Search results for: Drought tolerance
93 Modelling Optimal Control of Diabetes in the Workplace
Authors: Eunice Christabel Chukwu
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Introduction: Diabetes is a chronic medical condition which is characterized by high levels of glucose in the blood and urine; it is usually diagnosed by means of a glucose tolerance test (GTT). Diabetes can cause a range of health problems if left unmanaged, as it can lead to serious complications. It is essential to manage the condition effectively, particularly in the workplace where the impact on work productivity can be significant. This paper discusses the modelling of optimal control of diabetes in the workplace using a control theory approach. Background: Diabetes mellitus is a condition caused by too much glucose in the blood. Insulin, a hormone produced by the pancreas, controls the blood sugar level by regulating the production and storage of glucose. In diabetes, there may be a decrease in the body’s ability to respond to insulin or a decrease in insulin produced by the pancreas which will lead to abnormalities in the metabolism of carbohydrates, proteins, and fats. In addition to the health implications, the condition can also have a significant impact on work productivity, as employees with uncontrolled diabetes are at risk of absenteeism, reduced performance, and increased healthcare costs. While several interventions are available to manage diabetes, the most effective approach is to control blood glucose levels through a combination of lifestyle modifications and medication. Methodology: The control theory approach involves modelling the dynamics of the system and designing a controller that can regulate the system to achieve optimal performance. In the case of diabetes, the system dynamics can be modelled using a mathematical model that describes the relationship between insulin, glucose, and other variables. The controller can then be designed to regulate the glucose levels to maintain them within a healthy range. Results: The modelling of optimal control of diabetes in the workplace using a control theory approach has shown promising results. The model has been able to predict the optimal dose of insulin required to maintain glucose levels within a healthy range, taking into account the individual’s lifestyle, medication regimen, and other relevant factors. The approach has also been used to design interventions that can improve diabetes management in the workplace, such as regular glucose monitoring and education programs. Conclusion: The modelling of optimal control of diabetes in the workplace using a control theory approach has significant potential to improve diabetes management and work productivity. By using a mathematical model and a controller to regulate glucose levels, the approach can help individuals with diabetes to achieve optimal health outcomes while minimizing the impact of the condition on their work performance. Further research is needed to validate the model and develop interventions that can be implemented in the workplace.Keywords: mathematical model, blood, insulin, pancreas, model, glucose
Procedia PDF Downloads 5992 Contribution to the Understanding of the Hydrodynamic Behaviour of Aquifers of the Taoudéni Sedimentary Basin (South-eastern Part, Burkina Faso)
Authors: Kutangila Malundama Succes, Koita Mahamadou
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In the context of climate change and demographic pressure, groundwater has emerged as an essential and strategic resource whose sustainability relies on good management. The accuracy and relevance of decisions made in managing these resources depend on the availability and quality of scientific information they must rely on. It is, therefore, more urgent to improve the state of knowledge on groundwater to ensure sustainable management. This study is conducted for the particular case of the aquifers of the transboundary sedimentary basin of Taoudéni in its Burkinabe part. Indeed, Burkina Faso (and the Sahel region in general), marked by low rainfall, has experienced episodes of severe drought, which have justified the use of groundwater as the primary source of water supply. This study aims to improve knowledge of the hydrogeology of this area to achieve sustainable management of transboundary groundwater resources. The methodological approach first described lithological units regarding the extension and succession of different layers. Secondly, the hydrodynamic behavior of these units was studied through the analysis of spatio-temporal variations of piezometric. The data consists of 692 static level measurement points and 8 observation wells located in the usual manner in the area and capturing five of the identified geological formations. Monthly piezometric level chronicles are available for each observation and cover the period from 1989 to 2020. The temporal analysis of piezometric, carried out in comparison with rainfall chronicles, revealed a general upward trend in piezometric levels throughout the basin. The reaction of the groundwater generally occurs with a delay of 1 to 2 months relative to the flow of the rainy season. Indeed, the peaks of the piezometric level generally occur between September and October in reaction to the rainfall peaks between July and August. Low groundwater levels are observed between May and July. This relatively slow reaction of the aquifer is observed in all wells. The influence of the geological nature through the structure and hydrodynamic properties of the layers was deduced. The spatial analysis reveals that piezometric contours vary between 166 and 633 m with a trend indicating flow that generally goes from southwest to northeast, with the feeding areas located towards the southwest and northwest. There is a quasi-concordance between the hydrogeological basins and the overlying hydrological basins, as well as a bimodal flow with a component following the topography and another significant component deeper, controlled by the regional gradient SW-NE. This latter component may present flows directed from the high reliefs towards the sources of Nasso. In the source area (Kou basin), the maximum average stock variation, calculated by the Water Table Fluctuation (WTF) method, varies between 35 and 48.70 mm per year for 2012-2014.Keywords: hydrodynamic behaviour, taoudeni basin, piezometry, water table fluctuation
Procedia PDF Downloads 6391 Rheological and Sensory Attributes of Dough and Crackers Including Amaranth Flour (Amaranthus spp.)
