Search results for: mechanism of action

Authors: Koryukaeva Ksenia, Jinfeng Sun

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Europe has been a traditional importer of Russian natural gas for more than 50 years. In 2021, Russian state-owned company Gazprom supplied about a third of all gas consumed in Europe. The Russia-Europe mutual dependence in terms of natural gas supplies has been causing many concerns about the energy security of the two sides for a long period of time. These days the issue has become more urgent than ever considering recent Russian invasion in Ukraine followed by increased large-scale geopolitical conflicts, making the future of Russian natural gas supplies and global gas markets as well highly uncertain. Hence, the main purpose of this study is to get insight into the possible futures of Russian pipeline natural gas exports by a scenario planning method based on Monte-Carlo simulation within LUSS model framework, and propose Russian pipeline natural gas export strategies based on the obtained scenario planning results. The scenario analysis revealed that recent geopolitical disputes disturbed the traditional, longstanding model of Russian pipeline gas exports, and, as a result, the prospects and the pathways for Russian pipeline gas on the world markets will differ significantly from those before 2022. Specifically, our main findings show, that (i) the events of 2022 generated many uncertainties for the long-term future of Russian pipeline gas export perspectives on both western and eastern supply directions, including geopolitical, regulatory, economic, infrastructure and other uncertainties; (ii) according to scenario modelling results, Russian pipeline exports will face many challenges in the future, both on western and eastern directions. A decrease in pipeline gas exports will inevitably affect country’s natural gas production and significantly reduce fossil fuel export revenues, jeopardizing the energy security of the country; (iii) according to proposed strategies, in order to ensure the long-term stable export supplies in the changing environment, Russia may need to adjust its traditional export strategy by performing export flows and product diversification, entering new markets, adapting its contracting mechanism, increasing competitiveness and gaining a reputation of a reliable gas supplier.

Keywords: Russian natural gas, Pipeline natural gas, Uncertainty, Scenario simulation, Export strategy

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Authors: Ana Paula S. A. Correa, Allan K. R. Galardo, Luana A. Lima, Talita F. Sobral, Josiane N. Muller, Jessica F. S. Barroso, Nercy V. R. Furtado, Ednaldo C. Rêgo., Jose B. P. Lima

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Malaria is a public health problem in the Brazilian Legal Amazon. Among the integrated approaches for anopheline control, the Indoor Residual Spraying (IRS) remains one of the main tools in the basic strategy applied in the Amazonian States, where the National Malaria Control Program currently uses one of the insecticides from the pyrethroid class, the Etofenprox WP. Understanding the residual efficacy of insecticides on different surfaces is essential to determine the spray cycles, in order to maintain a rational use and to avoid product waste. The aim of this study was to evaluate the residual efficacy of Etofenprox - VECTRON ® 20 WP on surfaces of Unplastered Cement (UC) and Unpainted Wood (UW) on panels, in field, and in semi-field evaluation of Brazil’s Amapa State. The evaluation criteria used was the cone bioassay test, following the World Health Organization (WHO) recommended method, using plastic cones and female mosquitos of Anopheles sp. The tests were carried out in laboratory panels, semi-field evaluation in a “test house” built in the Macapa municipality, and in the field in 20 houses, being ten houses per surface type (UC and UW), in an endemic malaria area in Mazagão’s municipality. The residual efficacy was measured from March to September 2017, starting one day after the spraying, repeated monthly for a period of six months. The UW surface presented higher residual efficacy than the UC. In fact, the UW presented a residual efficacy of the insecticide throughout the period of this study with a mortality rate above 80% in the panels (= 95%), in the "test house" (= 86%) and in field houses ( = 87%). On the UC surface it was observed a mortality decreased in all the tests performed, with a mortality rate of 45, 47 and 29% on panels, semi-field and in field, respectively; however, the residual efficacy ≥ 80% only occurred in the first evaluation after the 24-hour spraying bioassay in the "test house". Thus, only the UW surface meets the specifications of the World Health Organization Pesticide Evaluation Scheme (WHOPES) regarding the duration of effective action (three to six months). To sum up, the insecticide residual efficacy presented variability on the different surfaces where it was sprayed. Although the IRS with Etofenprox WP was efficient on UW surfaces, and it can be used in spraying cycles at 4-month intervals, it is important to consider the diversity of houses in the Brazilian Legal Amazon, in order to implement alternatives for vector control, including the evaluation of new products or different formulations types for insecticides.

Keywords: Anopheles, vector control, insecticide, bioassay

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Authors: Farida Azzouz-Olden, Arthur G. Hunt, Gloria Degrandi-Hoffman

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Bees are confronting several environmental challenges, including the intermingled effects of malnutrition and disease. Intuitively, pollen is the healthiest nutritional choice; however, commercial substitutes, such as BeePro and MegaBee, are widely used. Herein we examined how feeding natural and artificial diets shapes transcription in the abdomen of the honey bee, and how transcription shifts in combination with Nosema parasitism. Gene ontology enrichment revealed that, compared with poor diet (carbohydrates (C)), bees fed pollen (P > C), BeePro (B > C), and MegaBee (M > C) showed a broad upregulation of metabolic processes, especially lipids; however, pollen feeding promoted more functions and superior proteolysis. The superiority of the pollen diet was also evident through the remarkable overexpression of vitellogenin in bees fed pollen instead of MegaBee or BeePro. Upregulation of bioprocesses under carbohydrates feeding compared to pollen (C > P) provided a clear poor nutritional status, uncovering stark expression changes that were slight or absent relatively to BeePro (C > B) or MegaBee (C > M). Poor diet feeding (C > P) induced starvation response genes and hippo signaling pathway, while it repressed growth through different mechanisms. Carbohydrate feeding (C > P) also elicited ‘adult behavior’, and developmental processes suggesting transition to foraging. Finally, it altered the ‘circadian rhythm’, reflecting the role of this mechanism in the adaptation to nutritional stress in mammals. Nosema-infected bees fed pollen compared to carbohydrates (PN > CN) upheld certain bioprocesses of uninfected bees (P > C). Poor nutritional status was more apparent against pollen (CN > PN) than BeePro (CN > BN) or MegaBee (CN > MN). Nosema accentuated the effects of malnutrition since more starvation-response genes and stress response mechanisms were upregulated in CN > PN compared to C > P. The bioprocess ‘Macromolecular complex assembly’ was also enriched in CN > PN, and involved genes associated with human HIV and/or influenza, thus providing potential candidates for bee-Nosema interactions. Finally, the enzyme Duox emerged as essential for guts defense in bees, similarly to Drosophila. These results provide evidence of the superior nutritional status of bees fed pollen instead of artificial substitutes in terms of overall health, even in the presence of a pathogen.

Keywords: honeybee, immunity, Nosema, nutrition, RNA-seq

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Authors: Krystof Kryniski, Asa Kassman Rudolphi, Su Zhao, Per Lindholm

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ABB offers range of turbochargers from 500 kW to 80+ MW diesel and gas engines. Those operate on ships, power stations, generator-sets, diesel locomotives and large, off-highway vehicles. The units need to sustain harsh operating conditions, exposure to high speeds, temperatures and varying loads. They are expected to work at over-critical speeds damping effectively any transients and encountered resonances. Components are often connected via friction joints. Designs of those interfaces need to account for surface roughness, texture, pre-stress, etc. to sustain against fretting fatigue. The experience from field contributed with valuable input on components performance in hash sea environment and their exposure to high temperature, speed and load conditions. Study of tribological interactions of oxide formations provided an insight into dynamic activities occurring between the surfaces. Oxidation was recognized as the dominant factor of a wear. Microscopic inspections of fatigue cracks on turbine indicated insufficient damping and unrestrained structural stress leading to catastrophic failure, if not prevented in time. The contact interface exhibits strongly non-linear mechanism and to describe it the piecewise approach was used. Set of samples representing the combinations of materials, texture, surface and heat treatment were tested on a friction rig under range of loads, frequencies and excitation amplitudes. Developed numerical technique extracted the friction coefficient, tangential contact stiffness and damping. Vast amount of experimental data was processed with the multi-harmonics balance (MHB) method to categorize the components subjected to the periodic excitations. At the pre-defined excitation level both force and displacement formed semi-elliptical hysteresis curves having the same area and secant as the actual ones. By cross-correlating the terms remaining in the phase and out of the phase, respectively it was possible to separate an elastic energy from dissipation and derive the stiffness and damping characteristics.

