Search results for: aging mechanisms

Authors: Xincheng Jiang, Yanyan An, Yaoyao Huang, Wei Ding, Manli Sun, Hong Li, Huaili Zheng

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The residual antibiotics in the environment will pose a threat to the environment and human health. Thus, efficient removal and rapid detection of norfloxacin (NOR) in wastewater is very important. The main sources of NOR pollution are the agricultural, pharmaceutical industry and hospital wastewater. The total consumption of NOR in China can reach 5440 tons per year. It is found that neither animals nor humans can totally absorb and metabolize NOR, resulting in the excretion of NOR into the environment. Therefore, residual NOR has been detected in water bodies. The hazards of NOR in wastewater lie in three aspects: (1) the removal capacity of the wastewater treatment plant for NOR is limited (it is reported that the average removal efficiency of NOR in the wastewater treatment plant is only 68%); (2) NOR entering the environment will lead to the emergence of drug-resistant strains; (3) NOR is toxic to many aquatic species. At present, the removal and detection technologies of NOR are applied separately, which leads to a cumbersome operation process. The development of simultaneous adsorption-flocculation removal and FTIR detection of pollutants has three advantages: (1) Adsorption-flocculation technology promotes the detection technology (the enrichment effect on the material surface improves the detection ability); (2) The integration of adsorption-flocculation technology and detection technology reduces the material cost and makes the operation easier; (3) FTIR detection technology endows the water treatment agent with the ability of molecular recognition and semi-quantitative detection for pollutants. Thus, it is of great significance to develop a smart water treatment material with high removal capacity and detection ability for pollutants. This study explored the feasibility of combining NOR removal method with the semi-quantitative detection method. A magnetic Cu-Ni-S/Ni foam was synthesized by in-situ loading Cu-Ni-S nanostructures on the surface of Ni foam. The novelty of this material is the combination of adsorption-flocculation technology and semi-quantitative detection technology. Batch experiments showed that Cu-Ni-S/Ni foam has a high removal rate of NOR (96.92%), wide pH adaptability (pH=4.0-10.0) and strong ion interference resistance (0.1-100 mmol/L). According to the Langmuir fitting model, the removal capacity can reach 417.4 mg/g at 25 °C, which is much higher than that of other water treatment agents reported in most studies. Characterization analysis indicated that the main removal mechanisms are surface complexation, cation bridging, electrostatic attraction, precipitation and flocculation. Transmission FTIR detection experiments showed that NOR on Cu-Ni-S/Ni foam has easily recognizable FTIR fingerprints; the intensity of characteristic peaks roughly reflects the concentration information to some extent. This semi-quantitative detection method has a wide linear range (5-100 mg/L) and a low limit of detection (4.6 mg/L). These results show that Cu-Ni-S/Ni foam has excellent removal performance and semi-quantitative detection ability of NOR molecules. This paper provides a new idea for designing and preparing multi-functional water treatment materials to achieve simultaneous removal and semi-quantitative detection of organic pollutants in water.

Keywords: adsorption-flocculation, antibiotics detection, Cu-Ni-S/Ni foam, norfloxacin

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Authors: Orkide Donma, Mustafa M. Donma

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Childhood obesity, which may lead to increased risk for heart diseases in children as well as adults, is one of the most important health problems throughout the world. Prevalences of morbid obesity and metabolic syndrome (MetS) are being increased during childhood age group. MetS is a cluster of metabolic and vascular abnormalities including hypercoagulability and an increased risk of cardiovascular diseases (CVDs). There are also some relations between some components of MetS and leukocytes. The aim of this study is to investigate complete blood cell count parameters that differ between morbidly obese boys and girls with MetS diagnosis. A total of 117 morbid obese children with MetS consulted to Department of Pediatrics in Faculty of Medicine Hospital at Namik Kemal University were included into the scope of the study. The study population was classified based upon their genders (60 girls and 57 boys). Their heights and weights were measured and body mass index (BMI) values were calculated. WHO BMI-for age and sex percentiles were used. The values above 99 percentile were defined as morbid obesity. Anthropometric measurements were performed. Waist-to-hip and head-to-neck ratios as well as homeostatic model assessment of insulin resistance (HOMA-IR) were calculated. Components of MetS (central obesity, glucose intolerance, high blood pressure, high triacylglycerol levels, low levels of high density lipoprotein cholesterol) were determined. Hematological variables were measured. Statistical analyses were performed using SPSS. The degree for statistical significance was p ≤ 0.05. There was no statistically significant difference between the ages (11.2±2.6 years vs 11.2±3.0 years) and BMIs (28.6±5.2 kg/m² vs 29.3±5.2 kg/m²) of boys and girls (p ≥ 0.05), respectively. Significantly increased waist-to-hip ratios were obtained for boys (0.94±0.08 vs 0.91±0.06; p=0.023). Significantly elevated values of hemoglobin (13.55±0.98 vs 13.06±0.82; p=0.004), mean corpuscular hemoglobin concentration (33.79±0.91 vs 33.21±1.14; p=0.003), eosinophils (0.300±0.253 vs 0.196±0.197; p=0.014), and platelet (347.1±81.7 vs 319.0±65.9; p=0.042) were detected for boys. There was no statistically significant difference between the groups in terms of neutrophil/lymphocyte ratios as well as HOMA-IR values (p ≥ 0.05). Statistically significant gender-based differences were found for hemoglobin as well as mean corpuscular hemoglobin concentration and hence, separate reference intervals for two genders should be considered for these parameters. Eosinophils may contribute to the development of thrombus in acute coronary syndrome. Eosinophils are also known to make an important contribution to mechanisms related to thrombosis pathogenesis in acute myocardial infarction. Increased platelet activity is observed in patients with MetS and these individuals are more susceptible to CVDs. In our study, elevated platelets described as dominant contributors to hypercoagulability and elevated eosinophil counts suggested to be related to the development of CVDs observed in boys may be the early indicators of the future cardiometabolic complications in this gender.

Keywords: children, complete blood count, gender, metabolic syndrome

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Authors: Faris Mohsin Alabeedi

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Pemphigus Vulgaris (PV) is a life-threatening autoimmune blistering disease characterized by the presence of autoantibodies directed against the epidermis's surface proteins. There are two forms of PV, mucocutaneous and mucosal-dominant PV. Disruption of the cell junctions is a hallmark of PV due to the autoantibodies targeting the desmosomal cadherins, desmoglein-3 (Dsg3) and desmoglein-1, leading to acantholysis in the skin and mucous membrane. Although the pathogenesis of PV is known, the detailed molecular events remain not fully understood. Our recent study has shown that both the PV sera and pathogenic anti-Dsg3 antibody AK23 can induce ROS and cause oxidative stress in cultured keratinocytes. In line with our finding, other independent studies also demonstrate oxidative stress in PV. Since Nrf2 plays a crucial role in cellular anti-oxidative stress response, we hypothesize that the expression of Nrf2 may alter in PV. Thus, treatment of cells with PV sera or AK23 may cause changes in Nrf2 expression and distribution. The purpose of this study was to examine the effect of AK23 and PV sera on Nrf2 in a normal human keratinocyte cell line, such as NTERT cells. Both a time-course and dose-dependent experiments with AK23, alongside the matched isotype control IgG, were performed in keratinocyte cultures and analysed by immunofluorescence for Nrf2 and Dsg3. Additionally, the same approach was conducted with the sera from PV patients and healthy individuals that served as a control in this study. All the fluorescent images were analysed using ImageJ software. Each experiment was repeated twice. In general, variations were observed throughout this study. In the dose-response experiments, although enhanced Dsg3 expression was consistently detected in AK23 treated cells, the expression of Nrf2 showed no consistent findings between the experiments, although changes in its expression were noticeable in cells treated with AK23. In the time-course study, a trend with induction of Nrf2 over time was shown in control cells treated with mouse isotype IgG. Treatment with AK23 showed a reduction of Nrf2 in a time-dependent manner, especially at the 24-hour time point. However, the earlier time points, such as 2 hours and 6 hours with AK23 treatments, detected somewhat variations. Finally, PV sera caused a decrease of Dsg3, but on the other hand, variations were observed in Nrf2 expression in PV sera treated cells. In general, PV sera seemed to cause a reduction of Nrf2 in the majority of PV sera treated samples. In addition, more pronounced cytoplasmic expression of Nrf2 has been observed in PV sera treated cells than those treated with AK23, suggesting that polyclonal and monoclonal IgG might induce a different effect on Nrf2 expression and distribution. Further experimental studies are crucial to obtain a more coincide global view of Nrf2-mediated gene regulation. In particular, Pemphigus Voulgaris studies assessing how the Nrf2-dependent network changes from a physiological to a pathological condition can provide insight into disease mechanisms and perhaps initiate further treatment approaches.