Authors: Claudia Cabezas-Zabala, Jairo Lindarte-Artunduaga, Carlos Mario Zuluaga-Dominguez
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Amaranth is an emerging pseudocereal rich in such essential nutrients as protein and dietary fiber, which was employed as an ingredient in the formulation of crackers to evaluate the rheological performance and sensory acceptability of the obtained food. A completely randomized factorial design was used with two factors: (A) ratio of wheat and amaranth flour used in the preparation of the dough, in proportion 90:10 and 80:20 (% w/w) and (B) two levels of inulin addition of 8.4% and 16.7 %, having two control doughs made from amaranth and wheat flour, respectively. Initially, the functional properties of the formulations mentioned were measured, showing no significant differences in the water absorption capacity (WAC) and swelling power (SP), having mean values between 1.66 and 1.81 g/g for WAC and between 1.75 and 1.86 g/g for SP, respectively. The amaranth flour had the highest water holding capacity (WHR) of 8.41 ± 0.15 g/g and emulsifying activity (EA) of 74.63 ± 1.89 g/g. Moreover, the rheological behavior, measured through the use of farinograph, extensograph, Mixolab, and falling index, showed that the formulation containing 20% of amaranth flour and 7.16% of inulin had a rheological behavior similar to the control produced exclusively with wheat flour, being the former, the one selected for the preparation of crackers. For this formulation, the farinograph showed a mixing tolerance index of 11 UB, indicating a strong and cohesive dough; likewise, the Mixolab showed dough reaches stability at 6.47 min, indicating a good resistance to mixing. On the other hand, the extensograph exhibited a dough resistance of 637 UB, as well as extensibility of 13.4 mm, which corresponds to a strong dough capable of resisting the laminate. Finally, the falling index was 318 s, which indicates the crumb will retain enough air to enhance the crispness of a characteristic cracker. Finally, a sensory consumer test did not show significant differences in the evaluation of aroma between the control and the selected formulation, while this latter had a significantly lower rating in flavor. However, a purchase intention of 70 % was observed among the population surveyed. The results obtained in this work give perspectives for the industrial use of amaranth in baked goods. Additionally, amaranth has been a product typically linked to indigenous populations in the Andean South American countries; therefore, the search for diversification and alternatives of use for this pseudocereal has an impact on the social and economic conditions of such communities. The technological versatility and nutritional quality of amaranth is an advantage for consumers, favoring the consumption of healthy products with important contributions of dietary fiber and protein.Keywords: amaranth, crackers, rheology, pseudocereals, kneaded products
Procedia PDF Downloads 11690 Harnessing Renewable Energy as a Strategy to Combating Climate Change in Sub Saharan Africa
Authors: Gideon Nyuimbe Gasu
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Sub Saharan Africa is at a critical point, experiencing rapid population growth, particularly in urban areas and young growing force. At the same time, the growing risk of catastrophic global climate change threatens to weaken food production system, increase intensity and frequency of drought, flood, and fires and undermine gains on development and poverty reduction. Although the region has the lowest per capital greenhouse gas emission level in the world, it will need to join global efforts to address climate change, including action to avoid significant increases and to encourage a green economy. Thus, there is a need for the concept of 'greening the economy' as was prescribed at Rio Summit of 1992. Renewable energy is one of the criterions to achieve this laudable goal of maintaining a green economy. There is need to address climate change while facilitating continued economic growth and social progress as energy today is critical to economic growth. Fossil fuels remain the major contributor of greenhouse gas emission. Thus, cleaner technologies such as carbon capture storage, renewable energy have emerged to be commercially competitive. This paper sets out to examine how to achieve a low carbon economy with minimal emission of carbon dioxide and other greenhouse gases which is one of the outcomes of implementing