Search results for: specific emotions

Authors: Mark Bezner, Shani Deri, Tom Trigano, Kfir Ben-Harush

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Intermediate filament (IF) proteins-based fibers are among the toughest fibers in nature, as was shown by native hagfish slime threads and by synthetic fibers that are based on type V IF-proteins, the nuclear lamins. It is assumed that their mechanical performance stems from two major factors: (1) the transition from elastic -helices to stiff-sheets during tensile load; and (2) the specific organization of the coiled-coil proteins into a hierarchical network of nano-filaments. Here, we investigated the interrelationship between these two factors by using wet-spun fibers based on C. elegans (Ce) lamin. We found that Ce-lamin fibers, whether assembled in aqueous or alcoholic solutions, had the same nonlinear mechanical behavior, with the elastic region ending at ~5%. The pattern of the transition was, however, different: the ratio between -helices and -sheets/random coils was relatively constant until a 20% strain for fibers assembled in an aqueous solution, whereas for fibers assembled in 70% ethanol, the transition ended at a 6% strain. This structural phenomenon in alcoholic solution probably occurred through the transition between compacted and extended conformation of the random coil, and not between -helix and -sheets, as cycle analyses had suggested. The different transition pattern can also be explained by the different higher order organization of Ce-lamins in aqueous or alcoholic solutions, as demonstrated by introducing a point mutation in conserved residue in Ce-lamin gene that alter the structure of the Ce-lamins’ nano-fibrils. In addition, biomimicking the layered structure of silk and hair fibers by coating the Ce-lamin fiber with a hydrophobic layer enhanced fiber toughness and lead to a reversible transition between -helix and the extended conformation. This work suggests that different hierarchical structures, which are formed by specific assembly conditions, lead to diverse secondary structure transitions patterns, which in turn affect the fibers’ mechanical properties.

Keywords: protein-based fibers, intermediate filaments (IF) assembly, toughness, structure-property relationships

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Authors: Min Chang Shin, Byung Hun Jeong, Jeong Sik Han, Jung Hoon Park

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In modern times, as flight speeds have increased due to improvements in aircraft and missile engine performance, thermal loads have also increased. Because of the friction heat of air flow with high speed on the surface of the vehicle, it is not easy to cool the superheat of the vehicle by the simple air cooling method. For this reason, a cooling method through endothermic heat is attracting attention by using a fuel that causes an endothermic reaction in a high-speed vehicle. There are two main ways of cooling the fuel through the endothermic reaction. The first is physical heat absorption. When the temperature rises, there is a sensible heat that accompanies it. The second is the heat of reaction corresponding to the chemical heat absorption, which absorbs heat during the fuel decomposes. Generally, since the decomposition reaction of the fuel proceeds at a high temperature, it does not achieve a great efficiency in cooling the high-speed flight body. However, when the catalyst is used, decomposition proceeds at a low temperature thereby increasing the cooling efficiency. However, when the catalyst is used as a powder, the catalyst enters the engine and damages the engine or the catalyst can deteriorate the performance due to the sintering. On the other hand, when used in the form of pellets, catalyst loss can be prevented. However, since the specific surface of pellet is small, the efficiency of the catalyst is low. And it can interfere with the flow of fuel, resulting in pressure loss and problems with fuel injection. In this study, we tried to maximize the performance of the catalyst by preparing a hollow fiber type pellet for zeolite ZSM-5, which has a higher amount of heat absorption, than other conventional pellets. The hollow fiber type pellet was prepared by phase inversion method. The hollow fiber type pellet has a finger-like pore and sponge-like pore. So it has a higher specific surface area than conventional pellets. The crystal structure of the prepared ZSM-5 catalyst was confirmed by XRD, and the characteristics of the catalyst were analyzed by TPD/TPR device. This study was conducted as part of the Basic Research Project (Pure-17-20) of Defense Acquisition Program Administration.

Keywords: catalyst, endothermic reaction, high-speed vehicle cooling, zeolite, ZSM-5

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Authors: Valentina Talu, Giulia Tola

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Current researches and applications aimed at exploring the role of spatial configuration as a means for improving the autonomy of people with ASD (Autism Spectrum Disorder), almost exclusively focus on the definition of criteria for the design of closed, separated, private spaces devoted only to people - mainly children - with ASD. In fact, very few researches specifically investigate the relation between the city and people with autism, focusing on their sensory experiences related to the interaction with the urban environment. The growing incidence of ASD and the need to guarantee during adulthood the actual opportunity to exercise the achieved level of autonomy and independency, emphasizes the necessity to ‘broaden’ the research perspective by investigating also the specific contribution of urban mobility policies and urban design to the enhancement of the quality of life of people with ASD. Starting from these considerations, the paper describes an ongoing research focused on the relation between the city and people with autism spectrum disorder, with the specific aim of promoting their possibility of walking across the city at the neighborhood scale, thus making the access to relevant urban spaces and services possible. In the first part, the paper proposes a framework for illustrating the commonly recurring problems that people with ASD face in their daily life when they interact with the urban environment (with reference to the capability approach). Subsequently, with the support of an in depth analysis of existing contributions (researches and projects) and an exchange with different experts (neuropsychiatrists, teachers, parents), are identified two urban requirements, then 'translated' into an integrated system of urban mobility policies and extra-small tactical project aimed at enhancing the actual possibility for people with ASD of walking through the city autonomously and safely. According to this vision, the promotion of the autonomy of people with ASD through the adoption of mobility policies and micro tactical urban projects can represent an opportunity for promoting and improving the overall quality of urban life.

Keywords: city and people with ASD, quality of urban life of disadvantaged people, urban capabilities, urban design

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Authors: Aikaterini Tavoulari, Michael Proulx, Karin Petrini

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Objective: This study aims to explore the unique challenges faced by young individuals with vision impairment (VI) during key life transitions, utilizing a community-based participatory research (CBPR) approach to identify limitations and positive aspects of existing support systems, with a focus on accessibility and diversity. Design: The study employs a qualitative CBPR design, engaging young participants with VI through online and in-person working groups over six months, prioritizing their active involvement and diverse perspectives. Methods: Twenty-one young individuals with VI from across the UK and with different VI conditions were recruited to participate in the study via a climbing and virtual reality event and stakeholders’ support. Data collection methods included open discussions, forum exchanges, and qualitative questionnaires. The data were analyzed with NVivo using inductive thematic analysis to identify key themes and patterns related to the challenges and experiences of life transitions for this diverse population. Results: The analysis revealed barriers to accessibility, such as assumptions about what a person with VI can do, inaccessibility to material, noisy environments, and insufficient training with assistive technologies. Enablers included guidance from diverse professionals and peers, multisensory approaches (beyond tactile), and peer collaborations. This study underscores the need for developing accessible and tailored strategies together with these young people to address the specific needs of this diverse population during critical life transitions (e.g., to independent living, employment and higher education). Conclusion: Engaging and co-designing effective approaches and tools with young people with VI is key to tackling the specific accessibility barriers they encounter. These approaches should be targeted at different transitional periods of their life journey, promoting diversity and inclusion.