Keywords: pemphigus vulgaris, monoclonal antibody against desmoglein-3, Nrf2 oxidative stress, keratinocyte cultures

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Authors: Lamia Bouzgarrou, Amira Omrane, Leila Mrabet, Taoufik Khalfallah

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Background and aims: School accidents are one of the leading causes of morbidity and mortality among pupils and students. Indeed, they may induce an elevated number of lost school days, heavy emotional and physical disabilities, and financial costs on the victims and their families. This study aims to evaluate the annual incidence of school accidents in the central Tunisian governorate of Mahdia and to identify the epidemiological profile of victims and risk factors of these accidents. Methods: A retrospective study was conducted over the period of 5 school years, focusing on school accidents that occurred in public educational institutions (primary, basic, secondary and university) in the governorate of Mahdia (area = 2 966 km² and number of inhabitants in 2014 = 410 812). All accidents declared near the only official insurance of this type of injuries (MASU: Mutual School and University Accidents), and initially taken in charge at the University Hospital of Mahdia were included. Data was collected from the MASU reporting forms and the medical records of emergency and other specialized hospital departments. Results: With 3248 identified victims, the annual incidence of school accidents was equal to 0.69 per 100 pupils and students per year. The average age of victims was 14.51 ± 0.059 years and the sex ratio was 1.58. Pupils aged between 12 and 15 years, were concerned by 46.7% of the identified accidents. The practice of sports was the most relevant circumstances of these accidents (76.2 %). In 56.58 % of cases, falls were the leading mechanism. Bruises and fractures were the most frequent lesions (32.43 % and 30.51 %). Serious school accidents were noted in 28% of cases with hospitalization in 2.27 % of them. The average lost school days, was 12.23±1.73 days. Accidents occurring during sports or leisure activities were significantly more serious (p= 0.021). Furthermore, the frequency of hospitalization was significantly higher among boys (2.81% vs. 1.43%; p= 0.035), students ≤11 years (p= 0.008), and following crush trauma (p= 0.000). In addition, the surgical interventions were statistically more frequent among male victims (p=0.00), accidents occurring during physical education sessions (p=0.000); those associated to falls (p=0.000) and to crushes mechanisms (p=0.002), and injuries affecting lower limbs (p=0.000). Following this Multi-varied analysis concluded that the severity of school accident is correlated to the activity practiced during the trauma and the geographical location of the school. Conclusion: Children and adolescents are one of the most vulnerable groups against incidents with the risk of permanent disability, mainly related to the perturbation of the growth process and physiological limitations. Our five-year study, objectified a real elevate incidence of school accident among children and adolescents, with a considerable rate of severe injuries. In any community, the promotion of adolescents and children’s health is an important indicator of the public health level. Thus, it’s important to develop a multidisciplinary prevention strategy of school accident, based on safety and security rules and adapted to the specificity of our context.

Keywords: children and adolescents, children health, injuries and disability, school accident

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Authors: Shosh Shahrabani, Sharon Teitler-Regev, Helena Desivilya Syna, Fotini Voulgaris, Evangelos Tsoukatos, Vitor Ambrosio, Sandra M. Correia Loureiro

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International crises that affect tourism, such as terror attacks, political unrest, and economic crises have become more frequent, and their influence has become broader. The influence of such extreme events depends on their salience in the tourists' awareness. Hence, it is important to understand the mechanisms underlying tourists' selection of travel destinations, especially their perceptions of crisis-related events and the impact of the sociopolitical and economic context in their countries of origin. The current study examined how the socio-political and economic context in the home countries of potential young tourists affected their selection of travel destinations. The objective was to elucidate how the salience of various crises (economic and political) in the tourists' perceptions, due to their experiences at home, color their construal of destinations affected by similar hazards and influence their travel intentions. The study focused on student tourists from Israel, Greece, and Portugal. Today about a fifth of international tourism is based on young people, especially students. These countries were chosen since Greece and Portugal are in the midst of economic crises. In addition, Greece and Portugal have experienced political instability, while Israel has security-related problems (including terrorist incidents). In 2013, a total of 648 students, responded to a questionnaire that included questions concerning attitudes and risk perceptions regarding travel to destinations with various risk hazards as well as socio-demographic details. The results indicate that over half of the Israelis intend to visit Greece or Portugal. The majority of the Portuguese intend to visit Greece, while less than a third of them intend to visit Israel. About half of the Greeks intend to visit Portugal, and most of them do not intend to visit Israel. The results indicate that greater perceived importance of economic crises mitigates the intention to travel to destinations with economic crises for tourists from origin countries that are also marked by economic crises, such as Greece and Portugal. However, for tourists from Israel, a country with a relatively stable economy, issues related to the economy barely affect their intention to travel to the other two countries. The findings also suggest that Greeks and Portuguese who are highly concerned about political unrest are unlikely to select Israel as a tourist destination. In addition, strong apprehension regarding terrorism impedes the intention to travel to destinations marked by terrorist incidents, such as Israel. The current research contributes to the existing literature by highlighting the impact of travelers' personal previous experience with crisis on their risk perceptions and in turn on their intentions to travel to countries with similar risks. Therefore, in a world where such incidents are on the rise, understanding tourists' risk perceptions and behavior and the factors influencing their destination-related decisions are crucial for countries that wish to increase the numbers of incoming tourists.

Keywords: economic crises, political instability, risk perception, young tourists

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Authors: Carlos Herrera Sierralta, Husain M. Muslim, Meshal T. Alsaiari, Daniel Fischer

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Preventing piping fatigue flow induced vibration in the Oil & Gas sector demands not only the constant development of engineering design methodologies based on available software packages, but also special piping support technologies for designing safe and reliable piping systems. The vast majority of piping vibration problems in the Oil & Gas industry are provoked by the process flow characteristics which are basically intrinsically related to the fluid properties, the type of service and its different operational scenarios. In general, the corrective actions recommended for flow induced vibration in piping systems can be grouped in two major areas: those which affect the excitation mechanisms typically associated to process variables, and those which affect the response mechanism of the pipework per se, and the pipework associated steel support structure. Where possible the first option is to try to solve the flow induced problem from the excitation mechanism perspective. However, in producing facilities the approach of changing process parameters might not always be convenient as it could lead to reduction of production rates or it may require the shutdown of the system in order to perform the required piping modification. That impediment might lead to a second option, which is to modify the response of the piping system to excitation generated by the type of process flow. In principle, the action of shifting the natural frequency of the system well above the frequency inherent to the process always favours the elimination, or considerably reduces, the level of vibration experienced by the piping system. Tightening up the clearances at the supports (ideally zero gap), and adding new static supports at the system, are typical ways of increasing the natural frequency of the piping system. However, only stiffening the piping system may not be sufficient to resolve the vibration problem, and in some cases, it might not be feasible to implement it at all, as the available piping layout could create limitations on adding supports due to thermal expansion/contraction requirements. In these cases, utilization of viscous damper supports could be recommended as these devices can allow relatively large quasi-static movement of piping while providing sufficient capabilities of dissipating the vibration. Therefore, when correctly selected and installed, viscous damper supports can provide a significant effect on the response of the piping system over a wide range of frequencies. Viscous dampers cannot be used to support sustained, static loads. This paper shows over a real case example, a methodology which allows to determine the selection of the viscous damper supports via a dynamic analysis model. By implementing this methodology, it was possible to resolve the piping vibration problem throughout redesigning adequately the existing static piping supports and by adding new viscous dampers supports. This was conducted on-stream at the oil crude pipeline in question without the necessity of reducing the production of the plant. Concluding that the application of the methodology of this paper can be applied to solve similar cases in a straightforward manner.

Keywords: dynamic analysis, flow induced vibration, piping supports, turbulent flow, slug flow, viscous damper

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Authors: De-Shin Liu, Po-Chun Wen, Zhen-Wei Zhuang, Hsueh-Chih Liu, Pei-Chen Huang

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Wafer probing tests play an important role in semiconductor manufacturing procedures in accordance with the yield and reliability requirement of the wafer after the backend-of-the-line process. Accordingly, the stable physical and electrical contact between the probe and the tested wafer during wafer probing is regarded as an essential issue in identifying the known good die. The probe card can be integrated with multiple probe needles, which are classified as vertical, cantilever and micro-electro-mechanical systems type probe selections. Among all potential probe types, the vertical probe has several advantages as compared with other probe types, including maintainability, high probe density and feasibility for high-speed wafer testing. In the present study, the mechanical response of the wafer probing test with the vertical cobra probe on 720 μm thick silicon (Si) substrate with a 1.4 μm thick aluminum (Al) pad is investigated by the experiment and transient dynamic simulation approach. Because the deformation mechanism of the vertical cobra probe is determined by both bending and buckling mechanisms, the stable correlation between contact forces and overdrive (OD) length must be carefully verified. Moreover, the decent OD length with corresponding contact force contributed to piercing the native oxide layer of the Al pad and preventing the probing test-induced damage on the interconnect system. Accordingly, the scratch depth of the Al pad under various OD lengths is estimated by the atomic force microscope (AFM) and simulation work. In the wafer probing test configuration, the contact phenomenon between the probe needle and the tested object introduced large deformation and twisting of mesh gridding, causing the subsequent numerical divergence issue. For this reason, the arbitrary Lagrangian-Eulerian method is utilized in the present simulation work to conquer the aforementioned issue. The analytic results revealed a slight difference when the OD is considered as 40 μm, and the simulated is almost identical to the measured scratch depths of the Al pad under higher OD lengths up to 70 μm. This phenomenon can be attributed to the unstable contact of the probe at low OD length with the scratch depth below 30% of Al pad thickness, and the contact status will be being stable when the scratch depth over 30% of pad thickness. The splash of the Al pad is observed by the AFM, and the splashed Al debris accumulates on a specific side; this phenomenon is successfully simulated in the transient dynamic simulation. Thus, the preferred testing OD lengths are found as 45 μm to 70 μm, and the corresponding scratch depths on the Al pad are represented as 31.4% and 47.1% of Al pad thickness, respectively. The investigation approach demonstrated in this study contributed to analyzing the mechanical response of wafer probing test configuration under large strain conditions and assessed the geometric designs and material selections of probe needles to meet the requirement of high resolution and high-speed wafer-level probing test for thinned wafer application.