a green economy. Also, the paper examines the different renewable energy sources such as nuclear, wind, hydro, biofuel, and solar voltaic as a panacea to the looming climate change menace. Finally, the paper assesses the different renewable energy and energy efficiency as a propeller to generating new sources of income and jobs and in turn reduces carbon emission. The research shall engage qualitative, evaluative and comparative methods. The research will employ both primary and secondary sources of information. The primary sources of information shall be drawn from the sub Saharan African region and the global environmental organizations, energy legislation, policies and related industries and the judicial processes. The secondary sources will be made up of some books, journal articles, commentaries, discussions, observations, explanations, expositions, suggestions, prescriptions and other material sourced from the internet on renewable energy as a panacea to climate change. All information obtained from these sources will be subject to content analysis. The research result will show that the entire planet is warming as a result of the activities of mankind which is clear evidence that the current development is fundamentally unsustainable. Equally, the study will reveal that a low carbon development pathway in the sub Saharan African region should be embraced to minimize emission of greenhouse gases such as using renewable energy rather than coal, oil, and gas. The study concludes that until adequate strategies are devised towards the use of renewable energy the region will continue to add and worsen the current climate change menace and other adverse environmental conditions.Keywords: carbon dioxide, climate change, legislation/law, renewable energy
Procedia PDF Downloads 22589 The Influence of a Radio Intervention on Farmers’ Practices in Climate Change Mitigation and Adaptation in Kilifi, Kenya
Authors: Fiona Mwaniki
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Climate change is considered a serious threat to sustainable development globally and as one of the greatest ecological, economic and social challenges of our time. The global demand for food is projected to increase by 60% by 2050. Small holder farmers who are vulnerable to the adverse effects of climate change are expected to contribute to this projected demand. Effective climate change education and communication is therefore required for smallholder and subsistence farmers’ in order to build communities that are more climate change aware, prepared and resilient. In Kenya radio is the most important and dominant mass communication tool for agricultural extension. This study investigated the potential role of radio in influencing farmers’ understanding and use of climate change information. The broad aims of this study were three-fold. Firstly, to identify Kenyan farmers’ perceptions and responses to the impacts of climate change. Secondly, to develop radio programs that communicate climate change information to Kenyan farmers and thirdly, to evaluate the impact of information disseminated through radio on farmers’ understanding and responses to climate change mitigation and adaptation. This study was conducted within the farming community of Kilifi County, located along the Kenyan coast. Education and communication about climate change was undertaken using radio to make available information understandable to different social and cultural groups. A mixed methods pre-and post-intervention design that provided the opportunity for triangulating results from both quantitative and qualitative data was used. Quantitative and qualitative data was collected simultaneously, where quantitative data was collected through semi structured surveys with 421 farmers’ and qualitative data was derived from 11 focus group interviews, six interviews with key informants and nine climate change experts. The climate change knowledge gaps identified in the initial quantitative and qualitative data were used in developing radio programs. Final quantitative and qualitative data collection and analysis enabled an assessment of the impact of climate change messages aired through radio on the farming community in Kilifi County. Results of this study indicate that 32% of the farmers’ listened to the radio programs and 26% implemented technologies aired on the programs that would help them adapt to climate change. The most adopted technologies were planting drought tolerant crops including indigenous