Keywords: contact interface, fatigue, rotor-dynamics, torsional resonances

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Authors: Inês Boticas, Diana P. Ferreira, Ana Eusébio, Carlos Silva, Pedro Magalhães, Ricardo Silva, Raul Fangueiro

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Since the beginning of the 20^th century, sportswear has a major contribution to the impact of fashion on our lives. Nowadays, the embracing of sportswear fashion/looks is undoubtedly noticeable, as the modern consumer searches for high comfort and linear aesthetics for its clothes. This compromise lead to the arise of the athleisure trend. Athleisure surges as a new style area that combines both wearability and fashion sense, differentiated from the archetypal sportswear, usually associated to “gym clothes”. Additionally, the possibility to functionalize and implement new technologies have shifted and progressively empowers the connection between the concepts of physical activities practice and well-being, allowing clothing to be more interactive and responsive with its surroundings. In this study, a design inspired in retro and urban lifestyle was envisioned, engineering textile structures that can respond to external stimuli. These structures are enhanced to be responsive to heat, water vapor and humidity, integrating shape memory polymers (SMP) to improve the breathability and heat-responsive behavior of the textiles and zinc oxide nanoparticles (ZnO NPs) to heighten the surface hydrophobic properties. The best results for hydrophobic exhibited superhydrophobic behavior with water contact angle (WAC) of more than 150 degrees. For the breathability and heat-response properties, SMP-coated samples showed an increase in water vapour permeability values of about 50% when compared with non SMP-coated samples. These innovative technological approaches were endorsed to design innovative clothing, in line with circular economy and eco-design principles, by assigning a substantial degree of mutability and versatility to the clothing. The development of a coat and shirt, in which different parts can be purchased separately to create multiple products, aims to combine the technicality of both the fabrics used and the making of the garments. This concept translates itself into a real constructive mechanism through the symbiosis of high-tech functionalities and the timeless design that follows the athleisure aesthetics.

Keywords: breathability, sportswear and casual clothing, sustainable design, superhydrophobicity

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Authors: Olayemi Bakre

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The majoritant of the South African rural populace are directly or indirectly engaged in agricultural practices for a livelihood. However, impediments such as the climate change and inadequacy of governmental support has undermined the once thriving subsistence farming communities of South Africa. Furthermore, the poor leadership in hydrology, coupled with lack of depths in skills to facilitate the understanding and acceptance of groundwater from national level to local governance has made it near impossible for subsistence farmers to optimally benefit from the groundwater beneath their feet. The 2012 drought experienced in South Africa paralysed the farming activities across several subsistence farming communities across the KwaZulu-Natal Province. To revamp subsistence farming, a variety of interventions and strategies such as the Resource Poor Farmers (RPF) and Water Allocation Reforms (WAR) have been launched by the Department of Water and Sanitation (DWS) as an agendum to galvanising the defunct subsistence farming communities of KwaZulu-Natal as well as other subsistence farming communities across South Africa. Despite the enormous resources expended on the subsistence farming communities whom often fall under the Historically Disadvantaged Individuals (HDI); indicators such as the unsustainable farming practices, poor crop yield, pitiable living condition as well as the poor standard of living, are evidential to the claim that these afore cited interventions and a host of other similar strategies indicates that these initiatives have not yield the desired result. Thus, this paper seeks to suggest practicable interventions aimed at salvaging the vulnerability of subsistence farmers within the province understudy. The study pursued a qualitative approach as the view of experts on ground water and similarly related fields from the DWS were solicited as an agendum to obtaining in-depth perspective into the current study. Some of the core challenges undermining the sustainability and growth of subsistence farming in the area of study were - inadequacy of experts (engineers, scientist, researchers) in ground water; water shortages; lack of political will as well as lack of coordination among stakeholders. As an agendum to optimising the ground water usage for subsistence farming, this paper advocates the strengthening of geohydrological skills, development of technical training capacity, interactive participation among stakeholders as well as the initiation of Participatory Action Research as an agenda to optimising the available ground water in KwaZulu-Natal which is intended to orchestrate a sustainable and viable subsistence farming practice within the province.

Keywords: subsistence farming, ground water optimisation, resource poor farmers, and water allocation reforms, hydrology

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Authors: J. Hakula

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Discussion on euthanasia is a continuous process. Euthanasia is defined as 'deliberately ending a patient's life by administering life-ending drugs at the patient's explicit request'. With few exceptions, worldwide in most countries human societies have not been able to agree on some fundamental issues concerning ultimate decisions of life and death. Outranking methods in voting oriented social choice theory and multicriteria decision-making (MCDM) can be applied to issues in medical ethics. There is a wide range of voting methods, and using different methods the same group of voters can end up with different outcomes. In the MCDM context, decision alternatives can be substituted for candidates, and criteria for voters. The view chosen here is that of a single decision-maker. Initially, three alternatives and three criteria are chosen. Pairwise and basic positional voting rules - plurality, anti-plurality and the Borda count - are applied. In the MCDM solution, criteria are put weights by giving them the more 'votes'; the more important the decision-maker ranks them. A hypothetical example on evaluating properties of euthanasia consists of three alternatives A, B, and C, which are ranked according to three criteria - the patient’s willingness to cooperate, general action orientation (active/passive), and cost-effectiveness - the criteria having weights 7, 5, and 4, respectively. Using the plurality rule and the weights given to criteria, A is the best alternative, B and C thereafter. In pairwise comparisons, both B and C defeat A with weight scores 7 to 9. On the other hand, B is defeated by C with weights 11 to 5. Thus, C (i.e. the so-called Condorcet winner) defeats both A and B. The best alternative using the plurality principle is not necessarily the best in the pairwise sense, the conflict remaining unsolved with or without additional weights. Positional rules are sensitive to variations in alternative sets. In the example above, the plurality rule gives the rank ABC. If we leave out C, the plurality ranking between A and B results in BA. Withdrawing B or A the ranking is CA and CB, respectively. In pairwise comparisons an analogous problem emerges when the number of criteria is varied. Cyclic preferences may lead to a total tie, and no (rational) choice between the alternatives can be made. In conclusion, the choice of the best commitment to re-evaluate euthanasia, with criteria left unchanged, depends entirely on the evaluation method used. The right strategies matter, too. Future studies might concern the problem of an abstention - a situation where voters do not vote - and still their best candidate may win. Or vice versa, actively giving the ballot to their first rank choice might lead to a total loss. In MCDM terms, a decision might occur where some central criteria are not actively involved in the best choice made.

Keywords: medical ethics, euthanasia, voting methods, multicriteria decision-making

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Authors: Asma Bashir, Neha Farid, Kashif Ali, Kiran Fatima

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Background: Bacteriocins are a subclass of antimicrobial peptides that are becoming extremely important in treatments. It is possible to utilise bacteriocins in place of or in addition to traditional antibiotics. It is possible to treat a variety of infections, including Vancomycin-Resistant Staphylococcus aureus (VRSA) and Methicillin-Resistant Staphylococcus aureus (MRSA), using the targeted spectrum of activity of these microorganisms. Method: This study aimed to examine the efficiency of antibiotics and bacteriocin against VRSA and MRSA. The effects of bacteriocins, such as enterocin KAE01, enterocin KAE03, enterocin KAE05, and enterocin KAE06 isolated from Enterococcus faecium strains, alone and in combination with vancomycin and methicillin antibiotics were examined. The selection technique utilized the minimum inhibitory concentrations (MICs) against Gram-positive indicator strain ATCC 6538 Methicillin-Resistant Staphylococcus aureus (MRSA) and indicator strain KSA 02 Vancomycin-Resistant Staphylococcus aureus (VRSA). Results: We report the isolation and identification of enterocins KAE01, KAE03, KAE05, and KAE06 from food isolates of Enterococcus faecium (KAE01, KAE03, KAE05, and KAE06). After isolating the protein, it was partially purified with ammonium sulphate precipitation and purified with fast protein liquid chromatography (FPLC) procedures. Combinations of enterocin KAE01, 1 citric acid, 1 lactic acid, and microcin J25, 1 reuterin, 1 citric acid, and microcin J25, 1 reuterin, 1 lactic acid shown synergistic benefits (FIC index = 0.5) against Vancomycin-Resistant Staphylococcus aureus (VRSA). In addition, a moderately synergistic (FIC index = 0.75) interaction was seen between pediocin PA-1, 1 citric acid, 1 lactic acid, and reuterin 1 citric acid, 1 lactic acid against L. ivanovii HPB28. In the presence of acids, nisin Z exhibited a modestly synergistic effect (FIC index = 0.625-0.75); however, it exhibited additive effects (FIC index = 1) when combined with reuterin or pediocin PA-1 against L. ivanovii HPB28. The efficacy of synergistic consortiums against Gram-positive bacteria was examined. Conclusion: Combining antimicrobials with various modes of action boosted efficacy and expanded the spectrum of inhibition, particularly against multidrug-resistant pathogens, according to our research.