Keywords: wafer probing test, vertical probe, probe mark, mechanical response, FEA simulation

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Authors: Elizabeth M. Annoni, Elena G. Tolkacheva

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Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia that is a known prognostic marker for stroke, heart failure and death. Reentrant mechanisms of rotor formation, which are stable electrical sources of cardiac excitation, are believed to cause AF. No existing commercial mapping systems have been demonstrated to consistently and accurately predict rotor locations outside of the pulmonary veins in patients with persistent AF. There is a clear need for robust spatio-temporal techniques that can consistently identify rotors using unique characteristics of the electrical recordings at the pivot point that can be applied to clinical intracardiac mapping. Recently, we have developed four new signal analysis approaches – Shannon entropy (SE), Kurtosis (Kt), multi-scale frequency (MSF), and multi-scale entropy (MSE) – to identify the pivot points of rotors. These proposed techniques utilize different cardiac signal characteristics (other than local activation) to uncover the intrinsic complexity of the electrical activity in the rotors, which are not taken into account in current mapping methods. We validated these techniques using high-resolution optical mapping experiments in which direct visualization and identification of rotors in ex-vivo Langendorff-perfused hearts were possible. Episodes of ventricular tachycardia (VT) were induced using burst pacing, and two examples of rotors were used showing 3-sec episodes of a single stationary rotor and figure-8 reentry with one rotor being stationary and one meandering. Movies were captured at a rate of 600 frames per second for 3 sec. with 64x64 pixel resolution. These optical mapping movies were used to evaluate the performance and robustness of SE, Kt, MSF and MSE techniques with respect to the following clinical limitations: different time of recordings, different spatial resolution, and the presence of meandering rotors. To quantitatively compare the results, SE, Kt, MSF and MSE techniques were compared to the “true” rotor(s) identified using the phase map. Accuracy was calculated for each approach as the duration of the time series and spatial resolution were reduced. The time series duration was decreased from its original length of 3 sec, down to 2, 1, and 0.5 sec. The spatial resolution of the original VT episodes was decreased from 64x64 pixels to 32x32, 16x16, and 8x8 pixels by uniformly removing pixels from the optical mapping video.. Our results demonstrate that Kt, MSF and MSE were able to accurately identify the pivot point of the rotor under all three clinical limitations. The MSE approach demonstrated the best overall performance, but Kt was the best in identifying the pivot point of the meandering rotor. Artifacts mildly affect the performance of Kt, MSF and MSE techniques, but had a strong negative impact of the performance of SE. The results of our study motivate further validation of SE, Kt, MSF and MSE techniques using intra-atrial electrograms from paroxysmal and persistent AF patients to see if these approaches can identify pivot points in a clinical setting. More accurate rotor localization could significantly increase the efficacy of catheter ablation to treat AF, resulting in a higher success rate for single procedures.

Keywords: Atrial Fibrillation, Optical Mapping, Signal Processing, Rotors

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Authors: Petra Gruber, Ariana Rupp, Peter Niewiarowski

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This paper presents a concept for a biomimetic fablab as a physical space for education, research and development of innovation inspired by nature. Biomimetics as a discipline finds increasing recognition in academia and has started to be institutionalized at universities in programs and centers. The Biomimicry Research and Innovation Center was founded in 2012 at the University of Akron as an interdisciplinary venture for the advancement of innovation inspired by nature and is part of a larger community fostering the approach of bioimimicry in the Great Lakes region of the US. With 30 faculty members the center has representatives from Colleges of Arts and Sciences (e.g., biology, chemistry, geoscience, and philosophy) Engineering (e.g., mechanical, civil, and biomedical), Polymer Science, and Myers School of Arts. A platform for training PhDs in Biomimicry (17 students currently enrolled) is co-funded by educational institutions and industry partners. Research at the center touches on many areas but is also currently biased towards materials and structures, with highlights being materials based on principles found in spider silk and gecko attachment mechanisms. As biomimetics is also a novel scientific discipline, there is little standardisation in programming and the equipment of research facilities. As a field targeting innovation, design and prototyping processes are fundamental parts of the developments. For experimental design and prototyping, MIT's maker space concept seems to fit well to the requirements, but facilities need to be more specialised in terms of accessing biological systems and knowledge, specific research, production or conservation requirements. For the education and research facility BRIC we conceptualize the concept of a biomimicry fablab, that ties into the existing maker space concept and creates the setting for interdisciplinary research and development carried out in the program. The concept takes on the process of biomimetics as a guideline to define core activities that shall be enhanced by the allocation of specific spaces and tools. The limitations of such a facility and the intersections to further specialised labs housed in the classical departments are of special interest. As a preliminary proof of concept two biomimetic design courses carried out in 2016 are investigated in terms of needed tools and infrastructure. The spring course was a problem based biomimetic design challenge in collaboration with an innovation company interested in product design for assisted living and medical devices. The fall course was a solution based biomimetic design course focusing on order and hierarchy in nature with the goal of finding meaningful translations into art and technology. The paper describes the background of the BRIC center, identifies and discusses the process of biomimetics, evaluates the classical maker space concept and explores how these elements can shape the proposed research facility of a biomimetic fablab by examining two examples of design courses held in 2016.

Keywords: biomimetics, biomimicry, design, biomimetic fablab

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Authors: Faride Peña, Teresita Castillo, Concepción Campo

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Sexual violence, and particularly child sexual abuse, is a serious problem all over the world, México included. Given its importance, there are several preventive and care programs done by the government and the civil society all over the country but most of them are developed in urban areas even though these problems are especially serious in rural areas. Yucatán, a state in southern México, occupies one of the first places in child sexual abuse. Considering the above, the University Unit of Clinical Research and Victimological Attention (UNIVICT) of the Autonomous University of Yucatan, designed, implemented and is currently evaluating the program named “Sharing Mouth to Mouth: My Body, Nobody Can Touch It”, a program to prevent child sexual abuse in rural communities of Yucatán, México. Its aim was to develop skills for the detection of risk situations, providing protection strategies and mechanisms for prevention through culturally relevant psycho-educative strategies to increase personal resources in children, in collaboration with parents, teachers, police and municipal authorities. The diagnosis identified that a particularly vulnerable population were children between 4 and 10 years. The program run during 2015 in primary schools in the municipality whose inhabitants are mostly Mayan. The aim of this paper is to present its evaluation in terms of its effectiveness and efficiency. This evaluation included documental analysis of the work done in the field, psycho-educational and recreational activities with children, evaluation of knowledge by participating children and interviews with parents and teachers. The results show high efficiency in fulfilling the tasks and achieving primary objectives. The efficiency shows satisfactory results but also opportunity areas that can be resolved with minor adjustments to the program. The results also show the importance of including culturally relevant strategies and activities otherwise it minimizes possible achievements. Another highlight is the importance of participatory action research in preventive approaches to child sexual abuse since by becoming aware of the importance of the subject people participate more actively; in addition to design culturally appropriate strategies and measures so that the proposal may not be distant to the people. Discussion emphasizes the methodological implications of prevention programs (convenience of using participatory action research (PAR), importance of monitoring and mediation during implementation, developing detection skills tools in creative ways using psycho-educational interactive techniques and working assessment issued by the participants themselves). As well, it is important to consider the holistic character this type of program should have, in terms of incorporating social and culturally relevant characteristics, according to the community individuality and uniqueness, consider type of communication to be used and children’ language skills considering that there should be variations strongly linked to a specific cultural context.

Keywords: child sexual abuse, evaluation, PAR, prevention

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Authors: Christian Bruss, Simona Gamba, Davide Azzolini, Federico Podestà

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In this paper, the authors assess the impact of different political and environmental shocks on the size and on the age and gender composition of asylum-related migration flows to Europe. With this paper, the authors contribute to the literature by looking at the impact of different political and environmental shocks on the gender and age composition of migration flows in addition to the size of these flows. Conflicting theories predict different outcomes concerning the relationship between political and environmental shocks and the migration flows composition. Analyzing the relationship between the causes of migration and the composition of migration flows could yield more insights into the mechanisms behind migration decisions. In addition, this research may contribute to better informing national authorities in charge of receiving these migrant, as women and children/the elderly require different assistance than young men. To be prepared to offer the correct services, the relevant institutions have to be aware of changes in composition based on the shock in question. The authors analyze the effect of different types of shocks on the number, the gender and age composition of first time asylum seekers originating from 154 sending countries. Among the political shocks, the authors consider: violence between combatants, violence against civilians, infringement of political rights and civil liberties, and state terror. Concerning environmental shocks, natural disasters (such as droughts, floods, epidemics, etc.) have been included. The data on asylum seekers applying to any of the 32 Schengen Area countries between 2008 and 2015 is on a monthly basis. Data on asylum applications come from Eurostat, data on shocks are retrieved from various sources: georeferenced conflict data come from the Uppsala Conflict Data Program (UCDP), data on natural disasters from the Centre for Research on the Epidemiology of Disasters (CRED), data on civil liberties and political rights from Freedom House, data on state terror from the Political Terror Scale (PTS), GDP and population data from the World Bank, and georeferenced population data from the Socioeconomic Data and Applications Center (SEDAC). The authors adopt a Difference-in-Differences identification strategy, exploiting the different timing of several kinds of shocks across countries. The highly skewed distribution of the dependent variable is taken into account by using count data models. In particular, a Zero Inflated Negative Binomial model is adopted. Preliminary results show that different shocks - such as armed conflict and epidemics - exert weak immediate effects on asylum-related migration flows and almost non-existent effects on the gender and age composition. However, this result is certainly affected by the fact that no time lags have been introduced so far. Finding the correct time lags depends on a great many variables not limited to distance alone. Therefore, finding the appropriate time lags is still a work in progress. Considering the ongoing refugee crisis, this topic is more important than ever. The authors hope that this research contributes to a less emotionally led debate.

