Search results for: stress crack resistance

Authors: Istvan Szilagyi, Marko Pavlovic, Paul Rouster

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Antioxidant enzymes are the most efficient defense systems against reactive oxygen species, which cause severe damage in living organisms and industrial products. However, their supplementation is problematic due to their high sensitivity to the environmental conditions. Immobilization on carrier nanoparticles is a promising research direction towards the improvement of their functional and colloidal stability. In that way, their applications in biomedical treatments and manufacturing processes in the food, textile and cosmetic industry can be extended. The main goal of the present research was to prepare and formulate antioxidant bionanocomposites composed of superoxide dismutase (SOD) enzyme, anionic clay (layered double hydroxide, LDH) nanoparticle and heparin (HEP) polyelectrolyte. To characterize the structure and the colloidal stability of the obtained compounds in suspension and solid state, electrophoresis, dynamic light scattering, transmission electron microscopy, spectrophotometry, thermogravimetry, X-ray diffraction, infrared and fluorescence spectroscopy were used as experimental techniques. LDH-SOD composite was synthesized by enzyme immobilization on the clay particles via electrostatic and hydrophobic interactions, which resulted in a strong adsorption of the SOD on the LDH surface, i.e., no enzyme leakage was observed once the material was suspended in aqueous solutions. However, the LDH-SOD showed only limited resistance against salt-induced aggregation and large irregularly shaped clusters formed during short term interval even at lower ionic strengths. Since sufficiently high colloidal stability is a key requirement in most of the applications mentioned above, the nanocomposite was coated with HEP polyelectrolyte to develop highly stable suspensions of primary LDH-SOD-HEP particles. HEP is a natural anticoagulant with one of the highest negative line charge density among the known macromolecules. The experimental results indicated that it strongly adsorbed on the oppositely charged LDH-SOD surface leading to charge inversion and to the formation of negatively charged LDH-SOD-HEP. The obtained hybrid materials formed stable suspension even under extreme conditions, where classical colloid chemistry theories predict rapid aggregation of the particles and unstable suspensions. Such a stabilization effect originated from electrostatic repulsion between the particles of the same sign of charge as well as from steric repulsion due to the osmotic pressure raised during the overlap of the polyelectrolyte chains adsorbed on the surface. In addition, the SOD enzyme kept its structural and functional integrity during the immobilization and coating processes and hence, the LDH-SOD-HEP bionanocomposite possessed excellent activity in decomposition of superoxide radical anions, as revealed in biochemical test reactions. In conclusion, due to the improved colloidal stability and the good efficiency in scavenging superoxide radical ions, the developed enzymatic system is a promising antioxidant candidate for biomedical or other manufacturing processes, wherever the aim is to decompose reactive oxygen species in suspensions.

Keywords: clay, enzyme, polyelectrolyte, formulation

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Authors: Elodie Niemiec, Philippe Champagne, Jean-Francois Blach, Philippe Moreau, Anthony Thuault, Arnaud Tricoteaux

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Hygiene of equipment in contact with users is an important issue in the railroad industry. The numerous cleanings to eliminate bacteria and dirt cost a lot. Besides, mechanical solicitations on contact parts are observed daily. It should be interesting to elaborate on a self-cleaning and antibacterial coating with sufficient adhesion and good resistance against mechanical and chemical solicitations. Thus, a Hauts-de-France and Maubeuge Val-de-Sambre conurbation authority co-financed Ph.D. thesis has been set up since October 2017 based on anterior studies carried by the Laboratory of Ceramic Materials and Processing. To accomplish this task, a soft chemical route has been implemented to bring a lotus effect on metallic substrates. It involves nanometric liquid zinc oxide synthesis under 100°C. The originality here consists in a variation of surface texturing by modification of the synthesis time of the species in solution. This helps to adjust wettability. Nanostructured zinc oxide has been chosen because of the inherent photocatalytic effect, which can activate organic substance degradation. Two methods of heating have been compared: conventional and microwave assistance. Tested subtracts are made of stainless steel to conform to transport uses. Substrate preparation was the first step of this protocol: a meticulous cleaning of the samples is applied. The main goal of the elaboration protocol is to fix enough zinc-based seeds to make them grow during the next step as desired (nanorod shaped). To improve this adhesion, a silica gel has been formulated and optimized to ensure chemical bonding between substrate and zinc seeds. The last step consists of deposing a wide carbonated organosilane to improve the superhydrophobic property of the coating. The quasi-proportionality between the reaction time and the nanorod length will be demonstrated. Water Contact (superior to 150°) and Roll-off Angle at different steps of the process will be presented. The antibacterial effect has been proved with Escherichia Coli, Staphylococcus Aureus, and Bacillus Subtilis. The mortality rate is found to be four times superior to a non-treated substrate. Photocatalytic experiences were carried out from different dyed solutions in contact with treated samples under UV irradiation. Spectroscopic measurements allow to determinate times of degradation according to the zinc quantity available on the surface. The final coating obtained is, therefore, not a monolayer but rather a set of amorphous/crystalline/amorphous layers that have been characterized by spectroscopic ellipsometry. We will show that the thickness of the nanostructured oxide layer depends essentially on the synthesis time set in the hydrothermal growth step. A green, easy-to-process and control coating with self-cleaning and antibacterial properties has been synthesized with a satisfying surface structuration.

Keywords: antibacterial, biomimetism, soft-chemistry, zinc oxide

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Authors: Sanjay Ranade

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Traditional film theory assumes the cinema audience in a darkened room where cinema is projected on to a white screen, and the audience suspends their sense of reality. Shifts in audiences due to changes in cultural tastes or trends have been studied for decades. In the past two decades, however, the audience, especially the youth, has shifted to digital media for the consumption of cinema. As a result, not only are audiences watching cinema on different devices, they are also consuming cinema in places and ways never imagined before. Public transport often crowded to the brim with a lot of ambient content, and a variety of workplaces have become sites for cinema viewing. Cinema is watched piecemeal and at different times of the day. Audiences use devices such as mobile phones and tablets to watch cinema. The cinema viewing experience is getting redesigned by the user. The emerging design allows the spectator to not only consume images and narratives but also produce, reproduce, and manipulate existing images and narratives, thereby participating in the process and influencing it. Spectatorship studies stress on the importance of subjectivity when dealing with the structure of the film text and the cultural and psychological implications in the engagement between the spectator and the film text. Indian cinema has been booming and contributing to global movie production significantly. In 2005 film production was 1000 films a year and doubled to 2000 by 2016. Digital technology helped push this growth in 2012. Film studies in India have had a decided Euro-American bias. The studies have chiefly analysed the content for ideological leanings or myth or as reflections of society, societal changes, or articulation of identity or presented retrospectives of directors, actors, music directors, etc. The one factor relegated to the background has been the spectator. If they have been addressed, they are treated as a collective of class or gender. India has a performative tradition going back several centuries. How Indians receive cinema is an important aspect to study with respect to film studies. This exploratory and descriptive study looked at 162 young media students studying cinema at the undergraduate and postgraduate levels. The students, speaking as many as 20 languages amongst them, were drawn from across the country’s media schools. The study looked at nine film societies registered with the Federation of Film Societies of India. A structured questionnaire was made and distributed online through media teachers for the students. The film societies were approached through the regional office of the FFSI in Mumbai. Lastly, group discussions were held in Mumbai with students and teachers of media. A group consisted of between five and twelve student participants, along with one or two teachers. All the respondents looked at themselves as spectators and shared their experiences of spectators of cinema, providing a very rich insight into Indian conditions of viewing cinema and challenges for cinema ahead.

Keywords: audience, digital, film studies, reception, reception spectatorship

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Authors: Cinthia G. P. Calou, Franz J. Antezana, Ana I. O. Nicolau, Eveliny S. Martins, Paula R. A. L. Soares, Glauberto S. Quirino, Dayanne R. Oliveira, Priscila S. Aquino, Régia C. M. B. Castro, Ana K. B. Pinheiro

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Introduction: As an integral part of the health-disease process, gestation is a period in which the social insertion of women can influence, in a positive or negative way, the course of the pregnancy-puerperal cycle. Thus, evaluating the quality of life of this population can redirect the implementation of innovative practices in the quest to make them more effective and real for the promotion of a more humanized care. This study explores the associations between the obstetric factors with affected areas of health-related quality of life of pregnant women with habitual risk. Methods: This is a cross-sectional, quantitative study conducted in three public facilities and a private service that provides prenatal care in the city of Fortaleza, Ceara, Brazil. The sample consisted of 261 pregnant women who underwent low-risk prenatal care and were interviewed from September to November 2014. The collection instruments were a questionnaire containing socio-demographic and obstetric variables, in addition to the Brazilian version of the Mother scale Generated Index (MGI) characterized by being a specific and objective instrument, consisting of a single sheet and subdivided into three stages. It allows identifying the areas of life of the pregnant woman that are most affected, which could go unnoticed by the pre-formulated measurement instruments. The obstetric data, as well as the data concerning the application of the MGI scale, were compiled and analyzed through the statistical program Statistical Package for the Social Sciences (SPSS), version 20.0. After the compilation, a descriptive analysis was carried out. Then, associations were made between some variables. The tests applied were the Pearson Chi-Square and the Fisher's exact test. The odds ratio was also calculated. These associations were considered statistically significant when the p (probability) value was less than or equal to a level of 5% (α = 0.05) in the tests performed. Results: The variables that negatively reflected the quality of life of the pregnant women and presented a significant association with the polaciuria were: gestational age (p = 0.022) and parity (p = 0.048). Episodes of nausea and vomiting also showed significant with gestational age correlation (p = 0.0001). Evaluating the crossing of stress, we observed a significant association with parity (p = 0.0001). In turn, emotional lability revealed dependence on the variable type of delivery (p = 0.009). Conclusion: The health professionals involved in the assistance to the pregnant woman can understand how the process of gestation is experienced, considering all its peculiar transformations; to meet their individual needs, stimulating their autonomy and their power of choice, envisaging the achievement of a better quality of life related to health in the perspective of health promotion.

