inhibited four DnaGs (Mtb, Ba, Ft, Vc). MS50 inhibited Ba and Vc DnaGs. And some of the inhibitors inhibited only one DnaGs. Thus we found the broad and specific inhibitors for different bacterial DnaGs, and their Structure-activity analysis(SAR) was done. Further, We tried to explain the similarities among the enzyme DnaGs from different bacteria based on their inhibition pattern.

Keywords: DNA replication, DnaG, okazaki fragments, antibiotic drugs

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Authors: Cajethan U. Ugwuoke

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Agriculture is taught in secondary schools to develop skills in students which will empower them to contribute to national economic development. Unfortunately, our educational system emphasizes the application of conventional teaching methods in delivering instructions, which fails to produce students competent enough to carry out agricultural production. This study was therefore aimed at examining the application of digital technologies as tools for transformative instructional delivery. Four specific purposes, research questions and hypotheses guided the study. The study adopted a descriptive survey research design where 80 subjects representing 64 teachers of agriculture and 16 principals in the Udenu local government area of Enugu State, Nigeria, participated in the study. A structured questionnaire was used to collect data. The assumption of normality was ascertained by subjecting the data collected to a normality test. Data collected were later subjected to mean, Pearson product-moment correlation, ANOVA and t-test to answer the research questions and test the hypotheses at a 5% significant level. The result shows that the application of digital technologies helps to reduce learners’ boredom (3.52.75), improves learners’ performance (3.63.51), and is used as a visual aid for learners (3.56.61), among others. There was a positive, strong and significant relationship between the application of digital technologies and effective instructional delivery (+.895, p=.001<.05, F=17.73), competency of teachers to the application of digital technologies and effective instructional delivery (+998, p=.001<0.5, F=16263.45), and frequency of the application of digital technologies and effective instructional delivery (+.999, p=.001<.05, F=31436.14). There was no evidence of autocorrelation and multicollinearity in the regression models between the application of digital technologies and effective instructional delivery (2.03, Tolerance=1.00, VIF=1.00), competency of teachers in the application of digital technologies and effective instructional delivery (2.38, Tolerance=1.00, VIF=1.00) and frequency of the application of digital technologies and effective instructional delivery (2.00, Tolerance=1.00, VIF=1.00). Digital technologies should be therefore applied in teaching to facilitate effective instructional delivery in agriculture.

Keywords: agricultural science, digital technologies, instructional delivery, learning

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Authors: Abir Dey, Shams Noman

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Introduction: Offshore Island is the remote and isolated area from the terrestrial mainland. They are deprived of their needs. The children from an offshore island are usually underserved in the case of health care because it is a remote area where the health care systems are quite poor compared to mainland. So, the proper information is required for appropriate planning to reduce underlying causes behind visual deprivation among the surviving children of the Offshore Island. Purpose: The purpose of this study was to determine ocular morbidities, knowledge, and barriers of eye care services among children in an Offshore Island. Methods: The study team visited, and all data were collected from different rural communities at Sandwip Upazila, Chittagong district for screening the children aged 5-16 years old by doing spot examination. The whole study was conducted in both qualitative and quantitative methods. To determine ocular status of children, examinations were done under skilled Ophthalmologists and Optometrists. A focus group discussion was held. The sample size was 490. It was a community based descriptive study and the sampling method was purposive sampling. Results: In total 490 children, about 56.90% were female and 43.10% were male. Among them 456 were school-going children (93.1%) and 34 were non-school going children (6.9%). In this study the most common ocular morbidity was Allergic Conjunctivitis (35.2%). Other mentionable ocular morbidities were Refractive error (27.7%), Blepharitis (13.8%), Meibomian Gland Dysfunction (7.5%), Strabismus (6.3%) and Amblyopia (6.3%). Most of the non-school going children were involved in different types of domestic work like farming, fishing, etc. About 90.04% children who had different ocular abnormalities could not attend to the doctor due to various reasons. Conclusions: The ocular morbidity was high in rate on the offshore island. Eye health care facility was also not well established there. Awareness should be raised about necessity of maintaining hygiene and eye healthcare among the island people. Timely intervention through available eye care facilities and management can reduce the ocular morbidity rate in that area.

