Search results for: solar potential

Authors: Pawel Martynowicz

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Vibrations are a crucial problem for slender structures such as towers, masts, chimneys, wind turbines, bridges, high buildings, etc., that is why most of them are equipped with vibration attenuation or fatigue reduction solutions. In this work, a slender structure (i.e., wind turbine tower-nacelle model) equipped with nonlinear, semiactive tuned vibration absorber(s) is analyzed. For this study purposes, magnetorheological (MR) dampers are used as semiactive actuators. Several optimal-based approaches to structural vibration attenuation are investigated against the standard ‘ground-hook’ law and passive tuned vibration absorber(s) implementations. The common approach to optimal control of nonlinear systems is offline computation of the optimal solution, however, so determined open loop control suffers from lack of robustness to uncertainties (e.g., unmodelled dynamics, perturbations of external forces or initial conditions), and thus perturbation control techniques are often used. However, proper linearization may be an issue for highly nonlinear systems with implicit relations between state, co-state, and control. The main contribution of the author is the development as well as numerical and experimental verification of the Pontriagin maximum-principle-based vibration control concepts that produce directly actuator control input (not the demanded force), thus force tracking algorithm that results in control inaccuracy is entirely omitted. These concepts, including one-step optimal control, quasi-optimal control, and optimal-based modified ‘ground-hook’ law, can be directly implemented in online and real-time feedback control for periodic (or semi-periodic) disturbances with invariant or time-varying parameters, as well as for non-periodic, transient or random disturbances, what is a limitation for some other known solutions. No offline calculation, excitations/disturbances assumption or vibration frequency determination is necessary, moreover, all of the nonlinear actuator (MR damper) force constraints, i.e., no active forces, lower and upper saturation limits, hysteresis-type dynamics, etc., are embedded in the control technique, thus the solution is optimal or suboptimal for the assumed actuator, respecting its limitations. Depending on the selected method variant, a moderate or decisive reduction in the computational load is possible compared to other methods of nonlinear optimal control, while assuring the quality and robustness of the vibration reduction system, as well as considering multi-pronged operational aspects, such as possible minimization of the amplitude of the deflection and acceleration of the vibrating structure, its potential and/or kinetic energy, required actuator force, control input (e.g. electric current in the MR damper coil) and/or stroke amplitude. The developed solutions are characterized by high vibration reduction efficiency – the obtained maximum values of the dynamic amplification factor are close to 2.0, while for the best of the passive systems, these values exceed 3.5.

Keywords: magnetorheological damper, nonlinear tuned vibration absorber, optimal control, real-time structural vibration attenuation, wind turbines

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Authors: Antonia Egli, Theo Lynn, Pierangelo Rosati, Gary Sinclair

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The World Health Organization (WHO) defines vaccine hesitancy as the postponement or complete denial of vaccines and estimates a direct linkage to approximately 1.5 million avoidable deaths annually. This figure is not immune to public health developments, as has become evident since the global spread of COVID-19 from Wuhan, China in early 2020. Since then, the proliferation of influential, but oftentimes inaccurate, outdated, incomplete, or false vaccine-related information on social media has impacted hesitancy levels to a degree described by the WHO as an infodemic. The COVID-19 pandemic and related vaccine hesitancy levels have in 2022 resulted in the largest drop in childhood vaccinations of the 21st century, while the prevalence of online stigma towards vaccine hesitant consumers continues to grow. Simultaneously, a second disease has risen to global importance: Monkeypox is an infection originating from west and central Africa and, due to racially motivated online hate, was in August 2022 set to be renamed by the WHO. To better understand public reactions towards two viral infections that became global threats to public health no two years apart, this research examines user replies to threads published by the WHO on Twitter. Replies to two Tweets from the @WHO account declaring COVID-19 and Monkeypox as ‘public health emergencies of international concern’ on January 30, 2020, and July 23, 2022, are gathered using the Twitter application programming interface and user mention timeline endpoint. Research methodology is unique in its analysis of stigmatizing, racist, and hateful content shared on social media within the vaccine discourse over the course of two disease outbreaks. Three distinct analyses are conducted to provide insight into (i) the most prevalent topics and sub-topics among user reactions, (ii) changes in sentiment towards the spread of the two diseases, and (iii) the presence of stigma, racism, and online hate. Findings indicate an increase in hesitancy to accept further vaccines and social distancing measures, the presence of stigmatizing content aimed primarily at anti-vaccine cohorts and racially motivated abusive messages, and a prevalent fatigue towards disease-related news overall. This research provides value to non-profit organizations or government agencies associated with vaccines and vaccination programs in emphasizing the need for public health communication fitted to consumers' vaccine sentiments, levels of health information literacy, and degrees of trust towards public health institutions. Considering the importance of addressing fears among the vaccine hesitant, findings also illustrate the risk of alienation through stigmatization, lead future research in probing the relatively underexamined field of online, vaccine-related stigma, and discuss the potential effects of stigma towards vaccine hesitant Twitter users in their decisions to vaccinate.

Keywords: social marketing, social media, public health communication, vaccines

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Authors: Charlotte K. Lee, Henrique R. N. Aguiar, Ralph Smith, James Baldock, Sam Botchey

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Background: Femoral neck stress fractures (FNSF) are uncommon, making up 1 to 7.2% of stress fractures in healthy subjects. FNSFs are prevalent in young women, military recruits, endurance athletes, and individuals with energy deficiency syndrome or female athlete triad. Presentation is often non-specific and is often misdiagnosed following the initial examination. There is limited research addressing the return–to–activity time after FNSF. Previous studies have demonstrated prognostic time predictions based on various imaging techniques. Here, (1) OxSport clinic FNSF practice standards are retrospectively reviewed, (2) FNSF cohort demographics are examined, (3) Regression models were used to predict return–to–activity prognosis and consequently determine bone stress risk factors. Methods: Patients with a diagnosis of FNSF attending Oxsport clinic between 01/06/2020 and 01/01/2020 were selected from the Rheumatology Assessment Database Innovation in Oxford (RhADiOn) and OxSport Stress Fracture Database (n = 14). (1) Clinical practice was audited against five criteria based on local and National Institute for Health Care Excellence guidance, with a 100% standard. (2) Demographics of the FNSF cohort were examined with Student’s T-Test. (3) Lastly, linear regression and Random Forest regression models were used on this patient cohort to predict return–to–activity time. Consequently, an analysis of feature importance was conducted after fitting each model. Results: OxSport clinical practice met standard (100%) in 3/5 criteria. The criteria not met were patient waiting times and documentation of all bone stress risk factors. Importantly, analysis of patient demographics showed that of the population with complete bone stress risk factor assessments, 53% were positive for modifiable bone stress risk factors. Lastly, linear regression analysis was utilized to identify demographic factors that predicted return–to–activity time [R2 = 79.172%; average error 0.226]. This analysis identified four key variables that predicted return-to-activity time: vitamin D level, total hip DEXA T value, femoral neck DEXA T value, and history of an eating disorder/disordered eating. Furthermore, random forest regression models were employed for this task [R2 = 97.805%; average error 0.024]. Analysis of the importance of each feature again identified a set of 4 variables, 3 of which matched with the linear regression analysis (vitamin D level, total hip DEXA T value, and femoral neck DEXA T value) and the fourth: age. Conclusion: OxSport clinical practice could be improved by more comprehensively evaluating bone stress risk factors. The importance of this evaluation is demonstrated by the population found positive for these risk factors. Using this cohort, potential bone stress risk factors that significantly impacted return-to-activity prognosis were predicted using regression models.

Keywords: eating disorder, bone stress risk factor, femoral neck stress fracture, vitamin D

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Authors: Michela Del Vicario, Walter Quattrociocchi, Antonio Scala, Ana Lucía Schmidt, Fabiana Zollo

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Information, rumors, and debates may shape and impact public opinion heavily. In the latest years, several concerns have been expressed about social influence on the Internet and the outcome that online debates might have on real-world processes. Indeed, on online social networks users tend to select information that is coherent to their system of beliefs and to form groups of like-minded people –i.e., echo chambers– where they reinforce and polarize their opinions. In this way, the potential benefits coming from the exposure to different points of view may be reduced dramatically, and individuals' views may become more and more extreme. Such a context fosters misinformation spreading, which has always represented a socio-political and economic risk. The persistence of unsubstantiated rumors –e.g., the hypothetical and hazardous link between vaccines and autism– suggests that social media do have the power to misinform, manipulate, or control public opinion. As an example, current approaches such as debunking efforts or algorithmic-driven solutions based on the reputation of the source seem to prove ineffective against collective superstition. Indeed, experimental evidence shows that confirmatory information gets accepted even when containing deliberately false claims while dissenting information is mainly ignored, influences users’ emotions negatively and may even increase group polarization. Moreover, confirmation bias has been shown to play a pivotal role in information cascades, posing serious warnings about the efficacy of current debunking efforts. Nevertheless, mitigation strategies have to be adopted. To generalize the problem and to better understand social dynamics behind information spreading, in this work we rely on a tight quantitative analysis to investigate the behavior of more than 300M users w.r.t. news consumption on Facebook over a time span of six years (2010-2015). Through a massive analysis on 920 news outlets pages, we are able to characterize the anatomy of news consumption on a global and international scale. We show that users tend to focus on a limited set of pages (selective exposure) eliciting a sharp and polarized community structure among news outlets. Moreover, we find similar patterns around the Brexit –the British referendum to leave the European Union– debate, where we observe the spontaneous emergence of two well segregated and polarized groups of users around news outlets. Our findings provide interesting insights into the determinants of polarization and the evolution of core narratives on online debating. Our main aim is to understand and map the information space on online social media by identifying non-trivial proxies for the early detection of massive informational cascades. Furthermore, by combining users traces, we are finally able to draft the main concepts and beliefs of the core narrative of an echo chamber and its related perceptions.