Keywords: vision impairement, life transitions, qualitative research, community-based participatory design, accessibility

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Authors: Yousef Barahmeh

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This paper is a linguistic and pragmatic analysis of the use of the diminutive in Colloquial Jordanian Arabic (CJA). It demonstrates a peculiar form of the diminutive in CJA inflected by means of feminine plural ends with -aat suffix. The analysis shows that the pragmatic function(s) of the diminutive in CJA refers primarily to ‘littleness’ while the morphological inflection conveys the message of ‘the plethora’. Examples of this linguistic phenomenon are intelligible and often include a large number of words that are culture-specific to the rural dialect in the north of Jordan. In both cases, the diminutive in CJA is an adaptive strategy relative to its pragmatic and social contexts.

Keywords: Colloquial Jordanian Arabic, diminutive, morphology, pragmatics

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Authors: Saimir Heta, Kers Kapaj, Rialda Xhizdari, Ilma Robo

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Despite the existence of different dental specialties, the dentist-patient relationship is unique, in the very fact that the treatment is performed by one doctor and the patient identifies the malpractice presented as part of that doctor's practice; this is in complete contrast to cases of medical treatments where the patient can be presented to a team of doctors, to treat a specific pathology. The rules of dental ethics are almost the same as the rules of medical ethics. The appearance of dental malpractice affects exactly this two-party relationship, created on the basis of professionalism, without deviations in this direction, between the dentist and the patient, but with very narrow individual boundaries, compared to cases of medical malpractice. Main text: Malpractice can have different reasons for its appearance, starting from professional negligence, but also from the lack of professional knowledge of the dentist who undertakes the dental treatment. It should always be seen in perspective that we are not talking about the individual - the dentist who goes to work with the intention of harming their patients. Malpractice can also be a consequence of the impossibility, for anatomical or physiological reasons of the tooth under dental treatment, to realize the predetermined dental treatment plan. On the other hand, the dentist himself is an individual who can be affected by health conditions, or have vices that affect the systemic health of the dentist as an individual, which in these conditions can cause malpractice. So, depending on the reason that led to the appearance of malpractice, the method of treatment from a legal point of view also varies, for the dentist who committed the malpractice, evaluating the latter if the malpractice came under the conditions of applying the rules of dental ethics. Conclusions: The deviation from the predetermined dental plan is the minimum sign of malpractice and the latter should not be definitively related only to cases of difficult dental treatments. The identification of the reason for the appearance of malpractice is the initial element, which makes the difference in the way of its treatment, from a legal point of view, and the involvement of the dentist in the assessment of the malpractice committed, must be based on the legislation in force, which must be said to have their specific changes in different states. Malpractice should be referred to, or included in the lectures or in the continuing education of professionals, because it serves as a method of obtaining professional experience in order not to repeat the same thing several times, by different professionals.

Keywords: dental ethics, malpractice, negligence, legal basis, continuing education, dental treatments

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Authors: Afrouz Yousefi, Mohtada Sadrzadeh

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The widespread presence of poly- and perfluoroalkyl substances (PFAS) poses a significant concern due to their ability to accumulate in living organisms and their persistence in the environment, thanks to their robust carbon-fluorine (C-F) bonds, which require substantial energy to break (485 kJ/mol). The prevalence of toxic PFAS compounds can be highly detrimental to ecosystems, wildlife, and human health. Ongoing efforts are dedicated to investigating methods for fully breaking down and eliminating PFAS from the environment. Among the various techniques employed, advanced oxidation processes have shown promise in completely breaking down emerging contaminants in wastewater. However, the drawback lies in the relatively slow reaction rates of these processes and the substantial energy input required, which currently impedes their widespread commercial adoption. We developed a hybrid process, comprising electro-Fenton as an advanced oxidation process and membrane distillation, to simultaneously degrade organic PFAS pollutants and extract pure water from the mixture. In this study, environmentally persistent perfluorooctanoic acid (PFOA), as an emerging contaminant, was used to study the effectiveness of the electro-Fenton/membrane distillation hybrid system. The PFOA degradation studies were conducted in two modes: electro-Fenton and electro-Fenton coupled with membrane distillation. High-performance liquid chromatography with ultraviolet detection (HPLC-UV), ion-chromatography (measuring fluoride ion concentration), total organic carbon (TOC) decay, mineralization current efficiency (MCE), and specific energy consumption (SEC) were evaluated for a single EF and hybrid EF-MD processes. In contrast to a single EF reaction, TOC decay improved significantly in the EF-MD process. Overall, the MCE of hybrid processes surpassed 100% while it remained under 50% for a single EF reaction. Calculations of specific energy consumption (SEC) demonstrated a substantial decrease of nearly one-third in energy usage when integrating the EF reaction with the MD process.

Keywords: water treatment, PFAS, membrane distillation, electro-Fenton, advanced oxidation

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Authors: Huailei Wen

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The Kramers vs. Kramers (1979) is a film that comprehensively examines the role and status of women under the traditional secular vision, where women have become subordinate to the patriarchal society and family. Through the construction of the protagonist Joanna's dissatisfaction with the social and ethical status quo, her struggle to subvert the existing status of women, and her return to her own self, the story comprehensively reflects the difficult journey of women, represented by Joanna, to subvert the stereotypes and return to their own selves in the specific historical context of the time, revealing the self-value of Joanna's phenomenon to modern women.

Keywords: star image, feminism, Kramers vs. Kramers, Hollywood

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Authors: Dar-Bin Shieh, Gwo-Bin Lee, Chen-Ming Chang, Chen Sheng Yeh, Chih-Chia Huang, Tsung-Ju Li

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Mitochondrial defects have a significant impact in many human diseases and aging associated phenotypes. The pathogenic mitochondrial DNA (mtDNA) mutations are diverse and usually present as heteroplasmic. mtDNA 4977bps deletion is one of the common mtDNA defects, and the ratio of mutated versus normal copy is significantly associated with clinical symptoms thus their quantitative detection has become an important unmet needs for advanced disease diagnosis and therapeutic guidelines. This study revealed a Micro-electro-mechanical-system (MEMS) enabled automatic microfluidic chip that only required minimal sample. The system integrated multiple laboratory operation steps into a Lab-on-a-Chip for high-sensitive and prompt measurement. The entire process including magnetic nanoparticle based mtDNA extraction in chip, mutation selective photonic DNA cleavage, and nanoparticle accelerated photonic quantitative polymerase chain reaction (qPCR). All subsystems were packed inside a miniature three-dimensional micro structured system and operated in an automatic manner. Integration of magnetic beads with microfluidic transportation could promptly extract and enrich the specific mtDNA. The near infrared responsive magnetic nanoparticles enabled micro-PCR to be operated by pulse-width-modulation controlled laser pulsing to amplify the desired mtDNA while quantified by fluorescence intensity captured by a complementary metal oxide system array detector. The proportions of pathogenic mtDNA in total DNA were thus obtained. Micro capillary electrophoresis module was used to analyze the amplicone products. In conclusion, this study demonstrated a new magnetophotonic based qPCR MEMS system that successfully detects and quantify specific disease related DNA mutations thus provides a promising future for rapid diagnosis of mitochondria diseases.