Keywords: morbidities, screening, barriers, offshore island, knowledge

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Authors: T. Nishimura, K. Doi, H. Fujimoto, Y. Hoshikawa, T. Wada

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In Japan, it is expected that reasonable accommodation for persons with disabilities will progress further. In particular, there is an urgent need to enhance information support for visually impaired persons who have difficulty accessing information. Recently, tactile symbols have been attached to various surfaces, such as the content labels of containers and packaging of various everyday products. The advantage of tactile symbols is that they are useful for visually impaired persons who cannot read Braille. The method of displaying tactile symbols is prescribed by the International Organization for Standardization (ISO). However, the quantitative data on the shapes and dimensions of tactile symbols is insufficient. In this study, through an evaluation experiments, we examine the easy-to-distinguish shapes and dimensions of tactile symbols used for various applications, including the content labels on containers and packaging. Visually impaired persons participated in the experiments. They used tactile symbols on a daily basis. The details and processes of the experiments were orally explained to the participants prior to the experiments, and the informed consent of the participants was obtained. They were instructed to touch the test pieces of tactile symbols freely with both hands. These tactile symbols were selected because they were likely to be easily distinguishable symbols on the content labels of top surfaces of containers and packaging based on a hearing survey that involved employees of an organization of visually impaired and a social welfare corporation, as well as academic experts of support technology for visually impaired. The participants then answered questions related to ease of distinguishing of tactile symbols on a scale of 5 (where 1 corresponded to ‘difficult to distinguish’ and 5 corresponded to ‘easy to distinguish’). Hearing surveys were also performed in an oral free answer manner with the participants after the experiments. This study revealed the shapes and dimensions regarding easily distinguishable tactile symbols attached to containers and packaging. We expect that this knowledge contributes to improvement of the quality of life of visually impaired persons.

Keywords: visual impairment, accessible design, tactile symbol, containers and packaging

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Authors: Obasa Joshua Ifeoluwa

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Phonetics is the foundation and most important part of language learning. This article, through an acoustic experiment as well as using Praat software, uses Yoruba students’ Chinese consonants, vowels, and tones pronunciation to carry out a visual comparison with that of native Chinese speakers. This article is aimed at Yoruba native speakers learning Chinese phonetics; therefore, Yoruba students are selected. The students surveyed are required to be at an elementary level and have learned Chinese for less than six months. The students selected are all undergraduates majoring in Chinese Studies at the University of Lagos. These students have already learned Chinese Pinyin and are all familiar with the pinyin used in the provided questionnaire. The Chinese students selected are those that have passed the level two Mandarin proficiency examination, which serves as an assurance that their pronunciation is standard. It is discovered in this work that in terms of Mandarin’s consonants pronunciation, Yoruba students cannot distinguish between the voiced and voiceless as well as the aspirated and non-aspirated phonetics features. For instance, while pronouncing [ph] it is clearly shown in the spectrogram that the Voice Onset Time (VOT) of a Chinese speaker is higher than that of a Yoruba native speaker, which means that the Yoruba speaker is pronouncing the unaspirated counterpart [p]. Another difficulty is to pronounce some affricates like [tʂ]、[tʂʰ]、[ʂ]、[ʐ]、 [tɕ]、[tɕʰ]、[ɕ]. This is because these sounds are not in the phonetic system of the Yoruba language. In terms of vowels, some students find it difficult to pronounce some allophonic high vowels such as [ɿ] and [ʅ], therefore pronouncing them as their phoneme [i]; another pronunciation error is pronouncing [y] as [u], also as shown in the spectrogram, a student pronounced [y] as [iu]. In terms of tone, it is most difficult for students to differentiate between the second (rising) and third (falling and rising) tones because these tones’ emphasis is on the rising pitch. This work concludes that the major error made by Yoruba students while pronouncing Chinese sounds is caused by the interference of their first language (LI) and sometimes by their lingua franca.

Keywords: Chinese, Yoruba, error analysis, experimental phonetics, consonant, vowel, tone