Keywords: Enterococcus faecium, bacteriocin, antimicrobial resistance, antagonistic activity, vancomycin-resistant Staphylococcus aureus, methicillin-resistant Staphylococcus aureus

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Authors: Bonguen Onouck Rolande Carole, Ndongo Barthelemy

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The climate change effects on the Lake Chad, coupled with population growth, have pushed large masses of people of various origins towards the lower part of the lower Logonewatershed in search of the benefits of environmental services, causing pressure on the environment and its resources. Economic services are therefore threatened, and the decrease in resources contributes to the deterioration of the social wellbeing resulting to conflicts among/between local communities, immigrants, displaced people, and foreigners. This paper is an information contribution on ethnical conflicts drivers in the area and the provided local management mechanisms such can help mitigate present or future conflicts in similar areas. It also prints out the necessity to alleviate water access deficit and encourage good practices for the population wellbeing. In order to meet the objective, in 2018, through the interface of the World Bank-Cameroon project-PULCI, data were collected on the field directly by discussing with the population and visiting infrastructures, indirectly by a questionnaire survey. Two administrative divisions were chosen (Logoneet Chari, Mayo-Danay) in which targeted localities were Zina, Mazera, Lahai, Andirni near the Waza Park and Yagoua, Tekele, Pouss, respectively. Due to some sociocultural and religious reasons, some information were acquired through the traditional chiefs. A desk study analysis based on resources access and availability conflicts history, and management mechanism was done. As results, roots drivers of ethnical conflicts are struggles over natural resources access, and the possibility of conflicts increases as the scarcity and vulnerabilities persist, creating more sociocultural gaps and tensions. The mitigation mechanisms though fruitful, are limited. There is poor documentation on the topic, the resources management policies of this basin are unsuitable and ineffective for some. Therefore, the restoration of environmental and ecosystems, the mitigation of climate change effects, and food insecurity are the challenges that must be met to alleviate conflicts in these localities.

Keywords: ethnic, communities, conflicts, mitigation mechanisms, natural resources, logone basin

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Authors: Ludmila Vucolova

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The thought is a process that underlies consciousness and cognition and understanding its origin and processes is a longstanding goal of many academic disciplines. By integrating over twenty novel ideas and hypotheses of this theoretical proposal, we can speculate that thought is an emergent property of coded neural events, translating the electro-chemical interactions of the body with its environment—the objects of sensory stimulation, X, and Y. The latter is a self- generated feedback entity, resulting from the arbitrary pattern of the motion of a body’s motor repertory (M). A culmination of these neural events gives rise to a thought: a state of identity between an observed object X and a symbol Y. It manifests as a “state of awareness” or “state of knowing” and forms our perception of the physical world. The values of the variables of a construct—X (object), S1 (sense for the perception of X), Y (object), S2 (sense for perception of Y), and M (motor repertory that produces Y)—will specify the particular conscious percept at any given time. The proposed principle of interaction between the elements of a construct (X, Y, S1, S2, M) is universal and applies for all modes of communication (normal, deaf, blind, deaf and blind people) and for various language systems (Chinese, Italian, English, etc.). The particular arrangement of modalities of each of the three modules S1 (5 of 5), S2 (1 of 3), and M (3 of 3) defines a specific mode of communication. This multifaceted paradigm demonstrates a predetermined pattern of relationships between X, Y, and M that passes from generation to generation. The presented analysis of a cognitive experience encompasses the key elements of embodied cognition theories and unequivocally accords with the scientific interpretation of cognition as the mental action or process of acquiring knowledge and understanding through thought, experience, and the senses, and cognition means thinking and awareness. By assembling the novel ideas presented in twelve sections, we can reveal that in the invisible “chaos”, there is an order, a structure with landmarks and principles of operations and mental processes (thoughts) are physical and have a biological basis. This innovative proposal explains the phenomenon of mental imagery; give the first insight into the relationship between mental states and brain states, and support the notion that mind and body are inseparably connected. The findings of this theoretical proposal are supported by the current scientific data and are substantiated by the records of the evolution of language and human intelligence.

Keywords: agent, awareness, cognitive, element, experience, feedback, first person, imagery, language, mental, motor, object, sensory, symbol, thought

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Authors: Vahid Asadzadeh, Amin Ataee

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Since the advent of social media, there has been a wave of optimism among researchers and civic activists about the influence of virtual networks on the democratization process, which has gradually waned. One of the lesser-known concerns is how to increase the possibility of hearing the voices of different minorities. According to the theory of media logic, the media, using their technological capabilities, act as a structure through which events and ideas are interpreted. Social media, through the use of the learning machine and the use of algorithms, has formed a kind of structure in which the voices of minorities and less popular topics are lost among the commotion of the trends. In fact, the recommended systems and algorithms used in social media are designed to help promote trends and make popular content more popular, and content that belongs to minorities is constantly marginalized. As social networks gradually play a more active role in politics, the possibility of freely participating in the reproduction and reinterpretation of structures in general and political structures in particular (as Laclau‎ and Mouffe had in mind‎) can be considered as criteria to democracy in action. The point is that the media logic of virtual networks is shaped by the rule and even the tyranny of the majority, and this logic does not make it possible to design a self-foundation and self-revolutionary model of democracy. In other words, today's social networks, though seemingly full of variety But they are governed by the logic of homogeneity, and they do not have the possibility of multiplicity as is the case in immanent radical democracies (influenced by Gilles Deleuze). However, with the emergence and increasing popularity of Clubhouse as a new social media, there seems to be a shift in the social media space, and that is the diminishing role of algorithms and systems reconditioners as content delivery interfaces. This has led to the fact that in the Clubhouse, the voices of minorities are better heard, and the diversity of political tendencies manifests itself better. The purpose of this article is to show, first, how social networks serve the elimination of minorities in general, and second, to argue that the media logic of social networks must adapt to new interpretations of democracy that give more space to minorities and human rights. Finally, this article will show how the Clubhouse serves the new interpretations of democracy at least in a minimal way. To achieve the mentioned goals, in this article by a descriptive-analytical method, first, the relation between media logic and postmodern democracy will be inquired. The political economy popularity in social media and its conflict with democracy will be discussed. Finally, it will be explored how the Clubhouse provides a new horizon for the concepts embodied in radical democracy, a horizon that more effectively serves the rights of minorities and human rights in general.

Keywords: algorithmic tyranny, Clubhouse, minority rights, radical democracy, social media