Keywords: mitochondrial DNA, micro-electro-mechanical-system, magnetophotonics, PCR

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Authors: Zelalem B. Gurmessa, Ignatius W. Ferreira, Henry F. Wissink

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The aim of this paper is to critically examine the factors contributing to academic brain drain in the Sub-Saharan Africa with specific reference to the higher education sector. Africa in general and Sub-Saharan African (SSA) countries, in particular, are experiencing an exodus of highly trained, qualified and competent human resources to other developing and developed countries thereby threatening the overall development of the relevant regions and impeding both public and private service delivery systems in the nation states. The region is currently in a dire situation in terms of health care services, education, science, and technology. The contribution of SSA countries to Science, Technology and Innovation is relatively minimal owing to the migration of skilled professionals due to both push and pull factors. The phenomenon calls for both international and trans-boundary, regional, national and institutional interventions to curb the exodus. Based on secondary data and the review of the literature, the article conceptualizes the antecedents and impacts of human capital flight or brain drain in the SSA countries from a higher education perspective. To this end, the article explores the magnitude, causes, and impacts of brain drain in the region. Despite the lack of consistent data on the magnitude of academic brain drain in the region, a critical analysis of the existing sources shows that pay disparity between developing and developed countries, the lack of enabling working conditions at source countries, fear of security due to political turmoil or unrest, the availability of green pastures and opportunity for development in the receiving countries were identified as major factors contributing to academic brain drain in the region. This hampers the socio-economic, technological and political development of the region. The paper also recommends that further research can be undertaken on the magnitude, causes, characteristics and impact of brain drain on the sustainability and competitiveness of SSA higher education institutions in the region.

Keywords: brain drain, higher education, sub-Saharan Africa, sustainable development

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Authors: Rolivhuwa Bishop Ramagoma1*, Lynn Cairncross1, , Saartjie Roux1

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According to the world health organisation, colon cancer is among the most common cancers diagnosed in both men and women. Specifically, it is the second leading cause of cancer related deaths accounting for over 860 000 deaths worldwide in 2018. Currently, chemotherapy has become an essential component of most cancer treatments. Despite progress in cancer drug development over the previous years, traditional chemotherapeutic drugs still have low selectivity for targeting tumour tissues and are frequently constrained by dose-limiting toxicity. The creation of nanoscale delivery vehicles capable of directly directing treatment into cancer cells has recently caught the interest of researchers. Herein, the development of peptide-functionalized polyethylene glycol gold nanoparticles (Peptide-PEG-AuNPs) as a cellular probe and delivery agent is described, with the higher aim to develop a specific diagnostic prototype and assess their specificity not only against cell lines but primary human cells as well. Gold nanoparticles (AuNPs) were synthesized and stabilized through chemical conjugation. The synthesized AuNPs were characterized, stability in physiological solutions was assessed, their cytotoxicity against colon carcinoma and non-carcinoma skin fibroblasts was also studied. Furthermore, genetic effect through real-time polymerase chain reaction (RT-PCR), localization and uptake, peptide specificity were also determined. In this study, different peptide-AuNPs were found to have preferential toxicity at higher concentrations, as revealed by cell viability assays, however, all AuNPs presented immaculate stability for over 3 months following the method of synthesis. The final obtained peptide-PEG-AuNP conjugates showed good biocompatibility in the presence of high ionic solutions and biological media and good cellular uptake. Formulation of colon cancer specific targeting peptide was successful, additionally, the genes/pathways affected by the treatments were determined through RT-PCR. Primary cells study is still on going with promising results thus far.

Keywords: nanotechnology, cancer, diagnosis, therapeutics, gold nanoparticles.

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Authors: M. A. C. S. Sampath Fernando, James M. Curran, Renate Meyer

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Model assessment, in the Bayesian context, involves evaluation of the goodness-of-fit and the comparison of several alternative candidate models for predictive accuracy and improvements. In posterior predictive checks, the data simulated under the fitted model is compared with the actual data. Predictive model accuracy is estimated using information criteria such as the Akaike information criterion (AIC), the Bayesian information criterion (BIC), the Deviance information criterion (DIC), and the Watanabe-Akaike information criterion (WAIC). The goal of an information criterion is to obtain an unbiased measure of out-of-sample prediction error. Since posterior checks use the data twice; once for model estimation and once for testing, a bias correction which penalises the model complexity is incorporated in these criteria. Cross-validation (CV) is another method used for examining out-of-sample prediction accuracy. Leave-one-out cross-validation (LOO-CV) is the most computationally expensive variant among the other CV methods, as it fits as many models as the number of observations. Importance sampling (IS), truncated importance sampling (TIS) and Pareto-smoothed importance sampling (PSIS) are generally used as approximations to the exact LOO-CV and utilise the existing MCMC results avoiding expensive computational issues. The reciprocals of the predictive densities calculated over posterior draws for each observation are treated as the raw importance weights. These are in turn used to calculate the approximate LOO-CV of the observation as a weighted average of posterior densities. In IS-LOO, the raw weights are directly used. In contrast, the larger weights are replaced by their modified truncated weights in calculating TIS-LOO and PSIS-LOO. Although, information criteria and LOO-CV are unable to reflect the goodness-of-fit in absolute sense, the differences can be used to measure the relative performance of the models of interest. However, the use of these measures is only valid under specific circumstances. This study has developed 11 models using normal, log-normal, gamma, and student’s t distributions to improve the PCR stutter prediction with forensic data. These models are comprised of four with profile-wide variances, four with locus specific variances, and three which are two-component mixture models. The mean stutter ratio in each model is modeled as a locus specific simple linear regression against a feature of the alleles under study known as the longest uninterrupted sequence (LUS). The use of AIC, BIC, DIC, and WAIC in model comparison has some practical limitations. Even though, IS-LOO, TIS-LOO, and PSIS-LOO are considered to be approximations of the exact LOO-CV, the study observed some drastic deviations in the results. However, there are some interesting relationships among the logarithms of pointwise predictive densities (lppd) calculated under WAIC and the LOO approximation methods. The estimated overall lppd is a relative measure that reflects the overall goodness-of-fit of the model. Parallel log-likelihood profiles for the models conditional on equal posterior variances in lppds were observed. This study illustrates the limitations of the information criteria in practical model comparison problems. In addition, the relationships among LOO-CV approximation methods and WAIC with their limitations are discussed. Finally, useful recommendations that may help in practical model comparisons with these methods are provided.