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Authors: Yasser Aboel-Magd

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This research addresses the critical issue of accessibility for individuals with special needs and the broader implications of disability on one's ability to lead an independent and integrated life within society. It highlights the consequences of injury, illness, or disability not only on the physical level but also on psychological, social, educational, economic, and functional aspects of life. The study emphasizes the importance of inclusive design in urban spaces, reflecting on how a society's treatment of individuals with disabilities serves as a measure of its progress. The research delves into the challenges faced by people with special needs in the Kingdom, where, despite advancements in various sectors, there is a noticeable lack of accommodating public opportunities for this significant demographic. It argues for the necessity of a Saudi building code that considers the needs of a diverse population during the design phase. The paper discusses the role of urban space as a fundamental element in urban formation and its impact on the societal integration of individuals with special needs. The study explores a variety of inclusive design principles, ranging from physical features like ramps and tactile paving to digital and cognitive accessibility measures such as screen readers, closed captions, plain language, and visual aids. It also considers the impact of wayfinding and appropriate lighting design on the orientation and assistance of individuals within urban spaces at the lowest cost. The researchers connect inclusive design with sustainable practices, advocating for environments that are not only environmentally friendly but also adaptable and lasting. The paper concludes with the assertion that the integration of accessibility, universal design, and sustainability signifies a society's commitment to inclusivity and the empowerment of all individuals, paving the way for a future where everyone can participate fully and independently in society.

Keywords: accessibility, inclusive design, Saudi building code, disability inclusion, socioeconomic progress

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Authors: Deonie Botha

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Digital transformation and the digitization of occupational health and safety training have grown exponentially due to a variety of contributing factors. The literature suggests that digitalization has numerous benefits but also has associated challenges. The aim of the paper is to develop an understanding of both the perceived benefits and challenges of digitalization in an occupational health and safety context in an effort to design and develop e-learning interventions that will optimize the benefits of digitalization and address the associated challenges. The paper proposes, deliberate and tests the design principles of an e-learning intervention to ensure alignment with the requirements of a digitally transformed environment. The results of the research are based on a literature review regarding the requirements and effect of the Fourth Industrial Revolution on learning and e-learning in particular. The findings of the literature review are enhanced with empirical research in the form of a case study conducted in an organization that designs and develops e-learning content in the occupational health and safety industry. The primary findings of the research indicated that: (i) The requirements of learners and organizations in respect of e-learning are different than previously (i.e., a pre-Fourth Industrial Revolution related work setting). (ii) The design principles of an e-learning intervention need to be aligned with the entire value chain of the organization. (iii) Digital twins support and enhance the design and development of e-learning. (iv)Learning should incorporate a multitude of sensory experiences and should not only be based on visual stimulation. (v) Data that are generated as a result of e-learning interventions should be incorporated into big data streams to be analyzed and to become actionable. It is therefore concluded that there is general consensus on the requirements that e-learning interventions need to adhere to in a digitally transformed occupational health and safety work environment. The challenge remains for organizations to incorporate data generated as a result of e-learning interventions into the digital ecosystem of the organization.

Keywords: digitalization, training, fourth industrial revolution, big data

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Authors: Min-Feng Hsieh

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Nowadays, we are facing a highly competitive environment in which the situation for survival has come even more critical than ever before. The challenge we will be confronted with is no longer can be dealt with the single system of knowledge. The abilities we urgently need to acquire is something that can lead us to cross over the boundaries between different disciplines and take us to a neutral ground that gathers and integrates powers and intelligence that surrounds us. This paper aims at discussing how a trans-disciplinary design course organized by the College of Design at Chaoyang University can react to this modern challenge. By orchestrating an experimental course format and by developing a series of coaching strategies, a trans-disciplinary learning environment has been created and practiced in which students selected from five different departments, including Architecture, Interior Design, Visual Design, Industrial Design, Landscape and Urban Design, are encouraged to think outside their familiar knowledge pool and to learn with/from each other. In the course of implementing this program, a parallel research has been conducted alongside by adopting the theory and principles of Action Research which is a research methodology that can provide the course organizer emergent, responsive, action-oriented, participative and critically reflective insights for the immediate changes and amendments in order to improve the effect of teaching and learning experience. In the conclusion, how the learning and teaching experience of this trans-disciplinary design studio can offer us some observation that can help us reflect upon the constraints and division caused by the subject base curriculum will be pointed out. A series of concepts for course design and teaching strategies developed and implemented in this trans-disciplinary course are to be introduced as a way to promote learners’ self-motivated, collaborative, cross-disciplinary and student-centered learning skills. The outcome of this experimental course can exemplify an alternative approach that we could adopt in pursuing a remedy for dealing with the problematic issues of the current educational practice.