Keywords: information spreading, misinformation, narratives, online social networks, polarization

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Authors: Ching-Yu Liao, Ju-Joan Wong

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Recent years have shown a trend of younger stroke patients and an increase in ischemic strokes with the rise in stroke incidence. This has led to a growing demand for telemedicine, particularly during the COVID-19 pandemic, which has made the need for telemedicine even more urgent. This shift in healthcare is also closely related to advancements in Internet of Things (IoT) technology. Stroke-induced hemiparesis is a significant issue for patients. The medical community believes that if intervention occurs within three to six months of stroke onset, 80% of the residual effects can be restored to normal, a period known as the stroke golden period. During this time, patients undergo treatment and rehabilitation, and neural plasticity is at its best. Lower limb rehabilitation for stroke generally includes exercises such as support standing and walking posture, typically involving the healthy limb to guide the affected limb to achieve rehabilitation goals. Existing gait training aids in hospitals usually involve balance gait, sitting posture training, and precise muscle control, effectively addressing issues of poor gait, insufficient muscle activity, and inability to train independently during recovery. However, home training aids, such as braced and wheeled devices, often rely on the healthy limb to pull the affected limb, leading to lower usage of the affected limb, worsening circular walking, and compensatory movement issues. IoT technology connects devices via the internet to record, receive data, provide feedback, and adjust equipment for intelligent effects. Therefore, this study aims to explore how IoT can be integrated into existing gait training aids to monitor and sensor home rehabilitation movements, improve gait training compensatory issues through real-time feedback, and enable healthcare professionals to quickly understand patient conditions and enhance medical communication. To understand the needs of hemiparetic patients, a review of relevant literature from the past decade will be conducted. From the perspective of user experience, participant observation will be used to explore the use of home training aids by stroke patients and therapists, and interviews with physical therapists will be conducted to obtain professional opinions and practical experiences. Design specifications for home training aids for hemiparetic patients will be summarized. Applying IoT technology to lower limb training aids for stroke hemiparesis can help promote walking function recovery in hemiparetic patients, reduce muscle atrophy, and allow healthcare professionals to immediately grasp patient conditions and adjust gait training plans based on collected and analyzed information. Exploring these potential development directions provides a valuable reference for the further application of IoT technology in the field of medical rehabilitation.

Keywords: stroke, hemiplegia, rehabilitation, gait training, internet of things technology

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Authors: Tshimangadzo Jeanette Raedani, Edgar Musie, Afsatou Traore

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Background: Street-vended meats, including chicken, pork, and beef, are popular in urban areas worldwide due to their convenience and affordability. However, these meats often pose a significant risk of foodborne diseases. The high water activity, protein content, and nearly neutral pH of meat create conditions conducive to the growth of pathogenic bacteria. Street foods, particularly meats, are frequently linked to outbreaks of foodborne illnesses due to potential contamination from improper handling and preparation. This study aimed to assess the microbial quality and safety of street-vended ready-to-eat meat sold in the Thohoyandou area. Method: The study involved collecting 168 samples of street-vended meat, split evenly between chicken (n=84) and beef (n=84), from various vendors around Thohoyandou. The samples were randomly selected and transported in sterile conditions to the Department of Food Microbiology at the University of Venda for analysis. Each 10-gram sample was cultured in selective media: MSA for Staphylococcus aureus, EMB for E. coli O157, XLD agar for Salmonella, and Sorbitol McConkey for Shigella. After initial culturing, the presumptive colonies were sub-cultured for purification and identified through Gram staining and biochemical tests, including Catalase, API 20E, Klingler Iron Agar Test, and Vitek 2 system. Antibiotic susceptibility was tested using agents such as Ampicillin, Chloramphenicol, Penicillin, Neomycin, Tetracycline, Streptomycin, and Amoxicillin. Molecular characterization was performed to identify E. coli pathotypes using multiplex PCR. Results: Out of 168 samples tested, 32 (19%) were positive for Staphylococcus spp., with the highest prevalence found in cooked chicken meat. The most common staphylococcus species identified were S. xylosus (13.2%) and S. saprophyticus (10.5%). E. coli was present in 29 (19.3%) of the samples, with the highest prevalence in fried chicken. Antibiotic susceptibility testing showed that 100% of E. coli isolates were resistant to Ampicillin, Tetracycline, and Penicillin, but 100% were susceptible to Neomycin. Staphylococcus spp. isolates were also 100% resistant to Ampicillin and 100% susceptible to Neomycin. The study detected a range of virulence genes in E. coli, with prevalence rates from 13.33% to 86.67%. The identified pathotypes included EPEC, EHEC, ETEC, EAEC, and EIEC, with many isolates showing mixed pathotypes. Conclusion: The study highlighted that the microbial quality and safety of street-vended meats in Thohoyandou are inadequate, rendering them unsafe for consumption. The presence of pathogenic microorganisms in both beef and chicken samples indicates significant risks associated with poor personal hygiene and food preparation practices. This underscores the need for improved monitoring and stricter food safety measures to prevent foodborne diseases and ensure consumer safety.

Keywords: meat, microbial analysis, street vendors, E. coli

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Authors: Lucas Nascimento, Ana Rita, Margarida Soares, André Ribeiro, Zlatina Genisheva, Hugo Silva, Joana Carvalho

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The footwear industry is an essential fashion industry, focusing on producing various types of footwear, such as shoes, boots, sandals, sneakers, and slippers. Global footwear consumption has doubled every 20 years since the 1950s. It is estimated that in 1950, each person consumed one new pair of shoes yearly; by 2005, over 20 billion pairs of shoes were consumed. To meet global footwear demand, production reached $24.2 billion, equivalent to about $74 per person in the United States. This means three new pairs of shoes per person worldwide. The issue of footwear waste is related to the fact that shoe production can generate a large amount of waste, much of which is difficult to recycle or reuse. This waste includes scraps of leather, fabric, rubber, plastics, toxic chemicals, and other materials. The search for alternative solutions for waste treatment and valorization is increasingly relevant in the current context, mainly when focused on utilizing waste as a source of substitute materials. From the perspective of the new circular economy paradigm, this approach is of utmost importance as it aims to preserve natural resources and minimize the environmental impact associated with sending waste to landfills. In this sense, the incorporation of waste into industrial sectors that allow for the recovery of large volumes, such as road construction, becomes an urgent and necessary solution from an environmental standpoint. This study explores the use of plastic waste from the footwear industry as a substitute for virgin polymers in bitumen modification, a solution that presents a more sustainable future. Replacing conventional polymers with plastic waste in asphalt composition reduces the amount of waste sent to landfills and offers an opportunity to extend the lifespan of road infrastructures. By incorporating waste into construction materials, reducing the consumption of natural resources and the emission of pollutants is possible, promoting a more circular and efficient economy. In the initial phase of this study, waste materials from end-of-life footwear were selected, and plastic waste with the highest potential for application was separated. Based on a literature review, EVA (ethylene vinyl acetate) and PU (polyurethane) were identified as the polymers suitable for modifying 50/70 classification bitumen. Each polymer was analysed at concentrations of 3% and 5%. The production process involved the polymer's fragmentation to a size of 4 millimetres after heating the materials to 180 ºC and mixing for 10 minutes at low speed. After was mixed for 30 minutes in a high-speed mixer. The tests included penetration, softening point, viscosity, and rheological assessments. With the results obtained from the tests, the mixtures with EVA demonstrated better results than those with PU, as EVA had more resistance to temperature, a better viscosity curve and a greater elastic recovery in rheology.

Keywords: footwear waste, hot asphalt pavement, modified bitumen, polymers

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Authors: Mustafa Metin Donma, Orkide Donma

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Childhood obesity is an important clinical problem because it may lead to chronic diseases during the adulthood period of the individual. Obesity is a metabolic disease associated with low-grade inflammation. The liver occurs at the center of metabolic pathways. Adropin, fibroblast growth factor-21 (FGF-21), and fetuin-A are hepatokines. Due to the immense participation of the liver in glucose metabolism, these liver-derived factors may be associated with insulin resistance (IR), which is a phenomenon discussed within the scope of obesity problems. The aim of this study is to determine the concentrations of adropin, FGF-21, and fetuin-A in childhood obesity, to point out possible differences between the obesity groups, and to investigate possible associations among these three hepatokines in obese and morbidly obese children. A total of one hundred and thirty-two children were included in the study. Two obese groups were constituted. The groups were matched in terms of mean ± SD values of ages. Body mass index values of obese and morbidly obese groups were 25.0 ± 3.5 kg/m² and 29.8 ± 5.7 kg/m², respectively. Anthropometric measurements including waist circumference, hip circumference, head circumference, and neck circumference were recorded. Informed consent forms were taken from the parents of the participants. The ethics committee of the institution approved the study protocol. Blood samples were obtained after overnight fasting. Routine biochemical tests, including glucose- and lipid-related parameters, were performed. Concentrations of the hepatokines (adropin, FGF-21, fetuin A) were determined by enzyme-linked immunosorbent assay. Insulin resistance indices such as homeostasis model assessment for IR (HOMA-IR), alanine transaminase-to aspartate transaminase ratio (ALT/AST), diagnostic obesity notation model assessment laboratory index, diagnostic obesity notation model assessment metabolic syndrome index as well as obesity indices such as diagnostic obesity notation model assessment-II index, and fat mass index were calculated using the previously derived formulas. Statistical evaluation of the study data as well as findings of the study was performed by SPSS for Windows. Statistical difference was accepted significant when p is smaller than 0.05. Statistically significant differences were found for insulin, triglyceride, high-density lipoprotein cholesterol levels of the groups. A significant increase was observed for FGF-21 concentrations in the morbidly obese group. Higher adropin and fetuin-A concentrations were observed in the same group in comparison with the values detected in the obese group (p > 0.05). There was no statistically significant difference between the ALT/AST values of the groups. In all of the remaining IR and obesity indices, significantly increased values were calculated for morbidly obese children. Significant correlations were detected between HOMA-IR and each of the hepatokines. The highest one was the association with fetuin-A (r=0.373, p=0.001). In conclusion, increased levels observed in adropin, FGF-21, and fetuin-A have shown that these hepatokines possess increasing potential going from obese to morbid obese state. Out of the correlations found with the IR index, the most affected hepatokine was fetuin-A, the parameter possibly used as the indicator of the advanced obesity stage.