Keywords: cross-validation, importance sampling, information criteria, predictive accuracy

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Authors: Marine Reymond, Michael Descostes, Marie Muguet, Clemence Besancon, Martine Leermakers, Catherine Beaucaire, Sophie Billon, Patricia Patrier

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²²⁶Ra is one of the radionuclides resulting from the disintegration of ²³⁸U. Due to its half-life (1600 y) and its high specific activity (3.7 x 1010 Bq/g), ²²⁶Ra is found at the ultra-trace level in the natural environment (usually below 1 Bq/L, i.e. 10-13 mol/L). Because of its decay in ²²²Rn, a radioactive gas with a shorter half-life (3.8 days) which is difficult to control and dangerous for humans when inhaled, ²²⁶Ra is subject to a dedicated monitoring in surface waters especially in the context of uranium mining. In natural waters, radionuclides occur in dissolved, colloidal or particular forms. Due to the size of colloids, generally ranging between 1 nm and 1 µm and their high specific surface areas, the colloidal fraction could be involved in the transport of trace elements, including radionuclides in the environment. The colloidal fraction is not always easy to determine and few existing studies focus on ²²⁶Ra. In the present study, a complete multidisciplinary approach is proposed to assess the colloidal transport of ²²⁶Ra. It includes water sampling by conventional filtration (0.2µm) and the innovative Diffusive Gradient in Thin Films technique to measure the dissolved fraction (<10nm), from which the colloidal fraction could be estimated. Suspended matter in these waters were also sampled and characterized mineralogically by X-Ray Diffraction, infrared spectroscopy and scanning electron microscopy. All of these data, which were acquired on a rehabilitated former uranium mine, allowed to build a geochemical model using the geochemical calculation code PhreeqC to describe, as accurately as possible, the colloidal transport of ²²⁶Ra. Colloidal transport of ²²⁶Ra was found, for some of the sampling points, to account for up to 95% of the total ²²⁶Ra measured in water. Mineralogical characterization and associated geochemical modelling highlight the role of barite, a barium sulfate mineral well known to trap ²²⁶Ra into its structure. Barite was shown to be responsible for the colloidal ²²⁶Ra fraction despite the presence of kaolinite and ferrihydrite, which are also known to retain ²²⁶Ra by sorption.

Keywords: colloids, mining context, radium, transport

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Authors: Zinaida I. Ivanova, Olga V. Yudenkova

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The article addresses the pressing need to implement the principle of the biosphere compatibility as the core prerequisite for sustainable development. The co-authors argue that a careful attitude towards the biosphere, termination of its overutilization, analysis of the ratio between the biospheric potential of a specific area and its population numbers, coupled with population regulation techniques represent the factors that may solve the problems of ecological depletion. However these problems may only be tackled through the employment of the high-quality human capital, capable of acting with account for the principles of nature conservation.

Keywords: biosphere compatibility, eco-centered conscience, human capital, sustainable development

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Authors: Wei-Chou Hsu, Ching-Sung Lee, Han-Yin Liu

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This work uses H2O2 oxidation technique to improve the pH sensitivity of the AlGaN/GaN-based ion-sensitive field-effect transistors (ISFETs). 10-nm-thick Al2O3 was grown on the surface of the AlGaN. It was found that the pH sensitivity was improved from 41.6 mV/pH to 55.2 mV/pH. Since the H2O2-grown Al2O3 was served as a passivation layer and the problem of Fermi-level pinning was suppressed for the ISFET with the H2O2 oxidation process. Hysteresis effect in the ISFET with the H2O2 treatment also became insignificant. The hysteresis effect was observed by dipping the ISFETs into different pH value solutions and comparing the voltage difference between the initial and final conditions. The hysteresis voltage (Vhys) of the ISFET with the H2O2 oxidation process was improved from 8.7 mV to 4.8 mV. The hysteresis effect is related to the buried binding sites which are related to the material defects like threading dislocations in the AlGaN/GaN heterostructure which was grown by the hetero-epitaxy technique. The H2O2-grown Al2O3 passivate these material defects and the Al2O3 has less material defects. The long-term stability of the ISFET is estimated by the drift effect measurement. The drift measurement was conducted by dipping the ISFETs into a specific pH value solution for 12 hours and the ISFETs were operating at a specific quiescent point. The drift rate is estimated by the drift voltage divided by the total measuring time. It was found that the drift rate of the ISFET was improved from 10.1 mV/hour to 1.91 mV/hour in the pH 7 solution, from 14.06 mV/hour to 6.38 mV/pH in the pH 2 solution, and from 12.8 mV/hour to 5.48 mV/hour in the pH 12 solution. The drift effect results from the capacitance variation in the electric double layer. The H2O2-grown Al2O3 provides an additional capacitance connection in series with the electric double layer. Therefore, the capacitance variation of the electric double layer became insignificant. Generally, the H2O2 oxidation process is a simple, fast, and cost-effective method for the AlGaN/GaN-based ISFET. Furthermore, the performance of the AlGaN/GaN ISFET was improved effectively and the non-ideal effects were suppressed.

Keywords: AlGaN/GaN, Al2O3, hysteresis effect, drift effect, reliability, passivation, pH sensors

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Authors: Cristina Gutiérrez Carranza

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Digital nomadism is a trend and lifestyle which combines work and traveling. This tourism tendency is motivated by the desire to have a fixed source of financial income while becoming independent from a specific work location. This study contextualizes Costa Rica and its potential prospects to take advantage of this tourism market niche. It explores the dynamics of digital nomadism in the context of Costa Rica, analyzing the current scenario, challenges, and opportunities related to this global phenomenon. The research covers several areas, including the conceptualization of digital nomadism, its historical background, and contemporary manifestations. The investigation delves into the present state of digital nomadism, evaluating the extent of digitalization in Costa Rica, mobile phone coverage, and fixed internet access. As part of the strategies implemented, as the study develops, mapping the most common destinations of digital nomads is a key factor, bringing a sight on the aspects that make Costa Rica an attractive location for this emerging tourist group. Additionally, the paper draws insights from hosting entrepreneurs and digital nomads with work visas in Costa Rica, offering a comprehensive understanding of the experiences and perspectives from both sides. Hence, the study includes data from a sample of 20 digital nomads holding visas for Costa Rica, offering a detailed analysis of their professional activities, experiences and needs as remote workers in the country. As well it adds in perceptions from 10 entrepreneurs engaged in providing accommodation services to digital nomads contribute to a degree of understanding of the way they have faced this growing movement. This research provides significant insights on the dynamics of digital nomadism in Costa Rica by integrating data from specific sources. Policymakers, entrepreneurs, and other stakeholders are anticipated to gain valuable data from the findings regarding the opportunities and challenges of hosting and accommodating digital nomads, which will ultimately aid in the creation of plans to capitalize on this worldwide trend for the nation's socioeconomic development.