Keywords: health-related quality of life, obstetric nursing, pregnant women, prenatal care

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Authors: Bernard Morais Joosa

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Kerala, the southern state of India, is known for its accomplishments in universal education and enrollments. Through this mission, the Government proposes comprehensive educational reforms including 1000 Government schools into international standards during the first phase. The idea is not only to improve the infrastructural facilities but also to reform the teaching and learning process to the present day needs by introducing ICT enabled learning and providing smart classrooms. There will be focus on creating educational programmes which are useful for differently abled students. It is also meant to reinforce the teaching–learning process by providing ample opportunities to each student to construct their own knowledge using modern technology tools. The mission will redefine the existing classroom learning process, coordinate resource mobilization efforts and develop ‘Janakeeya Vidyabhyasa Mathruka.' Special packages to support schools which are in existence for over 100 years will also be attempted. The implementation will enlist full involvement and partnership of the Parent Teacher Association. Kerala was the first state in the country to attain 100 percent literacy more than two and a half decades ago. Since then the State has not rested on its laurels. It has moved forward in leaps and bounds conquering targets that no other State could achieve. Now the government of Kerala is taking off towards new goal of comprehensive educational reforms. And it focuses on Betterment of educational surroundings, use of technology in education, renewal of learning method and 1000 schools will be uplifted as Smart Schools. Need to upgrade 1000 schools into international standards and turning classrooms from standard 9 to 12 in high schools and higher secondary into high-tech classrooms and a special unique package for the renovation of schools, which have completed 50 and 100 years. The government intends to focus on developing standards first to eighth standards in tune with the times by engaging the teachers, parents, and alumni to recapture the relevance of public schools. English learning will be encouraged in schools. The idea is not only to improve the infrastructure facilities but also reform the curriculum to the present day needs. Keeping in view the differently-abled friendly approach of the government, there will be focus on creating educational program which is useful for differently abled students. The idea is to address the infrastructural deficiencies being faced by such schools. There will be special emphasis on ensuring internet connectivity to promote IT-friendly existence. A task-force and a full-time chief executive will be in charge of managing the day to day affairs of the mission. Secretary of the Public Education Department will serve as the Mission Secretary and the Chairperson of Task Force. As the Task Force will stress on teacher training and the use of information technology, experts in the field, as well as Directors of SCERT, IT School, SSA, and RMSA, will also be a part of it.

Keywords: educational standards, methodology, pedagogy, technology

Procedia PDF Downloads 117

Authors: Wanvipa Thongborisute, Punyaphat Sirithanabadeekul, Pichit Suvanprakorn, Anan Jiraviroon

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Background: Acne vulgaris is one of the most common dermatologic problems, and can have a significant psychological and physical effect on patients. Propionibacterium acnes' roles in acne vulgaris involve the activation of toll-like receptor 4 (TLR4), and toll-like receptor 2 (TLR2) pathways. By activating these pathways, inflammatory events of acne lesions, comedogenesis and sebaceous lipogenesis can occur. Currently, there are several topical agents commonly use in treating acne vulgaris that are known to have an effect on TLRs, such as retinoic acid and adapalene, but these drugs still have some irritating effects. At present, there is an alarming increase in rate of bacterial resistance due to irrational used of antibiotics both orally and topically. For this reason, acne treatments should contain bioactive molecules targeting at the site of action for the most effective therapeutic effect with the least side effects. Sparganium stoloniferumis a Chinese aquatic herb containing a compound called Sparstolonin B (SsnB), which has been reported to selectively blocks Toll-like receptor 2 (TLR2) and Toll-like receptor 4 (TLR4)-mediated inflammatory signals. Therefore, this topical TLR2 and TLR4 antagonist, in a form of Sparganium stoloniferum-derived compound containing SsnB, should give a benefit in reducing inflammation of acne vulgaris lesions and providing an alternative treatments for patients with this condition. Materials and Methods: The objectives of this randomized double blinded split faced placebo controlled trial is to study the safety and efficacy of the Sparganium stoloniferum-derived compound. 32 volunteered patients with mild to moderate degree of acne vulgaris according to global acne grading system were included in the study. After being informed and consented the subjects were given 2 topical treatments for acne vulgaris, one being topical 2.40% Sparganium stoloniferum extraction (containing Sparstolonin B) and the other, placebo. The subjects were asked to apply each treatment to either half of the face daily morning and night by randomization for 8 weeks, and come in for a weekly follow up. For each visit, the patients went through a procedure of lesion counting, including comedones, papules, nodules, pustules, and cystic lesions. Results: During 8 weeks of experimentation, the result shows a reduction in total lesions number between the placebo and the treatment side show statistical significance starting at week 4, where the 95% confidence interval begin to no longer overlap, and shows a trend of continuing to be further apart. The decrease in the amount of total lesions between week 0 and week 8 of the placebo side shows no statistical significant at P value >0.05. While the decrease in the amount of total lesions of acne vulgaris of the treatment side comparing between week 0 and week 8 shows statistical significant at P value <0.001. Conclusion: The data demonstrates that 2.40% Sparganium stoloniferum extraction (containing Sparstolonin B) is more effective in treating acne vulgaris comparing to topical placebo in treating acne vulgaris, by showing significant reduction in the total numbers of acne lesions. Therefore, this topical Sparganium stoloniferum extraction could become a potential alternative treatment for acne vulgaris.

Keywords: acne vulgaris, sparganium stoloniferum, sparstolonin B, toll-like receptor 2, toll-like receptor 4

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Authors: Hamed Movahedi, Nicolas Bovet, Henning Friis Poulsen

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Following the advent of the Industrial Revolution, there has been a significant increase in the extraction and utilization of hydrocarbon and fossil fuel resources. However, a new era has emerged, characterized by a shift towards sustainable practices, namely the reduction of carbon emissions and the promotion of renewable energy generation. Given the substantial number of mature oil and gas wells that have been developed inside the petroleum reservoir domain, it is imperative to establish an environmental strategy and adopt appropriate measures to effectively seal and decommission these wells. In general, the cement plug serves as a material for plugging purposes. Nevertheless, there exist some scenarios in which the durability of such a plug is compromised, leading to the potential escape of hydrocarbons via fissures and fractures within cement plugs. Furthermore, cement is often not considered a practical solution for temporary plugging, particularly in the case of well sites that have the potential for future gas storage or CO2 injection. The Danish oil and gas industry has promising potential as a prospective candidate for future carbon dioxide (CO2) injection, hence contributing to the implementation of carbon capture strategies within Europe. The primary reservoir component consists of chalk, a rock characterized by limited permeability. This work focuses on the development and characterization of a novel hydrogel variant. The hydrogel is designed to be injected via a low-permeability reservoir and afterward undergoes a transformation into a high-viscosity gel. The primary objective of this research is to explore the potential of this hydrogel as a new solution for effectively plugging well flow. Initially, the synthesis of polyacrylamide was carried out using radical polymerization inside the confines of the reaction flask. Subsequently, with the application of the Hoffman rearrangement, the polymer chain undergoes partial amination, facilitating its subsequent reaction with the crosslinker and enabling the formation of a hydrogel in the subsequent stage. The organic crosslinker, glutaraldehyde, was employed in the experiment to facilitate the formation of a gel. This gel formation occurred when the polymeric solution was subjected to heat within a specified range of reservoir temperatures. Additionally, a rheological survey and gel time measurements were conducted on several polymeric solutions to determine the optimal concentration. The findings indicate that the gel duration is contingent upon the starting concentration and exhibits a range of 4 to 20 hours, hence allowing for manipulation to accommodate diverse injection strategies. Moreover, the findings indicate that the gel may be generated in environments characterized by acidity and high salinity. This property ensures the suitability of this substance for application in challenging reservoir conditions. The rheological investigation indicates that the polymeric solution exhibits the characteristics of a Herschel-Bulkley fluid with somewhat elevated yield stress prior to solidification.

Keywords: polyacrylamide, hofmann rearrangement, rheology, gel time

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Authors: Esther Friedlander, Philip Friedlander

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The use of immunotherapy that inhibits programmed death-1 (PD-1) or its ligand PD-L1 confers survival benefits in patients with non-small cell lung cancer (NSCLC). However, approximately 45% of patients experience primary treatment resistance, necessitating the development of strategies to improve efficacy. While the renin-angiotensin system (RAS) has systemic hemodynamic effects, tissue-specific regulation exists along with modulation of immune activity in part through regulation of myeloid cell activity, leading to the hypothesis that RAS inhibition may improve anti-PD-1/L-1 efficacy. A retrospective analysis was conducted that included 173 advanced solid tumor cancer patients treated at Valley Hospital, a community Hospital in New Jersey, USA, who were treated with a PD-1/L-1 inhibitor in a defined time period showing a statistically significant relationship between RAS pathway inhibition (RASi through concomitant treatment with an ACE inhibitor or angiotensin receptor blocker) and positive efficacy to the immunotherapy that was independent of age, gender and cancer type. Subset analysis revealed strong numerical benefit for efficacy in both patients with squamous and nonsquamous NSCLC as determined by documented clinician assessment of efficacy and by duration of therapy. A PUBMED literature search was now conducted to identify studies assessing the effect of RAS pathway inhibition on anti-PD-1/L1 efficacy in advanced solid tumor patients and compare these findings to those seen in the Valley Hospital retrospective study with a focus on NSCLC specifically. A total of 11 articles were identified assessing the effects of RAS pathway inhibition on the efficacy of checkpoint inhibitor immunotherapy in advanced cancer patients. Of the 11 studies, 10 assessed the effect on survival of RASi in the context of treatment with anti-PD-1/PD-L1, while one assessed the effect on CTLA-4 inhibition. Eight of the studies included patients with NSCLC, while the remaining 2 were specific to genitourinary malignancies. Of the 8 studies, two were specific to NSCLC patients, with the remaining 6 studies including a range of cancer types, of which NSCLC was one. Of these 6 studies, only 2 reported specific survival data for the NSCLC subpopulation. Patient characteristics, multivariate analysis data and efficacy data seen in the 2 NSLCLC specific studies and in the 2 basket studies, which provided data on the NSCLC subpopulation, were compared to that seen in the Valley Hospital retrospective study supporting a broader effect of RASi on anti-PD-1/L1 efficacy in advanced NSLCLC with the majority of studies showing statistically significant benefit or strong statistical trends but with one study demonstrating worsened outcomes. This comparison of studies extends published findings to the community hospital setting and supports prospective assessment through randomized clinical trials of efficacy in NSCLC patients with pharmacodynamic components to determine the effect on immune cell activity in tumors and on the composition of the tumor microenvironment.