Keywords: adropin, fetuin A, fibroblast growth factor-21, insulin resistance, pediatric obesity

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Authors: K. Yu Vlasova, M. A. Abakumov, H. Wishwarsao, M. Sokolsky, N. V. Nukolova, A. G. Majouga, Y. I. Golovin, N. L. Klyachko, A. V. Kabanov

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Introduction:Nowadays pharmaceutical medicine is aimed to create systems for combined therapy, diagnostic, drug delivery and controlled release of active molecules to target cells. Magnetic nanoparticles (MNPs) are used to achieve this aim. MNPs can be applied in molecular diagnostics, magnetic resonance imaging (T1/T2 contrast agents), drug delivery, hyperthermia and could improve therapeutic effect of drugs. The most common drug containers, containing MNPs, are liposomes, micelles and polymeric molecules bonded to the MNPs surface. Usually superparamagnetic nanoparticles are used (the general diameter is about 5-6 nm) and all effects of high frequency magnetic field (MF) application are based on Neel relaxation resulting in heating of surrounded media. In this work we try to develop a new method to improve drug release from MNPs under super low frequency MF. We suppose that under low frequency MF exposures the Brown’s relaxation dominates and MNPs rotation could occur leading to conformation changes and release of bioactive molecules immobilized on MNPs surface.The aim of this work was to synthesize different systems with active drug (biopolymers coated MNPs nanoclusters with immobilized enzymes and doxorubicin (Dox) loaded magnetic liposomes/micelles) and investigate the effect of super low frequency MF on these drug containers. Methods: We have synthesized MNPs of magnetite with magnetic core diameter 7-12 nm . The MNPs were coated with block-copolymer of polylysine and polyethylene glycol. Superoxide dismutase 1 (SOD1) was electrostatically adsorbed on the surface of the clusters. Liposomes were prepared as follow: MNPs, phosphatidylcholine and cholesterol were dispersed in chloroform, dried to get film and then dispersed in distillated water, sonicated. Dox was added to the solution, pH was adjusted to 7.4 and excess of drug was removed by centrifugation through 3 kDa filters. Results: Polylysine coated MNPs formed nanosized clusters (as observed by TEM) with intensity average diameter of 112±5 nm and zeta potential 12±3 mV. After low frequency AC MF exposure we observed change of immobilized enzyme activity and hydrodynamic size of clusters. We suppose that the biomolecules (enzymes) are released from the MNPs surface followed with additional aggregation of complexes at the MF in medium. Centrifugation of the nanosuspension after AC MF exposures resulted in increase of positive charge of clusters and change in enzyme concentration in comparison with control sample without MF, thus confirming desorption of negatively charged enzyme from the positively charged surface of MNPs. Dox loaded magnetic liposomes had average diameter of 160±8 nm and polydispersity index (PDI) 0.25±0.07. Liposomes were stable in DW and PBS at pH=7.4 at 370C during a week. After MF application (10 min of exposure, 50 Hz, 230 mT) diameter of liposomes raised to 190±10 nm and PDI was 0.38±0.05. We explain this by destroying and/or reorganization of lipid bilayer, that leads to changes in release of drug in comparison with control without MF exposure. Conclusion: A new application of low frequency AC MF for drug delivery and controlled drug release was shown. Investigation was supported by RSF-14-13-00731 grant, K1-2014-022 grant.

Keywords: magnetic nanoparticles, low frequency magnetic field, drug delivery, controlled drug release

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Authors: Oibar Martinez, Clara Oliver, Jose Miguel Miranda

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In this paper, we discuss the standard improvements which can be made to reduce the earth resistance in difficult terrains for optimum lightning protection, what are the practical limitations, and how the modeling can be refined for accurate diagnostics and ground resistance minimization. Ground resistance minimization can be made via three different approaches: burying vertical electrodes connected in parallel, burying horizontal conductive plates or meshes, or modifying the own terrain, either by changing the entire terrain material in a large volume or by adding earth-enhancing compounds. The use of vertical electrodes connected in parallel pose several practical limitations. In order to prevent loss of effectiveness, it is necessary to keep a minimum distance between each electrode, which is typically around five times larger than the electrode length. Otherwise, the overlapping of the local equipotential lines around each electrode reduces the efficiency of the configuration. The addition of parallel electrodes reduces the resistance and facilitates the measurement, but the basic parallel resistor formula of circuit theory will always underestimate the final resistance. Numerical simulation of equipotential lines around the electrodes overcomes this limitation. The resistance of a single electrode will always be proportional to the soil resistivity. The electrodes are usually installed with a backfilling material of high conductivity, which increases the effective diameter. However, the improvement is marginal, since the electrode diameter counts in the estimation of the ground resistance via a logarithmic function. Substances that are used for efficient chemical treatment must be environmentally friendly and must feature stability, high hygroscopicity, low corrosivity, and high electrical conductivity. A number of earth enhancement materials are commercially available. Many are comprised of carbon-based materials or clays like bentonite. These materials can also be used as backfilling materials to reduce the resistance of an electrode. Chemical treatment of soil has environmental issues. Some products contain copper sulfate or other copper-based compounds, which may not be environmentally friendly. Carbon-based compounds are relatively inexpensive and they do have very low resistivities, but they also feature corrosion issues. Typically, the carbon can corrode and destroy a copper electrode in around five years. These compounds also have potential environmental concerns. Some earthing enhancement materials contain cement, which, after installation acquire properties that are very close to concrete. This prevents the earthing enhancement material from leaching into the soil. After analyzing different configurations, we conclude that a buried conductive ring with vertical electrodes connected periodically should be the optimum baseline solution for the grounding of a large size structure installed on a large resistivity terrain. In order to show this, a practical example is explained here where we simulate the ground resistance of a conductive ring buried in a terrain with a resistivity in the range of 1 kOhm·m.

Keywords: grounding improvements, large scale scientific instrument, lightning risk assessment, lightning standards

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Authors: Alan Walsh, Peter Walker

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Differences in commercial, professional and personal cultural traditions between western consultants and project sponsors in the Gulf Cooperation Council (GCC) region are potentially significant in the workplace, and this can impact on project outcomes. These cultural differences can, for example, result in conflict amongst senior managers, which can negatively impact the megaproject. New entrants to the GCC often experience ‘culture shock’ as they attempt to integrate into their unfamiliar environments. Megaprojects are unique ventures with individual project characteristics, which need to be considered when managing their associated risks. Megaproject research to date has mostly ignored the significance of the absence of cultural congruence in the GCC, which is surprising considering that there are large volumes of megaprojects in various stages of construction in the GCC. An initial step to dealing with cultural issues is to acknowledge culture as a significant risk factor (SRF). This paper seeks to understand the criticality for western consultants to address these risks. It considers the cultural barriers that exist between GCC sponsors and western consultants and examines the cultural distance between the key actors. Initial findings suggest the presence to a certain extent of ethnocentricity. Other cultural clashes arise out of a lack of appreciation of the customs, practices and traditions of ‘the Other’, such as the need for avoiding public humiliation and the hierarchal significance rankings. The concept and significance of cultural shock as part of the integration process for new arrivals are considered. Culture shock describes the state of anxiety and frustration resulting from the immersion in a culture distinctly different from one's own. There are potentially substantial project risks associated with underestimating the process of cultural integration. This paper examines two distinct but intertwined issues: the societal and professional culture differences associated with expatriate assignments. A case study examines the cultural congruences between GCC sponsors and American, British and German consultants, over a ten-year cycle. This provides indicators as to which nationalities encountered the most profound cultural issues and the nature of these. GCC megaprojects are typically intensive fast track demanding ventures, where consultant turnover is high. The study finds that building trust-filled relationships is key to successful project team integration and therefore, to successful megaproject execution. Findings indicate that both professional and social inclusion processes have steep learning curves. Traditional risk management practice is to approach any uncertainty in a structured way to mitigate the potential impact on project outcomes. This research highlights cultural risk as a significant factor in the management of GCC megaprojects. These risks arising from high staff turnover typically include loss of project knowledge, delays to the project, cost and disruption in replacing staff. This paper calls for cultural risk to be recognised as an SRF, as the first step to developing risk management strategies, and to reduce staff turnover for western consultants in GCC megaprojects.