Keywords: digital nomads, tourism, sustainability, digital nomads visa, remote jobs

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Authors: Lubna M. A. Hassan, Nasir Brema, Abdallah Mamy, Insaf Yahya, Tanzil A. G., Ahmed M. M. Hasoba, Omer A. Suliman

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The Nubian ibex species has been categorized as vulnerable by the International Union for Conservation of Nature (IUCN) due to a lack of population data in specific regions within their habitat. This species faces numerous challenges, including habitat loss caused by agricultural practices, livestock rearing, mining activity, and infrastructure development. Additionally, competition with non-native species and hunting pose significant threats to their survival. Unfortunately, studies on the distribution, conservation status, ecology, and health of the ibex are limited and primarily descriptive in nature. In order to bridge this knowledge gap, recent surveys were conducted in the Red Sea State of Sudan during specific periods in 2015, 2016, 2019, and 2021. These surveys have provided valuable insights into the distribution, habitats, and conservation status of the Nubian ibex in the Red Sea State. The findings indicate that the Capra nubiana ibex can be found across more than 17 mountains in the Red Sea State. However, the total population estimate from recent years suggests that there are fewer than 250 individuals remaining. The study has also identified the highest altitude at which the Nubian ibex habitats existed in Sudan's Red Sea State, measuring 1675 m. This area harbors a diverse array of Nubian ibex habitats, encompassing a total of 21 wild plant species from 10 distinct families. The region experiences an average annual temperature ranging from 20.64°C in January to 33.30°C in August. Precipitation occurs in November and December, although it is characterized by unreliability and erratic patterns. It is important to note that these population estimates were obtained through surveys conducted in collaboration with rangers and local communities, and adjustments to survey methods are necessary to accommodate the challenging mountainous terrain, such as utilizing aerial surveys. To effectively address these threats, it is imperative to establish comprehensive long-term monitoring programs.

Keywords: Nubian ibex, distribution, population, habitats

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Authors: Clarence Dissanayake, Anishka A. Hettiarachchi

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Landscape architecture needs to encompass a placemaking process carefully composing and manipulating landscape elements to address perceptual needs of humans, especially aesthetic, psychological and spiritual. The objective of this qualitative investigation is to inquire the impact of elements of rock and water combination on landscape perception and related feelings, emotions, and behavior. The past empirical studies have assessed the impact of landscape elements in isolation on user preference, yet the combined effect of elements have been less considered. This research was conducted with reference to the verity of qualities of water and rock through a visual landscape quality assessment focusing on landscape qualities derived from five visual concepts (coherence, historicity imageability, naturalness, and ephemera). 'Kaludiya Pokuna' archeological site in Anuradhapura was investigated with a sample of University students (n=19, male 14, female 5, age 20-25) using a five-point Likert scale via a perception based questionnaire and a visitor employed photographic survey (VEP). Two hypothetical questions were taken into investigation concerning biophilic (naturalness) and topophilic (historicity) aspects of humans to prefer a landscape with rock and water. The findings revealed that this combination encourages both biophilic and topophilic aspects, but in varying degrees. The identified hierarchy of visual concepts based on visitor’s preference signify coherence (93%), historicity (89%), imageability (79%), naturalness (75%) and ephemera (70%) respectively. It was further revealed that this combination creates a scenery more coherent dominating information processing aspect of humans to perceive a landscape over the biophilic and topophilic aspects. Different characteristics and secondary landscape effects generated by rock and water combination were found to affect in transforming a space into a place, full filling the aesthetic and spiritual aspects of the visitors. These findings enhance a means of making places for people, resource management and historical landscape conservation. Equalization of gender based participation, taking diverse cases and increasing the sample size with more analytical photographic analysis are recommended to enhance the quality of further research.

Keywords: landscape perception, visitor’s preference, rock and water combination, visual concepts

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Authors: Stephen Anim, Emmanuel O. Sarpong, Daniel Apaak

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This study investigates the relationship between morphological predictors and running ability, emphasizing gender-specific variations among male and female athletes in Cape Coast Metropolis (CCM), Ghana. The dynamic interplay between an athlete's physique and their performance capabilities holds particular relevance in the realm of sports science, influencing training methodologies and talent identification processes. The research aims to contribute comprehensive insights into the morphological determinants of running proficiency, with a specific focus on the local athletic community in Cape Coast Metropolis. Utilizing a correlational research design, a thorough analysis of morphological features, encompassing 22 morphological features including body weight, 6 measurements related to body length, 7 body girth, and knee diameter, and 7 skinfold measurements against 50m dash, among male and female athletes, was conducted. The study involved 420 athletes both male (N=210) and female (N=210) aged 16-22 from 10 Senior High Schools (SHS) in the Cape Coast Metropolis, providing a representative sample of the local athletic community. The collected data were statistically analysed using means and standard deviation, and stepwise multiple regression to determine how morphological variables contribute to and predict running proficiency outcomes. The investigation revealed that athletes from Senior High Schools (SHS) in Cape Coast Metropolis (CCM) exhibit well-developed physiques and sufficient fitness levels suitable for overall athletic performance, taking into account gender differences. Moreover, the findings suggested that approximately 77% of running ability could be attributed to morphological factors, leading to diverse predictive models for male and female athletes within SHS in CCM, Ghana. Consequently, these formulated equations hold promise for predicting running ability among young athletes, particularly in the context of SHS environments.

Keywords: body fat, body girth, body length, morphological features, running ability, senior high school

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Authors: Svetlana Strinyuk, Viacheslav Lanin

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Academic English has become lingua franca for international scientific community which stimulates universities to introduce English for Specific Purposes (EAP) courses into curriculum. Teaching L2 EAP students might be fulfilled with corpus technologies and digital stylistics. A special software developed to reach the manifold task of teaching, assessing and researching academic writing of L2 students on basis of digital stylistics and multidimensional analysis was created. A set of annotations (style markers) – grammar, lexical and syntactic features most significant of academic writing was built. Contrastive comparison of two corpora “model corpus”, subject domain limited papers published by competent writers in leading academic journals, and “students’ corpus”, subject domain limited papers written by last year students allows to receive data about the features of academic writing underused or overused by L2 EAP student. Both corpora are tagged with a special software created in GATE Developer. Style markers within the framework of research might be replaced depending on the relevance and validity of the result which is achieved from research corpora. Thus, selecting relevant (high frequency) style markers and excluding less relevant, i.e. less frequent annotations, high validity of the model is achieved. Software allows to compare the data received from processing model corpus to students’ corpus and get reports which can be used in teaching and assessment. The less deviation from the model corpus students demonstrates in their writing the higher is academic writing skill acquisition. The research showed that several style markers (hedging devices) were underused by L2 EAP students whereas lexical linking devices were used excessively. A special software implemented into teaching of EAP courses serves as a successful visual aid, makes assessment more valid; it is indicative of the degree of writing skill acquisition, and provides data for further research.