crop varieties, planting trees, water harvesting and use of manure. The proportion of farmers who indicated they knew “a fair amount” about climate change increased significantly (Z= -5.1977, p < 0.001) from 33% (at the pre intervention phase of this study) to 64% (post intervention). However, 68% of the farmers felt they needed “a lot more” information on agriculture interventions (43%), access to financial resources (21%) and the effects of climate change (15%). The challenges farmers’ faced when adopting the interventions included lack of access to financial resources (18%), high cost of adaptation measures (17%), and poor access to water (10%). This study concludes that radio effectively complements other agricultural extension methods and has the potential to engage farmers’ on climate change issues and motivate them to take action.Keywords: climate change, climate change intervention, farmers, radio
Procedia PDF Downloads 33788 Automatic Aggregation and Embedding of Microservices for Optimized Deployments
Authors: Pablo Chico De Guzman, Cesar Sanchez
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Microservices are a software development methodology in which applications are built by composing a set of independently deploy-able, small, modular services. Each service runs a unique process and it gets instantiated and deployed in one or more machines (we assume that different microservices are deployed into different machines). Microservices are becoming the de facto standard for developing distributed cloud applications due to their reduced release cycles. In principle, the responsibility of a microservice can be as simple as implementing a single function, which can lead to the following issues: - Resource fragmentation due to the virtual machine boundary. - Poor communication performance between microservices. Two composition techniques can be used to optimize resource fragmentation and communication performance: aggregation and embedding of microservices. Aggregation allows the deployment of a set of microservices on the same machine using a proxy server. Aggregation helps to reduce resource fragmentation, and is particularly useful when the aggregated services have a similar scalability behavior. Embedding deals with communication performance by deploying on the same virtual machine those microservices that require a communication channel (localhost bandwidth is reported to be about 40 times faster than cloud vendor local networks and it offers better reliability). Embedding can also reduce dependencies on load balancer services since the communication takes place on a single virtual machine. For example, assume that microservice A has two instances, a1 and a2, and it communicates with microservice B, which also has two instances, b1 and b2. One embedding can deploy a1 and b1 on machine m1, and a2 and b2 are deployed on a different machine m2. This deployment configuration allows each pair (a1-b1), (a2-b2) to communicate using the localhost interface without the need of a load balancer between microservices A and B. Aggregation and embedding techniques are complex since different microservices might have incompatible runtime dependencies which forbid them from being installed on the same machine. There is also a security concern since the attack surface between microservices can be larger. Luckily, container technology allows to run several processes on the same machine in an isolated manner, solving the incompatibility of running dependencies and the previous security concern, thus greatly simplifying aggregation/embedding implementations by just deploying a microservice container on the same machine as the aggregated/embedded microservice container. Therefore, a wide variety of deployment configurations can be described by combining aggregation and embedding to create an efficient and robust microservice architecture. This paper presents a formal method that receives a declarative definition of a microservice architecture and proposes different optimized deployment configurations by aggregating/embedding microservices. The first prototype is based on i2kit, a deployment tool also submitted to ICWS 2018. The proposed prototype optimizes the following parameters: network/system performance, resource usage, resource costs and failure tolerance.Keywords: aggregation, deployment, embedding, resource allocation
Procedia PDF Downloads 20287 Effects of Abiotic Stress on the Phytochemical Content and Bioactivity of Pistacia lentiscus L.