Keywords: age, asylum, Europe, forced migration, gender

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Authors: Maria Fatima Almeida, Rodrigo Calili, George Soares, João Krause, Myrthes Marcele Dos Santos, Anna Carolina Suzano E. Silva, Marcos Alexandre Da

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In Brazil, the building sector accounts for 1/6 of energy consumption and 50% of electricity consumption. A complex sector with several driving actors plays an essential role in the country's economy. Currently, the digitalization readiness in this sector is still low, mainly due to the high investment costs and the difficulty of estimating the benefits of digital technologies in buildings. Nevertheless, the potential contribution of digitalization for increasing energy efficiency in the building sector in Brazil has been pointed out as relevant in the political and sectoral contexts, both in the medium and long-term horizons. To contribute to the debate on the possible evolving trajectories of digitalization in the building sector in Brazil and to subsidize the formulation or revision of current public policies and managerial decisions, three future scenarios were created to anticipate the potential energy efficiency in the building sector in Brazil due to digitalization by 2050. This work aims to present these scenarios as a basis to foresight the potential energy efficiency in this sector, according to different digitalization paces - slow, moderate, or fast in the 2050 horizon. A methodological approach was proposed to create alternative prospective scenarios, combining the Global Business Network (GBN) and the Laboratory for Investigation in Prospective Strategy and Organisation (LIPSOR) methods. This approach consists of seven steps: (i) definition of the question to be foresighted and time horizon to be considered (2050); (ii) definition and classification of a set of key variables, using the prospective structural analysis; (iii) identification of the main actors with an active role in the digital and energy spheres; (iv) characterization of the current situation (2021) and identification of main uncertainties that were considered critical in the development of alternative future scenarios; (v) scanning possible futures using morphological analysis; (vi) selection and description of the most likely scenarios; (vii) foresighting the potential energy efficiency in each of the three scenarios, namely slow digitalization; moderate digitalization, and fast digitalization. Each scenario begins with a core logic and then encompasses potentially related elements, including potential energy efficiency. Then, the first scenario refers to digitalization at a slow pace, with induction by the government limited to public buildings. In the second scenario, digitalization is implemented at a moderate pace, induced by the government in public, commercial, and service buildings, through regulation integrating digitalization and energy efficiency mechanisms. Finally, in the third scenario, digitalization in the building sector is implemented at a fast pace in the country and is strongly induced by the government, but with broad participation of private investments and accelerated adoption of digital technologies. As a result of the slow pace of digitalization in the sector, the potential for energy efficiency stands at levels below 10% of the total of 161TWh by 2050. In the moderate digitalization scenario, the potential reaches 20 to 30% of the total 161TWh by 2050. Furthermore, in the rapid digitalization scenario, it will reach 30 to 40% of the total 161TWh by 2050.

Keywords: building digitalization, energy efficiency, scenario building, prospective structural analysis, morphological analysis

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Authors: Nazila Dehbari, Javad Tavakoli, Yakani Kambu, Youhong Tang

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Superabsorbent hydrogels (SAP), as an enviro-sensitive material have been widely used for industrial and biomedical applications due to their unique structure and capabilities. Poor mechanical properties of SAPs - which is extremely related to their large volume change – count as a great weakness in adopting for high-tech applications. Therefore, improving SAPs’ mechanical properties via toughening methods by mixing different types of cross-linked polymer or introducing energy-dissipating mechanisms is highly focused. In this work, in order to change the intrinsic brittle character of commercialized Poly Acrylic Acid (here as SAP) to be semi-ductile, a commercial available highly branched tree-like dendritic polymers with numerous –OH end groups known as hyper-branched polymer (HB) has been added to PAA-SAP system in a single step, cost effective and environment friendly solvent casting method. Samples were characterized by FTIR, SEM and TEM and their physico-chemical characterization including swelling capabilities, hydraulic permeability, surface tension and thermal properties had been performed. Toughness energy, stiffness, elongation at breaking point, viscoelastic properties and samples extensibility were mechanical properties that had been performed and characterized as a function of samples lateral cracks’ length in different HB concentration. Addition of HB to PAA-SAP significantly improved mechanical and surface properties. Increasing equilibrium swelling ratio by about 25% had been experienced by the SAP-HB samples in comparison with SAPs; however, samples swelling kinetics remained without changes as initial rate of water uptake and equilibrium time haven’t been subjected to any changes. Thermal stability analysis showed that HB is participating in hybrid network formation while improving mechanical properties. Samples characterization by TEM showed that, the aggregated HB polymer binders into nano-spheres with diameter in range of 10–200 nm. So well dispersion in the SAP matrix occurred as it was predictable due to the hydrophilic character of the numerous hydroxyl groups at the end of HB which enhance the compatibility of HB with PAA-SAP. As the profused -OH groups in HB could react with -COOH groups in the PAA-SAP during the curing process, the formation of a 2D structure in the SAP-HB could be attributed to the strong interfacial adhesion between HB and the PAA-SAP matrix which hinders the activity of PAA chains (SEM analysis). FTIR spectra introduced new peaks at 1041 and 1121 cm-1 that attributed to the C–O(–OH) stretching hydroxyl and O–C stretching ester groups of HB polymer binder indicating the incorporation of HB polymer into the SAP structure. SAP-HB polymer has significant effects on the final mechanical properties. The brittleness of PAA hydrogels are decreased by introducing HB as the fracture energies of hydrogels increased from 8.67 to 26.67. PAA-HBs’ stretch ability enhanced about 10 folds while reduced as a function of different notches depth.

Keywords: superabsorbent polymer, toughening, viscoelastic properties, hydrogel network

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Authors: Nathalie Gagnon, Andréanne Gagné, Julie Courcy

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Quebec's vocational education teachers experience an atypical induction process into the workplace and thus face unique challenges. In contrast to elementary and high school teachers, who must undergo initial teacher training in order to access the profession, vocational education teachers, in most cases, are hired based on their professional expertise in the trade they are teaching, without prior pedagogical training. In addition to creating significant stress, which does not foster the acquisition of teaching roles and skills, this approach also forces recruits into a particular posture during their practical training: that of juggling their dual identities as teacher and trainee simultaneously. Recruits are supported by Cooperating Teachers (CPs) who, as experienced educators, take a critical and constructive look at their practices, observe them in the classroom, give them constructive feedback, and encourage them in their reflective practice. Thus, the vocational setting CP also assumes a distinctive posture and role due to the characteristics of the trainees they support. Although it is recognized that preparation, training, and supervision of CPs are essential factors in improving the support provided to trainees, there is little research about how CPs develop their support skills, and very little research focuses on the distinct posture they occupy. However, in order for them to be properly equipped for the important role they play in recruits’ practical training, it is vital to know more about their experience. An individual’s competencies cannot be studied without first examining what characterizes their experience, how they experience any given situation on cognitive, emotional, and motivational levels, in addition to how they act and react in situ. Depending on its nature, the experience will or will not promote the development of a specific competency. The research from which this communication originates focuses on describing the overall experience of vocational education CP in an effort to better understand the mechanisms linked to the development of their mentoring competencies. Experience and competence were, therefore, the two main theoretical concepts leading the research. As per methodology choices, case study methods were used since it proves to be adequate to describe in a rich and detailed way contemporary phenomena within contexts of life. The set of data used was collected from semi-structured interviews conducted with 15 vocational education CP in Quebec (Canada), followed by the use of a data-driven semi-inductive analysis approach to let the categories emerge organically. Focusing on the development needs of vocational education CP to improve their mentoring skills, this paper presents the results of our research, namely the importance of adequate training, better support offered by university supervisors, greater recognition of their role, and specific time slots dedicated to trainee support. The knowledge resulting from this research could improve the quality of support for trainee teachers in vocational education settings and to a more successful induction into the workplace. This communication also presents recommendations regarding the development of training systems that meet the specific needs of vocational education CP.

Keywords: development of competencies, cooperating teacher, mentoring trainee teacher, practical training, vocational education

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Authors: Maureen Kamau, Gulnaz Mohamoud, Adelaide Lusambili, Njeri Nyanja

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Life expectancy has increased over the last century amongst older individuals, and in particular, those 60 years and over. The World Health Organization estimates that the world's population of persons over 60 years will rise to 22 per cent by the year 2050. Ageing is associated with increasing disability, multiple chronic conditions, and an increase in the use of health services. These multiple chronic conditions are managed with polypharmacy. Polypharmacy has numerous adverse effects including non-adherence, poor compliance to the various medications, reduced appetite, and risk of fall. Studies on polypharmacy and ageing are few and poorly understood especially in low and middle - income countries. The aim of this study was to explore the knowledge, attitudes and beliefs of older people towards polypharmacy. A qualitative study of 15 patients aged 60 years and above, taking more than five medications per day were conducted at the Aga Khan University using Semi-structured in-depth interviews. Three interviews were pilot interviews, and data analysis was performed on 12 interviews. Data were analyzed using NVIVO 12 software. A thematic qualitative analysis was carried out guided by Braun and Clarke (2006) framework. Themes identified; - knowledge of their co-morbidities and of the medication that older persons take, sources of information about medicines, and storage of the medication, experiences and attitudes of older patients towards polypharmacy both positive and negative, older peoples beliefs and their coping mechanisms with polypharmacy. The study participants had good knowledge on their multiple co-morbidities, and on the medication they took. The patients had positive attitudes towards medication as it enhanced their health and well-being, and enabled them to perform their activities of daily living. There was a strong belief among older patients that the medications were necessary for their health. All these factors enhanced compliance to the multiple medication. However, some older patients had negative attitudes due to the pill burden, side effects of the medication, and stigma associated with being ill. Cost of healthcare was a concern, with most of the patients interviewed relying on insurance to cover the cost of their medication. Older patients had accepted that the medication they were prescribed were necessary for their health, as it enabled them to complete their activities of daily living. Some concerns about the side effects of the medication arose, and brought about the need for patient education that would ensure that the patients are aware of the medications they take, and potential side effects. The effect that the COVID 19 pandemic had in the healthcare of the older patients was evident by the number of the older patients avoided coming to the hospital during the period of the pandemic. The relationship with the primary care physician and the older patients is an important one, especially in LMICs such as Kenya, as many of the older patients trusted the doctors wholeheartedly to make the best decision about their health and about their medication. Prescription review is important to avoid the use of potentially inappropriate medication.