Keywords: corpus technologies in EAP teaching, multidimensional analysis, GATE Developer, corpus stylistics

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Authors: Diandra Cristache

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The transition of traditional manuscript studies into the digital framework closely affects the methodological premises upon which manuscript descriptions are modeled, created, and questioned for the purpose of research. This paper intends to explore the issue by presenting a methodological investigation into the process of modeling, creating, and questioning manuscript metadata. The investigation is founded on a close observation of the Polonsky Greek Manuscripts Project, a collaboration between the Universities of Cambridge and Heidelberg. More than just providing a realistic ground for methodological exploration, along with a complete metadata set for computational demonstration, the case study also contributes to a broader purpose: outlining general methodological principles for making the most out of manuscript metadata by means of research-oriented digital outputs. The analysis mainly focuses on the scholarly approach to manuscript descriptions, in the specific instance where the act of metadata recording does not have a programmatic research purpose. Close attention is paid to the encounter of 'traditional' practices in manuscript studies with the formal constraints of the digital framework: does the shift in practices (especially from the straight narrative of free writing towards the hierarchical constraints of the TEI encoding model) impact the structure of metadata and its capability to respond specific research questions? It is argued that flexible structure of TEI and traditional approaches to manuscript description lead to a proliferation of markup: does an 'encyclopedic' descriptive approach ensure the epistemological relevance of the digital outputs to metadata? To provide further insight on the computational approach to manuscript metadata, the metadata of the Polonsky project are processed with techniques of distant reading and data networking, thus resulting in a new group of digital outputs (relational graphs, geographic maps). The computational process and the digital outputs are thoroughly illustrated and discussed. Eventually, a retrospective analysis evaluates how the digital outputs respond to the scientific expectations of research, and the other way round, how the requirements of research questions feed back into the creation and enrichment of metadata in an iterative loop.

Keywords: digital manuscript studies, digital outputs to manuscripts metadata, metadata interoperability, methodological issues

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Authors: Eric Bang

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Interactions between receptors and ligands are crucial for many essential biological processes, including neurotransmission and metabolism. Ligand-receptor analyses that examine cell behavior and interactions often utilize cell type-specific RNA expressions from single-cell RNA sequencing (scRNA-seq) data. Using CellPhoneDB, a public repository consisting of ligands, receptors, and ligand-receptor interactions, the cell-cell interactions were explored in a specific scRNA-seq dataset from kidney tissue and portrayed the results with dot plots and heat maps. Depending on the type of cell, each ligand-receptor pair was aligned with the interacting cell type and calculated the positori probabilities of these associations, with corresponding P values reflecting average expression values between the triads and their significance. Using single-cell data (sample kidney cell references), genes in the dataset were cross-referenced with ones in the existing CellPhoneDB dataset. For example, a gene such as Pleiotrophin (PTN) present in the single-cell data also needed to be present in the CellPhoneDB dataset. Using the single-cell transcriptomics data via slide-seq and reference data, the CellPhoneDB program defines cell types and plots them in different formats, with the two main ones being dot plots and heat map plots. The dot plot displays derived measures of the cell to cell interaction scores and p values. For the dot plot, each row shows a ligand-receptor pair, and each column shows the two interacting cell types. CellPhoneDB defines interactions and interaction levels from the gene expression level, so since the p-value is on a -log10 scale, the larger dots represent more significant interactions. By performing an interaction analysis, a significant interaction was discovered for myeloid and T-cell ligand-receptor pairs, including those between Secreted Phosphoprotein 1 (SPP1) and Fibronectin 1 (FN1), which is consistent with previous findings. It was proposed that an effective protocol would involve a filtration step where cell types would be filtered out, depending on which ligand-receptor pair is activated in that part of the tissue, as well as the incorporation of the CellPhoneDB data in a streamlined workflow pipeline. The filtration step would be in the form of a Python script that expedites the manual process necessary for dataset filtration. Being in Python allows it to be integrated with the CellPhoneDB dataset for future workflow analysis. The manual process involves filtering cell types based on what ligand/receptor pair is activated in kidney cells. One limitation of this would be the fact that some pairings are activated in multiple cells at a time, so the manual manipulation of the data is reflected prior to analysis. Using the filtration script, accurate sorting is incorporated into the CellPhoneDB database rather than waiting until the output is produced and then subsequently applying spatial data. It was envisioned that this would reveal wherein the cell various ligands and receptors are interacting with different cell types, allowing for easier identification of which cells are being impacted and why, for the purpose of disease treatment. The hope is this new computational method utilizing spatially explicit ligand-receptor association data can be used to uncover previously unknown specific interactions within kidney tissue.

Keywords: bioinformatics, Ligands, kidney tissue, receptors, spatial transcriptome

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Authors: Shreya Poddar

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Legal drafting and revising are recognized as highly demanding tasks for legal professionals. This paper introduces an approach to automate and refine these processes through the use of advanced Artificial Intelligence (AI). The method employs Large Language Models (LLMs), with a specific focus on 'Chain of Thoughts' (CoT) and knowledge injection via prompt engineering. This approach differs from conventional methods that depend on comprehensive training or fine-tuning of models with extensive legal knowledge bases, which are often expensive and time-consuming. The proposed method incorporates knowledge injection directly into prompts, thereby enabling the AI to generate more accurate and contextually appropriate legal texts. This approach substantially decreases the necessity for thorough model training while preserving high accuracy and relevance in drafting. Additionally, the concept of guardrails is introduced. These are predefined parameters or rules established within the AI system to ensure that the generated content adheres to legal standards and ethical guidelines. The practical implications of this method for legal work are considerable. It has the potential to markedly lessen the time lawyers allocate to document drafting and revision, freeing them to concentrate on more intricate and strategic facets of legal work. Furthermore, this method makes high-quality legal drafting more accessible, possibly reducing costs and expanding the availability of legal services. This paper will elucidate the methodology, providing specific examples and case studies to demonstrate the effectiveness of 'Chain of Thoughts' and knowledge injection in legal drafting. The potential challenges and limitations of this approach will also be discussed, along with future prospects and enhancements that could further advance legal work. The impact of this research on the legal industry is substantial. The adoption of AI-driven methods by legal professionals can lead to enhanced efficiency, precision, and consistency in legal drafting, thereby altering the landscape of legal work. This research adds to the expanding field of AI in law, introducing a method that could significantly alter the nature of legal drafting and practice.