Authors: S. Mamoucha, N. Tsafantakis, Α. Ioannidis, S. Chatzipanagiotou, C. Nikolaou, L. Skaltsounis, N. Fokialakis, N. Christodoulakis
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Introduction: Plant secondary metabolites (SM) can be grouped into three chemically distinct groups: terpenes, phenolics, and nitrogen-containing compounds. For many years the adaptive significance of SM was unknown. They were thought to be functionless end-products. Currently it is accepted that many secondary metabolites (also known as natural products) have important ecological roles in plants. For instance, they serve as attractants (odor, color, taste) for pollinators and seed-dispersing animals. Moreover, they protect plants from herbivores, microbial pathogens and from environmental stress (high and low temperatures, drought, alkalinity, salinity, radiation etc). It is well known that both biotic and abiotic stress often increase the accumulation of SM. The local climatic conditions, seasonal changes, external factors such as light, temperature, humidity affect the biosynthesis and composition of secondary metabolites. A well known dioecious evergreen plant, Pistacia lentiscus L. (mastic tree), was selected in order to study the metabolic variations occur in response to the different climate conditions, due to the seasonal variation and its effect on the biosynthesis of bioactive compounds. Materials-methods: Young and mature leaves were collected in January and July 2014, dried and extracted by accelerated solvent extraction (Dionex ASE™ 350) using solvents of increased polarity (DCM, MeOH, and H2O). GC-MS and UHPLC-HRMS analysis were carried out in order to define the nature and the relative abundance of SM. The antibacterial activity was evaluated by using the Agar Disc Diffusion Assay against ATCC and clinical isolates strains: Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Candida albicans, Streptococcus mutans and Klebsiella pneumoniae. All tests were carried out in duplicate and the average radii of the inhibition zones were calculated for each extract. Results: According to the phytochemical profile obtained from each extract, the biosynthesis of SM varied both qualitatively and quantitatively under the two different types of seasonal stress. With exception of the biologically inactive nonpolar DCM extract of July, all extracts inhibited the growth of most of the investigated microorganisms. A clear positive correlation has been observed between the relative abundance of SM and the bioactivity of the DCM extracts of January and July. Observed changes during phytochemical analysis were mainly focused on the triterpenoid content. On the other hand, the bioactivity of the polar extracts (MeOH and H2O) of January and July resulted practically invariable against most of the microorganisms, besides the significant variation of the SM content due to the seasonal variation. Conclusion: Our results clearly confirmed the hypothesis of abiotic stress as an important regulating factor that significantly affects the biosynthesis of secondary metabolites and thus the presence of bioactive compounds. Acknowledgment: This work was supported by IKY - State Scholarship Foundation, Athens, Greece.Keywords: antibacterial screening, phytochemical profile, Pistacia lentiscus, abiotic stress
Procedia PDF Downloads 25586 Vitamin D Levels of Patients with Rheumatoid Arthritis in Kosova
Authors: Mjellma Rexhepi, Blerta Rexhepi Kelmendi, Blana Krasniqi, Shaip Krasniqi
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Rheumatoid arthritis is a chronic disease that causes inflammation of the joints which can be so severe that can cause not only deformities but also impairment of function that limits movement. This also contributes to the pain that accompanies this disease. This remains a problematic and challenging disease of modern medicine because treatment is still symptomatic. The main purpose of drug treatment is to reduce the activity of the disease, achieve remission, avoid disability and death. The etiology of the disease is idiopathic, but can also be linked to genetic, nongenetic factors such as hormonal, environmental or infectious. Current scientific evidence shows that vitamin D plays an important role in immune regulation mechanisms. Lack of this vitamin has been linked to loss of immune tolerance and the appearance of autoimmune processes, including rheumatoid arthritis. The purpose of the work was to define Vitamin D in patients hospitalized with rheumatoid arthritis in University Clinical Center of Kosova, as a basis of their connection with lifestyle and physical inactivity. The sample for the work was selected from patients with criteria met for rheumatoid arthritis who were hospitalized at the tertiary level of health care in Kosova. During the work have been investigated 100 consecutive patients fulfilling diagnostic criteria for rheumatoid arthritis, whereas in addition to the general characteristics are also determined the values of vitamin D at the beginning of hospitalization. The average age of the sample analyzed was 50.9±5.7 years old, with an average duration of rheumatoid arthritis disease 7.8±3.4 years. At the beginning of hospitalization, before treatment was initiated, the average value of vitamin D was 15.86±3.43, which according to current reference values is classified into the category of insufficient values. Correlating the duration of the disease, from the time of diagnosis to the day of hospitalization, on one side and the level of vitamin D on the other side, the negative correlation of a lower degree derived (r =-0.1). Physical activity affects the concentration of vitamin D in the blood through increased metabolism of fat and the release of vitamin D and its metabolites from adipose tissue. To now it is evident that physical activity is also accompanied by higher levels of vitamin D. In patients with rheumatoid arthritis, vitamin D levels were low compared to normal. Future works should be oriented toward investigating in detail the bone structure, quality of life and pain in patients with rheumatoid arthritis. More detailed scientific projects, with larger numbers of participants, should be designed for the future to clarify more possible mechanisms as factors related to this phenomenon, such as inactivity, lifestyle and the duration of the disease, as well as the importance of keeping vitamin D values at normal limits.Keywords: hospitalization, lifestyle, rheumatoid arthritis, vitamin D.