Keywords: course design, coaching strategy, subject base curriculum, trans-disciplinary

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Authors: WonSun Chen, James Boylan, Erwin Muharemovic, Denny Meyer

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In Australia, drivers aged between 18 and 24 remained at high risk of road fatality over the last decade. Despite the successful implementation of the Graduated Licensing System (GLS) that supports young drivers in their early phases of driving, the road fatality statistics for these drivers remains high. In response to these statistics, studies conducted in Australia prior to the start of the COVID-19 pandemic have demonstrated the benefits of using telematics devices for improving driving behaviour, However, the impact of COVID-19 lockdown on young drivers’ driving behaviour has emerged as a global concern. Therefore, this naturalistic study aimed to evaluate and compare the driving behaviour(such as acceleration, braking, speeding, etc.) of young drivers with the adoption of in-vehicle telematics devices. Forty-two drivers aged between 18 and 30 and residing in the Australian state of Victoria participated in this study during the period of May to October 2022. All participants drove with the telematics devices during the first 30-day. At the start of the second 30-day, twenty-one participants were randomised to an intervention group where they were provided with an additional telematics ray device that provided visual feedback to the drivers, especially when they committed to aggressive driving behaviour. The remaining twenty-one participants remined their driving journeys without the extra telematics ray device (control group). Such trustworthy data enabled the assessment of changes in the driving behaviour of these young drivers using a machine learning approach in Python. Results are expected to show participants from the intervention group will show improvements in their driving behaviour compared to those from the control group.Furthermore, the telematics data enable the assessment and quantification of such improvements in driving behaviour. The findings from this study are anticipated to shed some light in guiding the development of customised campaigns and interventions to further address the high road fatality among young drivers in Australia.

Keywords: driving behaviour, naturalistic study, telematics data, young drivers

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Authors: Eli Buchbinder

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Introduction. Language is the basis to our experience as human being. We use language in describing our experiences and construct meaning and narratives from experiences. Metaphors are a valuable linguistic tool commonly use. Metaphors link two domains that are ordinarily not related. Metaphors achieve simultaneously multi-level integration: abstract and concrete, rational and imaginative, familiar and the unfamiliar, conscious and preconscious/unconscious. As such, metaphors epistemological and ontological tool that are important in social work in every field and domain. Goals and Methods The presentation’s aim is to validate the value of metaphors through the first psychiatric breakdown is a traumatic for families. The presentation is based on two pooled qualitative studies. The first study focused on 12 spouses: 7 women and 5 men, between the ages of 22 and 57, regarding their experiences and meanings of the first psychiatric hospitalization of their partners diagnosed with affective disorders. The second study focused on 10 parents, between the ages of 47 and 62, regarding their experiences and meanings following their child's first psychotic breakdown during young adulthood. Results Two types of major metaphors evolved from the interviews in farming the trauma of the first mental breakdown. The first mode - orientation (spatial) metaphors, reflect symbolic expression of the loss of a secure base, represented in the physical environment, e.g., describing hospitalization as "falling into an abyss." The second mode- ontological metaphors, reflect how parents and spouses present their traumatic experiences of hospitalization in terms of discrete, powerful and coherent entities, e.g., describing the first hospitalization as "swimming against the tide." The two metaphors modes reflect the embodiment of the unpredictability, being mired in distress, shock, intense pain and the experience the collapse of continuity on the life course and cuts off the experience of control. Conclusions Metaphors are important and powerful guide in assessing individuals and families’ phenomenological reality. As such, metaphors are useful for understanding and orientated therapeutic intervening, in the studies above, with the first psychiatric hospitalization experienced, as well as in others social workers’ interventions.

Keywords: first mental breakdown, metaphors, family perspective, qualitative research

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Authors: Yun-Chin Chung, Nileema Divate, Gen-Hung Chen, Pei-Ru Huang, Rupesh Divate

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Many environmental factors, such as glucose concentration, ethanol, temperature, osmotic pressure and pH, decrease the production rate of ethanol using yeast as a starter. Fermentation starters with high tolerance to various stresses are always demanded for brewing industry. Trehalose, a storage carbohydrate in cell wall of yeast, plays an important role in tolerance of environmental stress by preserving integrity of plasma membrane and stabilizing proteins. Furan aldehydes are toxic to yeast and the growth rate of yeast is significantly reduced if furan aldehydes were present in the fermentation medium. In yeast, aldehyde reductase is involved in the detoxification of reactive aldehydes and consequently the growth of yeast is improved. The aims of this study were to construct a genetic recombinant Saccharomyces cerevisiae or Pichia pastoris with furfural and HMF degrading and high ethanol tolerance capacities. Yeast strains were engineered by genetic recombination for overexpression of trehalose-6-phosphate synthase gene (tps1) and aldehyde reductase gene (ari1). TPS1 gene was cloned from S. cerevisiae by reverse transcription-polymerase chain reaction (RT-PCR) and then ligated with pGAPZαC vector. The constructed vector, pGAPZC-tps1, was transformed to recombinant yeasts strain with overexpression of ari1. The transformants with pGAPZC-tps1-ari1 were generated called STA (S. cerevisiae) and PTA (P. pastoris) with overexpression of tps1, ari1. PCR with tps1-specific primers and western blot with his-tag confirmed the gene insertion and protein expression of tps1 in the transformants, respectively. The neutral trehalase gene (nth1) of STA was successfully deleted and the novel strain STAΔN will be used for further study, including the measurement of trehalose concentration and ethanol, furfural tolerance assay.