Keywords: immunotherapy, cancer, angiotensin, efficacy, PD-1, lung cancer, NSCLC

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Authors: Marina Sofia, Alexios Giannakopoulos, Antonia Touloudi, Dimitris C Chatzopoulos, Zoi Athanasakopoulou, Vassiliki Spyrou, Charalambos Billinis

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Fertility of dairy cattle can be affected by heat stress when the ambient temperature increases above 30°C and the relative humidity ranges from 35% to 50%. The present study was conducted on dairy cattle farms during summer months in Greece and aimed to identify the serological profile against pathogens that could affect fertility and to associate the positive serological results at herd level with temperature factors. A total of 323 serum samples were collected from clinically healthy dairy cows of 8 herds, located in Central and Northern Greece. ELISA tests were performed to detect antibodies against selected pathogens that affect fertility, namely Chlamydophila abortus, Coxiella burnetii, Neospora caninum, Toxoplasma gondii and Infectious Bovine Rhinotracheitis Virus (IBRV). Eleven climatic variables were derived from the WorldClim version 1.4. and ArcGIS V.10.1 software was used for analysis of the spatial information. Five different MaxEnt models were applied to associate the temperature variables with the locations of seropositive Chl. abortus, C. burnetii, N. caninum, T. gondii and IBRV herds (one for each pathogen). The logistic outputs were used for the interpretation of the results. ROC analyses were performed to evaluate the goodness of fit of the models’ predictions. Jackknife tests were used to identify the variables with a substantial contribution to each model. The seropositivity rates of pathogens varied among the 8 herds (0.85-4.76% for Chl. abortus, 4.76-62.71% for N. caninum, 3.8-43.47% for C. burnetii, 4.76-39.28% for T. gondii and 47.83-78.57% for IBRV). The variables of annual temperature range, mean diurnal range and maximum temperature of the warmest month gave a contribution to all five models. The regularized training gains, the training AUCs and the unregularized training gains were estimated. The mean diurnal range gave the highest gain when used in isolation and decreased the gain the most when it was omitted in the two models for seropositive Chl.abortus and IBRV herds. The annual temperature range increased the gain when used alone and decreased the gain the most when it was omitted in the models for seropositive C. burnetii, N. caninum and T. gondii herds. In conclusion, antibodies against Chl. abortus, C. burnetii, N. caninum, T. gondii and IBRV were detected in most herds suggesting circulation of pathogens that could cause infertility. The results of the spatial analyses demonstrated that the annual temperature range, mean diurnal range and maximum temperature of the warmest month could affect positively the possible pathogens’ presence. Acknowledgment: This research has been co‐financed by the European Regional Development Fund of the European Union and Greek national funds through the Operational Program Competitiveness, Entrepreneurship and Innovation, under the call RESEARCH–CREATE–INNOVATE (project code: T1EDK-01078).

Keywords: dairy cows, seropositivity, spatial analysis, temperature factors

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Authors: Steven Sam, Ximena Schmidt, Hugh Dickinson, Jens Jensen

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The goal of this study is to explore the potential of data science and citizen science approaches to develop an interactive, digital, open infrastructure that pulls together African indigenous agriculture and food systems data from multiple sources, making it accessible and reusable for policy, research and practice in modern food production efforts. The World Bank has recognised that African Indigenous Knowledge (AIK) is innovative and unique among local and subsistent smallholder farmers, and it is central to sustainable food production and enhancing biodiversity and natural resources in many poor, rural societies. AIK refers to tacit knowledge held in different languages, cultures and skills passed down from generation to generation by word of mouth. AIK is a key driver of food production, preservation, and consumption for more than 80% of citizens in Africa, and can therefore assist modern efforts of reducing food insecurity and hunger. However, the documentation and dissemination of AIK remain a big challenge confronting librarians and other information professionals in Africa, and there is a risk of losing AIK owing to urban migration, modernisation, land grabbing, and the emergence of relatively small-scale commercial farming businesses. There is also a clear disconnect between the AIK and scientific knowledge and modern efforts for sustainable food production. The study combines data science and citizen science approaches through active community participation to generate and share AIK for facilitating learning and promoting knowledge that is relevant for policy intervention and sustainable food production through a curated digital platform based on FAIR principles. The study adopts key informant interviews along with participatory photo and video elicitation approach, where farmers are given digital devices (mobile phones) to record and document their every practice involving agriculture, food production, processing, and consumption by traditional means. Data collected are analysed using the UK Science and Technology Facilities Council’s proven methodology of citizen science (Zooniverse) and data science. Outcomes are presented in participatory stakeholder workshops, where the researchers outline plans for creating the platform and developing the knowledge sharing standard framework and copyrights agreement. Overall, the study shows that learning from AIK, by investigating what local communities know and have, can improve understanding of food production and consumption, in particular in times of stress or shocks affecting the food systems and communities. Thus, the platform can be useful for local populations, research, and policy-makers, and it could lead to transformative innovation in the food system, creating a fundamental shift in the way the North supports sustainable, modern food production efforts in Africa.

Keywords: Africa indigenous agriculture knowledge, citizen science, data science, sustainable food production, traditional food system

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Authors: Evgeniya V. Gavrilova, Sofya S. Belova

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The present study was aimed at clarifying the relationship between general intellectual abilities and efficiency in free recall and rhymed words generation task after incidental exposure to linguistic stimuli. The theoretical frameworks stress that general intellectual abilities are based on intentional mental strategies. In this context, it seems to be crucial to examine the efficiency of incidentally presented information processing in cognitive task and its relation to general intellectual abilities. The sample consisted of 32 Russian students. Participants were exposed to pairs of words. Each pair consisted of two common nouns or two city names. Participants had to decide whether a city name was presented in each pair. Thus words’ semantics was processed intentionally. The city names were considered to be focal stimuli, whereas common nouns were considered to be peripheral stimuli. Along with that each pair of words could be rhymed or not be rhymed, but this phonemic aspect of stimuli’s characteristic (rhymed and non-rhymed words) was processed incidentally. Then participants were asked to produce as many rhymes as they could to new words. The stimuli presented earlier could be used as well. After that, participants had to retrieve all words presented earlier. In the end, verbal and non-verbal abilities were measured with number of special psychometric tests. As for free recall task intentionally processed focal stimuli had an advantage in recall compared to peripheral stimuli. In addition all the rhymed stimuli were recalled more effectively than non-rhymed ones. The inverse effect was found in words generation task where participants tended to use mainly peripheral stimuli compared to focal ones. Furthermore peripheral rhymed stimuli were most popular target category of stimuli that was used in this task. Thus the information that was processed incidentally had a supplemental influence on efficiency of stimuli processing as well in free recall as in word generation task. Different patterns of correlations between intellectual abilities and efficiency in different stimuli processing in both tasks were revealed. Non-verbal reasoning ability correlated positively with free recall of peripheral rhymed stimuli, but it was not related to performance on rhymed words’ generation task. Verbal reasoning ability correlated positively with free recall of focal stimuli. As for rhymed words generation task, verbal intelligence correlated negatively with generation of focal stimuli and correlated positively with generation of all peripheral stimuli. The present findings lead to two key conclusions. First, incidentally processed stimuli had an advantage in free recall and word generation task. Thus incidental information processing appeared to be crucial for subsequent cognitive performance. Secondly, it was demonstrated that incidentally processed stimuli were recalled more frequently by participants with high nonverbal reasoning ability and were more effectively used by participants with high verbal reasoning ability in subsequent cognitive tasks. That implies that general intellectual abilities could benefit from operating by different levels of information processing while cognitive problem solving. This research was supported by the “Grant of President of RF for young PhD scientists” (contract № is 14.Z56.17.2980- MK) and the Grant № 15-36-01348a2 of Russian Foundation for Humanities.

Keywords: focal and peripheral stimuli, general intellectual abilities, incidental information processing

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Authors: Shahriyar Keshtgar, Mahmoud Reza Heyhat, Sasan Bagheri, Ebrahim Gholami, Seyed Naser Raiisosadat

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The eastern Iranian range is a Z-shaped sigmoidal outcrop appearing with a NS-trending general strike on the satellite images, has already been known as the Sistan suture zone, recently identified as the product of an orogenic event introduced either by the Paleogene or Sistan orogen names. The flysch sedimentary basin of eastern Iran was filled by a huge volume of fine-grained Eocene turbiditic sediments, smaller amounts of pelagic deposits and Cretaceous ophiolitic slices, which are entirely remnants of older accretionary prisms appeared in a fold-thrust belt developed onto a subduction zone under the Lut/Afghan block, portions of the Cimmerian superterrane. In these ranges, there are Triassic sedimentary and carbonate sequences (equivalent to Nayband and Shotori Formations) along with scattered outcrops of Permian limestones (equivalent to Jamal limestone) and greenschist-facies metamorphic rocks, probably belonging to the basement of the Lut block, which have tectonic contacts with younger rocks. Moreover, the younger Eocene detrital-volcanic rocks were also thrusted onto the Cretaceous or younger turbiditic deposits. The first generation folds (parallel folds) and thrusts with slaty cleavage appeared parallel to the NE edge of the Lut block. Structural analysis shows that the most vergence of thrusts is toward the southeast so that the Permo-Triassic units in Lut have been thrusted on the younger rocks, including older (probably Jurassic) granites. Additional structural studies show that the regional transport direction in this deformation event is from northwest to the southeast where, from the outside to the inside of the orogen in the Sechengi area. Younger thrusts of the second deformation event were either directly formed as a result of the second deformation event, or they were older thrusts that reactivated and folded so that often, two sets or more slickenlines can be recognized on the thrust planes. The recent thrusts have been redistributed in directions nearly perpendicular to the edge of the Lut block and parallel to the axial surfaces of the northwest second generation large-scale folds (radial folds). Some of these younger thrusts follow the out-of-the-syncline thrust system. The both axial planes of these folds and associated penetrative shear cleavage extended towards northwest appeared with both northeast and southwest dips parallel to the younger thrusts. The large-scale buckling with the layer-parallel stress field has created this deformation event. Such consecutive deformation events perpendicular to each other cannot be basically explained by the simple linear orogen models presented for eastern Iran so far and are more consistent with the oroclinal buckling model.