Keywords: western consultants in megaprojects, national culture impacts on GCC megaprojects, significant risk factors in megaprojects, professional culture in megaprojects

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Authors: Yulia V. Krasavtseva, Tatiana V. Kornilova

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Risk-taking behaviors are not only dictated by cognitive components but also involve emotional aspects. Anticipatory emotions, involving both cognitive and affective mechanisms, are involved in decision-making in general, and risk-taking in particular. Affective reactions are prompted when an expectation or prediction is either validated or invalidated in the achieved result. This study aimed to combine predictions, anticipatory emotions, affective reactions, and personality traits in the context of risk-taking behaviors. An experimental online method Emotion and Prediction In a Casino (EPIC) was used, based on a casino-like roulette game. In a series of choices, the participant is presented with progressively riskier roulette combinations, where the potential sums of wins and losses increase with each choice and the participant is given a choice: to 'walk away' with the current sum of money or to 'play' the displayed roulette, thus accepting the implicit risk. Before and after the result is displayed, participants also rate their emotions, using the Self-Assessment Mannequin [Bradley, Lang, 1994], picking a picture, representing the intensity of pleasure, arousal, and dominance. The following personality measures were used: 1) Personal Decision-Making Factors [Kornilova, 2003] assessing risk and rationality; 2) I7 – Impulsivity Questionnaire [Kornilova, 1995] assessing impulsiveness, risk readiness, and empathy and 3) Subjective Risk Intelligence Scale [Craparo et al., 2018] assessing negative attitude toward uncertainty, emotional stress vulnerability, imaginative capability, and problem-solving self-efficacy. Two groups of participants took part in the study: 1) 98 university students (Mage=19.71, SD=3.25; 72% female) and 2) 94 online participants (Mage=28.25, SD=8.25; 89% female). Online participants were recruited via social media. Students with high rationality rated their pleasure and dominance before and after choices as lower (ρ from -2.6 to -2.7, p < 0.05). Those with high levels of impulsivity rated their arousal lower before finding out their result (ρ from 2.5 - 3.7, p < 0.05), while also rating their dominance as low (ρ from -3 to -3.7, p < 0.05). Students prone to risk-rated their pleasure and arousal before and after higher (ρ from 2.5 - 3.6, p < 0.05). High empathy was positively correlated with arousal after learning the result. High emotional stress vulnerability positively correlates with arousal and pleasure after the choice (ρ from 3.9 - 5.7, p < 0.05). Negative attitude to uncertainty is correlated with high anticipatory and reactive arousal (ρ from 2.7 - 5.7, p < 0.05). High imaginative capability correlates negatively with anticipatory and reactive dominance (ρ from - 3.4 to - 4.3, p < 0.05). Pleasure (.492), arousal (.590), and dominance (.551) before and after the result were positively correlated. Higher predictions positively correlated with reactive pleasure and arousal. In a riskier scenario (6/8 chances to win), anticipatory arousal was negatively correlated with the pleasure emotion (-.326) and vice versa (-.265). Correlations occur regardless of the roulette outcome. In conclusion, risk-taking behaviors are linked not only to personality traits but also to anticipatory emotions and affect in a modeled casino setting. Acknowledgment: The study was supported by the Russian Foundation for Basic Research, project 19-29-07069.

Keywords: anticipatory emotions, casino game, risk taking, impulsiveness

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Authors: Gabriel Malgaresi, Sara Borazjani, Hadi Madani, Pavel Bedrikovetsky

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Suspension-Colloidal flow in porous media occurs in numerous engineering fields, such as industrial water treatment, the disposal of industrial wastes into aquifers with the propagation of contaminants and low salinity water injection into petroleum reservoirs. The main effects are particle mobilization and captured by the porous rock, which can cause pore plugging and permeability reduction which is known as formation damage. Various factors such as fluid salinity, pH, temperature, and rock properties affect particle detachment. Formation damage is unfavorable specifically near injection and production wells. One way to control formation damage is pre-treatment of the rock with nanoparticles. Adsorption of nanoparticles on fines and rock surfaces alters zeta-potential of the surfaces and enhances the attachment force between the rock and fine particles. The main objective of this study is to develop a two-stage mathematical model for (1) flow and adsorption of nanoparticles on the rock in the pre-treatment stage and (2) fines migration and permeability reduction during the water production after the pre-treatment. The model accounts for adsorption and desorption of nanoparticles, fines migration, and kinetics of particle capture. The system of equations allows for the exact solution. The non-self-similar wave-interaction problem was solved by the Method of Characteristics. The analytical model is new in two ways: First, it accounts for the specific boundary and initial condition describing the injection of nanoparticle and production from the pre-treated porous media; second, it contains the effect of nanoparticle sorption hysteresis. The derived analytical model contains explicit formulae for the concentration fronts along with pressure drop. The solution is used to determine the optimal injection concentration of nanoparticle to avoid formation damage. The mathematical model was validated via an innovative laboratory program. The laboratory study includes two sets of core-flood experiments: (1) production of water without nanoparticle pre-treatment; (2) pre-treatment of a similar core with nanoparticles followed by water production. Positively-charged Alumina nanoparticles with the average particle size of 100 nm were used for the rock pre-treatment. The core was saturated with the nanoparticles and then flushed with low salinity water; pressure drop across the core and the outlet fine concentration was monitored and used for model validation. The results of the analytical modeling showed a significant reduction in the fine outlet concentration and formation damage. This observation was in great agreement with the results of core-flood data. The exact solution accurately describes fines particle breakthroughs and evaluates the positive effect of nanoparticles in formation damage. We show that the adsorbed concentration of nanoparticle highly affects the permeability of the porous media. For the laboratory case presented, the reduction of permeability after 1 PVI production in the pre-treated scenario is 50% lower than the reference case. The main outcome of this study is to provide a validated mathematical model to evaluate the effect of nanoparticles on formation damage.

Keywords: nano-particles, formation damage, permeability, fines migration

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Authors: Yichao Liu, Peter Fransson, Julian Heidecke, Jonas Wallin, Joacim Rockloev

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Dengue, a mosquito-borne viral disease, poses a significant public health challenge in endemic tropical or subtropical countries, including Sri Lanka. To reveal insights into the complexity of the dynamics of this disease and study the drivers, a comprehensive model capable of both robust forecasting and insightful inference of drivers while capturing the co-circulating of several virus strains is essential. However, existing studies mostly focus on only one aspect at a time and do not integrate and carry insights across the siloed approach. While mechanistic models are developed to capture immunity dynamics, they are often oversimplified and lack integration of all the diverse drivers of disease transmission. On the other hand, purely data-driven methods lack constraints imposed by immuno-epidemiological processes, making them prone to overfitting and inference bias. This research presents a hybrid model that combines machine learning techniques with mechanistic modelling to overcome the limitations of existing approaches. Leveraging eight years of newly reported dengue case data, along with socioeconomic factors, such as human mobility, weekly climate data from 2011 to 2018, genetic data detecting the introduction and presence of new strains, and estimates of seropositivity for different districts in Sri Lanka, we derive a data-driven vector (SEI) to human (SEIR) model across 16 regions in Sri Lanka at the weekly time scale. By conducting ablation studies, the lag effects allowing delays up to 12 weeks of time-varying climate factors were determined. The model demonstrates superior predictive performance over a pure machine learning approach when considering lead times of 5 and 10 weeks on data withheld from model fitting. It further reveals several interesting interpretable findings of drivers while adjusting for the dynamics and influences of immunity and introduction of a new strain. The study uncovers strong influences of socioeconomic variables: population density, mobility, household income and rural vs. urban population. The study reveals substantial sensitivity to the diurnal temperature range and precipitation, while mean temperature and humidity appear less important in the study location. Additionally, the model indicated sensitivity to vegetation index, both max and average. Predictions on testing data reveal high model accuracy. Overall, this study advances the knowledge of dengue transmission in Sri Lanka and demonstrates the importance of incorporating hybrid modelling techniques to use biologically informed model structures with flexible data-driven estimates of model parameters. The findings show the potential to both inference of drivers in situations of complex disease dynamics and robust forecasting models.

Keywords: compartmental model, climate, dengue, machine learning, social-economic

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Authors: Prescilla Lambert, Christophe Roos, Mounim Lebrini

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For several years, the Caribbean islands and West Africa have had to deal with the massive arrival of the brown seaweed Sargassum. Overall, this macroalgae, which constitutes a habitat for a great diversity of marine organisms, is also an additional stress factor for the marine environment (e.g., coral reefs). In addition, the accumulation followed by the significant decomposition of the Sargassum spp. biomass on the coast leads to the release of toxic gases (H₂S and NH₃), which calls into question the functioning of the economic, health and tourist life of the island and the other interested territories. Originally, these algae are formed by the eutrophication of the oceans accentuated by global warming. Unfortunately, scientists predict a significant recurrence of these Sargassum strandings for years to come. It is therefore more than necessary to find solutions by putting in place a sustainable management plan for this phenomenon. Martinique, a small island in the Caribbean arc, is one of the many areas impacted by Sargassum seaweed strandings. Since 2011, there has been a constant increase in the degradation of the materials present in this region, largely due to toxic/corrosive gases released by the algae decomposition. In order to protect the structures and the vulnerable building materials while limiting the use of synthetic/petroleum based molecules as much as possible, research is being conducted on molecules of natural origin. Thus, thanks to the chemical composition, which comprise molecules with interesting properties, algae such as Sargassum could potentially help to solve many issues. Therefore, this study focuses on the green extraction and characterization of molecules from the species Sargassum fluitans and Sargassum natans present in Martinique. The secondary metabolites found in these extracts showed variability in yield rates due to local climatic conditions. The tests carried out shed light on the anticorrosive and antibacterial potential of the algae. These extracts can thus be described as natural inhibitors. The effect of variation in inhibitor concentrations was tested in electrochemistry using electrochemical impedance spectroscopy and polarization curves. The analysis of electrochemical results obtained by direct immersion in the extracts and self-assembled molecular layers (SAMs) for Sargassum fluitans III, Sargassum natans I and VIII species was conclusive in acid and alkaline environments. The excellent results obtained reveal an inhibitory efficacy of 88% at 50mg/L for the crude extract of Sargassum fluitans III and efficacies greater than 97% for the chemical families of Sargassum fluitans III. Similarly, microbiological tests also suggest a bactericidal character. Results for Sargassum fluitans III crude extract show a minimum inhibitory concentration (MIC) of 0.005 mg/mL on Gram-negative bacteria and a MIC greater than 0.6 mg/mL on Gram-positive bacteria. These results make it possible to consider the management of local and international issues while valuing a biomass rich in biodegradable molecules. The next step in this study will therefore be the evaluation of the toxicity of Sargassum spp..