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Authors: Danni Cheng

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Background: Preclinical and epidemiological studies have reported potential protective effects of low-density lipoprotein cholesterol (LDL-C) lowering drugs on head and neck squamous cell cancer (HNSCC) survival, but the causality was not consistent. Genetic variants associated with LDL-C lowering drug targets can predict the effects of their therapeutic inhibition on disease outcomes. Objective: We aimed to evaluate the causal association of genetically proxied cholesterol-lowering drug targets and circulating lipid traits with cancer survival in HNSCC patients stratified by human papillomavirus (HPV) status using two-sample Mendelian randomization (MR) analyses. Method: Single-nucleotide polymorphisms (SNPs) in gene region of LDL-C lowering drug targets (HMGCR, NPC1L1, CETP, PCSK9, and LDLR) associated with LDL-C levels in genome-wide association study (GWAS) from the Global Lipids Genetics Consortium (GLGC) were used to proxy LDL-C lowering drug action. SNPs proxy circulating lipids (LDL-C, HDL-C, total cholesterol, triglycerides, apoprotein A and apoprotein B) were also derived from the GLGC data. Genetic associations of these SNPs and cancer survivals were derived from 1,120 HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) and 2,570 non-HPV-driven HNSCC patients in VOYAGER program. We estimated the causal associations of LDL-C lowering drugs and circulating lipids with HNSCC survival using the inverse-variance weighted method. Results: Genetically proxied HMGCR inhibition was significantly associated with worse overall survival (OS) in non-HPV-drive HNSCC patients (inverse variance-weighted hazard ratio (HR IVW), 2.64[95%CI,1.28-5.43]; P = 0.01) but better OS in HPV-positive OPSCC patients (HR IVW,0.11[95%CI,0.02-0.56]; P = 0.01). Estimates for NPC1L1 were strongly associated with worse OS in both total HNSCC (HR IVW,4.17[95%CI,1.06-16.36]; P = 0.04) and non-HPV-driven HNSCC patients (HR IVW,7.33[95%CI,1.63-32.97]; P = 0.01). A similar result was found that genetically proxied PSCK9 inhibitors were significantly associated with poor OS in non-HPV-driven HNSCC (HR IVW,1.56[95%CI,1.02 to 2.39]). Conclusion: Genetically proxied long-term HMGCR inhibition was significantly associated with decreased OS in non-HPV-driven HNSCC and increased OS in HPV-positive OPSCC. While genetically proxied NPC1L1 and PCSK9 had associations with worse OS in total and non-HPV-driven HNSCC patients. Further research is needed to understand whether these drugs have consistent associations with head and neck tumor outcomes.

Keywords: Mendelian randomization analysis, head and neck cancer, cancer survival, cholesterol, statin

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Authors: Saeed Bagherifam, Trevor Brown, Chris Fellows, Ravi Naidu

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Over the last century, rapid urbanization, industrial emissions, and mining activities have resulted in widespread contamination of the environment by heavy metal(loid)s. Arsenic (As) is a toxic metalloid belonging to group 15 of the periodic table, which occurs naturally at low concentrations in soils and the earth’s crust, although concentrations can be significantly elevated in natural systems as a result of dispersion from anthropogenic sources, e.g., mining activities. Bioavailability is the fraction of a contaminant in soils that is available for uptake by plants, food chains, and humans and therefore presents the greatest risk to terrestrial ecosystems. Numerous attempts have been made to establish in situ and ex-situ technologies of remedial action for remediation of arsenic-contaminated soils. In situ stabilization techniques are based on deactivation or chemical immobilization of metalloid(s) in soil by means of soil amendments, which consequently reduce the bioavailability (for biota) and bioaccessibility (for humans) of metalloids due to the formation of low-solubility products or precipitates. This study investigated the effectiveness of two different types of synthetic manganese and iron oxides (birnessite and goethite) for stabilization of As in a soil spiked with 1000 mg kg⁻¹ of As and treated with 10% dosages of soil amendments. Birnessite was made using HCl and KMnO₄, and goethite was synthesized by the dropwise addition of KOH into Fe(NO₃) solution. The resulting contaminated soils were subjected to a series of chemical extraction studies including sequential extraction (BCR method), single-step extraction with distilled (DI) water, 2M HNO₃ and simplified bioaccessibility extraction tests (SBET) for estimation of bioaccessible fractions of As in two different soil fractions ( < 250 µm and < 2 mm). Concentrations of As in samples were measured using inductively coupled plasma mass spectrometry (ICP-MS). The results showed that soil with birnessite reduced bioaccessibility of As by up to 92% in both soil fractions. Furthermore, the results of single-step extractions revealed that the application of both birnessite and Goethite reduced DI water and HNO₃ extractable amounts of arsenic by 75, 75, 91, and 57%, respectively. Moreover, the results of the sequential extraction studies showed that both birnessite and goethite dramatically reduced the exchangeable fraction of As in soils. However, the amounts of recalcitrant fractions were higher in birnessite, and Goethite amended soils. The results revealed that the application of both birnessite and goethite significantly reduced bioavailability and the exchangeable fraction of As in contaminated soils, and therefore birnessite and Goethite amendments might be considered as promising adsorbents for stabilization and remediation of As contaminated soils.

Keywords: arsenic, bioavailability, in situ stabilisation, metalloid(s) contaminated soils

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Authors: Mateen A Khan, Taj Mohammad, Md. Imtaiyaz Hassan

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Alzheimer’s disease is characterized by the accumulation of the processing products of the amyloid beta peptide cleaved by amyloid precursor protein (APP). Iron increases the synthesis of amyloid beta peptides, which is why iron is present in Alzheimer's disease patients' amyloid plaques. Iron misregulation in the brain is linked to the overexpression of APP protein, which is directly related to amyloid-β aggregation in Alzheimer’s disease. The APP 5'-UTR region encodes a functional iron-responsive element (IRE) stem-loop that represents a potential target for modulating amyloid production. Targeted regulation of APP gene expression through the modulation of 5’-UTR sequence function represents a novel approach for the potential treatment of AD because altering APP translation can be used to improve both the protective brain iron balance and provide anti-amyloid efficacy. The molecular docking analysis of APP IRE RNA with eukaryotic translation initiation factors yields several models exhibiting substantial binding affinity. The finding revealed that the interaction involved a set of functionally active residues within the binding sites of eIF4F. Notably, APP IRE RNA and eIF4F interaction were stabilized by multiple hydrogen bonds with residues of APP IRE RNA and eIF4F. It was evident that APP IRE RNA exhibited a structural complementarity that tightly fit within binding pockets of eIF4F. The simulation studies further revealed the stability of the complexes formed between RNA and eIF4F, which is crucial for assessing the strength of these interactions and subsequent roles in the pathophysiology of Alzheimer’s disease. In addition, MD simulations would capture conformational changes in the IRE RNA and protein molecules during their interactions, illustrating the mechanism of interaction, conformational change, and unbinding events and how it may affect aggregation propensity and subsequent therapeutic implications. Our binding studies correlated well with the translation efficiency of APP mRNA. Overall, the outcome of this study suggests that the genomic modification and/or inhibiting the expression of amyloid protein by targeting APP IRE RNA can be a viable strategy to identify potential therapeutic targets for AD and subsequently be exploited for developing novel therapeutic approaches.

Keywords: Alzheimer's disease, Protein-RNA interaction analysis, molecular docking simulations, conformational dynamics, binding stability, binding kinetics, protein synthesis.

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Authors: Evangelos G. Ilias, Panagiotis G. Ilias, Vasileios T. Popotas

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The United Kingdom has one of the oldest railway networks in the world dating back to 1825 when the world’s first passenger railway was opened. The network has some 40,000 bridges of various construction types using a wide range of materials including masonry, steel, cast iron, wrought iron, concrete and timber. It is commonly accepted that the successful operation of the network is vital for the economy of the United Kingdom, consequently the cost effective maintenance of the existing infrastructure is a high priority to maintain the operability of the network, prevent deterioration and to extend the life of the assets. Every bridge on the railway network is required to be assessed every eighteen years and a structured approach to assessments is adopted with three main types of progressively more detailed assessments used. These assessment types include Level 0 (standardized spreadsheet assessment tools), Level 1 (analytical hand calculations) and Level 2 (generally finite element analyses). There is a degree of conservatism in the first two types of assessment dictated to some extent by the relevant standards which can lead to some structures not achieving the required load rating. In these situations, a Level 2 Assessment is often carried out using finite element analysis to uncover ‘latent strength’ and improve the load rating. If successful, the more sophisticated analysis can save on costly strengthening or replacement works and avoid disruption to the operational railway. This paper presents the ‘strengthening by assessment’ achieved by Level 2 analyses. The use of more accurate analysis assumptions and the implementation of non-linear modelling and functions (material, geometric and support) to better understand buckling modes and the structural behaviour of historic construction details that are not specifically covered by assessment codes are outlined. Metallic bridges which are susceptible to loss of section size through corrosion have largest scope for improvement by the Level 2 Assessment methodology. Three case studies are presented, demonstrating the effectiveness of the sophisticated Level 2 Assessment methodology using finite element analysis against the conservative approaches employed for Level 0 and Level 1 Assessments. One rail overbridge and two rail underbridges that did not achieve the required load rating by means of a Level 1 Assessment due to the inadequate restraint provided by U-Frame action are examined and the increase in assessed capacity given by the Level 2 Assessment is outlined.