Keywords: thrust, tectonic vergence, orocline buckling, sechangi, eastern iranian ranges

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Authors: Maya de Vries Kedem, Abir Jubran, Diana Baron

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Employment in Israel offers Palestinian workers an income double what they can earn in the West Bank. The need to support their families leads many educated Palestinians to forgo finding work in their profession in the Palestinian Authority and instead look for employment in those sectors open to them in Israel, particularly the construction, agriculture, and industry sectors. The International Labor Organization estimated that about 1,200 workers in Israel die every year because of occupational diseases (diseases caused by working conditions). Construction workers in Israel are constantly exposed to dust, noise, chemical materials, and work in awkward postures, which require prolonged bending, repetitive motion, and other risk factors that can lead to illnesses and death. Occupational health is vastly neglected in Israel and construction workers are particularly at risk . As of June 2022, the Israeli quota in the construction sector for Palestinian workers stood at 80,000. Kav LaOved released a new study on the state of occupational health among Palestinian workers employed in construction in Israel. The study Roadmap to Health: Palestinian Workers in Israel's Construction Sector reviews the extent to which the health of Palestinian workers is protected at work in Israel. The report includes analysis of a survey administered to 256 workers as well as interviews with 10 workers and with 5 Israeli occupational health experts. Report highlights: • Among survey respondents, 63.9% stated that safety procedures to protect their health are rarely followed in their workplace (e.g., taking breaks, using protective gear, following restrictions on lifting heavy items, and having inspectors regularly on site to monitor safety). • All 256 Palestinian workers who participated to the survey said that their health has been directly or indirectly harmed by working in Israel and reported suffering from the following problems: orthopedic problems such as joint, hand, leg or knee problems (100%); headaches (75%); back problems (36.3%); eye problems (23.8%); breathing problems (17.6%); chronic pain (14.8%); heart problems (7.8%); and skin problems (3.5%). • Workers who are injured or do not feel well often continue working for fear of losing their payment for that day. About half of the 256 survey respondents reported that they pay brokerage fees to find an employer with a work permit, often paying between 2,000 and 3,000 NIS per month. “I have an obligation—I pay about NIS 120 a day for my permit, [and] I have to pay for it whether I work or not" a worker said. • Most Palestinian construction workers suffer from stress and mental health problems. Workers pointed to several issues that greatly affect their mood and mental state: daily crossings at crowded checkpoints where workers stand for hours; lack of sleep due to leaving home daily at 3:00-3:30 am; commuting two to four hours to work in each direction; and abusive work environments. A worker told KLO that the sight of thousands of workers standing together at the checkpoint causes “high blood pressure and the feeling that you are going to be squeezed.” Another said, “I felt that my bones would break.” In the survey workers reported suffering from insomnia (70.1%), breathing difficulties (35.8%), chest pressure (27.6%), or rapid pulse rate (12.2%).

Keywords: construction sector, palestinian workers, occupational health, Israel, occupation

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Authors: Jenny Fairthorne, Yuka Mori, Helen Leonard

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Background: Primary care-givers of children with autism spectrum disorder (ASD) or intellectual disability (ID) have poorer health and quality of life (QoL) than primary care-givers (hereafter referred to as just care-givers) of typically developing children. We aimed to review original research which described factors impacting the health of care-givers of children with ASD or ID and to discuss how these factors might influence care-giver health. Methods: We searched Web of Knowledge, Medline, Scopus and Google Scholar using selections of words from each of three groups. The first comprised terms associated with ASD and ID and included autism, pervasive development disorder, intellectual disability, mental retardation, disability, disabled, Down and Asperger. The second included terms related to health such as depression, physical, mental, psychiatric, psychological and well-being. The third was terms related to care-givers such as mother, parent and care-giver. We included an original paper in our review if it was published between 1st January 1990 and 31st December, 2016, described original research in a peer-reviewed journal and was written in English. Additional criteria were that the research used a study population of 15 persons or more; described a risk or protective factor for the health of care-givers of a child with ASD, ID or a sub-type (such as ASD with ID or Down syndrome). Using previous research, we developed a simple and objective five-level tool to assess the strength of evidence provided by the reviewed papers. Results: We retained 33 papers. Factors impacting primary care-giver health included child behaviour, level of support, socio-economic status (SES) and diagnostic issues. Challenging child behaviour, the most commonly identified risk factor for poorer care-giver health and QoL was reported in ten of the studies. A higher level of support was associated with improved care-giver health and QoL. For example, substantial evidence indicated that family support reduced care-giver burden in families with a child with ASD and that family and neighbourhood support was associated with improved care-giver mental health. Higher socio-economic status (SES) was a protective factor for care-giver health and particularly maternal health. Diagnostic uncertainty and an unclear prognosis are factors which can cause the greatest concern to care-givers of children with ASD and those for whom a cause of their child’s ID has not been identified. We explain how each of these factors might impact caregiver health and how they might act differentially in care-givers of children with different types of ASD or ID (such as Down syndrome and ASD without ID). Conclusion: Care-givers of children with ASD may be more likely to experience many risk factors and less likely to experience the protective factors we identified for poorer mental health. Interventions to reduce risk factors and increase protective factors could pave the way for improved care-giver health. For example, workshops to train care-givers to better manage challenging child behaviours and earlier diagnosis of ASD (and particularly ASD without ID) would seem likely to improve care-giver well-being. Similarly, helping to expand support networks might reduce care-giver burden and stress leading to improved health.

Keywords: autism, caregivers, health, intellectual disability, mothers, review

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Authors: Basavaraj Yenagi, P. Nagaraju, C. R. Patil

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Groundnut (Arachis hypohaea L.) is called as “King of oilseeds” and one of the most important food and cash crops in Indian subcontinent. Yield and quality of oil are negatively correlated with poor or imbalanced nutrition and constant exposure to both biotic and abiotic stress factors. Variety of diseases affect groundnut plant, most of them are caused by fungi and lead to severe yield loss. Imbalanced nutrition increases the concerns of environmental deterioration which includes soil fertility. Among different microbial antagonists, Pseudomonas is common member of the plant growth promoting rhizobacteria microflora present in the rhizosphere of groundnut. These are known to produce a beneficial effect on groundnut due to their high metabolic activity leading to the production of enzymes, exopolysaccharides, secondary metabolites, and antibiotics. The ability of pseudomonas lies on their ability to produce antibiotic metabolites such as 2, 4-diacetylphloroglucinol (DAPG). DAPG can inhibit the growth of fungal pathogens namely collar rot and stem rot and also increase the availability of plant nutrients through increased solubilization and uptake of nutrients. Hence, the present study was conducted for three consecutive years (2014 to 2016) in vertisol during the rainy season to assess the efficacy of DAPG producing fluorescent pseudomonas for enhancing nutrient use efficacy, bio-control of soil-borne diseases and yield of groundnut at University of Agricultural Sciences, Dharwad farm. The experiment was laid out in an RCBD with three replications and seven treatments. The mean of three years data revealed that the effect of DAPG-producing producing fluorescent pseudomonas enhanced groundnut yield, uptake of nitrogen and phosphorus and nutrient use efficiency and also found to be effective in bio-control of collar rot and stem rot incidence leading to increase pod yield of groundnut. Higher dry pod yield of groundnut was obtained with DAPG 2(3535 kg ha-1) closely followed by DAPG 4(3492 kg ha-1), FP 98(3443 kg ha-1), DAPG 1(3414 kg ha-1), FP 86(3361 kg ha-1) and Trichoderma spp. (3380 kg ha-1) over control(3173 kg ha-1). A similar trend was obtained with other growth and yield attributing parameters. N uptake ranged from 8.21 percent to FP 86 to 17.91 percent with DAPG 2 and P uptake ranged between 5.56 percent with FP 86 to 16.67 percent with DAPG 2 over control. The first year, there was no incidence of collar rot. During the second year, the control plot recorded 2.51 percent incidence and it ranged from 0.82 percent to 1.43 percent in different DAPG-producing fluorescent pseudomonas treatments. The similar trend was noticed in the third year with lower incidence. The stem rot incidence was recorded during all the three years. Mean data indicated that the control plot recorded 2.65 percent incidence and it ranged from 0.71 percent to 1.23 percent in different DAPG-producing fluorescent pseudomonas treatments. The increase in net monetary benefits ranged from Rs.5975 ha-1 to Rs.11407 ha 1 in different treatments. Hence, as a low-cost technology, seed treatment with available DAPG-producing fluorescent pseudomonas has a beneficial effect on groundnut for enhancing groundnut yield, nutrient use efficiency and bio-control of soil-borne diseases.

Keywords: groundnut, DAPG, fluorescent pseudomonas, nutrient use efficiency, collar rot, stem rot

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Authors: Corentin Jankowiak, Aggelos Zacharopoulos, Caterina Brandoni

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In a context of increasing stress put on the electricity network by the decarbonization of many sectors, energy storage is likely to be the key mitigating element, by acting as a buffer between production and demand. In particular, the highest potential for storage is when connected closer to the loads. Yet, low voltage storage struggles to penetrate the market at a large scale due to the novelty and complexity of the solution, and the competitive advantage of fossil fuel-based technologies regarding regulations. Strong and reliable numerical simulations are required to show the benefits of storage located near loads and promote its development. The present study was restrained from excluding aggregated control of storage: it is assumed that the storage units operate independently to one another without exchanging information – as is currently mostly the case. A computationally light battery model is presented in detail and validated by direct comparison with a domestic battery operating in real conditions. This model is then used to develop Peak-Shaving (PS) control strategies as it is the decentralized service from which beneficial impacts are most likely to emerge. The aggregation of flatter, peak- shaved consumption profiles is likely to lead to flatter and arbitraged profile at higher voltage layers. Furthermore, voltage fluctuations can be expected to decrease if spikes of individual consumption are reduced. The crucial part to achieve PS lies in the charging pattern: peaks depend on the switching on and off of appliances in the dwelling by the occupants and are therefore impossible to predict accurately. A performant PS strategy must, therefore, include a smart charge recovery algorithm that can ensure enough energy is present in the battery in case it is needed without generating new peaks by charging the unit. Three categories of PS algorithms are introduced in detail. First, using a constant threshold or power rate for charge recovery, followed by algorithms using the State Of Charge (SOC) as a decision variable. Finally, using a load forecast – of which the impact of the accuracy is discussed – to generate PS. A performance metrics was defined in order to quantitatively evaluate their operating regarding peak reduction, total energy consumption, and self-consumption of domestic photovoltaic generation. The algorithms were tested on load profiles with a 1-minute granularity over a 1-year period, and their performance was assessed regarding these metrics. The results show that constant charging threshold or power are far from optimal: a certain value is not likely to fit the variability of a residential profile. As could be expected, forecast-based algorithms show the highest performance. However, these depend on the accuracy of the forecast. On the other hand, SOC based algorithms also present satisfying performance, making them a strong alternative when the reliable forecast is not available.