Procedia PDF Downloads 885 Cassava Plant Architecture: Insights from Genome-Wide Association Studies
Authors: Abiodun Olayinka, Daniel Dzidzienyo, Pangirayi Tongoona, Samuel Offei, Edwige Gaby Nkouaya Mbanjo, Chiedozie Egesi, Ismail Yusuf Rabbi
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Cassava (Manihot esculenta Crantz) is a major source of starch for various industrial applications. However, the traditional cultivation and harvesting methods of cassava are labour-intensive and inefficient, limiting the supply of fresh cassava roots for industrial starch production. To achieve improved productivity and quality of fresh cassava roots through mechanized cultivation, cassava cultivars with compact plant architecture and moderate plant height are needed. Plant architecture-related traits, such as plant height, harvest index, stem diameter, branching angle, and lodging tolerance, are critical for crop productivity and suitability for mechanized cultivation. However, the genetics of cassava plant architecture remain poorly understood. This study aimed to identify the genetic bases of the relationships between plant architecture traits and productivity-related traits, particularly starch content. A panel of 453 clones developed at the International Institute of Tropical Agriculture, Nigeria, was genotyped and phenotyped for 18 plant architecture and productivity-related traits at four locations in Nigeria. A genome-wide association study (GWAS) was conducted using the phenotypic data from a panel of 453 clones and 61,238 high-quality Diversity Arrays Technology sequencing (DArTseq) derived Single Nucleotide Polymorphism (SNP) markers that are evenly distributed across the cassava genome. Five significant associations between ten SNPs and three plant architecture component traits were identified through GWAS. We found five SNPs on chromosomes 6 and 16 that were significantly associated with shoot weight, harvest index, and total yield through genome-wide association mapping. We also discovered an essential candidate gene that is co-located with peak SNPs linked to these traits in M. esculenta. A review of the cassava reference genome v7.1 revealed that the SNP on chromosome 6 is in proximity to Manes.06G101600.1, a gene that regulates endodermal differentiation and root development in plants. The findings of this study provide insights into the genetic basis of plant architecture and yield in cassava. Cassava breeders could leverage this knowledge to optimize plant architecture and yield in cassava through marker-assisted selection and targeted manipulation of the candidate gene.Keywords: Manihot esculenta Crantz, plant architecture, DArtseq, SNP markers, genome-wide association study
Procedia PDF Downloads 6884 Radar Cross Section Modelling of Lossy Dielectrics
Authors: Ciara Pienaar, J. W. Odendaal, J. Joubert, J. C. Smit
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Radar cross section (RCS) of dielectric objects play an important role in many applications, such as low observability technology development, drone detection, and monitoring as well as coastal surveillance. Various materials are used to construct the targets of interest such as metal, wood, composite materials, radar absorbent materials, and other dielectrics. Since simulated datasets are increasingly being used to supplement infield measurements, as it is more cost effective and a larger variety of targets can be simulated, it is important to have a high level of confidence in the predicted results. Confidence can be attained through validation. Various computational electromagnetic (CEM) methods are capable of predicting the RCS of dielectric targets. This study will extend previous studies by validating full-wave and asymptotic RCS simulations of dielectric targets with measured data. The paper will provide measured RCS data of a number of canonical dielectric targets exhibiting different material properties. As stated previously, these measurements are used to validate numerous CEM methods. The dielectric properties are accurately characterized to reduce the uncertainties in the simulations. Finally, an analysis of the sensitivity of oblique and normal incidence scattering predictions to material characteristics is also presented. In this paper, the ability of several CEM methods, including method of moments (MoM), and physical optics (PO), to calculate the RCS of dielectrics were validated with