Keywords: assessment, bridges, buckling, finite element analysis, non-linear modelling, strengthening

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Authors: Priyal Sepaha

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A refugee crisis is manifested by challenges, both for the refugees and the asylum giving state. The situation turns into a mega-crisis when the situation is prejudicially handled by the home state, inappropriate refugee laws, exploding refugee population, and above all, no hope of any foreseeable solution or remedy. This paper studies the impact on the capability of stateless Rohingyas to migrate and seek refuge due to the enforcement of rigid criteria of movement imposed both by Myanmar as well as the adjoining countries in the name of national security. This theoretical study identifies the issues and the key factors and players which have precipitated the crisis. It further discusses the possible ramifications in the home, asylum giving, and the adjoining countries for not discharging their roles aptly. Additionally, an attempt has been made to understand the scarce response given to the impending crisis by the regional organizations like SAARC, ASEAN and CHOGAM as well as international organizations like United Nations Human Rights Council, Security Council, Office of High Commissioner for Refugees and so on, in the name of inadequacy of monetary funds and physical resources. Based on the refugee laws and practices pertaining to the case of Rohingyas, this paper analyses that the Rohingya Crisis is in dire need of an effective action plan to curb and resolve the biggest humanitarian crisis situation of the century. This mounting human tragedy can be mitigated permanently, by strengthening existing and creating new interdependencies among all stakeholders, as further ignorance can drive the countries of the Indian Sub-continent, in particular, and South East Asia, by and large into a violent civil war for seizing long-awaited civil rights by the marginalized Rohingyas. To curb this mass crisis, it will require the application of coercive pressure and diplomatic pursuance on the home country to acknowledge the rights of its fleeing citizens. This further necessitates mustering adequate monetary funds and physical resources for the asylum providing state. Additional challenges such as devising mechanisms for the refugee’s safe return, comprehensive planning for their holistic economic development and rehabilitation plan are needed. These, however, can only come into effect with a conscious strive by the regional and international community to fulfil their assigned role.

Keywords: asylum, citizenship, crisis, humanitarian, human rights, refugee, rohingya

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Authors: Onyinyechi Joy Kingdom

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Mergers and Acquisitions (M&A) have been proposed as a mechanism through which, problems associated with inefficiency or poor performance in financial institution could be addressed. The aim of this study is to examine the proposition that recapitalization of banks, which encouraged Mergers and Acquisitions in Nigeria banking system, would strengthen the domestic banks, improve financial deepening and the confidence of depositors. Hence, this study examines the impact of the 2005 M&A in the Nigerian-banking sector on financial deepening using mixed method (quantitative and qualitative approach). The quantitative process of this study utilised annual time series for financial deepening indicator for the period of 1997 to 2012. While, the qualitative aspect adopted semi-structured interview to collate data from three merged banks and three stand-alone banks to explore, understand and complement the quantitative results. Furthermore, a framework thematic analysis is employed to analyse the themes developed using NVivo 11 software. Using the quantitative approach, findings from the equality of mean test (EMT) used suggests that M&A have significant impact on financial deepening. However, this method is not robust enough given its weak validity as it does not control for other potential factors that may determine financial deepening. Thus, to control for other factors that may affect the level of financial deepening, a Multiple Regression Model (MRM) and Interrupted Times Series Analysis (ITSA) were applied. The coefficient for M&A dummy turned negative and insignificant using MRM. In addition, the estimated linear trend of the post intervention when ITSA was applied suggests that after M&A, the level of financial deepening decreased annually; however, this was statistically insignificant. Similarly, using the qualitative approach, the results from the interview supported the quantitative results from ITSA and MRM. The result suggests that interest rate should fall when capital base is increased to improve financial deepening. Hence, this study contributes to the existing literature the importance of other factors that may affect financial deepening and the economy when policies that will enhance bank performance and the economy are made. In addition, this study will enable the use of valuable policy instruments relevant to monetary authorities when formulating policies that will strengthen the Nigerian banking sector and the economy.

Keywords: mergers and acquisitions, recapitalization, financial deepening, efficiency, financial crisis

Procedia PDF Downloads 396

Authors: Ozlem Oral, Emre Taskin, Aysel Yuce, Serap Dokmeci, Devrim Gozuacik

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Autophagy is an evolutionary conserved lysosome-dependent catabolic pathway, responsible for the degradation of long-lived proteins, abnormal aggregates and damaged organelles which cannot be degraded by the ubiquitin-proteasome system. Lysosomes degrade the substrates through the activity of lysosomal hydrolases and lysosomal membrane-bound proteins. Mutations in the coding region of these proteins cause malfunctional lysosomes, which contributes to the pathogenesis of lysosomal storage diseases. Gaucher disease is a lysosomal storage disease resulting from the mutation of a lysosomal membrane-associated glycoprotein called glucocerebrosidase and its cofactor saposin C. The disease leads to intracellular accumulation of glucosylceramide and other glycolipids. Because of the essential role of lysosomes in autophagic degradation, Gaucher disease may directly be linked to this pathway. In this study, we investigated the expression of autophagy and/or lysosome-related genes and proteins in fibroblast cells isolated from patients with different mutations. We carried out confocal microscopy analysis and examined autophagic flux by utilizing the differential pH sensitivities of RFP and GFP in mRFP-GFP-LC3 probe. We also evaluated lysosomal pH by active lysosome staining and lysosomal enzyme activity. Beside lysosomes, we also performed proteasomal activity and cell death analysis in patient samples. Our data showed significant attenuation in the expression of key autophagy-related genes and accumulation of their proteins in mutant cells. We found decreased the ability of autophagosomes to fuse with lysosomes, associated with elevated lysosomal pH and reduced lysosomal enzyme activity. Proteasomal degradation and cell death analysis showed reduced proteolytic activity of the proteasome, which consequently leads to increased susceptibility to cell death. Our data indicate that the major degradation pathways are affected by multifunctional lysosomes in mutant patient cells and may underlie in the mechanism of clinical severity of Gaucher patients. (This project is supported by TUBITAK-3501-National Young Researchers Career Development Program, Project No: 112T130).

Keywords: autophagy, Gaucher's disease, glucocerebrosidase, mutant fibroblasts

Procedia PDF Downloads 323

Authors: Kusmartono, Siti Chuzaemi, Hartutik dan Mashudi

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Two studies were conducted involving an in vitro (Expt 1) and in vivo (Expt 2) measurements. Expt 1. aimed to evaluate effects of adding CT extracts on gas production and efficiency of microbial protein synthesis (EMPS), Expt 2 aimed to evaluate effects of supplementing shrub/tree leaves as CT source on feed consumption, digestibility, N retention, body weight gain and dressing percentage of growing sheep fed on elephant grass (EG) as a basal diet.Ten shrub and tree leaves used as CT sources were wild sunflower (Tithonia diversifolia), mulberry (Morus macroura), cassava (Manihot utilissima), avicienna (Avicennia marina), calliandra (Calliandra calothyrsus), sesbania (Sesbania grandiflora), acacia (acacia vilosa), glyricidia (Glyricidia sepium), jackfruit (Artocarpus heterophyllus), moringa (Moringa oleifera). The treatments applied in Expt 1 were: T1=Elephant grass (60%)+concentrate (40%); T2 = T1 + CT (3% DM); T3= T2 + PEG; T4 = T1 + CT (3.5% DM); T5 = T4 + PEG; T6 = T1 + CT (4% DM) and T7 = T6 + PEG. Data obtained were analysed using Randomized Block Design. Statistical analyses showed that treatments significanty affected (P<0.05) total gas production and EMPS. The lowest values of total gas production (45.9 ml/500 mg DM) and highest value of EMPS (64.6 g/kg BOTR) were observed in the treatment T4 (3.5% CT from cassava leave extract). Based on this result it was concluded that this treatment was the best and was chosen for further investigation using in vivo method. The treatmets applied for in vivo trial were: T1 = EG (60%) + concentrate (40%); T2 = T1 + dried cassava leave (equivalent to 3.5% CT); T3 = T2 + PEG. 18 growing sheep aging of 8-9 months and weighing of 23.67kg ± 1.23 were used in Expt 2. Results of in vivo study showed that treatments significanty affected (P<0.05) nutrients intake and digestibility (DM, OM and CP). N retention for sheep receiving treatment T2 were significantly higher (P<0.05; 15.6 g/d) than T1 (9.1 g/d) and T3 (8.53 g/d). Similar results were obtained for daily weight gain where T2 were the highest (62.79 g/d), followed by T1 (51.9 g/d) and T3 (52.85 g/d). Dressing percentage of T2 was the highest (51.54%) followed by T1 (49.61%) and T3 (49.32%). It can be concluded that adding adding dried cassava leaves did not reduce palatability due to CT, but rather increased OM digestibility and hence feed consumption was improved. N retention was increased due to the action of CT in the cassava leaves and this may have explained a higher input of N into duodenum which was further led to higer daily weight gain and dressing percentage.