Keywords: Sargassum, secondary metabolites, anticorrosive, antibacterial, natural inhibitors

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Authors: Siddhant Sethi, Yasuharu Takashima, Shigetaka Nakamura, Kenzo Fujimoto

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Site-directed mutagenesis is a renowned technique to introduce specific mutations in the genome. To achieve site-directed mutagenesis, many chemical and enzymatic approaches have been reported in the past like disulphite induced genome editing, CRISPR-Cas9, TALEN etc. The chemical methods are invasive whereas the enzymatic approaches are time-consuming and expensive. Most of these techniques are unusable in the cellular application due to their toxicity and other limitations. Photo-chemical cytosine deamination, introduced in 2010, is one of the major technique for enzyme-free single-point mutation of cytosine to uracil in DNA and RNA, wherein, 3-cyanovinylcarbazole nucleoside (CNVK) containing oligodeoxyribonucleotide (ODN) having CNVK at -1 position to that of target cytosine is reversibly crosslinked to target DNA strand using 366 nm and then incubated at 90ºC to accommodate deamination. This technique is superior to enzymatic methods of site-directed mutagenesis but has a disadvantage that it requires the use of high temperature for the deamination step which restricts its applicability in the in vivo applications. This study has been focused on improving the technique by reducing the temperature required for deamination. Firstly, the photo-cross-linker, CNVK has been modified by replacing cyano group attached to vinyl group with methyl ester (OMeVK), amide (NH2VK), and carboxylic acid (OHVK) to observe the acceleration in the deamination of target cytosine cross-linked to vinylcarbazole derivative. Among the derivatives, OHVK has shown 2 times acceleration in deamination reaction as compared to CNVK, while the other two derivatives have shown deceleration towards deamination reaction. The trend of rate of deamination reaction follows the same order as that of hydrophilicity of the vinylcarbazole derivatives. OHVK being most hydrophilic has shown highest acceleration while OMeVK is least hydrophilic has proven to be least active for deamination. Secondly, in the related study, the counter-base of the target cytosine, guanine has been replaced by inosine, 2-aminopurine, nebularine, and 5-nitroindole having distinct hydrogen bonding patterns with target cytosine. Among the ODNs with these counter bases, ODN with inosine has shown 12 fold acceleration towards deamination of cytosine cross-linked to CNVK at physiological conditions as compared to guanosine. Whereas, when 2-aminopurine, nebularine, and 5-nitroindole were used, no deamination reaction took place. It can be concluded that inosine has potential to be used as the counter base of target cytosine for the CNVK mediated photo-cross-linking induced deamination of cytosine. The increase in rate of deamination reaction has been attributed to pattern and number of hydrogen bonding between the cytosine and counter base. One of the important factor is presence of hydrogen bond between exo-cyclic amino group of cytosine and the counter base. These results will be useful for development of more efficient technique for site-directed mutagenesis for C → U transformations in the DNA/RNA which might be used in the living system for treatment of various genetic disorders and genome engineering for making designer and non-native proteins.

Keywords: C to U transformation, DNA editing, genome engineering, ultra-fast photo-cross-linking

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Authors: Andrey A. Tyuftin, David Clarke, Malco C. Cruz-Romero, Declan Bolton, Seamus Fanning, Shashi K. Pankaj, Carmen Bueno-Ferrer, Patrick J. Cullen, Joe P. Kerry

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Prolonging of shelf-life is essential in order to address issues such as; supplier demands across continents, economical profit, customer satisfaction, and reduction of food wastage. Smart packaging solutions presented in the form of naturally occurred antimicrobially-active packaging may be a solution to these and other issues. Gelatin film forming solution with adding of natural sourced antimicrobials is a promising tool for the active smart packaging. The objective of this study was to coat conventional plastic hydrophobic packaging material with hydrophilic antimicrobial active beef gelatin coating and conduct shelf life trials on beef sub-primal cuts. Minimal inhibition concentration (MIC) of Caprylic acid sodium salt (SO) and commercially available Auranta FV (AFV) (bitter oranges extract with mixture of nutritive organic acids) were found of 1 and 1.5 % respectively against bacterial strains Bacillus cereus, Pseudomonas fluorescens, Escherichia coli, Staphylococcus aureus and aerobic and anaerobic beef microflora. Therefore SO or AFV were incorporated in beef gelatin film forming solution in concentration of two times of MIC which was coated on a conventional plastic LDPE/PA film on the inner cold plasma treated polyethylene surface. Beef samples were vacuum packed in this material and stored under chilling conditions, sampled at weekly intervals during 42 days shelf life study. No significant differences (p < 0.05) in the cook loss was observed among the different treatments compared to control samples until the day 29. Only for AFV coated beef sample it was 3% higher (37.3%) than the control (34.4 %) on the day 36. It was found antimicrobial films did not protect beef against discoloration. SO containing packages significantly (p < 0.05) reduced Total viable bacterial counts (TVC) compared to the control and AFV samples until the day 35. No significant reduction in TVC was observed between SO and AFV films on the day 42 but a significant difference was observed compared to control samples with a 1.40 log of bacteria reduction on the day 42. AFV films significantly (p < 0.05) reduced TVC compared to control samples from the day 14 until the day 42. Control samples reached the set value of 7 log CFU/g on day 27 of testing, AFV films did not reach this set limit until day 35 and SO films until day 42 of testing. The antimicrobial AFV and SO coated films significantly prolonged the shelf-life of beef steaks by 33 or 55% (on 7 and 14 days respectively) compared to control film samples. It is concluded antimicrobial coated films were successfully developed by coating the inner polyethylene layer of conventional LDPE/PA laminated films after plasma surface treatment. The results indicated that the use of antimicrobial active packaging coated with SO or AFV increased significantly (p < 0.05) the shelf life of the beef sub-primal. Overall, AFV or SO containing gelatin coatings have the potential of being used as effective antimicrobials for active packaging applications for muscle-based food products.

Keywords: active packaging, antimicrobials, edible coatings, food packaging, gelatin films, meat science

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Authors: Md. Samsuddin Ansari, Ashish Arora

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Every year 10 million people fall ill with one of the oldest diseases known as tuberculosis, caused by Mycobacterium tuberculosis. The success of M. tuberculosis as a pathogen is because of its ability to persist in host tissues. Multidrug resistance (MDR) mycobacteria cases increase every day, which is associated with efflux pumps controlled at the level of transcription. The transcription regulators of MDR transporters in bacteria belong to one of the following four regulatory protein families: AraC, MarR, MerR, and TetR. Phenolic acid decarboxylase repressor (PadR), like a family of transcription regulators, is closely related to the MarR family. Phenolic acid decarboxylase repressor (PadR) was first identified as a transcription factor involved in the regulation of phenolic acid stress response in various microorganisms (including Mycobacterium tuberculosis H37Rv). Recently research has shown that the PadR family transcription factors are global, multifunction transcription regulators. Rv0047c is a PadR subfamily-1 protein. We are exploring the biophysical and structural characterization of Rv0047c. The Rv0047 gene was amplified by PCR using the primers containing EcoRI and HindIII restriction enzyme sites cloned in pET-NH6 vector and overexpressed in DH5α and BL21 (λDE3) cells of E. coli following purification with Ni2+-NTA column and size exclusion chromatography. We did DSC to know the thermal stability; the Tm (transition temperature) of protein is 55.29ºC, and ΔH (enthalpy change) of 6.92 kcal/mol. Circular dichroism to know the secondary structure and conformation and fluorescence spectroscopy for tertiary structure study of protein. To understand the effect of pH on the structure, function, and stability of Rv0047c we employed spectroscopy techniques such as circular dichroism, fluorescence, and absorbance measurements in a wide range of pH (from pH-2.0 to pH-12). At low and high pH, it shows drastic changes in the secondary and tertiary structure of the protein. EMSA studies showed the specific binding of Rv0047c with its own 30-bp promoter region. To determine the effect of complex formation on the secondary structure of Rv0047c, we examined the CD spectra of the complex of Rv0047c with promoter DNA of rv0047. The functional role of Rv0047c was characterized by over-expressing the Rv0047c gene under the control of hsp60 promoter in Mycobacterium tuberculosis H37Rv. We have predicted the three-dimensional structure of Rv0047c using the Swiss Model and Modeller, with validity checked by the Ramachandra plot. We did molecular docking of Rv0047c with dnaA, through PatchDock following refinement through FireDock. Through this, it is possible to easily identify the binding hot-stop of the receptor molecule with that of the ligand, the nature of the interface itself, and the conformational change undergone by the protein pattern. We are using X-crystallography to unravel the structure of Rv0047c. Overall the studies show that Rv0047c may have transcription regulation along with providing an insight into the activity of Rv0047c in the pH range of subcellular environment and helps to understand the protein-protein interaction, a novel target to kill dormant bacteria and potential strategy for tuberculosis control.

Keywords: mycobacterium tuberculosis, phenolic acid decarboxylase repressor, Rv0047c, Circular dichroism, fluorescence spectroscopy, docking, protein-protein interaction

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Authors: Eduardo Martínez González, Mousumi Dey, Pekka Peljo

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Transitioning to a renewable energy model is inevitable owing to the effects of climate change. These energies are aimed at sustainability and a positive impact on the environment, but they are intermittent energies; their connection to the electrical grid depends on creating long-term, efficient, and low-cost energy storage devices. Redox flow batteries are attractive technologies to address this problem, as they store energy in solution through external tanks known as posolyte (solution to storage positive charge) and negolyte (solution to storage negative charge). During the charging process of the device, the posolyte and negolyte solutions are pumped into an electrochemical cell (which has the anode and cathode separated by an ionic membrane), where they undergo oxidation and reduction reactions at electrodes, respectively. The electrogenerated species should be stable and diffuse into the bulk solution. It has been possible to connect gigantic redox flow batteries to the electrical grid. However, the devices created do not fit with the sustainability criteria since their electroactive material consists of vanadium (material scarce and expensive) solutions dissolved in an acidic medium (e.g., 9 mol L-1 of H₂SO₄) that is highly corrosive; so, work is being done on the design of organic-electroactive electrolytes (posolytes and nogolytes) for their operation at different pH values, including neutral medium. As a main characteristic, negolyte species should have low reduction potential values, while the reverse is true for the oxidation process of posolytes. A wide variety of negolytes that store 1 and up to 2 electrons per molecule (in aqueous medium) have been publised. Gallocyanine compound was recently introduced as an electroactive material for developing alkaline flow battery negolytes. The system can storage two electrons per molecule, but its unexpectedly low water solubility was improved with an amino sulphonic acid additive. The cycling stability of and improved gallocyanine electrolyte was demonstrated by operating a flow battery cell (pairing the system to a posolyte composed of ferri/ferrocyanide solution) outside a glovebox. We also discovered that the additive improves the solubility of gallocyanine, but there is a kinetic price to pay for this advantage. Therefore, in this work, the effect of different amino sulphonic acid derivatives on the kinetics and solubility of gallocyanine compound was studied at alkaline solutions. The additive providing a faster electron transfer rate and high solubility was tested in a flow battery cell. An aqueous organic flow battery electrolyte working outside a glovebox with 15 mAhL-1 will be discussed. Acknowledgments: To Bi3BoostFlowBat Project (2021-2025), funded by the European Research Concil. For support with infrastructure, reagents, and a postdoctoral fellowship to Dr. Martínez-González.