Keywords: decentralised control, domestic integrated batteries, electricity network performance, peak-shaving algorithm

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Authors: Evija Silina, Maris Taube, Maksims Zolovs

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Background: Type 1 diabetes mellitus (T1D) is the most common chronic endocrine pathology in children. The management of type 1 diabetes requires a strong diet, physical activity, lifelong insulin therapy, and proper self-monitoring of blood glucose and is usually complicated and, therefore, may result in a variety of psychosocial problems for children, adolescents, and their families. Metabolic control of the disease is determined by glycated haemoglobin (HbA1c), the main criterion for diabetes compensation. A correlation was observed between anxiety and depression levels and glycaemic control in many previous studies. It is assumed that anxiety and depression symptoms negatively affect glycaemic control. Parental psychological distress was associated with higher child self-report of stress and depressive symptoms, and it had negative effects on diabetes management. Objective: The main objective of this paper is to evaluate the relationship between parental mental health conditions (depression and anxiety) and metabolic control of their adolescents with T1DM. Methods: This cross-sectional study recruited adolescents with T1D (N=251) and their parents (N=251). The respondents completed questionnaires. The 7-item Generalized Anxiety Disorder (GAD-7) scale measured anxiety level; The Patient Health Questionnaire – 9 (PHQ-9) measured depressive symptoms. Glycaemic control of patients was assessed using the last glycated haemoglobin (HbA1c) values. GLM mediation analysis was performed to determine the potential mediating effect of the parent’s mental health conditions (depression and anxiety) on the relationship between the mental health conditions (depression and anxiety) of a child on the level of glycated hemoglobin (HbA1c). To test the significance of the mediated effect (ME) for non-normally distributed data, bootstrapping procedures (10,000 bootstrapped samples) were used. Results: 502 respondents were eligible for screening to detect anxiety and depression symptoms. Mediation analysis was performed to assess the mediating role of parent GAD-7 on the linkage between a dependent variable (HbA1c) and independent variables (child GAD-7 un child PHQ-9). The results revealed that the total effect of child GAD-7 (B = 0.479, z = 4.30, p < 0.001) on HbA1c was significant but the total effect of child PHQ-9 (B = 0.166, z = 1.49, p = 0.135) was not significant. With the inclusion of the mediating variable (parent GAD-7), the impact of child GAD-7 on HbA1c was found insignificant (B = 0.113, z=0.98, p = 0.326), the impact of child PHQ-9 on HbA1c was found also insignificant (B = 0.068, z=0.74, p = 0.458). The indirect effect of child GAD-7 on HbA1c through parent GAD-7 was found significant (B = 0.366, z = 4.31, p < 0.001) and the indirect effect of child PHQ-9 on HbA1c through parent GAD-7 was found also significant (B = 0.098, z = 2.56, p = 0.010). This indicates that the relationship between a dependent variable (HbA1c) and independent variables (child GAD-7 un child PHQ-9) is fully mediated by parent GAD-7. Conclusion: The main result suggests that glycated haemoglobin in adolescents with Type 1 diabetes is related to adolescents’ mental health via parents’ anxiety. It means that parents’ anxiety plays a more significant role in the level of glycated haemoglobin in adolescents than depression and anxiety in the adolescent.

Keywords: type 1 diabetes, adolescents, parental diabetes-specific mental health conditions, glycated haemoglobin, anxiety, depression

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Authors: Emma J. Dale, Christina D. Buesching, Kevin R. Theis, David W. Macdonald

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This study investigates the oral and intestinal microbiomes of wild-living European badgers (Meles meles) and will relate inter-individual differences to social contact networks, somatic and reproductive fitness, varying susceptibility to bovine tuberculous (bTB) and to the olfactory advertisement. Badgers are an interesting model for this research, as they have great variation in body condition, despite living in complex social networks and having access to the same resources. This variation in somatic fitness, in turn, affects breeding success, particularly in females. We postulate that microbiota have a central role to play in determining the successfulness of an individual. Our preliminary results, characterising the microbiota of individual badgers, indicate unique compositions of microbiota communities within social groups of badgers. This basal information will inform further questions related to the extent microbiota influence fitness. Hitherto, the potential role of microbiota has not been considered in determining host condition, but also other key fitness variables, namely; communication and resistance to disease. Badgers deposit their faeces in communal latrines, which play an important role in olfactory communication. Odour profiles of anal and subcaudal gland secretions are highly individual-specific and encode information about group-membership and fitness-relevant parameters, and their chemical composition is strongly dependent on symbiotic microbiota. As badgers sniff/ lick (using their Vomeronasal organ) and over-mark faecal deposits of conspecifics, these microbial communities can be expected to vary with social contact networks. However, this is particularly important in the context of bTB, where badgers are assumed to transmit bTB to cattle as well as conspecifics. Interestingly, we have found that some individuals are more susceptible to bTB than are others. As acquired immunity and thus potential susceptibility to infectious diseases are known to depend also on symbiotic microbiota in other members of the mustelids, a role of particularly oral microbiota can currently not be ruled out as a potential explanation for inter-individual differences in infection susceptibility of bTB in badgers. Tri annually badgers are caught in the context of a long-term population study that began in 1987. As all badgers receive an individual tattoo upon first capture, age, natal as well as previous and current social group-membership and other life history parameters are known for all animals. Swabs (subcaudal ‘scent gland’, anal, genital, nose, mouth and ear) and fecal samples will be taken from all individuals, stored at -80oC until processing. Microbial samples will be processed and identified at Wayne State University’s Theis (Host-Microbe Interactions) Lab, using High Throughput Sequencing (16S rRNA-encoding gene amplification and sequencing). Acknowledgments: Gas-Chromatography/ Mass-spectrometry (in the context of olfactory communication) analyses will be performed through an established collaboration with Dr. Veronica Tinnesand at Telemark University, Norway.

Keywords: communication, energetics, fitness, free-ranging animals, immunology

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Authors: Modi Alsubaie, Chris Dickens, Barnaby Dunn, Andy Gibson, Obioha Ukoumunned, Alison Evans, Rachael Vicary, Manish Gandhi, Willem Kuyken

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Background: Depression co-occurs in 20% of people with cardiovascular disorders, can persist for years and predicts worse physical health outcomes. While psychosocial treatments have been shown to effectively treat acute depression in those with comorbid cardiovascular disorders, to date there has been no evaluation of approaches aiming to prevent relapse and treat residual depression symptoms in this group. Therefore, the current study aimed to examine the feasibility and acceptability of a randomised controlled trial design evaluating an adapted version of mindfulness-based cognitive therapy (MBCT) designed specifically for people with co-morbid depression and cardiovascular disorders. Methods: A 3-arm feasibility randomised controlled trial was conducted, comparing MBCT adapted for people with cardiovascular disorders plus treatment as usual (TAU), mindfulness-based stress reduction (MBSR) plus TAU, and TAU alone. Participants completed a set of self-report measures of depression severity, anxiety, quality of life, illness perceptions, mindfulness, self-compassion and affect and had their blood pressure taken immediately before, immediately after, and three months following the intervention. Those in the adapted-MBCT arm additionally underwent a qualitative interview to gather their views about the adapted intervention. Results: 3400 potentially eligible participants were approached when attending an outpatient appointment at a cardiology clinic or via a GP letter following a case note search. 242 (7.1%) were interested in taking part, 59 (1.7%) were screened as being suitable, and 33 (<1%) were eventually randomised to the three groups. The sample was heterogeneous in terms of whether they reported current depression or had a history of depression and the time since the onset of cardiovascular disease (one to 25 years). Of 11 participants randomised to adapted MBCT seven completed the full course, levels of home mindfulness practice were high, and positive qualitative feedback about the intervention was given. Twenty-nine out of 33 participants randomised completed all the assessment measures at all three-time points. With regards to the primary outcome (depression), five out of the seven people who completed the adapted MBCT and three out of five under MBSR showed significant clinical change, while in TAU no one showed any clinical change at the three-month follow-up. Conclusions: The adapted MBCT intervention was feasible and acceptable to participants. However, aspects of the trial design were not feasible. In particular, low recruitment rates were achieved, and there was a high withdrawal rate between screening and randomisation. Moreover, the heterogeneity in the sample was high meaning the adapted intervention was unlikely to be well tailored to all participants needs. This suggests that if the decision is made to move to a definitive trial, study recruitment procedures will need to be revised to more successfully recruit a target sample that optimally matches the adapted intervention.