Keywords: genetic recombinant, yeast, ethanol tolerance, trehalase, aldehyde reductase

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Authors: Yi Sun, George Ed Rainger, Steve P. Watson

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Background: Beyond the classical roles in haemostasis and thrombosis, platelets are important in the initiation and development of various thrombo-inflammatory diseases. In atherosclerosis and deep vein thrombosis, for example, platelets bridge monocytes with endothelium and form heterotypic aggregates with monocytes in the circulation. This can alter monocyte phenotype by inducing their activation, stimulating adhesion and migration. These interactions involve cell surface receptor-ligand pairs on both cells. This list is likely incomplete as new interactions of importance to platelet biology are continuing to be discovered as illustrated by our discovery of PEAR-1 binding to FcεR1α. Results: We have developed a highly sensitive avidity-based assay to identify novel extracellular interactions among 126 recombinantly-expressed platelet cell surface and secreted proteins involved in platelet aggregation. In this study, we will use this method to identify novel platelet-monocyte interactions. We aim to identify ligands for orphan receptors and novel partners of well-known proteins. Identified interactions will be studied in preliminary functional assays to demonstrate relevance to the inflammatory processes supporting atherogenesis. Conclusions: Platelet-monocyte interactions are essential for the development of thromboinflammatory disease. Up until relatively recently, technologies only allow us to limit our studies on each individual protein interaction at a single time. These studies propose for the first time to study the cell surface platelet-monocyte interactions in a systematic large-scale approach using a reliable screening method we have developed. If successful, this will likely to identify previously unknown ligands for important receptors that will be investigated in details and also provide a list of novel interactions for the field. This should stimulate studies on developing alternative therapeutic strategies to treat vascular inflammatory disorders such as atherosclerosis, DVT and sepsis and other clinically important inflammatory conditions.

Keywords: membrane proteins, large-scale screening, platelets, recombinant expression

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Authors: Jorn Fricke, Frans Melissen

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Citizens in urban areas are prone to increased levels of stress due to urbanization, inadequate and overburdened infrastructure and services, and environmental degradation. Moreover, communities are fragile and subject to shocks and stresses through various social and political processes. A loss of (a sense of) community is often seen as related to increasing political and civic disintegration. Feelings of community can manifest themselves in various ways but underlying all these manifestations is the need for trust between people. One of the main drivers of trust between individuals is (shared) experiences. It is these shared experiences that may play an important role in building resilience, i.e., the ability of a community and its members to adapt to and deal with stresses, as well as ensure the ongoing development of a community. So far, experience design, as a discipline and academic field, has mainly focused on designing products or services. However, people-to-people experiences are the ones that play a pivotal role in building inclusiveness, safety, and resilience in communities. These experiences represent challenging objects of design as they develop in an interactive space of spontaneity, serendipity, and uniqueness that is based on intuition, freedom of expression, and interaction. Therefore, there is a need for research to identify which elements are required in designing the social and physical environment (or ‘experience scape’) to increase the chance for people-to-people experiences to be successful and what elements are required for these experiences to help in building resilience in urban communities that can resist shocks and stresses. By means of a comparative case study approach in urban areas in Germany and the Netherlands, using a range of qualitative research methods such as in-depth interviews, focus groups, participant observation, storytelling techniques, and life stories, this research identifies relevant actors and their roles in creating building blocks of optimal experience scrapes for building resilience in communities.