Keywords: alkaline flow battery, gallocyanine electroactive material, amine-sulphonic acid additives, improved solubility

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Authors: Sarah Elshahat, Tina Moffat

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Suboptimal mental health is a considerable global public health challenge that leads to considerable inequalities worldwide. Newcomers are at elevated risk for developing mental health issues as a result of social exclusion, stigmatization, racism, unequal employment opportunities, and discrimination. The problem can be especially serious amongst Arabic-speaking immigrants and refugees (ASIR) whose mental wellness may have already been affected by exposure to political violence, persecution, hunger or war in their countries of origin. A scoping review was conducted to investigate pre- and post-migration mental health determinants amongst ASIR in North America (the U.S. and Canada), who are a rapidly growing population in both regions. Pertinent peer-reviewed papers and grey literature were located through a systematic search of five electronic databases (Medline, Embase, PsycINFO, Anthropology Plus, and Sociology Database). A stakeholder consultation was implemented to validate the analyzed findings of the included 44 studies. About 80% of the studies were carried out in the US, underscoring a lack of Canadian ASIR-mental health research. A gap in qualitative, mixed-method, and longitudinal research was detected, where approximately two-thirds of the studies adopted a cross-sectional method. Pre-migration determinants of mental health were related to the political unrest, violence and armed conflict in the Arab world, increasing post-traumatic stress disorder and psychological distress levels among ASIR. English language illiteracy and generational variations in acculturation patterns were major post-migration mental health triggering factors. Exposure to domestic violence, stigmatization, poverty, racialization, and harassment were significant post-migration mental health determinants that stem from social inequalities, triggering depression, and distress amongst ASIR. Family conflicts linked to child-rearing and gendered norms were considered as both pre- and post-migration mental health triggering factors. Most post-migration mental health protective factors were socio-culturally related and included the maintenance of positive ethnic identity, faith, family support, and community cohesion. Individual resilience, articulated as self-esteem and hope, was a significant negative predictor of depression and psychological distress among ASIR. Community-engaged, mixed-methods, and longitudinal studies are required to address the current gap in mental health research among ASIR in North America. A more thorough determination of potential mental health triggers and protective factors would help inform the development of mental wellness and resilience-promoting programs that are culturally sensitive to ASIR. On the policy level, the Health in All Policies framework of the World Health Organization can be potentially useful for addressing social and health inequalities among ASIR, reducing mental health challenges.

Keywords: depression, post-traumatic stress disorder, psychological distress, resilience

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Authors: Sarah Müller-Sägebrecht

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Today’s volatile environment challenges executives to make the right strategic decisions to gain sustainable success. Entrepreneurship scholars postulate mainly positive effects of environmental changes on entrepreneurship behavior, such as developing new business opportunities, promoting ingenuity, and the satisfaction of resource voids. A strategic solution approach to overcome threatening environmental changes and catch new business opportunities is business model innovation (BMI). Although this research stream has gained further importance in the last decade, BMI research is still insufficient. Especially BMI barriers, such as inefficient strategic decision-making processes, need to be identified. Strategic decisions strongly impact organizational future and are, therefore, usually made in groups. Although groups draw on a more extensive information base than single individuals, group-interaction effects can influence the decision-making process - in a favorable but also unfavorable way. Decisions are characterized by uncertainty and risk, whereby their intensity is perceived individually differently. The individual risk-willingness influences which option humans choose. The special nature of strategic decisions, such as in BMI processes, is that these decisions are not made individually but in groups due to their high organizational scope. These groups consist of different personalities whose individual risk-willingness can vary considerably. It is known from group decision theory that these individuals influence each other, observable in different group-interaction effects. The following research questions arise: i) How does group interaction shape BMI decision-making from managers’ perspective? ii) What are the potential interrelations among managers’ risk-willingness, group biases, and BMI decision-making? After conducting 26 in-depth interviews with executives from the manufacturing industry, applied Gioia methodology reveals the following results: i) Risk-averse decision-makers have an increased need to be guided by facts. The more information available to them, the lower they perceive uncertainty and the more willing they are to pursue a specific decision option. However, the results also show that social interaction does not change the individual risk-willingness in the decision-making process. ii) Generally, it could be observed that during BMI decisions, group interaction is primarily beneficial to increase the group’s information base for making good decisions, less than for social interaction. Further, decision-makers mainly focus on information available to all decision-makers in the team but less on personal knowledge. This work contributes to strategic decision-making literature twofold. First, it gives insights into how group-interaction effects influence an organization’s strategic BMI decision-making. Second, it enriches risk-management research by highlighting how individual risk-willingness impacts organizational strategic decision-making. To date, it was known in BMI research that risk aversion would be an internal BMI barrier. However, with this study, it becomes clear that it is not risk aversion that inhibits BMI. Instead, the lack of information prevents risk-averse decision-makers from choosing a riskier option. Simultaneously, results show that risk-averse decision-makers are not easily carried away by the higher risk-willingness of their team members. Instead, they use social interaction to gather missing information. Therefore, executives need to provide sufficient information to all decision-makers to catch promising business opportunities.

Keywords: business model innovation, cognitive biases, group-interaction effects, strategic decision-making, risk-willingness

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Authors: Carly Nesvat, Dominic Jarrett, Colin Thomson, Wilma Coltart, Thelma Bowers, Jan Thomson

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Introduction: Within Scotland, the Same As You strategy committed to moving people with learning disabilities out of long-stay hospital accommodation into homes in the community. Much of the focus of this movement was on the placement of people within individual homes. In order to achieve this, potentially excessive supports were put in place which created dependence, and carried significant ongoing cost primarily for local authorities. The greater focus on empowerment and community participation which has been evident in more recent learning disability strategy, along with the financial pressures being experienced across the public sector, created an imperative to re-examine that provision, particularly in relation to the use of expensive sleepover supports to individuals, and the potential for this to be appropriately scaled back through the use of telecare. Method: As part of a broader programme of redesigning overnight supports within North Ayrshire, a cluster of individuals living in close proximity were identified, who were in receipt of overnight supports, but who were identified as having the capacity to potentially benefit from their removal. In their place, a responder service was established (an individual staying overnight in a nearby service user’s home), and a variety of telecare solutions were placed within individual’s homes. Active and passive technology was connected to an Alarm Receiving Centre, which would alert the local responder service when necessary. Individuals and their families were prepared for the change, and continued to be informed about progress with the pilot. Results: 4 individuals, 2 of whom shared a tenancy, had their sleepover supports removed as part of the pilot. Extensive data collection in relation to alarm activation was combined with feedback from the 4 individuals, their families, and staff involved in their support. Varying perspectives emerged within the feedback. 3 of the individuals were clearly described as benefitting from the change, and the greater sense of independence it brought, while more concerns were evident in relation to the fourth. Some family members expressed a need for greater preparation in relation to the change and ongoing information provision. Some support staff also expressed a need for more information, to help them understand the new support arrangements for an individual, as well as noting concerns in relation to the outcomes for one participant. Conclusion: Developing a telecare response in relation to a cluster of individuals was facilitated by them all being supported by the same care provider. The number of similar clusters of individuals being identified within North Ayrshire is limited. Developing other solutions such as a response service for redesign will potentially require greater collaboration between different providers of home support, as well as continuing to explore the full range of telecare, including digital options. The pilot has highlighted the need for effective preparatory and ongoing engagement with staff and families, as well as the challenges which can accompany making changes to long-standing packages of support.

Keywords: challenges, change, engagement, telecare

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Authors: Laura N. Bolivar T.

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The tourism importance for regional development is mainly highlighted by the collaborative, cooperating and competitive relationships of the involved agents. The fostering of associativity processes, in particular, the cluster approach emphasizes the beneficial outcomes from the concentration of enterprises, where innovation and entrepreneurship flourish and shape the dynamics for tourism empowerment. Considering the department of Huila, it is located in the south-west of Colombia and holds the biggest coffee production in the country, although it barely contributes to the national GDP. Hence, its economic development strategy is looking for more dynamism and Huila could be consolidated as a leading destination for cultural, ecological and heritage tourism, if at least the public policy making processes for the tourism management of La Tatacoa Desert, San Agustin Park and Bambuco’s National Festival, were implemented in a more efficient manner. In this order of ideas, this study attempts to address the potential restrictions and beneficial factors for the consolidation of the tourism sector of Huila-Colombia as a cluster and how could it impact its regional development. Therefore, a set of theoretical frameworks such as the Tourism Routes Approach, the Tourism Breeding Environment, the Community-based Tourism Method, among others, but also a collection of international experiences describing tourism clustering processes and most outstanding problematics, is analyzed to draw up learning points, structure of proceedings and success-driven factors to be contrasted with the local characteristics in Huila, as the region under study. This characterization involves primary and secondary information collection methods and comprises the South American and Colombian context together with the identification of involved actors and their roles, main interactions among them, major tourism products and their infrastructure, the visitors’ perspective on the situation and a recap of the related needs and benefits regarding the host community. Considering the umbrella concepts, the theoretical and the empirical approaches, and their comparison with the local specificities of the tourism sector in Huila, an array of shortcomings is analytically constructed and a series of guidelines are proposed as a way to overcome them and simultaneously, raise economic development and positively impact Huila’s well-being. This non-exhaustive bundle of guidelines is focused on fostering cooperating linkages in the actors’ network, dealing with Information and Communication Technologies’ innovations, reinforcing the supporting infrastructure, promoting the destinations considering the less known places as well, designing an information system enabling the tourism network to assess the situation based on reliable data, increasing competitiveness, developing participative public policy-making processes and empowering the host community about the touristic richness. According to this, cluster dynamics would drive the tourism sector to meet articulation and joint effort, then involved agents and local particularities would be adequately assisted to cope with the current changing environment of globalization and competition.