Keywords: in vitro gas production, sheep, shrub and tree leaves, condensed tannin

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Authors: Tomokazu Nagata, Jawid Ahmad Baktash

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The goal of this paper is to explore the use of formal methods for Electronic Identity Card System. Nowadays, one of the core research directions in a constantly growing distributed environment is the improvement of the communication process. The responsibility for proper verification becomes crucial. Formal methods can play an essential role in the development and testing of systems. The thesis presents two different methodologies for assessing correctness. Our first approach employs abstract interpretation techniques for creating a trace based model for Electronic Identity Card System. The model was used for building a semi decidable procedure for verifying the system model. We also developed the code for the eID System and can cover three parts login to system sending of Acknowledgment from user side, receiving of all information from server side and log out from system. The new concepts of impasse and spawned sessions that we introduced led our research to original statements about the intruder’s knowledge and eID system coding with respect to secrecy. Furthermore, we demonstrated that there is a bound on the number of sessions needed for the analysis of System.Electronic identity (eID) cards promise to supply a universal, nation-wide mechanism for user authentication. Most European countries have started to deploy eID for government and private sector applications. Are government-issued electronic ID cards the proper way to authenticate users of online services? We use the eID project as a showcase to discuss eID from an application perspective. The new eID card has interesting design features, it is contact-less, it aims to protect people’s privacy to the extent possible, and it supports cryptographically strong mutual authentication between users and services. Privacy features include support for pseudonymous authentication and per service controlled access to individual data items. The article discusses key concepts, the eID infrastructure, observed and expected problems, and open questions. The core technology seems ready for prime time and government projects deploy it to the masses. But application issues may hamper eID adoption for online applications.

Keywords: eID, event-B, Pro-B, formal method, message passing

Procedia PDF Downloads 233

Authors: Fakhreldin O. Suliman, Alia H. Al-Battashi

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This work explored the interaction of three different imidazoline drugs, naphazoline nitrate (NPH), oxymetazoline hydrochloride (OXY) and xylometazoline hydrochloride (XYL) with two different synthesized cucurbit[n]urils CB[n], cucurbit[7]uril (CB[7]) and cucuribit[8]uril (CB[8]). Three binary inclusion complexes have been investigated in solution and in the solid state. The solid complexes were obtained by lyophilization, whereas the physical mixtures of guests and hosts at a stoichiometric ratio of 1:1 were obtained for each drug. 1HNMR, electrospray ionization mass spectrometry (ESI-MS), and matrix-assisted laser desorption-ionization time-of-flight (MALDI-TOF) mass spectrometry was used to study the complexes prepared in aqueous media. The lyophilized solid complexes were characterized by Fourier transform-infrared spectroscopy (FT-IR), powder X-ray diffractometry (PXRD), thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC). MS, FT-IR and PXRD experimental results established in this work reveal that NPH, OXY and XYL molecules form stable inclusion complexes with the two hosts. The TGA and DSC confirmed the enhancement of the thermal stability of each drug and the production of a thermally stable solid complex. The 1HNMR has shown that the protons of the guests faced shifting in ppm and broadening of their peaks upon the formation of inclusion complexes with the selected CB[n]. The aromatic protons of the guest exhibited the highest changes in the chemical shifts and shape of the NMR peaks, suggesting their inclusion into the cavity of the CB[n]. The diffusion coefficients (D), developed from the diffusion-controlled NMR Spectroscopy (DOSY) measurements, for the complexation of the selected imidazoline drugs with CB[7] and CB[8], were decreased in the presence of hosts compared to the free guests indicating the formation of the guest-host adduct. Furthermore, we conducted molecular dynamic simulations and quantum mechanics calculations on these complexes. The results of the theoretical study corroborate the experimental findings and have also shed light on the mechanism of inclusion of the guests into the two hosts. This study generates initial data for potential drug delivery or drug formulation systems for these three selected imidazoline drug compounds based on their inclusion into the CB[n] cavities.

Keywords: cucurbit[n]urils, imidazoline, inclusion complexes, molecular dynamics, DFT calculations, mass spectrometry

Procedia PDF Downloads 67

Authors: Semyachkina-Glushkovskaya Oxana, Fedosov Ivan, Blokhina Inna, Terskov Andrey, Evsukova Arina, Elovenko Daria, Adushkina Viktoria, Dubrovsky Alexander, Jürgen Kurths

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In modern neurobiology, sleep is considered a novel biomarker and a promising therapeutic target for brain diseases. This is due to recent discoveries of the nighttime activation of the brain lymphatic system (BLS), playing an important role in the removal of wastes and toxins from the brain and contributes neuroprotection of the central nervous system (CNS). In our review, we discuss that night stimulation of BLS might be a breakthrough strategy in a new treatment of Alzheimer’s and Parkinson’s disease, stroke, brain trauma, and oncology. Although this research is in its infancy, however, there are pioneering and promising results suggesting that night transcranial photostimulation (tPBM) stimulates more effectively lymphatic removal of amyloid-beta from mouse brain than daily tPBM that is associated with a greater improvement of the neurological status and recognition memory of animals. In our previous study, we discovered that tPBM modulates the tone and permeability of the lymphatic endothelium by stimulating NO formation, promoting lymphatic clearance of wastes and toxins from the brain tissues. We also demonstrate that tPBM can also lead to angio- and lymphangiogenesis, which is another mechanism underlying tPBM-mediated stimulation of BLS. Thus, photo-augmentation of BLS might be a promising therapeutic target for preventing or delaying brain diseases associated with BLS dysfunction. Here we present pioneering technology for simultaneous tPBM in humans and sleep monitoring for stimulation of BLS to remove toxins from CNS and modulation of brain immunity. The wireless-controlled gadget includes a flexible organic light-emitting diode (LED) source that is controlled directly by a sleep-tracking device via a mobile application. The designed autonomous LED source is capable of providing the required therapeutic dose of light radiation at a certain region of the patient’s head without disturbing of sleeping patient. To minimize patients' discomfort, advanced materials like flexible organic LEDs were used. Acknowledgment: This study was supported by RSF project No. 23-75-30001.

Keywords: brain diseases, brain lymphatic system, phototherapy, sleep

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Authors: Ludmila A. Gavriliuc, Jerry McLarty, Heather E. Kleiner, J. Michael Mathis

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Abstract -- Background: The citrus coumarine Auraptene (Aur) is an effective chemopreventive agent, as manifested in many models of diseases and cancer. Nuclear factor erythroid 2-related factor (Nrf2) is an important regulator of genes induced by oxidative stress, such as glutathione S-transferases, heme oxygenase-1, and peroxiredoxin 1, by activating the antioxidant response element (ARE). Genetic and biochemical evidence has demonstrated that glutathione (GSH) and glutathione-dependent enzymes, glutathione reductase (GR), glutathione peroxidases (GPs), glutathione S-transferases (GSTs) are responsible for the control of intracellular reduction-oxidation status and participate in cellular adaptation to oxidative stress. The effect of Aur on the activity of GR, GPs (Se-GP and Se-iGP), and content of GSH in the liver, kidney, and spleen is insufficiently explored. Aim: Our goal was the examination of the Aur influence on the redox-system of GSH in Nrf2 wild type and Nrf2 knockout mice via activation of Nrf2 and ARE. Methods: Twenty female mice, 10 Nrf2 wild-type (WT) and 10 Nrf2 (-/-) knockout (KO), were bred and genotyped for our study. The activity of GR, Se-GP, Se-iGP, GST, G6PD, CytP450 reductase, catalase (Cat), and content of GSH were analyzed in the liver, kidney, and spleen using Spectrophotometry methods. The results of the specific activity of enzymes and the amount of GSH were analyzed with ANOVA and Spearman statistical methods. Results: Aur (200 mg/kg) treatment induced hepatic GST, GR, Se-GP activity and inhibited their activity in the spleen of mice, most likely via activation of the ARE through Nrf2. Activation in kidney Se-GP and G6PD by Aur is also controlled, apparently through Nrf2. Results of the non-parametric Spearman correlation analysis indicated the strong positive correlation between GR and G6PD only in the liver in WT control mice (r=+0.972; p < 0.005) and in the kidney KO control mice (r=+0.958; p < 0.005). The observed low content of GSH in the liver of KO mice indicated an increase in its participation in the neutralization of toxic substances with the absence of induction of GSH-dependent enzymes, such as GST, GR, Se-GP, and Se-iGP. Activation of CytP450 in kidney and spleen and Cat in the liver in KO mice probably revealed another regulatory mechanism for these enzymes. Conclusion: Thereby, obtained results testify that Aur can modulate the activity of genes and antioxidant enzymatic redox-system of GSH, responsible for the control of intracellular reduction-oxidation status.