Keywords: mindfulness-based cognitive therapy (MBCT), depression, cardiovascular disorders, feasibility, acceptability

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Authors: Lalanthica Yogendran, Manassa Hany, Saira Pasha, Benjamin Chaucer, Simarpreet Kaur, Christopher Janusz

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Children and adolescent patients visit the Psychiatric Emergency Department (ED) for multiple reasons. Visiting the Psychiatric ED itself can be a traumatic experience that can affect an adolescents mental well-being, regardless of a history of mental illness. Despite this, limited research exists in this domain. Prospective studies have correlated adverse psychosocial determinants among adolescents to risk factors for poor well-being and unfavorable behavior outcomes. Studies have also shown that physiological stress is a contributor in the development of health problems and an increase in substance abuse in adolescents. This study aimed to retrospectively determine which psychosocial factors are associated with an increase in psychiatric ED visits. 600 charts of patients who had a psychiatric ED and inpatient admission visit from January 2014 through December 2014 were reviewed. Sociodemographics, diagnoses, ED visits and inpatient admissions were collected. Descriptive statistics, chi-square tests and independent t-test analyses were utilized to examine differences in the sample to determine which factors affected ED visits and admissions. The sample was 50% female, 35.2% self-identified black, and had a mean age of 13 years. The majority, 85%, went to public school and 17% were in special education. Attention Deficit Hyperactivity Disorder was the most common admitting diagnosis, found in 132(23%) responders. Most patients came from single parent household 305 (53%). The mean ages of patients that were sexually active, with legal issues, and reporting marijuana substance abuse were 15, 14.35, and 15 years respectively. Patients from two biological parent households had significantly fewer ED visits (1.2 vs. 1.7, p < 0.01) and admissions (0.09 vs. 0.26, p < 0.01). Among social factors, those who reported sexual, physical or emotional abuse had a significantly greater number of ED visits (2.1 vs. 1.5, p < 0.01) and admissions (0.61 vs. 0.14, p < 0.01) than those who did not. Patients that were sexually active or had legal issues or substance abuse with marijuana had a significantly greater number of admissions (0.43 vs. 0.17, p < 0.01), (0.54 vs. .18, p < 0.01) and (0.46 vs. 0.18, p < 0.01) respectively. This data supports the theory of the stability of a two parent home. Dual parenting plays a role in creating a safe space where a child can develop; this is shown by subsequent decreases in psychiatric ED visits and admissions. This may highlight the psychological protective role of a two parent household. Abuse can exacerbate existing psychiatric illness or initiate the onset of new disease. Substance abuse and legal issues result in early induction to the criminal system. Results show that this causes an increase in frequency of visits and severity of symptoms. Only marijuana, but not other illicit substances, correlated with higher incidence of psychiatric ED visits. This may speak to the psychotropic nature of tetrahydrocannabinols and their role in mental illness. This study demonstrates the array of psychosocial factors that lead to increased ED visits and admissions in children and adolescents.

Keywords: adolescent, child psychiatry, emergency department, substance abuse

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Authors: Niklas Ravn-Boess, Nainita Bhowmick, Takamitsu Hattori, Shohei Koide, Christopher Park, Dimitris Placantonakis

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Background: Glioblastoma (GBM) is the most common and deadly primary brain malignancy in adults. Tumor propagation, brain invasion, and resistance to therapy critically depend on GBM stem-like cells (GSCs); however, the mechanisms that regulate GSC self-renewal are incompletely understood. Given the aggressiveness and poor prognosis of GBM, it is imperative to find biomarkers that could also translate into novel drug targets. Along these lines, we have identified a cell surface antigen, CD97 (ADGRE5), an adhesion G protein-coupled receptor (GPCR), that is expressed on GBM cells but is absent from non-neoplastic brain tissue. CD97 has been shown to promote invasiveness, angiogenesis, and migration in several human cancers, but its frequency of expression and functional role in regulating GBM growth and survival, and its potential as a therapeutic target has not been investigated. Design: We assessed CD97 mRNA and protein expression in patient derived GBM samples and cell lines using publicly available RNA-sequencing datasets and flow cytometry, respectively. To assess CD97 function, we generated shRNA lentiviral constructs that target a sequence in the CD97 extracellular domain (ECD). A scrambled shRNA (scr) with no predicted targets in the genome was used as a control. We evaluated CD97 shRNA lentivirally transduced GBM cells for Ki67, Annexin V, and DAPI. We also tested CD97 KD cells for their ability to self-renew using clonogenic tumorsphere formation assays. Further, we utilized synthetic Abs (sAbs) generated against the ECD of CD97 to test for potential antitumor effects using patient-derived GBM cell lines. Results: CD97 mRNA expression was expressed at high levels in all GBM samples available in the TCGA cohort. We found high levels of surface CD97 protein expression in 6/6 patient-derived GBM cell cultures, but not human neural stem cells. Flow cytometry confirmed downregulation of CD97 in CD97 shRNA lentivirally transduced cells. CD97 KD induced a significant reduction in cell growth in 3 independent GBM cell lines representing mesenchymal and proneural subtypes, which was accompanied by reduced (~20%) Ki67 staining and increased (~30%) apoptosis. Incubation of GBM cells with sAbs (20 ug/ ml) against the ECD of CD97 for 3 days induced GSC differentiation, as determined by the expression of GFAP and Tubulin. Using three unique GBM patient derived cultures, we found that CD97 KD attenuated the ability of GBM cells to initiate sphere formation by over 300 fold, consistent with an impairment in GSC self-renewal. Conclusion: Loss of CD97 expression in patient-derived GBM cells markedly decreases proliferation, induces cell death, and reduces tumorsphere formation. sAbs against the ECD of CD97 reduce tumorsphere formation, recapitulating the phenotype of CD97 KD, suggesting that sAbs that inhibit CD97 function exhibit anti-tumor activity. Collectively, these findings indicate that CD97 is necessary for the proliferation and survival of human GBM cells and identify CD97 as a promising therapeutically targetable vulnerability in GBM.

Keywords: adhesion GPCR, CD97, GBM stem cell, glioblastoma

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Authors: Lola T. Alimkhodjaeva, Lola T. Zakirova, Soniya S. Ziyavidenova

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Background: Breast cancer (BC) is still one of the urgent oncology problems. The essential obstacle to the full anti-tumor therapy implementation is drug resistance development. Taking into account the fact that chemotherapy is main antitumor treatment in BC patients, the important task is to improve treatment results. Certain success in overcoming this situation has been associated with the use of methods of extracorporeal blood treatment (ECBT), plasmapheresis. Materials and Methods: We examined 129 women with resistant BC stages 3-4, aged between 56 to 62 years who had previously received 2 courses of CAF chemotherapy. All patients additionally underwent 2 courses of CAF chemotherapy but against the background ECBT with ultrasonic exposure. We studied the following parameters: 1. The highlights of peripheral blood before and after therapy. 2. The state of cellular immunity and identification of activation markers CD23 +, CD25 +, CD38 +, CD95 + on lymphocytes was performed using monoclonal antibodies. Evaluation of humoral immunity was determined by the level of main classes of immunoglobulins IgG, IgA, IgM in serum. 3. The degree of tumor regression was assessed by WHO recommended 4 gradations. (complete - 100%, partial - more than 50% of initial size, process stabilization–regression is less than 50% of initial size and tumor advance progressing). 4. Medical pathomorphism in the tumor was determined by Lavnikova. 5. The study of immediate and remote results, up to 3 years and more. Results and Discussion: After performing extracorporeal blood treatment anemia occurred in 38.9%, leukopenia in 36.8%, thrombocytopenia in 34.6%, hypolymphemia in 26.8%. Studies of immunoglobulin fractions in blood serum were able to establish a certain relationship between the classes of immunoglobulin A, G, M and their functions. The results showed that after treatment the values of main immunoglobulins in patients’ serum approximated to normal. Analysis of expression of activation markers CD25 + cells bearing receptors for IL-2 (IL-2Rα chain) and CD95 + lymphocytes that were mediated physiological apoptosis showed the tendency to increase, which apparently was due to activation of cellular immunity cytokines allocated by ultrasonic treatment. To carry out ECBT on the background of ultrasonic treatment improved the parameters of the immune system, which were expressed in stimulation of cellular immunity and correcting imbalances in humoral immunity. The key indicator of conducted treatment efficiency is the immediate result measured by the degree of tumor regression. After ECBT performance the complete regression was 10.3%, partial response - 55.5%, process stabilization - 34.5%, tumor advance progressing no observed. Morphological investigations of tumor determined therapeutic pathomorphism grade 2 in 15%, in 25% - grade 3 and therapeutic pathomorphism grade 4 in 60% of patients. One of the main criteria for the effect of conducted treatment is to study the remission terms in the postoperative period (up to 3 years or more). The remission terms up to 3 years with ECBT was 34.5%, 5-year survival was 54%. Carried out research suggests that a comprehensive study of immunological and clinical course of breast cancer allows the differentiated approach to the choice of methods for effective treatment.

Keywords: breast cancer, immunoglobulins, extracorporeal blood treatment, chemotherapy

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Authors: Nuno Biga

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Artificial Intelligence (AI) allows machines to interpret information and learn from context analysis, giving them the ability to make predictions adjusted to each specific situation. In addition to learning by performing deterministic and probabilistic calculations, the 'artificial brain' also learns through information and data provided by those who train it, namely its users. The "Assisted-BIGAMES" version of the Accident & Emergency (A&E) simulator introduces the concept of a "Virtual Assistant" (VA) that provides users with useful suggestions, namely to pursue the following operations: a) to relocate workstations in order to shorten travelled distances and minimize the stress of those involved; b) to identify in real time the bottleneck(s) in the operations system so that it is possible to quickly act upon them; c) to identify resources that should be polyvalent so that the system can be more efficient; d) to identify in which specific processes it may be advantageous to establish partnership with other teams; and e) to assess possible solutions based on the suggested KPIs allowing action monitoring to guide the (re)definition of future strategies. This paper is built on the BIGAMES© simulator and presents the conceptual AI model developed in a pilot project. Each Virtual Assisted BIGAME is a management simulator developed by the author that guides operational and strategic decision making, providing users with useful information in the form of management recommendations that make it possible to predict the actual outcome of different alternative management strategic actions. The pilot project developed incorporates results from 12 editions of the BIGAME A&E that took place between 2017 and 2022 at AESE Business School, based on the compilation of data that allows establishing causal relationships between decisions taken and results obtained. The systemic analysis and interpretation of this information is materialised in the Assisted-BIGAMES through a computer application called "BIGAMES Virtual Assistant" that players can use during the Game. Each participant in the Virtual Assisted-BIGAMES permanently asks himself about the decisions he should make during the game in order to win the competition. To this end, the role of the VA of each team consists in guiding the players to be more effective in their decision making through presenting recommendations based on AI methods. It is important to note that the VA's suggestions for action can be accepted or rejected by the managers of each team, and as the participants gain a better understanding of the game, they will more easily dispense with the VA's recommendations and rely more on their own experience, capability, and knowledge to support their own decisions. Preliminary results show that the introduction of the VA provides a faster learning of the decision-making process. The facilitator (Serious Game Controller) is responsible for supporting the players with further analysis and the recommended action may be (or not) aligned with the previous recommendations of the VA. All the information should be jointly analysed and assessed by each player, who are expected to add “Emotional Intelligence”, a component absent from the machine learning process.