Keywords: polypharmacy, older patients, multiple chronic conditions, Kenya, Africa, qualitative study, indepth interviews, primary care

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Authors: Julien Monnier, Isabelle Mouton, Francois Buy, Adrien Michel, Sylvain Ringeval, Joel Malaplate, Caroline Toffolon, Bernard Marini, Audrey Lechartier

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Chosen to design and assemble massive components for nuclear industry, the 316 Nb austenitic stainless steel (also called 316 Nb) suits well this function thanks to its mechanical, heat and corrosion handling properties. However, these properties might change during steel’s life due to thermal ageing causing changes within its microstructure. Our main purpose is to determine if the 316 Nb will keep its mechanical properties after an exposition to industrial temperatures (around 300 °C) during a long period of time (< 10 years). The 316 Nb is composed by different phases, which are austenite as main phase, niobium-carbides, and ferrite remaining from the ferrite to austenite transformation during the process. Our purpose is to understand thermal ageing effects on the material microstructure and properties and to submit a model predicting the evolution of 316 Nb properties as a function of temperature and time. To do so, based on Fe-Cr and 316 Nb phase diagrams, we studied the thermal ageing of 316 Nb steel alloys (1%v of ferrite) and welds (10%v of ferrite) for various temperatures (350, 400, and 450 °C) and ageing time (from 1 to 10.000 hours). Higher temperatures have been chosen to reduce thermal treatment time by exploiting a kinetic effect of temperature on 316 Nb ageing without modifying reaction mechanisms. Our results from early times of ageing show no effect on steel’s global properties linked to austenite stability, but an increase of ferrite hardness during thermal ageing has been observed. It has been shown that austenite’s crystalline structure (cfc) grants it a thermal stability, however, ferrite crystalline structure (bcc) favours iron-chromium demixion and formation of iron-rich and chromium-rich phases within ferrite. Observations of thermal ageing effects on ferrite’s microstructure were necessary to understand the changes caused by the thermal treatment. Analyses have been performed by using different techniques like Atomic Probe Tomography (APT) and Differential Scanning Calorimetry (DSC). A demixion of alloy’s elements leading to formation of iron-rich (α phase, bcc structure), chromium-rich (α’ phase, bcc structure), and nickel-rich (fcc structure) phases within the ferrite have been observed and associated to the increase of ferrite’s hardness. APT results grant information about phases’ volume fraction and composition, allowing to associate hardness measurements to the volume fractions of the different phases and to set up a way to calculate α’ and nickel-rich particles’ growth rate depending on temperature. The same methodology has been applied to DSC results, which allowed us to measure the enthalpy of α’ phase dissolution between 500 and 600_°C. To resume, we started from mechanical and macroscopic measurements and explained the results through microstructural study. The data obtained has been match to CALPHAD models’ prediction and used to improve these calculations and employ them to predict 316 Nb properties’ change during the industrial process.

Keywords: stainless steel characterization, atom probe tomography APT, vickers hardness, differential scanning calorimetry DSC, thermal ageing

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Authors: Fatima Boutaleb

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Entrepreneurship proves to be crucial for the economic growth and development, since it contributes to job creation and the improvement of the overall productivity thus generating a positive impact upon society at various levels. Promoting entrepreneurship stimulates therefore economic diversity that is key to the betterment and/or maintaining of the standard of living. In fact, recent research suggests that entrepreneurship contributes to development by creating businesses and jobs, stimulating innovation, creating social capital across borders, and channeling political and financial capital. However, different research studies indicate that among the main factors impeding the entrepreneurship are politico-economic as socio-cultural problems, with an intensity for those related to young people and to women. In the MENA region, discrimination inherent in gender is alarming: Only one woman in eight runs her own business against 1 in 3 men. In most countries, young women and young men are facing problems involving access to finance, inadequate infrastructure, lack of support and, in general, an ecosystem that is rather unfavorable. According to the International Labor Organization, North Africa and the Middle East has the highest unemployment rate in all other regions of the world. In other hand, nearly a quarter of the population under 30 is unemployed and youth unemployment costs more than $40 billion each year to the region. In the current context, the situations in the Middle East and North Africa region are singular, both in terms of demographic trends and socio-economic issues around the employment of a large and better trained youth, but still strongly affected by unemployment and under-employment. According to a study published in 2015 by McKinsey, the world gain 26% of additional GDP (47% in the MENA region), more than 28 trillion dollars by 2025, if women came to participate, as well as men, to the economy. Promoting entrepreneurship represents an excellent alternative for the countries whose productive fabric fails to integrate the contingent of young people entering the job market each year. The MENA region, presenting entrepreneurial activity rates below those of other regions in terms of comparable development, has undoubtedly leeway at this level, even though the region displays large national heterogeneity, namely in the priority given to the promotion of entrepreneurship. The objective of this article is therefore to examine the women entrepreneurial vocation in the MENA region, to see to what extent research on the determinant of gender can provide information on the trend of the emerging entrepreneurial activity whether driven by necessity or by opportunity and, on this basis, to submit public policy proposals for the improvement of the mechanisms of inclusion among the youth women people. The objective is not to analyze the causality models but rather to identify the entrepreneurial construct specific to the MENA region via the analysis of GEM data from 2017 to 2019 among adults belonging to 10 countries of the MENA region. Notably, the study shows that inclusion of young women may be enhanced. These disadvantaged segments frequently intend to become entrepreneurs, but they tend not to enact their vocational intentions.

Keywords: economic development, entrepreneurial activity, GEM, gender, informal sector

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Authors: Dianelys Vega, Carlos Magluta, Ney Roitman

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The simulation of loads induced by walking people in civil engineering structures is still challenging It has been the focus of considerable research worldwide in the recent decades due to increasing number of reported vibration problems in pedestrian structures. One of the most important key in the designing of slender structures is the Human-Structure Interaction (HSI). How moving people interact with structures and the effect it has on their dynamic responses is still not well understood. To rely on calibrated pedestrian models that accurately estimate the structural response becomes extremely important. However, because of the complexity of the pedestrian mechanisms, there are still some gaps in knowledge and more reliable models need to be investigated. On this topic several authors have proposed biodynamic models to represent the pedestrian, whether these models provide a consistent approximation to physical reality still needs to be studied. Therefore, this work comes to contribute to a better understanding of this phenomenon bringing an experimental validation of a pedestrian walking model and a Human-Structure Interaction model. In this study, a bi-dimensional bipedal walking model was used to represent the pedestrians along with an interaction model which was applied to a prototype footbridge. Numerical models were implemented in MATLAB. In parallel, experimental tests were conducted in the Structures Laboratory of COPPE (LabEst), at Federal University of Rio de Janeiro. Different test subjects were asked to walk at different walking speeds over instrumented force platforms to measure the walking force and an accelerometer was placed at the waist of each subject to measure the acceleration of the center of mass at the same time. By fitting the step force and the center of mass acceleration through successive numerical simulations, the model parameters are estimated. In addition, experimental data of a walking pedestrian on a flexible structure was used to validate the interaction model presented, through the comparison of the measured and simulated structural response at mid span. It was found that the pedestrian model was able to adequately reproduce the ground reaction force and the center of mass acceleration for normal and slow walking speeds, being less efficient for faster speeds. Numerical simulations showed that biomechanical parameters such as leg stiffness and damping affect the ground reaction force, and the higher the walking speed the greater the leg length of the model. Besides, the interaction model was also capable to estimate with good approximation the structural response, that remained in the same order of magnitude as the measured response. Some differences in frequency spectra were observed, which are presumed to be due to the perfectly periodic loading representation, neglecting intra-subject variabilities. In conclusion, this work showed that the bipedal walking model could be used to represent walking pedestrians since it was efficient to reproduce the center of mass movement and ground reaction forces produced by humans. Furthermore, although more experimental validations are required, the interaction model also seems to be a useful framework to estimate the dynamic response of structures under loads induced by walking pedestrians.

Keywords: biodynamic models, bipedal walking models, human induced loads, human structure interaction

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Authors: Nana Katsitadze, Tamar Atanelishvili, Mariam Kutateladze, Alexandre Tushishvili

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In the modern world, tourism has emerged as one of the most powerful economic sectors, and due to its high economic performance, it is attractive to the countries with various levels of economic development. The purpose of the present paper, dedicated to discussing the current problems of tourism development, is to find ways which will contribute to bringing more benefits to the country from the sector. Georgia has been successfully developing leisure tourism for the last ten years, and at the next stage of development business, tourism gains particular importance for Georgia as a means of mitigating the negative socio-economic effects caused by the seasonality of tourism and as a high-cost tourism market. Therefore, the object of the paper is to study the factors that contribute to the development of business tourism. The paper uses the research methods such as system analysis, synthesis, analogy, as well as historical, comparative, economic, and statistical methods of analysis. The information base for the research is made up of the statistics on the functioning of the tourism market of Georgia and foreign countries as well as official data provided by international organizations in the field of tourism. Based on the experience of business tourism around the world and identifying the successful start of business tourism development in Georgia and its causing factors, a business tourism development model for Georgia has been developed. The model might be useful as a methodological material for developing a business tourism development concept for the countries with limited financial resources but rich in tourism resources like Georgia. On the initial stage of development (in absence of conventional centers), the suggested concept of business tourism development involves organizing small and medium-sized meetings both in large cities and in regions by using high-class hotel infrastructure and event management services. Relocation of small meetings to the regions encourages inclusive development of the sector based on increasing the awareness of these regions as tourist sites as well as the increase in employment and sales of other tourism or consumer products. Business tourism increases the number of hotel visitors in the non-seasonal period and improves hotel performance indicators, which enhances the attractiveness of investing in the hotel business. According to the present concept of business tourism development, at the initial stage, development of business tourism is based on the existing markets, including internal market, neighboring markets and the markets of geographically relatively near countries and at the next stage, the concept involves generating tourists from other relatively distant target markets. As a result, by gaining experience in business tourism, enhancing professionalism, increasing awareness and stimulating infrastructure development, the country will prepare the basis to move to a higher stage of tourism development. In addition, the experience showed that for attracting large customers, peculiarities of the field require activation of state policy and active use of marketing mechanisms and tools of the state.