Keywords: community development, experiences, experience scapes, resilience

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Authors: Antonello Durante, James Duff, Kevin Kelly

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The visual needs of people in modern work based buildings are changing. Self-illuminated screens of computers, televisions, tablets and smart phones have changed the relationship between people and the lit environment. In the past, lighting design practice was primarily based on providing uniform horizontal illuminance on the working plane, but this has failed to ensure good quality lit environments. Lighting standards of today continue to be set based upon a 100 year old approach that at its core, considers the task illuminance of the utmost importance, with this task typically being located on a horizontal plane. An alternative method focused on appearance has been proposed, as opposed to the traditional performance based approach. Mean Room Surface Exitance (MRSE) and Target-Ambient Illuminance Ratio (TAIR) are two new metrics proposed to assess illumination adequacy in interiors. The hypothesis is that these factors will be superior to the existing metrics used, which are horizontal illuminance led. For the six past years, research has examined this, within the Dublin Institute of Technology, with a view to determining the suitability of this approach for application to general lighting practice. Since the start of this research, a number of key findings have been produced that centered on how occupants will react to various levels of MRSE. This paper provides a broad update on how this research has progressed. More specifically, this paper will: i) Demonstrate how MRSE can be measured using HDR images technology, ii) Illustrate how MRSE can be calculated using scripting and an open source lighting computation engine, iii) Describe experimental results that demonstrate how occupants have reacted to various levels of MRSE within experimental office environments.

Keywords: illumination hierarchy (IH), mean room surface exitance (MRSE), perceived adequacy of illumination (PAI), target-ambient illumination ratio (TAIR)

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Authors: Reihane Mehrparvar

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Human age could exceed further by altering gene expression through food intaking, although as a consequence of recent century eating patterns, human life-span getting shorter by emerging irregulating in autophagy mechanism, insulin, leptin, gut microbiota which are important etiological factors of type-2 diabetes, obesity, infertility, cancer, metabolic and autoimmune diseases. However, restricted calorie intake and vigorous exercise might be beneficial for losing weight and metabolic regulation in a short period but could not be implementable in the long term as a way of life. Therefore, the lack of a dietary program that is compatible with the genes of the body is essential. Sweet and high-glycemic-index (HGI) foods were associated with type-2 diabetes and cancer morbidity. The neuropsychological perspective characterizes the inclination of sweet and HGI-food consumption as addictive behavior; hence this process engages preference of gut microbiota, neural node, and dopaminergic functions. Moreover, meal composition is not the only factor that affects body hemostasis. In this narrative review, it is believed to attempt to investigate how the body responded to different food intakes and represent an accurate model based on current evidence. Eating frequently and ingesting unassimilable protein and carbohydrates may not be compatible with human genes and could cause impairments in the self-renovation mechanism. This trajectory indicates our body is more adapted to starvation and eating animal meat and marrow. Here has been recommended a model that takes into account three important factors: frequent eating, meal composition, and circadian rhythm, which may offer a promising intervention for obesity, inflammation, cardiovascular, autoimmune disorder, type-2 diabetes, insulin resistance, infertility, and cancer through intensifying autophagy-mechanism and eliminate medical costs.

Keywords: metabolic disease, anti-aging, type-2 diabetes, autophagy

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Authors: O. Benabdeljelil, A. Karioun, S. Amami, R. Rouger, M. Hamidine

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A model for preventing the risks related to climate conditions in the agricultural sector is presented. It will determine the yearly optimum premium to be paid by a producer in order to reach his required turnover. The model is based on both climatic stability and 'soft' responses of usually grown species to average climate variations at the same place and inside a safety ball which can be determined from past meteorological data. This allows the use of linear regression expression for dependence of production result in terms of driving meteorological parameters, the main ones of which are daily average sunlight, rainfall and temperature. By simple best parameter fit from the expert table drawn with professionals, optimal representation of yearly production is determined from records of previous years, and yearly payback is evaluated from minimum yearly produced turnover. The model also requires accurate pricing of commodity at N+1. Therefore, a pricing model is developed using 3 state variables, namely the spot price, the difference between the mean-term and the long-term forward price, and the long-term structure of the model. The use of historical data enables to calibrate the parameters of state variables, and allows the pricing of commodity. Application to beet sugar underlines pricer precision. Indeed, the percentage of accuracy between computed result and real world is 99,5%. Optimal premium is then deduced and gives the producer a useful bound for negotiating an offer by insurance companies to effectively protect its harvest. The application to beet production in French Oise department illustrates the reliability of present model with as low as 6% difference between predicted and real data. The model can be adapted to almost any agricultural field by changing state parameters and calibrating their associated coefficients.