Keywords: auraptene, glutathione, GST, Nrf2

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Authors: Martonovich Noa, Maman David, Alfandari Liad, Behrbalk Eyal.

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Introduction: The human body is designed for upright standing and walking, with the lower extremities and axial skeleton supporting weight-bearing. Constant weight-bearing on joints not meant for this action can lead to various pathologies, as seen in wheelchair users. Handstand practitioners use their wrists as weight-bearing joints during activities, but little is known about wrist injuries in this population. This study aims to investigate the epidemiology of wrist pain among handstand practitioners, as no such data currently exist. Methods: The study is a cross-sectional online survey conducted among athletes who regularly practice handstands. Participants were asked to complete a three-part questionnaire regarding their workout regimen, training habits, and history of wrist pain. The inclusion criteria were athletes over 18 years old who practice handstands more than twice a month for at least 4 months. All data were collected using Google Forms, organized and anonymized using Microsoft Excel, and analyzed using IBM SPSS 26.0. Descriptive statistics were calculated, and potential risk factors were tested using asymptotic t-tests and Fisher's tests. Differences were considered significant when p < 0.05. Results: This study surveyed 402 athletes who regularly practice handstands to investigate the prevalence of chronic wrist pain and potential risk factors. The participants had a mean age of 31.3 years, with most being male and having an average of 5 years of training experience. 56% of participants reported chronic wrist pain, and 14.4% reported a history of distal radial fracture. Yoga was the most practiced form, followed by Capoeira. No significant differences were found in demographic data between participants with and without chronic wrist pain, and no significant associations were found between chronic wrist pain prevalence and warm-up routines or protective aids. Conclusion: The lower half of the body is meant to handle weight-bearing and impact, while transferring the load to upper extremities can lead to various pathologies. Athletes who perform handstands are particularly prone to chronic wrist pain, which affects over half of them. Warm-up sessions and protective instruments like wrist braces do not seem to prevent chronic wrist pain, and there are no significant differences in age or training volume between athletes with and without the condition. Further research is needed to understand the causes of chronic wrist pain in athletes, given the growing popularity of sports and activities that can cause this type of injury.

Keywords: handstand, handbalance, wrist pain, hand and wrist surgery, yoga, calisthenics, circus, capoeira, movement.

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Authors: Victor Counted

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Staying true to self is complicated. In most cases, we might not fully come to terms with this realities. Just like any journey, a self-discovery experience with the ‘self’, is like a rollercoaster ride. The researcher attempts to engage the reader in an empirical study on authenticity tendencies of African Christian Millennials. Hence, attempting the all-important question: What does it actually mean to be true to self for the African youth? A comprehensive, yet an unfinished business that applies the authenticity theory in its exploratory navigations to uncover the “lived world” of the participants who were part of this study. Using a mixed methods approach, the researcher will exhaustively give account to the authenticity tendencies and experiences of the respondents in the study by providing the reader with a unique narrative for understanding what it means to be true to oneself in Africa. At the quantitative study, the participants recorded higher scores on the Authenticity Scale (AS) authentic living, while showing a significant correlation within the subscales. Hypotheses were tested at the quantitative phase, which statistically supported gender and church affiliation as possible predictors for the authenticity orientations of the participants, while being a Christian native and race/ethnicity were not impact factors statistically. The results helped the researcher to develop the objectives behind the qualitative study, where only fifteen AS-authentic living participants were interviewed to understand why they scored high on authentic living, in order to understand what it means to be authentic. The hallmark of the qualitative case study exploration was the common coping mechanism of splitting adopted by the respondents to deal with their self-crisis as they tried to remain authentic to self, whilst self-regulating and self-investing the self to discover ‘self’. Specifically, the researcher observed the concurrent utilization of some kind of the religious-self by the respondents to regulate their self crisis, as they relate with self fragmenting through different splitting stages in hope for some kind of redemption. It was an explanation that led to the conclusion that being authentic is the new pieces. Authenticity is in fragments. This proposition led the researcher to introduce a hermeneutical support-system that will enable future researchers engage more critically and responsibly with their “living human documents” in order to inspire timely solutions that resolve the concerns of authenticity and wellbeing among Millennials in Africa.

Keywords: authenticity, self, identity, self-fragmentation, weak self integration, postmodern self, splitting

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Authors: Hsiang-Ru Lin

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Cholesterol plays an essential role in the regulation of the progression of numerous important diseases including atherosclerosis and Alzheimer disease so the generation of suitable cholesterol-lowering reagents is urgent to develop. Liver X receptor (LXR) is a ligand-activated transcription factor whose natural ligands are cholesterols, oxysterols and glucose. Once being activated, LXR can transactivate the transcription action of various genes including CYP7A1, ABCA1, and SREBP1c, involved in the lipid metabolism, glucose metabolism and inflammatory pathway. Essentially, the upregulation of ABCA1 facilitates cholesterol efflux from the cells and attenuates the production of beta-amyloid (ABeta) 42 in brain so LXR is a promising target to develop the cholesterol-lowering reagents and preventative treatment of Alzheimer disease. Engelhardia roxburghiana is a deciduous tree growing in India, China, and Taiwan. However, its chemical composition is only reported to exhibit antitubercular and anti-inflammatory effects. In this study, four compounds, engelheptanoxides A, C, engelhardiol A, and B isolated from the root of Engelhardia roxburghiana were evaluated for their agonistic activity against LXR by the transient transfection reporter assays in the HepG2 cells. Furthermore, their interactive modes with LXR ligand binding pocket were generated by molecular modeling programs. By using the cell-based biological assays, engelheptanoxides A, C, engelhardiol A, and B showing no cytotoxic effect against the proliferation of HepG2 cells, exerted obvious LXR agonistic effects with similar activity as T0901317, a novel synthetic LXR agonist. Further modeling studies including docking and SAR (structure-activity relationship) showed that these compounds can locate in LXR ligand binding pocket in the similar manner as T0901317. Thus, LXR is one of nuclear receptors targeted by pharmaceutical industry for developing treatments of Alzheimer and atherosclerosis diseases. Importantly, the cell-based assays, together with molecular modeling studies suggesting a plausible binding mode, demonstrate that engelheptanoxides A, C, engelhardiol A, and B function as LXR agonists. This is the first report to demonstrate that the extract of Engelhardia roxburghiana contains LXR agonists. As such, these active components of Engelhardia roxburghiana or subsequent analogs may show important therapeutic effects through selective modulation of the LXR pathway.

Keywords: Liver X receptor (LXR), Engelhardia roxburghiana, CYP7A1, ABCA1, SREBP1c, HepG2 cells

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Authors: Scarlet Tabot Enanga Longsti

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Community-Based Health Insurance (CBHI) schemes have been proposed as a possible means to achieve affordable health care in low-and lower-middle-income countries. The existing evidence provides mixed results on the impact of CBHI schemes on healthcare utilisation and out -of-pocket payments (OOPP) for healthcare. Over 900 CBHI schemes have been implemented in underdeveloped countries, and these schemes have undergone different modifications over the years. Prior reviews have suggested that different designs of CBHI schemes may result in different outcomes. Objectives: This review sought to determine the interventions that affect the impact of CBHI schemes on OOPP and health service utilisation. Interventions in this study referred to any action or modification in the design of a CBHI scheme that affected the impact of the scheme on OOPP and/or healthcare utilization. Methods: Any CBHI study that was done in a lower middle-income country, that used an experimental design, that included OOPP or health care utilisation as outcome variables, and that was published in either English or French was included in this study. Studies were searched for in MEDLINE, Embase, CINAHL, EconLit, IBSS, Web of Science, Cochrane Library, and Global Index Medicus from July to August 2023. Bias was assessed using Joanna Brigs Institute tools for quality assessment for randomized control trials and quasi experimental studies. A narrative synthesis was done. Results: 12 studies were included in the review, with a total of 69 villages, 13,653 households, and 62,786 participants. Average premium collection was 4.8 USD/year. Most CBHI schemes had flat rates. The study revealed that a range of interventions impact OOPP and health care utilisation. Five categories of interventions were identified. The intervention with the highest impact on OOPP and utilisation was “Audit visits”. Next in line came external funds, training scheme workers, and engaging community leaders and village heads to advertise the scheme. Free healthcare led to a significant increase in utilisation of health services, a significant reduction in Catastrophic health expenditure, but an insignificant effect on OOPP among insured compared with uninsured. Conclusions: Community-Based Health Insurance could pave the way for Universal Health Care in low and middle-income countries. However, this can only be possible if careful thought is given to how schemes are designed. Due to the heterogeneity of studies and results on CBHI schemes, there is need for further research for more effective designs to be developed.