Keywords: hotel industry development, MICE model, MICE strategy, MICE tourism in Georgia

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Authors: Collen Tebogo Masilo, Erik Schmikl

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The demand for the DataMiner product by customers has presented a great challenge for the vendor in Skyline Communications in deploying its limited resources in the form of human resources, financial resources, and office space, to achieve high organisational performance in all its international operations. The rapid growth of the organisation has been unable to efficiently support its existing customers across the globe, and provide services to new customers, due to the limited number of approximately one hundred employees in its employ. The combined descriptive and explanatory case study research methods were selected as research design, making use of a survey questionnaire which was distributed to a sample of 100 respondents. A sample return of 89 respondents was achieved. The sampling method employed was non-probability sampling, using the convenient sampling method. Frequency analysis and correlation between the subscales (the four themes) were used for statistical analysis to interpret the data. The investigation was conducted into mechanisms that can be deployed to balance the high demand for products and the limited production capacity of the company’s Belgian operations across four aspects: demand management strategies, capacity management strategies, communication methods that can be used to align a sales management department, and reward systems in use to improve employee performance. The conclusions derived from the theme ‘demand management strategies’ are that the company is fully aware of the future market demand for its products. However, there seems to be no evidence that there is proper demand forecasting conducted within the organisation. The conclusions derived from the theme 'capacity management strategies' are that employees always have a lot of work to complete during office hours, and, also, employees seem to need help from colleagues with urgent tasks. This indicates that employees often work on unplanned tasks and multiple projects. Conclusions derived from the theme 'communication methods used to align sales management department with operations' are that communication is not good throughout the organisation. This means that information often stays with management, and does not reach non-management employees. This also means that there is a lack of smooth synergy as expected and a lack of good communication between the sales department and the projects office. This has a direct impact on the delivery of projects to customers by the operations department. The conclusions derived from the theme ‘employee reward systems’ are that employees are motivated, and feel that they add value in their current functions. There are currently no measures in place to identify unhappy employees, and there are also no proper reward systems in place which are linked to a performance management system. The research has made a contribution to the body of research by exploring the impact of the four sub-variables and their interaction on the challenges of organisational productivity, in particular where an organisation experiences a capacity problem during its growth stage during tough economic conditions. Recommendations were made which, if implemented by management, could further enhance the organisation’s sustained competitive operations.

Keywords: high demand for products, high organisational performance, limited production capacity, limited resources

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Authors: Rafael Alexandre Dos Reis

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Research has shown a substantial increase in the participation of Conventionally Fuelled Vehicles (CFVs) in the urban transport modal split. The reasons for this unsustainable reality are multiple, from economic interventions to individual behaviour. The development and delivery of positive incentives for the adoption of more environmental-friendly modes of transport is an emerging strategy to help in tackling the problem of excessive use of conventionally fuelled vehicles. The efficiency of this approach, like other information-based schemes, can benefit from the knowledge of their potential impacts in theoretical constructs of multiple behaviour change theories. The goal of this research is to critically analyse theories of behaviour that are relevant to transport research and the impacts of positive incentives on the theoretical determinants of behaviour, strengthening the current body of evidence about the benefits of this approach. The main method to investigate this will involve a literature review on two main topics: the current theories of behaviour that have empirical support in transport research and the past or ongoing positive incentives programs that had an impact on car use reduction. The reviewed programs of positive incentives were the following: The TravelSmart®; Spitsmijden®; Incentives for Singapore Commuters® (INSINC); COMMUTEGREENER®; MOVESMARTER®; STREETLIFE®; SUPERHUB®; SUNSET® and the EMPOWER® project. The theories analysed were the heory of Planned Behaviour (TPB); The Norm Activation Theory (NAM); Social Learning Theory (SLT); The Theory of Interpersonal Behaviour (TIB); The Goal-Setting Theory (GST) and The Value-Belief-Norm Theory (VBN). After the revisions of the theoretical constructs of each of the theories and their influence on car use, it can be concluded that positive incentives schemes impact on behaviour change in the following manners: -Changing individual’s attitudes through informational incentives; -Increasing feelings of moral obligations to reduce the use of CFVs; -Increase the perceived social pressure to engage in more sustainable mobility behaviours through the use of comparison mechanisms in social media, for example; -Increase the perceived control of behaviour through informational incentives and training incentives; -Increasing personal norms with reinforcing information; -Providing tools for self-monitoring and self-evaluation; -Providing real experiences in alternative modes to the car; -Making the observation of others’ car use reduction possible; -Informing about consequences of behaviour and emphasizing the individual’s responsibility with society and the environment; -Increasing the perception of the consequences of car use to an individual’s valued objects; -Increasing the perceived ability to reduce threats to environment; -Help establishing goals to reduce car use; - iving personalized feedback on the goal; -Increase feelings of commitment to the goal; -Reducing the perceived complexity of the use of alternatives to the car. It is notable that the emerging technique of delivering positive incentives are systematically connected to causal determinants of travel behaviour. The preliminary results of the reviewed programs evidence how positive incentives might strengthen these determinants and help in the process of behaviour change.

Keywords: positive incentives, private car use reduction, sustainable behaviour, voluntary travel behaviour change

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Authors: Hanan M. Hassan, Laila Abouzeid, Lamya H. Al-Wahaibi, George S. G. Shehatou, Ali A. El-Emam

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Cancer is a major public health problem and the second leading cause of death worldwide. In 2020, cancer diagnosis and treatment have been negatively affected by the coronavirus 2019 (COVID-19) pandemic. During the quarantine, because of the limited access to healthcare and avoiding exposure to COVID-19 as a contagious disease; patients of cancer suffered deferments in follow-up and treatment regimens leading to substantial worsening of disease, death, and increased healthcare costs. Thus, this study is designed to investigate the molecular mechanisms by which adamantne derivatives attenuate hepatocllular carcinoma experimentally and theoretically. There is a close association between increased resistance to anticancer drugs and defective apoptosis that considered a causative factor for oncogenesis. Cancer cells use different molecular pathways to inhibit apoptosis, BAX and Bcl-2 proteins have essential roles in the progression or inhibition of intrinsic apoptotic pathways triggered by mitochondrial dysfunction. Therefore, their balance ratio can promote the cellular apoptotic fate. In this study, the in vitro cytotoxic effects of seven synthetic adamantyl isothiorea derivatives were evaluated against five human tumor cell lines by MTT assay. Compounds 5 and 6 showed the best results, mostly against hepatocellular carcinoma (HCC). Hence, in vivo studies were performed in male Sprague-Dawley (SD) rats in which experimental hepatocellular carcinoma was induced with thioacetamide (TAA) (200 mg/kg, i.p., twice weekly) for 16 weeks. The most promising compounds, 5 and 6, were administered to treat liver cancer rats at a dose of 10 mg/kg/day for an additional two weeks, and the effects were compared with doxorubicin (DR), the anticancer drug. Hepatocellular carcinoma was evidenced by a dramatic increase in liver indices, oxidative stress markers, and immunohistochemical studies that were accompanied by a plethora of inflammatory mediators and alterations in the apoptotic cascade. Our results showed that treatment with adamantane derivatives 5 and 6 significantly suppressed fibrosis, inflammation, and other histopathological insults resulting in the diminished formation of hepatocyte tumorigenesis. Moreover, administration of the tested compounds resulted in amelioration of EGFR protein expression, upregulation of BAX, and lessening down of Bcl-2 levels that prove their role as apoptosis inducers. Also, the docking simulations performed for adamantane showed good fit and binding to the EGFR protein through hydrogen bond formation with conservative amino acids, which gives a shred of strong evidence for its hepatoprotective effect. In most analyses, the effects of compound 6 were more comparable to DR than compound 5. Our findings suggest that adamantane derivatives 5 and 6 are shown to have cytotoxic activity against HCC in vitro and in vivo, by more than one mechanism, possibly by inhibiting the TLR4-MyD88-NF-κB pathway and targeting EGFR signaling.

Keywords: adamantane, EGFR, HCC, apoptosis

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Authors: Catia Correia Caeiro, Kun Guo, Daniel Mills

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Despite its growing interest, emotions are still an understudied cognitive process and their origins are currently the focus of much debate among the scientific community. The use of facial expressions as traditional hallmarks of discrete and holistic emotions created a circular reasoning due to a priori assumptions of meaning and its associated appearance-biases. Ekman and colleagues solved this problem and laid the foundations for the quantitative and systematic study of facial expressions in humans by developing an anatomically-based system (independent from meaning) to measure facial behaviour, the Facial Action Coding System (FACS). One way of investigating emotion cognition processes is by applying comparative psychology methodologies and looking at either closely-related species (e.g. chimpanzees) or phylogenetically distant species sharing similar present adaptation problems (analogy). In this study, the domestic dog was used as a comparative animal model to look at facial expressions in social interactions in parallel with human facial expressions. The orofacial musculature seems to be relatively well conserved across mammal species and the same holds true for the domestic dog. Furthermore, the dog is unique in having shared the same social environment as humans for more than 10,000 years, facing similar challenges and acquiring a unique set of socio-cognitive skills in the process. In this study, the spontaneous facial movements of humans and dogs were compared when interacting with hetero- and conspecifics as well as in solitary contexts. In total, 200 participants were examined with FACS and DogFACS (The Dog Facial Action Coding System): coding tools across four different emotionally-driven contexts: a) Happiness (play and reunion), b) anticipation (of positive reward), c) fear (object or situation triggered), and d) frustration (negation of a resource). A neutral control was added for both species. All four contexts are commonly encountered by humans and dogs, are comparable between species and seem to give rise to emotions from homologous brain systems. The videos used in the study were extracted from public databases (e.g. Youtube) or published scientific databases (e.g. AM-FED). The results obtained allowed us to delineate clear similarities and differences on the flexibility of the facial musculature in the two species. More importantly, they shed light on what common facial movements are a product of the emotion linked contexts (the ones appearing in both species) and which are characteristic of the species, revealing an important clue for the debate on the origin of emotions. Additionally, we were able to examine movements that might have emerged for interspecific communication. Finally, our results are discussed from an evolutionary perspective adding to the recent line of work that supports an ancient shared origin of emotions in a mammal ancestor and defining emotions as mechanisms with a clear adaptive purpose essential on numerous situations, ranging from maintenance of social bonds to fitness and survival modulators.