Keywords: artificial intelligence (AI), gamification, key performance indicators (KPI), machine learning, management simulators, serious games, virtual assistant

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Authors: Ramprasad Srinivasan

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Engineers create inventions and put their ideas in concrete terms to design new products. Design drivers must be established, which requires, among other things, a complete understanding of the product design, load paths, etc. For Aerospace Vehicles, weight/strength ratio, strength, stiffness and stability are the important design drivers. A complex built-up structure is made up of an assemblage of primitive structural forms of arbitrary shape, which include 1D structures like beams and frames, 2D structures like membranes, plate and shell structures, and 3D solid structures. Justification through simulation involves a check for all the quantities of interest, namely stresses, deformation, frequencies, and buckling loads and is normally achieved through the finite element (FE) method. Over the past few decades, Fiber-reinforced composites are fast replacing the traditional metallic structures in the weight-sensitive aerospace and aircraft industries due to their high specific strength, high specific stiffness, anisotropic properties, design freedom for tailoring etc. Composite panel constructions are used in aircraft to design primary structure components like wings, empennage, ailerons, etc., while thin-walled composite beams (TWCB) are used to model slender structures like stiffened panels, helicopter, and wind turbine rotor blades, etc. The TWCB demonstrates many non-classical effects like torsional and constrained warping, transverse shear, coupling effects, heterogeneity, etc., which makes the analysis of composite structures far more complex. Conventional FE formulations to model 1D structures suffer from many limitations like shear locking, particularly in slender beams, lower convergence rates due to material coupling in composites, inability to satisfy, equilibrium in the domain and natural boundary conditions (NBC) etc. For 2D structures, the limitations of conventional displacement-based FE formulations include the inability to satisfy NBC explicitly and many pathological problems such as shear and membrane locking, spurious modes, stress oscillations, lower convergence due to mesh distortion etc. This mandates frequent re-meshing to even achieve an acceptable mesh (satisfy stringent quality metrics) for analysis leading to significant cycle time. Besides, currently, there is a need for separate formulations (u/p) to model incompressible materials, and a single unified formulation is missing in the literature. Hence coupled field formulation (CFF) is a unified formulation proposed by the author for the solution of complex 1D and 2D structures addressing the gaps in the literature mentioned above. The salient features of CFF and its many advantages over other conventional methods shall be presented in this paper.

Keywords: coupled field formulation, kinematic and material coupling, natural boundary condition, locking free formulation

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Authors: Natalia V. Minaeva, Natalia A. Zorina, Marina N. Khorobrikh, Philipp S. Sherstnev, Tatiana V. Krivokorytova, Alexander S. Luchinin, Maksim S. Minaev, Igor V. Paramonov

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Background. Over the last few decades, the Center for International Blood and Marrow Transplant Research (CIBMTR) and the World Marrow Donor Association (WMDA) have been actively working to ensure the safety of the hematopoietic stem cell (HSC) donation process. Registration of adverse events that may occur during the donation period and establishing a relationship between donation and side effects are included in the WMDA international standards. The level of blood serum N-terminal pro-brain natriuretic peptide (NT-proBNP) is an early marker of myocardial stress. Due to the high analytical sensitivity and specificity, laboratory assessment of NT-proBNP makes it possible to objectively diagnose myocardial dysfunction. It is well known that the main stimulus for proBNP synthesis and secretion from atrial and ventricular cardiac myocytes is myocyte stretch and increasement of myocardial extensibility and pressure in the heart chambers. Аim. The aim of the study was to assess the dynamic changes in the levels of blood serum N-terminal pro-brain natriuretic peptide of unrelated donors at various stages of hematopoietic stem cell mobilization. Materials. We have examined 133 unrelated donors, including 92 men and 41 women, that have been included into the study. The NT-proBNP levels were measured before the start of mobilization, then on the day of apheresis, and after the donation of allogeneic HSC. The relationship between NT-proBNP levels and body mass index (BMI), ferritin, hemoglobin, and white blood cells (WBC) levels was assessed on the day of apheresis. The median age of donors was 34 years. Mobilization of HSCs was managed with filgrastim administration at a dose of 10 μg/kg daily for 4-5 days. The first leukocytapheresis was performed on day 4 from the start of filgrastim administration. Quantitative values of the blood serum NT-proBNP level are presented as a median (Me), first and third quartiles (Q1-Q3). Comparative analysis was carried out using the t-test and correlation analysis as well by Spearman method. Results. The baseline blood serum NT-proBNP levels in all 133 donors were within the reference values (<125 pg/ml) and equaled 21,6 (10,0; 43,3) pg/ml. At the same time, the level of NT-proBNP in women was significantly higher than that of men. On the day of the HSC apheresis, a significant increase of blood serum NT-proBNP levels was detected and equald 131,2 (72,6; 165,3) pg/ml (p<0,001), with higher rates in female donors. A statistically significant weak inverse correleation was established between the level of NT-proBNP and the BMI of donors (-0.18, p = 0,03), as well as the level of hemoglobin (-0.33, p <0,001), and ferritin levels (-0.19, p = 0,03). No relationship has been established between the magnitude of WBC levels achieved as a result of the mobilization of HSC on the day of leukocytapheresis. A day after the apheresis, the blood serum NT-proBNP levels still exceeded the reference values, but there was a decreasing tendency. Conclusion. An increase of the blood serum NT-proBNP level in unrelated donors during the mobilization of HSC was established. Future studies should clarify the reason for this phenomenon, as well as its effects on donors' long-term health.

Keywords: unrelated donors, mobilization, hematopoietic stem cells, N-terminal pro-brain natriuretic peptide

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Authors: Ayse Gul Bilen

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Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed antidepressants that are used clinically for the treatment of anxiety disorders, obsessive-compulsive disorder (OCD), panic disorders and eating disorders. The first SSRI, fluoxetine (sold under the brand names Prozac and Sarafem among others), had an adverse effect profile better than any other available antidepressant when it was introduced because of its selectivity for serotonin receptors. They have been considered almost free of side effects and have become widely prescribed, however questions about the safety and tolerability of SSRIs have emerged with their continued use. Most SSRI side effects are dose-related and can be attributed to serotonergic effects such as nausea. Continuous use might trigger adverse effects such as hyponatremia, tremor, nausea, weight gain, sleep disturbance and sexual dysfunction. Moderate toxicity can be safely observed in the hospital for 24 hours, and mild cases can be safely discharged (if asymptomatic) from the emergency department once cleared by Psychiatry in cases of intentional overdose and after 6 to 8 hours of observation. Although fluoxetine is relatively safe in terms of overdose, it might still be cardiotoxic and inhibit platelet secretion, aggregation, and plug formation. There have been reported clinical cases of seizures, cardiac conduction abnormalities, and even fatalities associated with fluoxetine ingestions. While the medical literature strongly suggests that most fluoxetine overdoses are benign, emergency physicians need to remain cognizant that intentional, high-dose fluoxetine ingestions may induce seizures and can even be fatal due to cardiac arrhythmia. Our case is a 35-year old female patient who was sent to ER with symptoms of confusion, amnesia and loss of orientation for time and location after being found wandering in the streets unconsciously by police forces that informed 112. Upon laboratory examination, no pathological symptom was found except sinus tachycardia in the EKG and high levels of aspartate transaminase (AST) and alanine transaminase (ALT). Diffusion MRI and computed tomography (CT) of the brain all looked normal. Upon physical and sexual examination, no signs of abuse or trauma were found. Test results for narcotics, stimulants and alcohol were negative as well. There was a presence of dysrhythmia which required admission to the intensive care unit (ICU). The patient gained back her conscience after 24 hours. It was discovered from her story afterward that she had been using fluoxetine due to post-traumatic stress disorder (PTSD) for 6 months and that she had attempted suicide after taking 3 boxes of fluoxetine due to the loss of a parent. She was then transferred to the psychiatric clinic. Our study aims to highlight the need to consider toxicologic drug use, in particular, the abuse of selective serotonin reuptake inhibitors (SSRIs), which have been widely prescribed due to presumed safety and tolerability, for diagnosis of patients applying to the emergency room (ER).

Keywords: abuse, amnesia, fluoxetine, intoxication, SSRI

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Authors: Kuan Lun Pan, Moo Been Chang

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Volatile organic compounds (VOCs) are one of major air contaminants, and they can react with nitrogen oxides (NOx) in atmosphere to form ozone (O3) and peroxyacetyl nitrate (PAN) with solar irradiation, leading to environmental hazards. In addition, some VOCs are toxic at low concentration levels and cause adverse effects on human health. How to effectively reduce VOCs emission has become an important issue. Thermal catalysis is regarded as an effective way for VOCs removal because it provides oxidation route to successfully convert VOCs into carbon dioxide (CO2) and water (H2O(g)). Single perovskite-type catalysts are promising for VOC removal, and they are of good potential to replace noble metals due to good activity and high thermal stability. Single perovskites can be generally described as ABO3 or A2BO4, where A-site is often a rare earth element or an alkaline. Typically, the B-site is transition metal cation (Fe, Cu, Ni, Co, or Mn). Catalytic properties of perovskites mainly rely on nature, oxidation states and arrangement of B-site cation. Interestingly, single perovskites could be further synthesized to form double perovskite-type catalysts which can simply be represented by A2B’B”O6. Likewise, A-site stands for an alkaline metal or rare earth element, and the B′ and B′′ are transition metals. Double perovskites possess unique surface properties. In structure, three-dimensional of B-site with ordered arrangement of B’O6 and B”O6 is presented alternately, and they corner-share octahedral along three directions of the crystal lattice, while cations of A-site position between the void of octahedral. It has attracted considerable attention due to specific arrangement of alternating B-site structure. Therefore, double perovskites may have more variations than single perovskites, and this greater variation may promote catalytic performance. It is expected that activity of double perovskites is higher than that of single perovskites toward VOC removal. In this study, double perovskite-type catalyst (La2CoMnO6) is prepared and evaluated for VOC removal. Also, single perovskites including LaCoO3 and LaMnO3 are tested for the comparison purpose. Toluene (C7H8) is one of the important VOCs which are commonly applied in chemical processes. In addition to its wide application, C7H8 has high toxicity at a low concentration. Therefore, C7H8 is selected as the target compound in this study. Experimental results indicate that double perovskite (La2CoMnO6) has better activity if compared with single perovskites. Especially, C7H8 can be completely oxidized to CO2 at 300oC as La2CoMnO6 is applied. Characterization of catalysts indicates that double perovskite has unique surface properties and is of higher amounts of lattice oxygen, leading to higher activity. For durability test, La2CoMnO6 maintains high C7H8 removal efficiency of 100% at 300oC and 30,000 h-1, and it also shows good resistance to CO2 (5%) and H2O(g) (5%) of gas streams tested. For various VOCs including isopropyl alcohol (C3H8O), ethanal (C2H4O), and ethylene (C2H4) tested, as high as 100% efficiency could be achieved with double perovskite-type catalyst operated at 300℃, indicating that double perovskites are promising catalysts for VOCs removal, and possible mechanisms will be elucidated in this paper.