Keywords: innovative strategy, local development, network of tourism actors, tourism cluster

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Authors: Carly Madge, Melanie Zurba, Ryan Bullock

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The Boreal Forest has experienced some of the most drastic climate change-induced temperature rises in Canada, with average winter temperatures increasing by 3°C since 1948. One of the main concerns of the province of Saskatchewan, and particularly wildfire managers, is the increased risk of wildfires due to climate change. With these concerns in mind Sakaw Askiy Management Inc., a forestry corporation located in Prince Albert, Saskatchewan with operations in the Boreal Forest biome, is developing wildfire risk reduction strategies that are supported by the shareholders of the corporation as well as the stakeholders of the Prince Albert Forest Management Area (which includes citizens, hunters, trappers, cottage owners, and outfitters). In the past, wildfire management strategies implemented through harvesting have been received with skepticism by some community members of Prince Albert. Engagement of the stakeholders of the Prince Albert Management Area through the development of the wildfire risk reduction strategies aims to reduce this skepticism and rebuild some of the trust that has been lost between industry and community. This research project works with the framework of social learning, which is defined as the learning that occurs when individuals come together to form a group with the purpose of understanding environmental challenges and determining appropriate responses to them. The project evaluates the social learning processes that occur through the development of the risk reduction strategies and how the learning has allowed Sakaw to work towards implementing the strategies into their forest harvesting plans. The incorporation of wildfire risk reduction strategies works to increase the adaptive capacity of Sakaw, which in this case refers to the ability to adjust to climate change, moderate potential damages, take advantage of opportunities, and cope with consequences. Using semi-structured interviews and wildfire workshop meetings shareholders and stakeholders shared their knowledge of wildfire, their main wildfire concerns, and changes they would like to see made in the Prince Albert Forest Management Area. Interviews and topics discussed in the workshops were inductively coded for themes related to learning, adaptive capacity, areas of concern, and preferred methods of wildfire risk reduction strategies. Analysis determined that some of the learning that has occurred has resulted through social interactions and the development of networks oriented towards wildfire and wildfire risk reduction strategies. Participants have learned new knowledge and skills regarding wildfire risk reduction. The formation of wildfire networks increases access to information on wildfire and the social capital (trust and strengthened relations) of wildfire personnel. Both factors can be attributed to increases in adaptive capacity. Interview results were shared with the General Manager of Sakaw, where the areas of concern and preferred strategies of wildfire risk reduction will be considered and accounted for in the implementation of new harvesting plans. This research also augments the growing conceptual and empirical evidence of the important role of learning and networks in regional wildfire risk management efforts.

Keywords: adaptive capacity, community-engagement, social learning, wildfire risk reduction

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Authors: Pau Rodriguez, Jordi Gonzalez, Josep M. Gonfaus, Xavier Roca

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Image sharing in social networks has increased exponentially in the past years. Officially, there are 600 million Instagrammers uploading around 100 million photos and videos per day. Consequently, there is a need for developing new tools to understand the content expressed in shared images, which will greatly benefit social media communication and will enable broad and promising applications in education, advertisement, entertainment, and also psychology. Following these trends, our work aims to take advantage of the existing relationship between text and personality, already demonstrated by multiple researchers, so that we can prove that there exists a relationship between images and personality as well. To achieve this goal, we consider that images posted on social networks are typically conditioned on specific words, or hashtags, therefore any relationship between text and personality can also be observed with those posted images. Our proposal makes use of the most recent image understanding models based on neural networks to process the vast amount of data generated by social users to determine those images most correlated with personality traits. The final aim is to train a weakly-supervised image-based model for personality assessment that can be used even when textual data is not available, which is an increasing trend. The procedure is described next: we explore the images directly publicly shared by users based on those accompanying texts or hashtags most strongly related to personality traits as described by the OCEAN model. These images will be used for personality prediction since they have the potential to convey more complex ideas, concepts, and emotions. As a result, the use of images in personality questionnaires will provide a deeper understanding of respondents than through words alone. In other words, from the images posted with specific tags, we train a deep learning model based on neural networks, that learns to extract a personality representation from a picture and use it to automatically find the personality that best explains such a picture. Subsequently, a deep neural network model is learned from thousands of images associated with hashtags correlated to OCEAN traits. We then analyze the network activations to identify those pictures that maximally activate the neurons: the most characteristic visual features per personality trait will thus emerge since the filters of the convolutional layers of the neural model are learned to be optimally activated depending on each personality trait. For example, among the pictures that maximally activate the high Openness trait, we can see pictures of books, the moon, and the sky. For high Conscientiousness, most of the images are photographs of food, especially healthy food. The high Extraversion output is mostly activated by pictures of a lot of people. In high Agreeableness images, we mostly see flower pictures. Lastly, in the Neuroticism trait, we observe that the high score is maximally activated by animal pets like cats or dogs. In summary, despite the huge intra-class and inter-class variabilities of the images associated to each OCEAN traits, we found that there are consistencies between visual patterns of those images whose hashtags are most correlated to each trait.

Keywords: emotions and effects of mood, social impact theory in social psychology, social influence, social structure and social networks

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Authors: Dahna Alkahtani, Faryal Suraya, Fadah Alanazi

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Background: Buccal mucosal graft for urethral augmentation has surpassed other grafting options, and is now considered the standard of choice for substitution Urethroplasty. The graft has gained its popularity due to its excellent short and long-term results, easy harvesting as well as its ability in withstanding wet environments. However, although Buccal mucosal grafts are an excellent option, it is not free of complications, potential intraoral complications are bleeding, pain, swelling, injury to the nerve resulting in numbness, lip deviation or retraction. Objectives: The current study aims to evaluate the intraoral complications of buccal mucosa grafts harvested from one cheek, and used in Augmentation Urethroplasty. Methodology: The study was conducted retrospectively using the medical records of patients who underwent open augmentation urethroplasty with a buccal mucosa graft at King Khalid University Hospital, Saudi Arabia. Data collection of demographics included the type of graft used, presence or absence of strictures and its etiological factors. Pre-operative and post-operative evaluations were carried out on the subjects including the medical history, physical examination, uroflowmetry, retrograde urethrography, voiding cystourethrography and urine cultures were also noted. Further, the quality of life and complications of the procedure including the presence or occurrence of bleeding within 3-days post-procedure, the severity of pain, oral swelling after grafting, length of return to normal daily diet, painful surgical site, intake of painkillers, presence or absence of speech disturbance, numbness in the cheeks and lips were documented. Results: Thirty-two male subjects with ages ranging from 15 years to 72 years were included in the current study. Following the procedure, a hundred percent of the subjects returned to their normal daily diet by the sixth postoperative day. Further, the majority of the patients reported experiencing mild pain accounting for 61.3%, and 90.3% of the subjects reported using painkillers to control the pain. Surgical wound Pain was reportedly more common at the perineal site as 48.4% of the subjects experienced it; on the other hand, 41.9% of the patients experienced pain in the oral mucosa. The presence of speech disorders, as assessed through medical history, was found to be present in 3.2% of patients. The presence of numbness in the cheeks and lips was found in 3.2% of patients. Other complications such as parotid duct injury, delayed wound healing, non-healing wound and suture granuloma were rare as 90.3% of the subjects denied experiencing any of them, there were nonetheless reports of parotid duct injury by 6.5% of the patients, and non-healing wound by the 3.2% of patients. Conclusion: Buccal Mucosa Graft in Augmentation Urethroplasty is an ideal source of allograft, although not entirely painless; it is considerably safe with minimal intra-oral complication and undetectable strain on the patients’ quality of life.

Keywords: augmentation, buccal, graft, oral

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Authors: Jana Abu Ahmada, Zaineb Mohamed, Ilyasse Aksikas

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The linear quadratic control system of hyperbolic first order partial differential equations (PDEs) are presented. The aim of this research is to control chemical reactions. This is achieved by converting the PDEs system to ordinary differential equations (ODEs) using the method of characteristics to reduce the system to control it by using the integral reinforcement learning. The designed controller is applied to a catalytic cracking reactor. Background—Transport-Reaction systems cover a large chemical and bio-chemical processes. They are best described by nonlinear PDEs derived from mass and energy balances. As a main application to be considered in this work is the catalytic cracking reactor. Indeed, the cracking reactor is widely used to convert high-boiling, high-molecular weight hydrocarbon fractions of petroleum crude oils into more valuable gasoline, olefinic gases, and others. On the other hand, control of PDEs systems is an important and rich area of research. One of the main control techniques is feedback control. This type of control utilizes information coming from the system to correct its trajectories and drive it to a desired state. Moreover, feedback control rejects disturbances and reduces the variation effects on the plant parameters. Linear-quadratic control is a feedback control since the developed optimal input is expressed as feedback on the system state to exponentially stabilize and drive a linear plant to the steady-state while minimizing a cost criterion. The integral reinforcement learning policy iteration technique is a strong method that solves the linear quadratic regulator problem for continuous-time systems online in real time, using only partial information about the system dynamics (i.e. the drift dynamics A of the system need not be known), and without requiring measurements of the state derivative. This is, in effect, a direct (i.e. no system identification procedure is employed) adaptive control scheme for partially unknown linear systems that converges to the optimal control solution. Contribution—The goal of this research is to Develop a characteristics-based optimal controller for a class of hyperbolic PDEs and apply the developed controller to a catalytic cracking reactor model. In the first part, developing an algorithm to control a class of hyperbolic PDEs system will be investigated. The method of characteristics will be employed to convert the PDEs system into a system of ODEs. Then, the control problem will be solved along the characteristic curves. The reinforcement technique is implemented to find the state-feedback matrix. In the other half, applying the developed algorithm to the important application of a catalytic cracking reactor. The main objective is to use the inlet fraction of gas oil as a manipulated variable to drive the process state towards desired trajectories. The outcome of this challenging research would yield the potential to provide a significant technological innovation for the gas industries since the catalytic cracking reactor is one of the most important conversion processes in petroleum refineries.