Keywords: agriculture, production model, optimal price, meteorological factors, 3-factor model, parameter calibration, forward price

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Authors: Yong-Kian Lim, Khan Cheung, Xin Dang, Steven Roberts, Xiaotong Wang, Vengatesen Thiyagarajan

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Unprecedented rate of increased CO₂ level in the ocean and the subsequent changes in carbonate system including decreased pH, known as ocean acidification (OA), is predicted to disrupt not only the calcification process but also several other physiological and developmental processes in a variety of marine organisms, including edible oysters. Nonetheless, not all species are vulnerable to those OA threats, e.g., some species may be able to cope with OA stress using environmentally induced modifications on gene and protein expressions. For example, external environmental stressors, including OA, can influence the addition and removal of methyl groups through epigenetic modification (e.g., DNA methylation) process to turn gene expression “on or off” as part of a rapid adaptive mechanism to cope with OA. In this study, the above hypothesis was tested through testing the effect of OA, using decreased pH 7.4 as a proxy, on the DNA methylation pattern of an endemic and a commercially important estuary oyster species, Crassostrea hongkongensis, at the time of larval habitat selection and metamorphosis. Larval growth rate did not differ between control pH 8.1 and treatment pH 7.4. The metamorphosis rate of the pediveliger larvae was higher at pH 7.4 than those in control pH 8.1; however, over one-third of the larvae raised at pH 7.4 failed to attach to an optimal substrate as defined by biofilm presence. During larval development, a total of 130 genes were differentially methylated across the two treatments. The differential methylation in the larval genes may have partially accounted for the higher metamorphosis success rate under decreased pH 7.4 but with poor substratum selection ability. Differentially methylated loci were concentrated in the exon regions and appear to be associated with cytoskeletal and signal transduction, oxidative stress, metabolic processes, and larval metamorphosis, which implies the high potential of C. hongkongensis larvae to acclimate and adapt through non-genetic ways to OA threats within a single generation.

Keywords: adaptive plasticity, DNA methylation, larval metamorphosis, ocean acidification

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Authors: Mehrdad Abkenari, Orod Zarrinkafsh, Mohsen Ramezan Shirazi

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Construction projects initiate in complicated dynamic environments and, due to the close relationships between project parameters and the unknown outer environment, they are faced with several uncertainties and risks. Success in time, cost and quality in large scale construction projects is uncertain in consequence of technological constraints, large number of stakeholders, too much time required, great capital requirements and poor definition of the extent and scope of the project. Projects that are faced with such environments and uncertainties can be well managed through utilization of the concept of risk management in project’s life cycle. Although the concept of risk is dependent on the opinion and idea of management, it suggests the risks of not achieving the project objectives as well. Furthermore, project’s risk analysis discusses the risks of development of inappropriate reactions. Since evaluation and prioritization of construction projects has been a difficult task, the network structure is considered to be an appropriate approach to analyze complex systems; therefore, we have used this structure for analyzing and modeling the issue. On the other hand, we face inadequacy of data in deterministic circumstances, and additionally the expert’s opinions are usually mathematically vague and are introduced in the form of linguistic variables instead of numerical expression. Owing to the fact that fuzzy logic is used for expressing the vagueness and uncertainty, formulation of expert’s opinion in the form of fuzzy numbers can be an appropriate approach. In other words, the evaluation and prioritization of construction projects on the basis of risk factors in real world is a complicated issue with lots of ambiguous qualitative characteristics. In this study, evaluated and prioritization the risk parameters and factors with fuzzy logy method by combination of three method DEMATEL (Decision Making Trial and Evaluation), ANP (Analytic Network Process) and TOPSIS (Technique for Order-Preference by Similarity Ideal Solution) on Construction Management.

Keywords: fuzzy logy, risk, prioritization, assessment

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Authors: Mathew Wakefield, Matthew Mitchell, Lisa Wise, Christopher McCarthy

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The properties of memory representations in artificial neural networks have cognitive implications. Distributed representations that encode instances as a pattern of activity across layers of nodes afford memory compression and enforce the selection of a single point in instance space. These encoding schemes also appear to distort the representational space, as well as trading off the ability to validate that input information is within the bounds of past experience. In contrast, a localist representation which encodes some meaningful information into individual nodes in a network layer affords less memory compression while retaining the integrity of the representational space. This allows the validity of an input to be determined. The validity (or familiarity) of input along with the capacity of localist representation for multiple instance selections affords a memory sampling approach that dynamically balances the bias-variance trade-off. When the input is familiar, bias may be high by referring only to the most similar instances in memory. When the input is less familiar, variance can be increased by referring to more instances that capture a broader range of features. Using this approach in a localist instance memory network, an experiment demonstrates a relationship between representational conflict, generalization performance, and memorization demand. Relatively small sampling ranges produce the best performance on a classic machine learning dataset of visual objects. Combining memory validity with conflict detection produces a reliable confidence judgement that can separate responses with high and low error rates. Confidence can also be used to signal the need for supervisory input. Using this judgement, the need for supervised learning as well as memory encoding can be substantially reduced with only a trivial detriment to classification performance.