Keywords: comparative and evolutionary psychology, emotion, facial expressions, FACS

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Authors: Marcel Verwey, Anna M. Joubert, Elsie M. Nolte, Wolfgang Dohle, Barry V. L. Potter, Anne E. Theron

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A tetrahydroisoquinolinone (THIQ) core can be used to mimic the A,B-ring of colchicine site-binding microtubule disruptors such as 2-methoxyestradiol in the design of anti-cancer agents. Steroidomimeric microtubule disruptors were synthesized by introducing C'2 and C'3 of the steroidal A-ring to C'6 and C'7 of the THIQ core and by introducing a decorated hydrogen bond acceptor motif projecting from the steroidal D-ring to N'2. For this in vitro study, four non-steroidal THIQ-based analogues were investigated and comparative studies were done between the non-sulphamoylated compound STX 3450 and the sulphamoylated compounds STX 2895, STX 3329 and STX 3451. The objective of this study was to investigate the modes of cell death induced by these four THIQ-based analogues in A549 lung carcinoma epithelial cells and metastatic breast adenocarcinoma MDA-MB-231 cells. Cytotoxicity studies to determine the half maximal growth inhibitory concentrations were done using spectrophotometric quantification via crystal violet staining and lactate dehydrogenase (LDH) assays. Microtubule integrity and morphologic changes of exposed cells were investigated using polarization-optical transmitted light differential interference contrast microscopy, transmission electron microscopy and confocal microscopy. Flow cytometric quantification was used to determine apoptosis induction and the effect that THIQ-based analogues have on cell cycle progression. Signal transduction pathways were elucidated by quantification of the mitochondrial membrane integrity, cytochrome c release and caspase 3, -6 and -8 activation. Induction of autophagic cell death by the THIQ-based analogues was investigated by morphological assessment of fluorescent monodansylcadaverine (MDC) staining of acidic vacuoles and by quantifying aggresome formation via flow cytometry. Results revealed that these non-steroidal microtubule disrupting analogues inhibited 50% of cell growth at nanomolar concentrations. Immunofluorescence microscopy indicated microtubule depolarization and the resultant mitotic arrest was further confirmed through cell cycle analysis. Apoptosis induction via the intrinsic pathway was observed due to depolarization of the mitochondrial membrane, induction of cytochrome c release as well as, caspase 3 activation. Potential involvement of programmed cell death type II was observed due to the presence of acidic vacuoles and aggresome formation. Necrotic cell death did not contribute significantly, indicated by stable LDH levels. This in vitro study revealed the induction of the intrinsic apoptotic pathway as well as possible involvement of autophagy after exposure to these THIQ-based analogues in both MDA-MB-231- and A549 cells. Further investigation of this series of anticancer drugs still needs to be conducted to elucidate the temporal, mechanistic and functional crosstalk mechanisms between the two observed programmed cell deaths pathways.

Keywords: apoptosis, autophagy, cancer, microtubule disruptor

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Authors: Komal Rathore, Kiesha Pierre, Kyle Cogswell, Aaron Driscoll, Andres Tejada Martinez, Gita Iranipour, Luke Mulford, Aydin Sunol

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Modeling of Biological Wastewater Treatment Plants requires several parameters for kinetic rate expressions, thermo-physical properties, and hydrodynamic behavior. The kinetics and associated mechanisms become complex due to several biological processes taking place in wastewater treatment plants at varying times and spatial scales. A dynamic process model that incorporated the complex model for activated sludge kinetics was developed using the BioWin software platform for an Advanced Wastewater Treatment Plant in Valrico, Florida. Due to the extensive number of tunable parameters, an experimental design was employed for judicious selection of the most influential parameter sets and their bounds. The model was tuned using both the influent and effluent plant data to reconcile and rectify the forecasted results from the BioWin Model. Amount of mixed liquor suspended solids in the oxidation ditch, aeration rates and recycle rates were adjusted accordingly. The experimental analysis and plant SCADA data were used to predict influent wastewater rates and composition profiles as a function of time for extended periods. The lumped dynamic model development process was coupled with Computational Fluid Dynamics (CFD) modeling of the key units such as oxidation ditches in the plant. Several CFD models that incorporate the nitrification-denitrification kinetics, as well as, hydrodynamics was developed and being tested using ANSYS Fluent software platform. These realistic and verified models developed using BioWin and ANSYS were used to plan beforehand the operating policies and control strategies for the biological wastewater plant accordingly that further allows regulatory compliance at minimum operational cost. These models, with a little bit of tuning, can be used for other biological wastewater treatment plants as well. The BioWin model mimics the existing performance of the Valrico Plant which allowed the operators and engineers to predict effluent behavior and take control actions to meet the discharge limits of the plant. Also, with the help of this model, we were able to find out the key kinetic and stoichiometric parameters which are significantly more important for modeling of biological wastewater treatment plants. One of the other important findings from this model were the effects of mixed liquor suspended solids and recycle ratios on the effluent concentration of various parameters such as total nitrogen, ammonia, nitrate, nitrite, etc. The ANSYS model allowed the abstraction of information such as the formation of dead zones increases through the length of the oxidation ditches as compared to near the aerators. These profiles were also very useful in studying the behavior of mixing patterns, effect of aerator speed, and use of baffles which in turn helps in optimizing the plant performance.

Keywords: computational fluid dynamics, flow-sheet simulation, kinetic modeling, process dynamics

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Authors: Alexander Norbach

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The script in this paper describes the use of advanced simulation environment using electronic systems (Microcontroller, Operational Amplifiers, and FPGA). The simulation may be used for all dynamic systems with the diffusion and the ionisation behaviour also. By additionally required observer structure, the system works with parallel real-time simulation based on diffusion model and the state-space representation for other dynamics. The proposed deposited model may be used for electrodynamic effects, including ionising effects and eddy current distribution also. With the script and proposed method, it is possible to calculate the spatial distribution of the electromagnetic fields in real-time. For further purpose, the spatial temperature distribution may be used also. With upon system, the uncertainties, unknown initial states and disturbances may be determined. This provides the estimation of the more precise system states for the required system, and additionally, the estimation of the ionising disturbances that occur due to radiation effects. The results have shown that a system can be also developed and adopted specifically for space systems with the real-time calculation of the radiation effects only. Electronic systems can take damage caused by impacts with charged particle flux in space or radiation environment. In order to be able to react to these processes, it must be calculated within a shorter time that ionising radiation and dose is present. All available sensors shall be used to observe the spatial distributions. By measured value of size and known location of the sensors, the entire distribution can be calculated retroactively or more accurately. With the formation, the type of ionisation and the direct effect to the systems and thus possible prevent processes can be activated up to the shutdown. The results show possibilities to perform more qualitative and faster simulations independent of kind of systems space-systems and radiation environment also. The paper gives additionally an overview of the diffusion effects and their mechanisms. For the modelling and derivation of equations, the extended current equation is used. The size K represents the proposed charge density drifting vector. The extended diffusion equation was derived and shows the quantising character and has similar law like the Klein-Gordon equation. These kinds of PDE's (Partial Differential Equations) are analytically solvable by giving initial distribution conditions (Cauchy problem) and boundary conditions (Dirichlet boundary condition). For a simpler structure, a transfer function for B- and E- fields was analytically calculated. With known discretised responses g₁(k·Ts) and g₂(k·Ts), the electric current or voltage may be calculated using a convolution; g₁ is the direct function and g₂ is a recursive function. The analytical results are good enough for calculation of fields with diffusion effects. Within the scope of this work, a proposed model of the consideration of the electromagnetic diffusion effects of arbitrary current 'waveforms' has been developed. The advantage of the proposed calculation of diffusion is the real-time capability, which is not really possible with the FEM programs available today. It makes sense in the further course of research to use these methods and to investigate them thoroughly.

Keywords: advanced observer, electrodynamics, systems, diffusion, partial differential equations, solver

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Authors: Jean Ware, Susan W. Jones

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Background: The benefits of grammar instruction in the teaching of writing is contested in most English speaking countries. A majority of Anglophone countries abandoned the teaching of grammar in the 1950s based on the conclusions that it had no positive impact on learners’ development of reading, writing, and language. Although the decontextualised teaching of grammar is not helpful in improving writing, a curriculum with a focus on grammar in an embedded and meaningful way can help learners develop their understanding of the mechanisms of language. Although British learners are generally not taught grammar rules explicitly, learners in schools in France, the Netherlands, and Germany are taught explicitly about the structure of their own language. Exposing learners to grammatical analysis can help them develop their understanding of language. Indeed, if learners are taught that each part of speech has an identified role in the sentence. This means that rather than have to memorise lists of words or spelling patterns, they can focus on determining each word or phrase’s task in the sentence. These processes of categorisation and deduction are higher order thinking skills. When considering definitions of dyslexia available in Great Britain, the explicit teaching of grammar in context could help learners with persistent literacy difficulties. Indeed, learners with dyslexia often develop strengths in problem solving; the teaching of grammar could, therefore, help them develop their understanding of language by using analytical and logical thinking. Aims: This study aims at gaining a further understanding of how the explicit teaching of grammar in context can benefit learners with persistent literacy difficulties. The project is designed to identify ways of adapting existing grammar focussed teaching materials so that learners with specific learning difficulties such as dyslexia can use them to further develop their writing skills. It intends to improve educational practice through action, analysis and reflection. Research Design/Methods: The project, therefore, uses an action research design and multiple sources of evidence. The data collection tools used were standardised test data, teacher assessment data, semi-structured interviews, learners’ before and after attempts at a writing task at the beginning and end of the cycle, documentary data and lesson observation carried out by a specialist teacher. Existing teaching materials were adapted for use with five Year 9 learners who had experienced persistent literacy difficulties from primary school onwards. The initial adaptations included reducing the amount of content to be taught in each lesson, and pre teaching some of the metalanguage needed. Findings: Learners’ before and after attempts at the writing task were scored by a colleague who did not know the order of the attempts. All five learners’ scores were higher on the second writing task. Learners reported that they had enjoyed the teaching approach. They also made suggestions to be included in the second cycle, as did the colleague who carried out observations. Conclusions: Although this is a very small exploratory study, these results suggest that adapting grammar focused teaching materials shows promise for helping learners with persistent literacy difficulties develop their writing skills.