Keywords: PDEs, reinforcement iteration, method of characteristics, riccati equation, cracking reactor

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Authors: Myriam Benraad

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On 5 July 2016, just days before the bloody terrorist attack on the Promenade des Anglais in Nice, the Al-Hayat media centre, one of the official propaganda branches of the Islamic State, broadcast a French nasheed which paid tribute to the Paris and Brussels attacks of November 2015 and March 2016. Entitled 'My Revenge', the terrorist anthem was of rare vehemence. It mentioned, sequentially, 'huddled bodies', in a reference to the civilian casualties of Western air strikes in the Iraqi-Syrian zone, 'explosive belts', 'sharp knives', 'large-calibre weapons' as well as 'localised targets'. France was accused of bearing the responsibility for the wave of attacks on its territory since the Charlie Hebdo massacre of January 2015 due to its 'ruthless war' against the Muslim world. Evoking an 'old aggression' and the 'crimes and spoliations' of which France has made itself guilty, the jihadist hymn depicted the rebirth of the caliphate as 'laudable revenge'. The notion of revenge has always been central to contemporary jihadism, understood both as a revolutionary ideology and a global militant movement. In recent years, the attacks carried out in Europe and elsewhere in the world have, for most, been claimed in its name. Whoever says jihad, says drama, yet few studies, if any, have looked at its dramatic and emotional elements, most notably its tragic vengefulness. This seems all the more astonishing that jihad is filled with drama; it could even be seen as a drama in its own right. The jihadists perform a script and take on roles inspired by their respective group’s culture (norms, values, beliefs, and symbols). The militants stage and perform such a script for a designated audience, either partisan, sympathising or hostile towards them and their cause. This research paper will examine the dramaturgy of jihadism and in particular, the genre that best characterises its violence: revenge tragedy. Theoretically, the research will rely on the tools of social movement theory and the sociology of emotions. Methodologically, it will draw from dramaturgical analysis and a combination of qualitative and quantitative tools to attain valuable observations of a number of developments, trends, and patterns. The choice has been made to focus mainly – however not exclusively – on the attacks which have taken place since 2001 in the European Union and more specific member states that have been significantly hit by jihadist terrorism. The research looks at a number of representative longitudinal samples identifying continuities and discontinuities, similarities, but also substantial differences. The preliminary findings tend to establish the relevance and validity of this approach in helping make better sense of sensitisation, mobilisation, and survival dynamics within jihadist groups, and motivations among individuals who have embraced violence. Besides, they illustrate their pertinence for counterterrorism policymakers and practitioners. Through drama, jihadist groups ensure the unceasing regeneration of their militant cause as well as their legitimation among their partisans. Without drama, and without the spectacular ideological staging of reality, they would not be able to maintain their attraction potential and power of persuasion.

Keywords: Jihadism, dramaturgy, revenge, tragedy

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Authors: Vladimir Berezin, Aizhan Turmagambetova, Andrey Bogoyavlenskiy, Pavel Alexyuk, Madina Alexyuk, Irina Zaitceva, Nadezhda Sokolova

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Introduction: Influenza viruses could infect approximately 5% to 10% of the global human population annually, resulting in serious social and economic damage. Vaccination and etiotropic antiviral drugs are used for the prevention and treatment of influenza. Vaccination is important; however, antiviral drugs represent the second line of defense against new emerging influenza virus strains for which vaccines may be unsuccessful. However, the significant drawback of commercial synthetic anti-flu drugs is the appearance of drug-resistant influenza virus strains. Therefore, the search and development of new anti-flu drugs efficient against drug-resistant strains is an important medical problem for today. The aim of this work was a study of four phenolic acids of plant origin (Gallic, Syringic, Vanillic, and Protocatechuic acids) as a possible tool for treatment against influenza virus. Methods: Phenolic acids; gallic, syringic, vanillic, and protocatechuic have been prepared by extraction from plant tissues and purified using high-performance liquid chromatography fractionation. Avian influenza virus, strain A/Tern/South Africa/1/1961 (H5N3) and human epidemic influenza virus, strain A/Almaty/8/98 (H3N2) resistant to commercial anti-flu drugs (Rimantadine, Oseltamivir) were used for testing antiviral activity. Viruses were grown in the allantoic cavity of 10 days old chicken embryos. The chemotherapeutic index (CTI), determined as the ratio of an average toxic concentration of the tested compound (TC₅₀) to the average effective virus-inhibition concentration (EC₅₀), has been used as a criteria of specific antiviral action. Results: The results of study have shown that the structure of phenolic acids significantly affected their ability to suppress the reproduction of tested influenza virus strains. The highest antiviral activity among tested phenolic acids was detected for gallic acid, which contains three hydroxyl groups in the molecule at C3, C4, and C5 positions. Antiviral activity of gallic acid against A/H5N3 and A/H3N2 influenza virus strains was higher than antiviral activity of Oseltamivir and Rimantadine. gallic acid inhibited almost 100% of the infection activity of both tested viruses. Protocatechuic acid, which possesses 2 hydroxyl groups (C3 and C4) have shown weaker antiviral activity in comparison with gallic acid and inhibited less than 10% of virus infection activity. Syringic acid, which contains two hydroxyl groups (C3 and C5), was able to suppress up to 12% of infection activity. Substitution of two hydroxyl groups by methoxy groups resulted in the complete loss of antiviral activity. Vanillic acid, which is different from protocatechuic acid by replacing of C3 hydroxyl group to methoxy group, was able to suppress about 30% of infection activity of tested influenza viruses. Conclusion: For pronounced antiviral activity, the molecular of phenolic acid must have at least two hydroxyl groups. Replacement of hydroxyl groups to methoxy group leads to a reduction of antiviral properties. Gallic acid demonstrated high antiviral activity against influenza viruses, including Rimantadine and Oseltamivir resistant strains, and could be used as a potential candidate for the development of antiviral drug against influenza virus.

Keywords: antiviral activity, influenza virus, drug resistance, phenolic acids

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Authors: Sandy Elsayed, Aya Mohamed, Noha Nassar

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Introduction: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social deficits and repetitive behavior. Multiple studies suggest that oxidative stress and neuroinflammation are key factors in the etiology of ASD and often associated with worsening of ASD-related behaviors. Nuclear factor erythroid 2-related factor 2 (NRF-2) is a transcription factor that promotes expression of antioxidant response element genes in oxidative stress. In ASD subjects, decreased expression of NRF-2 in frontal cortex shifted the redox homeostasis towards oxidative stress, and resulted in inflammation evidenced by elevation of nuclear factor kappa B (NF-κB) transcriptional activity. Dimethyl fumarate (DMF) is a NRF-2 activator that is used in the treatment of psoriasis and multiple sclerosis. It participates in the transcriptional control of inflammatory factors via inhibition of NF-κB and its downstream targets. This study aimed to investigate the role of DMF in alleviating the cognitive impairments and behavior deficits associated with ASD through mitigation of oxidative stress and inflammation in prenatal valproic acid (VPA) rat model of autism. Methods: Pregnant female Wistar rats received a single intraperitoneal injection of VPA (600 mg/kg) to induce autistic-like-behavioral and neurobiological alterations in their offspring. Chronic oral gavage of DMF (150mg/kg/day) started from postnatal day (PND) 24 till PND62 (39 days). Prenatal VPA exposure elicited autistic behaviors including decreased social interaction and stereotyped behavior. Social interaction was evaluated using three-chamber sociability test and calculation of sociability index (SI), while stereotyped repetitive behavior and anxiety associated with ASD were assessed using marble burying test (MBT). Biochemical analyses were done on prefrontal cortex homogenates including NRF-2, and NF-κB expression. Moreover, inducible nitric oxide synthase (iNOS) gene expression and tumor necrosis factor (TNF-) protein expression were evaluated as markers of inflammation. Results: Prenatal VPA elicited decreased social interaction shown by decreased SI compared to control group (p < 0.001) and DMF enhanced SI (p < 0.05). In MBT, prenatal injection of VPA manifested stereotyped behavior and enhanced number of buried marbles compared to control (p < 0.05) and DMF reduced the anxiety-related behavior in rats exhibiting ASD-like behaviors (p < 0.05). In prefrontal cortex, NRF-2 expression was downregulated in prenatal VPA model (p < 0.0001) and DMF reversed this effect (p < 0.0001). The inflammatory transcription factor NF-κB was elevated in prenatal VPA model (p < 0.0001) and reduced (p < 0.0001) upon NRF-2 activation by DMF. Prenatal VPA expressed higher levels of proinflammatory cytokine TNF- compared to control group (p < 0.0001) and DMF reduced it (p < 0.0001). Finally, the gene expression of iNOS was downregulated upon NRF-2 activation by DMF (p < 0.01). Conclusion: This study proposes that DMF is a potential agent that can be used to ameliorate autistic-like-changes through NRF-2 activation along with NF-κB downregulation and therefore, it is a promising novel therapy for ASD.

Keywords: autism spectrum disorders, dimethyl fumarate, neuroinflammation, NRF-2

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