Keywords: volatile organic compounds, Toluene (C7H8), double perovskite-type catalyst, catalysis

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Authors: Grzegorz Raniszewski, Zbigniew Kolacinski, Lukasz Szymanski, Slawomir Wiak, Lukasz Pietrzak, Dariusz Koza

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One of the most promising area for carbon nanotubes (CNTs) application is medicine. One of the most devastating diseases is cancer. Carbon nanotubes may be used as carriers of a slowly released drug. It is possible to use of electromagnetic waves to destroy cancer cells by the carbon nanotubes (CNTs). In our research we focused on thermal ablation by ferromagnetic carbon nanotubes (Fe-CNTs). In the cancer cell hyperthermia functionalized carbon nanotubes are exposed to radio frequency electromagnetic field. Properly functionalized Fe-CNTs join the cancer cells. Heat generated in nanoparticles connected to nanotubes warm up nanotubes and then the target tissue. When the temperature in tumor tissue exceeds 316 K the necrosis of cancer cells may be observed. Several techniques can be used for Fe-CNTs synthesis. In our work, we use high-temperature methods where arc-discharge is applied. Low-temperature systems are microwave plasma with assisted chemical vapor deposition (MPCVD) and hybrid physical-chemical vapor deposition (HPCVD). In the arc discharge system, the plasma reactor works with a pressure of He up to 0,5 atm. The electric arc burns between two graphite rods. Vapors of carbon move from the anode, through a short arc column and forms CNTs which can be collected either from the reactor walls or cathode deposit. This method is suitable for the production of multi-wall and single-wall CNTs. A disadvantage of high-temperature methods is a low purification, short length, random size and multi-directional distribution. In MPCVD system plasma is generated in waveguide connected to the microwave generator. Then containing carbon and ferromagnetic elements plasma flux go to the quartz tube. The additional resistance heating can be applied to increase the reaction effectiveness and efficiency. CNTs nucleation occurs on the quartz tube walls. It is also possible to use substrates to improve carbon nanotubes growth. HPCVD system involves both chemical decomposition of carbon containing gases and vaporization of a solid or liquid source of catalyst. In this system, a tube furnace is applied. A mixture of working and carbon-containing gases go through the quartz tube placed inside the furnace. As a catalyst ferrocene vapors can be used. Fe-CNTs may be collected then either from the quartz tube walls or on the substrates. Low-temperature methods are characterized by higher purity product. Moreover, carbon nanotubes from tested CVD systems were partially filled with the iron. Regardless of the method of Fe-CNTs synthesis the final product always needs to be purified for applications in medicine. The simplest method of purification is an oxidation of the amorphous carbon. Carbon nanotubes dedicated for cancer cell thermal ablation need to be additionally treated by acids for defects amplification on the CNTs surface what facilitates biofunctionalization. Application of ferromagnetic nanotubes for cancer treatment is a promising method of fighting with cancer for the next decade. Acknowledgment: The research work has been financed from the budget of science as a research project No. PBS2/A5/31/2013

Keywords: arc discharge, cancer, carbon nanotubes, CVD, thermal ablation

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Authors: Vrushali Guhe, Shailza Singh

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Cutaneous leishmaniasis is neglected tropical disease present worldwide caused by the protozoan parasite Leishmania major, the therapeutic armamentarium for leishmaniasis are showing several limitations as drugs are showing toxic effects with increasing resistance by a parasite. Thus identification of novel therapeutic targets is of paramount importance. Previous studies have shown that autophagy, a cellular process, can either facilitate infection or aid in the elimination of the parasite, depending on the specific parasite species and host background in leishmaniasis. In the present study, our objective was to target the essential autophagy protein ATG8, which plays a crucial role in the survival, infection dynamics, and differentiation of the Leishmania parasite. ATG8 in Leishmania major and its homologue, LC3, in Homo sapiens, act as autophagic markers. Present study manifested the crucial role of ATG8 protein as a potential target for combating Leishmania major infection. Through bioinformatics analysis, we identified non-conserved motifs within the ATG8 protein of Leishmania major, which are not present in LC3 of Homo sapiens. Against these two non-conserved motifs, we generated a peptide library of 60 peptides on the basis of physicochemical properties. These peptides underwent a filtering process based on various parameters, including feasibility of synthesis and purification, compatibility with Selective Reaction Monitoring (SRM)/Multiple reaction monitoring (MRM), hydrophobicity, hydropathy index, average molecular weight (Mw average), monoisotopic molecular weight (Mw monoisotopic), theoretical isoelectric point (pI), and half-life. Further filtering criterion shortlisted three peptides by using molecular docking and molecular dynamics simulations. The direct interaction between ATG8 and the shortlisted peptides was confirmed through Surface Plasmon Resonance (SPR) experiments. Notably, these peptides exhibited the remarkable ability to penetrate the parasite membrane and exert profound effects on Leishmania major. The treatment with these peptides significantly impacted parasite survival, leading to alterations in the cell cycle and morphology. Furthermore, the peptides were found to modulate autophagosome formation, particularly under starved conditions, suggesting their involvement in disrupting the regulation of autophagy within Leishmania major. In vitro, studies demonstrated that the selected peptides effectively reduced the parasite load within infected host cells. Encouragingly, these findings were corroborated by in vivo experiments, which showed a reduction in parasite burden upon peptide administration. Additionally, the peptides were observed to affect the levels of LC3II within host cells. In conclusion, our findings highlight the efficacy of these novel peptides in targeting Leishmania major’s ATG8 and disrupting parasite survival. These results provide valuable insights into the development of innovative therapeutic strategies against leishmaniasis via targeting autophagy protein ATG8 of Leishmania major.

Keywords: ATG8, leishmaniasis, surface plasmon resonance, MD simulation, molecular docking, peptide designing, therapeutics

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Authors: Farhat Jabeen, Muhammad Asad

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The study assessed the curative potential of Moringa olifera seeds against copper oxide nanoparticles induced toxicity in Oreochromis mossambicus. In order to investigate the curative potential of M. olifera seeds, firstly we examine its chemical composition, secondary metabolites, and bioactive compounds including hydroxyl-cinnamic acids, flavanols and hydroxybenzoic acids through standard methods and high performance liquid chromatography. In current study, the potential sub-lethal toxic dose of CuO-NPs (0.12 mg/l) was investigated through pilot experiment and three non-lethal doses (low=32, medium=48 and high=96 mg/l) of M. olifera were selected on the basis of its LC50 value for O. mossambicus. The experimental fish, O. mossambicus (n=100 of approximately 20 g each) were procured from Manawan Fisheries Complex, Lahore, and acclimatized for two weeks in glass aquaria. Experiment was conducted in accordance with the guidelines of Institutional Animal Ethics Committee, Government College University Faisalabad, Pakistan. During acclimatization and experimental period, fish received the commercial fish feed at 2.5% body weight daily. In order to assess the curative effect of M. olifera against CuO NPs induced toxicity, O. mossambicus were randomly divided into five groups and were designated as control (C) without any treatment, positive control (G*) exposed to potential toxic dose of CuO-NPs at 0.12 mg/l, and three treated groups namely G1, G2, and G3 co-treated with 0.12 mg/l of CuO-NPs plus different doses of M. olifera seed extract at 32, 48, and 96 mg/l, respectively for 56 days. Fish were exposed to waterborne CuO NPs and M. olifera seed extract. CuO-NPs treatment was ceased after 28 days but the doses of M. olifera were continued for 56 days. Blood was taken after 28 and 56 days through caudal venipuncture. Liver and intestine were taken for oxidative stress and histological studies after 56 days. In M. olifera seeds, moisture contents, crude protein, lipids, carbohydrates and ash were recorded as 3.8, 37.83, 32.52, 46.12, and 7.75%, respectively on dry weight basis. Total energy was recorded as 627.36 kcal/100g. Qualitative analysis of M. olifera seeds showed the presence of terpenoids, saponins, flavonoids, alkaloids and phenolics, while its quantitative analysis showed the considerable amount of total phenolics, flavonoids, saponins, and alkaloids as 134.75, 170.15, 1.57, and 0.4 µg/mg, respectively. Analysis of bioactive compounds in M. olifera seeds showed the presence of hydroxy-cinnamic acids (6.07 µg/ml), flavanols (71.72 µg/ml), and hydroxyl benzoic acids (97.82 µg/ml). The results showed that M. oliefera seed extract at 48 and 56 mg/l was able to cure against the toxic effects of CuO-NPs. The significant changes were observed in G* and G1 for sero-hepatic enzymes, anti-oxidants and histological profile. The investigations of this study showed that M. olifera is a good curative agent against potential induced toxicity of CuO-NPs in O. mossambicus. The curative effect of M. olifera is attributed to the presence of higher amount of secondary metabolites and bioactive compounds. This study suggested the use of M. olifera to curate different ailments in fish and other organisms.

Keywords: CuO nanoparticles, curative, Moringa olifera, Oreochromis mossambicus

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