Keywords: explicit teaching of grammar in context, literacy acquisition, persistent literacy difficulties, writing skills

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Authors: Tammy Shel (Aboody)

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The integration of philosophy with ethnography, i.e., ethno-philosophy, or any qualitative method, is multi-dimensional. It is, thus, vital to the discourse on caring in the philosophy of education, and in therapy. These two significant dimensions are focal in this proposal’s discussion. The integration of grounded data with philosophy can shed light on cultural, gender, socio-economic and political diversities in the relationships and interactions between and among individuals and societies. This approach can explain miscommunication and, eventually, violent conflicts. The ethno-philosophy study in this proposal focuses on the term caring, through case studies of 5 non-white male and female elementary school teachers in Los Angeles County. The study examined the teachers’ views on caring and, consequently, the implications on their pedagogy. Subsequently, this method turned out to also be a caring approach in therapy. Ethnographic data was juxtaposed with western philosophy. Research discussion unraveled transformable gaps between western patriarchal and feminist philosophy on caring, and that of the teachers. Multiple interpretations and practices of caring were found due to cultural, gender, and socio-economic-political differences. Likewise, two dominant categories emerged. The first is inclusive caring, which is perceived as an ideal, as the compass of humanity that aims towards emancipation from the shackles of inner and external violence. The second is tribal caring, which illuminates the inherently dialectical substantial diversity in the interpretations and praxes of caring. Such angles are absent or minor in traditional western literature. Both categories teach of the incessant dynamic definition of caring, and its subliminal and repressed mechanisms. The multi-cultural aspects can teach us, however, that despite the inclusive common ground we share on caring, and despite personal and social awareness of cultural and gender differences, the hegemonic ruling-class governs the standardized conventional interpretation of caring. Second is the dimension of therapy in ethno-philosophy. Each patient is like a case study per se, and is a self-ethnographer. Thus, the patient is the self-observer and data collector, and the therapist is the philosopher who helps deconstruct into fragments the consciousness that comprises our well-being and self-esteem and acceptance. Together, they both identify and confront hurdles that hinder the pursuit of a more composed attitude towards ourselves and others. Together, they study and re-organize these fragments into a more comprehensible and composed self-acceptance. Therefore, the ethno-philosophy method, which stems from a caring approach, confronts the internal and external conflicts that govern our relationships with others. It sheds light on the dark and subliminal spots in our minds and hearts that operate us. Unveiling the hidden spots helps identify a shared ground that can supersede miscommunication and conflicts among and between people. The juxtaposition of ethnography with philosophy, as a caring approach in education and therapy, emphasizes that planet earth is like a web. Hence, despite the common mechanism that stimulates a caring approach towards the other, ethno-philosophy can help undermine the ruling patriarchal oppressive forces that define and standardize caring relationships, and to subsequently bridge gaps between people.

Keywords: caring, philosophy of education, ethnography, therapy, research

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Authors: Bello Gonzalez T. D. J., Setten Van M., Essen Van A., Brouwer M., Veldman K. T.

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Resistance to fluoroquinolones (FQ) has evolved increasingly over the years, posing a significant challenge for the treatment of human infections, particularly gastrointestinal tract infections caused by zoonotic bacteria transmitted through the food chain and environment. In broiler chickens, a relatively high proportion of FQ resistance has been observed in Escherichia coli indicator, Salmonella and Campylobacter isolates. We hypothesize that flumequine (Flu), used as a secondary choice for the treatment of poultry infections, could potentially be associated with a high proportion of FQ resistance. To evaluate this hypothesis, we used an in vitro fermentation chicken caeca model. Two continuous single-stage fermenters were used to simulate in real time the physiological conditions of the chicken caeca microbial content (temperature, pH, caecal content mixing, and anoxic environment). A pool of chicken caecal content containing FQ-resistant E. coli obtained from chickens at slaughter age was used as inoculum along with a spiked FQ-susceptible Campylobacter jejuni strain isolated from broilers. Flu was added to one of the fermenters (Flu-fermenter) every 24 hours for two days to evaluate the selection and maintenance of FQ resistance over time, while the other served as a control (C-Fermenter). The experiment duration was 5 days. Samples were collected at three different time points: before, during and after Flu administration. Serial dilutions were plated on Butzler culture media with and without Flu (8mg/L) and enrofloxacin (4mg/L) and on MacConkey culture media with and without Flu (4mg/L) and enrofloxacin (1mg/L) to determine the proportion of resistant strains over time. Positive cultures were identified by mass spectrometry and matrix-assisted laser desorption/ionization (MALDI). A subset of the obtained isolates were used for Whole Genome Sequencing analysis. Over time, E. coli exhibited positive growth in both fermenters, while C. jejuni growth was detected up to day 3. The proportion of Flu-resistant E. coli strains recovered remained consistent over time after antibiotic selective pressure, while in the C-fermenter, a decrease was observed at day 5; a similar pattern was observed in the enrofloxacin-resistant E. coli strains. This suggests that Flu might play a role in the selection and persistence of enrofloxacin resistance, compared to C-fermenter, where enrofloxacin-resistant E. coli strains appear at a later time. Furthermore, positive growth was detected from both fermenters only on Butzler plates without antibiotics. A subset of C. jejuni strains from the Flu-fermenter revealed that those strains were susceptible to ciprofloxacin (MIC < 0.12 μg/mL). A selection of E. coli strains from both fermenters revealed the presence of plasmid-mediated quinolone resistance (PMQR) (qnr-B19) in only one strain from the C-fermenter belonging to sequence type (ST) 48, and in all from Flu-fermenter belonged to ST189. Our results showed that Flu selective impact on PMQR-positive E. coli strains, while no effect was observed in C. jejuni. Maintenance of Flu-resistance was correlated with antibiotic selective pressure. Further studies into antibiotic resistance gene transfer among commensal and zoonotic bacteria in the chicken caeca content may help to elucidate the resistance spread mechanisms.

Keywords: fluoroquinolone-resistance, escherichia coli, campylobacter jejuni, in vitro model

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Authors: M. Koksal, T. Ozyazici, E. Gurdal, M. Yarım, E. Demirpolat, M. B. Y. Aycan

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The discovery of new drugs in cancer chemotherapy is still a major topic because of severe side effects, selectivity problems and resistance development potential of existing drugs. In recent years, combined anticancer therapies or multi-acting drugs are clinically preferred over traditional cytotoxic treatment, with the aim of avoiding resistance and toxic side effects. Arrangement of multi-acting targets can be carried out either by combination of several drugs with different mechanisms or by usage of a single chemical compound capable of regulating several targets of a disease with multiple factors. In literature, several pyrimidine and piperazine derivatives have been involved in the structure of many compounds which have been used as chemotherapeutic agents along with wide clinical applications. The aim of this study is to combine pyrimidine and piperazine core structures to research and develop novel piperazinylpyrimidine derivatives with selective cytotoxicity over cancer cells. In this study, a group of novel 6-fluorophenyl-3-[2-(substitutedpiperazinyl)ethyl] hexahydropyrimidine-2,4-dione derivatives designed to observe the desired anticancer activity due to pyrimidine and piperazine based scaffolds. Target compounds were obtained by the reaction of appropriate piperazine derivatives and 6-(2/4-fluorophenyl)-3-(2-chloroethyl)hexahydropyrimidine-2,4-dione. The synthetic pathway of 6-(2/4-fluorophenyl)-3-(2-chloroethyl)hexahydropyrimidine-2,4-dione was started with Rodionov reaction using aldehyde, malonic acid and ammonium acetate in ethanol. Isolated β-fluorophenyl-β-amino acids were treated with 2-chloroethylisocyanate in the presence of an aqueous sodium hydroxide solution at room temperature to yield the sodium salts of the corresponding ureido acids. By addition of a mineral acid, ureido acids were precipitated. Later, these ureido acids were refluxed in thionyl chloride to give the 6-(2/4-fluorophenyl)-3-(2-chloroethyl)hexahydropyrimidine-2,4-di-one which were furthermore treated with secondary amines. Structures of purified compounds were characterized with IR, 1H-NMR, 13C-NMR, mass spectroscopies and elemental analysis. All of the compounds gave satisfactory analytical and spectroscopic data, which were in full accordance with their depicted structures. In IR spectra of the compounds, N-H group was seen at 3230-3213 cm⁻¹. C-H was seen at 3100-2820 cm⁻¹ and C=O vibrational peaks were observed approximately at 1725 and 1665 cm⁻¹ in accordance with literature. In the NMR spectra of target compounds, the methylene protons of piperazine give two separate multiplet peaks around 3.5 and 4.5 ppm representing the successful N-alkylation of the structure. The cytotoxic activity of the synthesized compounds was investigated on human bronchial epithelial (BEAS 2B), lung (A549), colon adenocarcinoma (COLO205) and breast (MCF7) cell lines, by means of sulphorhodamine B (SRB) assays in triplicate. IC₅₀ values of the screened derivatives were found in range of 11.8-78 µM. This project was supported by The Scientific and Technological Research Council of Turkey (TUBITAK, Project no: 215S157).

Keywords: cytotoxicity, hexahydropyrimidine, piperazine, sulphorhodamine B assay

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