Keywords: AI-driven legal drafting, legal automation, futureoflegalwork, largelanguagemodels

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Authors: Lindsay Foreman

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Introduction: Goals have become synonymous with the quest for the good life and the pursuit of happiness, with coaching and positive psychology gaining popularity as an approach in recent decades. And yet mental health is on the rise and the leading cause of disability, wellbeing is on the decline, stress is leading to 50-60% of workday absences and the need for action is indisputable and urgent. Purpose: The purpose of this study is to better understand two things we cannot see, but that play the most significant role in these outcomes - what we think and how we feel. With many working on the assumption that positive thinking and an optimistic outlook are necessary or valuable components of goal pursuit, this study uncovers the reality of the ‘inner-game’ from the coachees perspective. Method: With a mixed methods design using a Q Method study of subjectivity to ‘make the unseen seen’. First, a wide-ranging universe of subjective thoughts and feelings experienced during goal pursuit are explored.. These are generated from literature and a Qualtrics survey to create a Q-Set of 40 statements. Then 19 participants in professional and organisational settings offer their perspectives on these 40 Q-Set statements. Each rank them in a semi-forced distribution from ‘most like me’ to ‘least like me’ using Q-Sort software. From these individual perspectives, clusters of perspectives are identified using factor analysis and four distinct viewpoints, have emerged. Findings: These Goal Pursuit Viewpoints offer insight into the states and self-talk experienced by coachees and may not reflect the assumption of positive thinking associated with achieving goals. The four Viewpoints are 1) the Positive View, 2) the Realistic View 3) The Dreamer View and 4) The Conflicted View. With only a quarter of the Dreamer View, and a third of the Positive view going on to achieve their goals, these assumptions need review. And with all the Realistic View going on to achieve their goals, the role of self-doubt, overwhelm and anxiousness in goal achievement cannot be overlooked. Contribution: This study offers greater insight and understanding of people's inner experiences as they pursue goals and highlights the necessary and normal negative states associated with goal achievement. It also offers a practical tool of 40 ‘Clarity Card’ Q-set statements to help coaches and coachees explore the current state and help navigate the journey towards goal achievement. It calls into question whether goals should always be part of coaching, and if values, identity, and purpose may play a greater role than goals

Keywords: self-talk, mental health, inner critic, inner coach

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Authors: Andreas Lind, Aitor Iriondo Pascual, Dan Hogberg, Lars Hanson

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Factory setup lifecycles are most often described and prepared in CAD environments; the preparation is based on experience and inputs from several cross-disciplinary processes. Early in the factory setup preparation, a so-called block layout is created. The intention is to describe a high-level view of the intended factory setup and to claim area reservations and allocations. Factory areas are then blocked, i.e., targeted to be used for specific intended resources and processes, later redefined with detailed factory setup layouts. Each detailed layout is based on the block layout and inputs from cross-disciplinary preparation processes, such as manufacturing sequence, productivity, workers’ workplace requirements, and resource setup preparation. However, this activity is often not carried out with all variables considered simultaneously, which might entail a risk of sub-optimizing the detailed layout based on manual decisions. Therefore, this work aims to realize a digital method for assembly manufacturing layout planning where productivity, area utilization, and ergonomics can be considered simultaneously in a cross-disciplinary manner. The purpose of the digital method is to support engineers in finding optimized designs of detailed layouts for assembly manufacturing factories, thereby facilitating better decisions regarding setups of future factories. Input datasets are company-specific descriptions of required dimensions for specific area reservations, such as defined dimensions of a worker’s workplace, material façades, aisles, and the sequence to realize the product assembly manufacturing process. To test and iteratively develop the digital method, a demonstrator has been developed with an adaptation of existing software that simulates and proposes optimized designs of detailed layouts. Since the method is to consider productivity, ergonomics, area utilization, and constraints from the automatically generated block layout, a multi-objective optimization approach is utilized. In the demonstrator, the input data are sent to the simulation software industrial path solutions (IPS). Based on the input and Lua scripts, the IPS software generates a block layout in compliance with the company’s defined dimensions of area reservations. Communication is then established between the IPS and the software EPP (Ergonomics in Productivity Platform), including intended resource descriptions, assembly manufacturing process, and manikin (digital human) resources. Using multi-objective optimization approaches, the EPP software then calculates layout proposals that are sent iteratively and simulated and rendered in IPS, following the rules and regulations defined in the block layout as well as productivity and ergonomics constraints and objectives. The software demonstrator is promising. The software can handle several parameters to optimize the detailed layout simultaneously and can put forward several proposals. It can optimize multiple parameters or weight the parameters to fine-tune the optimal result of the detailed layout. The intention of the demonstrator is to make the preparation between cross-disciplinary silos transparent and achieve a common preparation of the assembly manufacturing factory setup, thereby facilitating better decisions.

Keywords: factory setup, multi-objective, optimization, simulation

Procedia PDF Downloads 138

Authors: Ida Zubaidah

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With the advancement of information and communication technologies, in many cases, geographical distance is no longer considered as a main barrier in distance education. Geographical distance, even from a continent to another, between students and their instructor or students and their campus can be connected by the Internet, telephone or any other means of communication technology. Managing distance learning in an archipelagic country like Indonesia, however, has some different stories. Comprising more than 17,000 islands and 6.000 of them inhabited, Indonesia is considered as one of the most archipelagic countries in the world. In some areas or islands that have adequate public transportation and communication facilities the courses can be delivered quite well. In other areas that geographically very remote and dispersed islander, Universitas Terbuka, an open university in Indonesia, has to have very different strategies in overcoming the specific and even emergency situations in learning delivery. This ongoing research paper aims to share experiences of how Universitas Terbuka makes serious and unique efforts in overcoming the barriers and obstacles in providing educational service in part of difficult areas, especially in eastern areas of Indonesia. The data collection methods are observation of sample areas and in-depth interview with the head of regional offices of Universitas Terbuka in eastern Indonesia, staff, and tutors. Conducting educational deliveries in in difficult areas with no regular and adequate transportation has made the regional office have specific strategies in making the learning process run as smooth as possible. Sending a tutor to an area to meet some students and conducting a series of tutorial, which are supposed to be weekly, in several days is one of the strategies. Recruiting local people to manage the students in the area is another strategy. The absence of regular transportation from island to island, high tides, hurricanes, are among the obstacles faced by the regional offices in doing their job. Non geographical barriers such as unavailability of qualified tutor, inadequate tutor payment, are problems as well. The learning process, however, has to be done in any way, otherwise the distance education mission to reach unreachable cannot be achieved.