Keywords: community based health insurance, developing countries, health service utilisation, out of pocket payment

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Authors: Aneta Binkowska, Artur Kamecki

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The ability to provide first aid should be one of the basic skills of each of us. First aid by the Law on National Medical Emergency dated 8 September 2006 as amended, is a set of actions undertaken to save a person at the scene of an accident. In Poland, on the basis of Article 162 of the Criminal Code, we are obliged to provide first aid to the victim. In addition, according to a large part of society, unselfishness towards others in need of help is our moral obligation. The aim of the study was to learn the opinion of the members of Medical Rescue Teams (MRT) of the ‘Meditrans’ Provincial Ambulance and Sanitary Transport Service (PA and STS ‘Meditrans’) in Warsaw on how people react in real situations threatening life or health of the injured person. The study was conducted in the third quarter of 2015 on 335 members of medical rescue teams, including 77 W and 258 M, who provided medical services in the ‘Meditrans’ Provincial Ambulance and Sanitary Transport Service MRT in Warsaw. The research tool was an anonymous questionnaire survey of own design, which consisted of 12 questions: closed, half open and one open question. Respondents were divided into 3 age groups and by individual medical professions (doctor, paramedic, nurse). The straight majority of respondents encountered granting the first aid the event on the spot. However, the frequency of appearing in such proceedings isn’t too high. The first aid has most often been given in the street and in houses. The final audited fairly important element is the reason not to provide first aid by bystanders in the opinion of members of the medical teams. Respondents to this question, which was an open question were asked to name the reason for not taking any action while waiting for an ambulance. Over 50% of respondents could not answer. The most common answers were: fear, lack of knowledge and skills, reluctance, indifference, lack of training, lack of experience and fear that harm. Conclusion: The majority of respondents have encountered instances of first aid provision, but respondents assessed the frequency of such situations as low. Placing the victim in the recovery position is the simplest and most common form of first aid. Therefore, training should be introduced not only on CPR but also in the scope of helping persons in sudden health emergency, who do not have a sudden cardiac arrest. A statement can be formulated, as a main conclusion of the analysis, that only continuous education and in particular practical training will help people to overcome the barrier of their limitations in order to help others. Among the largest group of witnesses providing first aid are the elderly and youth, who are subjected to various forms of education related to first aid provision.

Keywords: BLS, first aid, medical rescue, resuscitation

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Authors: Viktor Kochkodan

Abstract:

The main problem arising upon water treatment and desalination using pressure driven membrane processes such as microfiltration, ultrafiltration, nanofiltration and reverse osmosis is membrane fouling that seriously hampers the application of the membrane technologies. One of the main approaches to mitigate membrane fouling is to minimize adhesion interactions between a foulant and a membrane and the surface coating of the membranes with polyelectrolytes seems to be a simple and flexible technique to improve the membrane fouling resistance. In this study composite polyamide membranes NF-90, NF-270, and BW-30 were modified using electrostatic deposition of polyelectrolyte multilayers made from various polycationic and polyanionic polymers of different molecular weights. Different anionic polyelectrolytes such as: poly(sodium 4-styrene sulfonate), poly(vinyl sulfonic acid, sodium salt), poly(4-styrene sulfonic acid-co-maleic acid) sodium salt, poly(acrylic acid) sodium salt (PA) and cationic polyelectrolytes such as poly(diallyldimethylammonium chloride), poly(ethylenimine) and poly(hexamethylene biguanide were used for membrane modification. An effect of deposition time and a number of polyelectrolyte layers on the membrane modification has been evaluated. It was found that degree of membrane modification depends on chemical nature and molecular weight of polyelectrolytes used. The surface morphology of the prepared composite membranes was studied using atomic force microscopy. It was shown that the surface membrane roughness decreases significantly as a number of the polyelectrolyte layers on the membrane surface increases. This smoothening of the membrane surface might contribute to the reduction of membrane fouling as lower roughness most often associated with a decrease in surface fouling. Zeta potentials and water contact angles on the membrane surface before and after modification have also been evaluated to provide addition information regarding membrane fouling issues. It was shown that the surface charge of the membranes modified with polyelectrolytes could be switched between positive and negative after coating with a cationic or an anionic polyelectrolyte. On the other hand, the water contact angle was strongly affected when the outermost polyelectrolyte layer was changed. Finally, a distinct difference in the performance of the noncoated membranes and the polyelectrolyte modified membranes was found during treatment of seawater in the non-continuous regime. A possible mechanism of the higher fouling resistance of the modified membranes has been discussed.

Keywords: contact angle, membrane fouling, polyelectrolytes, surface modification

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Authors: J. O. Ezekwesili-Ofili, L. I. Okorafor, S. C. Nsofor

Abstract:

Diabetes mellitus is a carbohydrate metabolism disorder due to an absolute or relative deficiency of insulin secretion, action or both. Many known hypoglycaemic drugs are known to produce serious side effects. However, the search for safer and more effective agents has shifted to plant products, including foods and spices. One of such is the rhizome of Curcuma longa or turmeric, which is a spice with high medicinal value. A drawback in the use of C. longa is the poor bioavailability of curcumin, the active ingredient. It has been reported that piperine, an alkaloid present in peppers increases the bioavailability of curcumin. This work therefore investigated the hypoglycaemic and antioxidant effects of ethanolic extract of C. longa rhizomes, alone and with two pepper adjuvants in alloxan-induced diabetic rats. A total of 48 rats were divided into 6 groups of 8 rats each. Groups A–E were induced with diabetes using 150mg/kg body weight of alloxan monohydrate, while group F was normoglycaemic: Group A: Diabetic; fed with 400 mg/g body weight of turmeric extract; group B: Diabetic, fed with 400 mg/kg b. w. and 200mg/kg b. w of ethanolic extract of seeds of Piper guinensee; group C: Diabetic, fed with 400 mg/kg b. w. and 200 mg /kg b. w. of ethanolic extract of seeds of Capsicum annum var cameroun, group D: Diabetic, treated with standard drug, glibenclamide (0.3mg/kg body weight), group E: Diabetic; no treatment i.e. Positive control and group F: non diabetic, no treatment i.e. Negative control. Blood glucose levels were monitored for 14 days using a glucometer. The levels of the antioxidant enzymes; glutathione peroxidase, catalase and superoxide dismutase were also assayed in serum. The ethanolic extracts of C. longa rhizomes at the dose given (400 mg/kg b. w) significantly reduced the blood glucose levels of the diabetic rats (p<0.05) comparable to the standard drug. Co administration of extract of the peppers did not significantly increase the efficiency of the extract, although C. annum var cameroun showed greater effect, though not significantly. The antioxidant effect of the extract was significant in diabetic rats. The use of piperine-containing peppers enhanced the antioxidant effect. Phytochemical analyses of the ethanolic extract of C. longa showed the presence of alkaloids, flavonoids, steroids, saponins, tannins, glycosides, and terpenoids. These results suggest that the ethanolic extract of C. longa had antidiabetic with antioxidant effects and could thus be of benefit in the treatment and management of diabetes as well as ameliorate pro-oxidant effects that may lead to diabetic complications. However, while the addition of piperine did not affect the antidiabetic effect of C. longa, the antioxidant effect was greatly enhanced.

Keywords: antioxidant, Curcuma longa rhizome, hypoglycaemic, pepper adjuvants, piperine

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