Keywords: artificial neural networks, representation, memory, conflict monitoring, confidence

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Authors: Neeraj Shetye

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A common phenomenon between the rise of leaders like Mussolini and Adolf Hitler in the 20th century is their 'charisma'. They possessed the ability to seduce the crowd not just by the things they said but also by the way they said it. Aristotle defined rhetoric as an art of persuasion and reasoning which is how social scientists understand the concept. Political rhetoric in a modern democracy has several complexities including the huge number of speakers, quantity of information, diverse viewpoints, number of candidates and the impact of digital age. Politics in India since the seventies have been 'visibly dominated' by uses of rhetorical language and with a number of slogans. This idea of how language can steer an individual to establish or adopt a certain viewpoint has not been a focus of study in the Indian discourse. In a linguistically diverse region such as India, the idea of political rhetoric is vast and may not be accomplished in a year. There are in-depth studies by western thinkers on European or American political rhetoric unlike their Asian counterparts such as China, India or any of the Pacific nations. India saw an integration of states based on languages. Keeping this idea in mind, this paper aims to cover one political party that rose to its prominence over five decades and most significantly known for its conservative expression: Shivsena. Shivsena’s rise during the eighties and eventually establishing their government in the nineties are two fascinating periods to focus especially with a simultaneous rise of Bombay underworld, Babri demolition and major economic policy changes in the form of liberalisation (1991) and globalization (1995). This project attempts to study this with a two-fold methodology: literature review and fieldwork. There is an immense literature on Shivsena by both its admirers and critiques, contributing to both sides of the debate. Scholars have been writing about this party over these years and have keenly observed its growing popularity amongst the masses. There is just one intention behind this project, and it is to connect and analyse the vast, dispersed literature that is available and contribute to a field that has not been adequately analysed in the academic discourse.

Keywords: India, language, political rhetoric, Shivsena, slogans

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Authors: Qin Yang, Fan Zhang, Juan Du, Chongkui Sun, Krishna Kota, Yun-Ling Zheng

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Telomeres are specialized structures at chromosome ends consisting of tandem repetitive DNA sequences [(TTAGGG)n in humans] and associated proteins, which are necessary for telomere function. Telomere lengths are tightly regulated within a narrow range in normal human somatic cells, the basis of cellular senescence and aging. Previous studies have extensively focused on how short telomeres are extended and have demonstrated that telomerase plays a central role in telomere maintenance through elongating the short telomeres. However, the molecular mechanisms of regulating excessively long telomeres are unknown. Here, we found that telomerase enzymatic component hTERT plays a dual role in the regulation of telomeres length. We analyzed single telomere alterations at each chromosomal end led to the discoveries that hTERT shortens excessively long telomeres and elongates short telomeres simultaneously, thus maintaining the optimal telomere length at each chromosomal end for an efficient protection. The hTERT-mediated telomere shortening removes large segments of telomere DNA rapidly without inducing telomere dysfunction foci or affecting cell proliferation, thus it is mechanistically distinct from rapid telomere deletion. We found that expression of hTERT generates telomeric circular DNA, suggesting that telomere homologous recombination may be involved in this telomere shortening process. Moreover, the hTERT-mediated telomere shortening is required its enzymatic activity, but telomerase RNA component hTR is not involved in it. Furthermore, shelterin protein TPP1 interacts with hTERT and recruits it on telomeres to mediate telomere shortening. In addition, telomere-associated proteins, DKC1 and TCAB1 also play roles in this process. This novel hTERT-mediated telomere shortening mechanism not only exists in cancer cells, but also in primary human cells. Thus, the hTERT-mediated telomere shortening is expected to shift the paradigm on current molecular models of telomere length maintenance, with wide-reaching consequences in cancer and aging fields.

Keywords: aging, hTERT, telomerase, telomeres, human cells

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