Keywords: distance education, Terbuka University, difficult area, geographical barrier, learning services

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Authors: Peter Krupa, Svetozár Malinarič

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Transient plane source method has been used to measure the thermal diffusivity and thermal conductivity of a compact isostatic electro-ceramics at room temperature. The samples were fired at temperatures from 100 up to 1320 degrees Celsius in steps of 50. Bulk density and specific heat capacity were also measured with their corresponding standard uncertainties. The results were compared with further thermal analysis (dilatometry and thermogravimetry). Structural processes during firing were discussed.

Keywords: TPS method, thermal conductivity, thermal diffusivity, thermal analysis, electro-ceramics, firing

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Authors: Hatem Abou-Senna

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Interstate 4 (I-4) is a primary east-west transportation corridor between Tampa and Daytona cities, serving commuters, commercial and recreational traffic. I-4 is known to have severe recurring congestion during peak hours. The congestion spans about 11 miles in the evening peak period in the central corridor area as it is considered the only non-tolled limited access facility connecting the Orlando Central Business District (CBD) and the tourist attractions area (Walt Disney World). Florida officials had been skeptical of tolling I-4 prior to the recent legislation, and the public through the media had been complaining about the excessive toll facilities in Central Florida. So, in search for plausible mitigation to the congestion on the I-4 corridor, this research is implemented to evaluate the effectiveness of different toll pricing alternatives that might divert traffic from I-4 to the toll facilities during the peak period. The network is composed of two main diverging limited access highways, freeway (I-4) and toll road (SR 417) in addition to two east-west parallel toll roads SR 408 and SR 528, intersecting the above-mentioned highways from both ends. I-4 and toll road SR 408 are the most frequently used route by commuters. SR-417 is a relatively uncongested toll road with 15 miles longer than I-4 and $5 tolls compared to no monetary cost on 1-4 for the same trip. The results of the calibrated Orlando PARAMICS network showed that percentages of route diversion vary from one route to another and depends primarily on the travel cost between specific origin-destination (O-D) pairs. Most drivers going from Disney (O1) or Lake Buena Vista (O2) to Lake Mary (D1) were found to have a high propensity towards using I-4, even when eliminating tolls and/or providing real-time information. However, a diversion from I-4 to SR 417 for these OD pairs occurred only in the cases of the incident and lane closure on I-4, due to the increase in delay and travel costs, and when information is provided to travelers. Furthermore, drivers that diverted from I-4 to SR 417 and SR 528 did not gain significant travel-time savings. This was attributed to the limited extra capacity of the alternative routes in the peak period and the longer traveling distance. When the remaining origin-destination pairs were analyzed, average travel time savings on I-4 ranged between 10 and 16% amounting to 10 minutes at the most with a 10% increase in the network average speed. High propensity of diversion on the network increased significantly when eliminating tolls on SR 417 and SR 528 while doubling the tolls on SR 408 along with the incident and lane closure scenarios on I-4 and with real-time information provided. The toll roads were found to be a viable alternative to I-4 for these specific OD pairs depending on the user perception of the toll cost which was reflected in their specific travel times. However, on the macroscopic level, it was concluded that route diversion through toll reduction or elimination on surrounding toll roads would only have a minimum impact on reducing I-4 congestion during the peak period.

Keywords: congestion pricing, dynamic feedback assignment, microsimulation, paramics, route diversion

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Authors: Salman Akrokayan

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Synthetic cDNA (ScDNA) of granulocyte colony-stimulating factor (G-CSF) was constructed using a DNA synthesizer with the aim to increase its expression level. 5' end of the ScDNA of G-CSF coding region was modified by decreasing the GC content without altering the predicted amino acids sequence. The identity of the resulting protein from ScDNA was confirmed by the highly specific enzyme-linked immunosorbent assay. In conclusion, a synthetic G-CSF cDNA in combination with the recombinant DNA protocol offers a rapid and reliable strategy for synthesizing the target protein. However, the commercial utilization of this methodology requires rigorous validation and quality control.

Keywords: synthetic cDNA, recombinant G-CSF, cloning, gene expression

Procedia PDF Downloads 269

Authors: Ernest Moles, Patricia Urbán, María Belén Jiménez-Díaz, Sara Viera-Morilla, Iñigo Angulo-Barturen, Maria Antònia Busquets, Xavier Fernàndez-Busquets

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Bearing in mind the absence of an effective vaccine against malaria and its severe clinical manifestations causing nearly half a million deaths every year, this disease represents nowadays a major threat to life. Besides, the basic rationale followed by currently marketed antimalarial approaches is based on the administration of drugs on their own, promoting the emergence of drug-resistant parasites owing to the limitation in delivering drug payloads into the parasitized erythrocyte high enough to kill the intracellular pathogen while minimizing the risk of causing toxic side effects to the patient. Such dichotomy has been successfully addressed through the specific delivery of immunoliposome (iLP)-encapsulated antimalarials to Plasmodium falciparum-infected red blood cells (pRBCs). Unfortunately, this strategy has not progressed towards clinical applications, whereas in vitro assays rarely reach drug efficacy improvements above 10-fold. Here, we show that encapsulation efficiencies reaching >96% can be achieved for the weakly basic drugs chloroquine (CQ) and primaquine using the pH gradient active loading method in liposomes composed of neutrally charged, saturated phospholipids. Targeting antibodies are best conjugated through their primary amino groups, adjusting chemical crosslinker concentration to retain significant antigen recognition. Antigens from non-parasitized RBCs have also been considered as targets for the intracellular delivery of drugs not affecting the erythrocytic metabolism. Using this strategy, we have obtained unprecedented nanocarrier targeting to early intraerythrocytic stages of the malaria parasite for which there is a lack of specific extracellular molecular tags. Polyethylene glycol-coated liposomes conjugated with monoclonal antibodies specific for the erythrocyte surface protein glycophorin A (anti-GPA iLP) were capable of targeting 100% RBCs and pRBCs at the low concentration of 0.5 μM total lipid in the culture, with >95% of added iLPs retained into the cells. When exposed for only 15 min to P. falciparum in vitro cultures synchronized at early stages, free CQ had no significant effect over parasite viability up to 200 nM drug, whereas iLP-encapsulated 50 nM CQ completely arrested its growth. Furthermore, when assayed in vivo in P. falciparum-infected humanized mice, anti-GPA iLPs cleared the pathogen below detectable levels at a CQ dose of 0.5 mg/kg. In comparison, free CQ administered at 1.75 mg/kg was, at most, 40-fold less efficient. Our data suggest that this significant improvement in drug antimalarial efficacy is in part due to a prophylactic effect of CQ found by the pathogen in its host cell right at the very moment of invasion.

Keywords: immunoliposomal nanoparticles, malaria, prophylactic-therapeutic polyvalent activity, targeted drug delivery

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