measured data. A few dielectrics, exhibiting different material properties, were selected and several canonical targets, such as flat plates and cylinders, were manufactured. The RCS of these dielectric targets were measured in a compact range at the University of Pretoria, South Africa, over a frequency range of 2 to 18 GHz and a 360° azimuth angle sweep. This study also investigated the effect of slight variations in the material properties on the calculated RCS results, by varying the material properties within a realistic tolerance range and comparing the calculated RCS results. Interesting measured and simulated results have been obtained. Large discrepancies were observed between the different methods as well as the measured data. It was also observed that the accuracy of the RCS data of the dielectrics can be frequency and angle dependent. The simulated RCS for some of these materials also exhibit high sensitivity to variations in the material properties. Comparison graphs between the measured and simulation RCS datasets will be presented and the validation thereof will be discussed. Finally, the effect that small tolerances in the material properties have on the calculated RCS results will be shown. Thus the importance of accurate dielectric material properties for validation purposes will be discussed.Keywords: asymptotic, CEM, dielectric scattering, full-wave, measurements, radar cross section, validation
Procedia PDF Downloads 23683 Unraveling the Evolution of Mycoplasma Hominis Through Its Genome Sequence
Authors: Boutheina Ben Abdelmoumen Mardassi, Salim Chibani, Safa Boujemaa, Amaury Vaysse, Julien Guglielmini, Elhem Yacoub
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Background and aim: Mycoplasma hominis (MH) is a pathogenic bacterium belonging to the Mollicutes class. It causes a wide range of gynecological infections and infertility among adults. Recently, we have explored for the first time the phylodistribution of Tunisian M. hominis clinical strains using an expanded MLST. We have demonstrated their distinction into two pure lineages, which each corresponding to a specific pathotype: genital infections and infertility. The aim of this project is to gain further insight into the evolutionary dynamics and the specific genetic factors that distinguish MH pathotypes Methods: Whole genome sequencing of Mycoplasma hominis clinical strains was performed using illumina Miseq. Denovo assembly was performed using a publicly available in-house pipeline. We used prokka to annotate the genomes, panaroo to generate the gene presence matrix and Jolytree to establish the phylogenetic tree. We used treeWAS to identify genetic loci associated with the pathothype of interest from the presence matrix and phylogenetic tree. Results: Our results revealed a clear categorization of the 62 MH clinical strains into two distinct genetic lineages, with each corresponding to a specific pathotype.; gynecological infections and infertility[AV1] . Genome annotation showed that GC content is ranging between 26 and 27%, which is a known characteristic of Mycoplasma genome. Housekeeping genes belonging to the core genome are highly conserved among our strains. TreeWas identified 4 virulence genes associated with the pathotype gynecological infection. encoding for asparagine--tRNA ligase, restriction endonuclease subunit S, Eco47II restriction endonuclease, and transcription regulator XRE (involved in tolerance to oxidative stress). Five genes have been identified that have a statistical association with infertility, tow lipoprotein, one hypothetical protein, a glycosyl transferase involved in capsule synthesis, and pyruvate kinase involved in biofilm formation. All strains harbored an efflux pomp that belongs to the family of multidrug resistance ABC transporter, which confers resistance to a wide range of antibiotics. Indeed many adhesion factors and lipoproteins (p120, p120', p60, p80, Vaa) have been checked and confirmed in our strains with a relatively 99 % to 96 % conserved domain and hypervariable domain that represent 1 to 4 % of the reference sequence extracted from gene bank. Conclusion: In summary, this study led to the identification of specific genetic loci associated with distinct pathotypes in M hominis.Keywords: mycoplasma hominis, infertility, gynecological infections, virulence genes, antibiotic resistance
Procedia PDF Downloads 9482 Advances in Genome Editing and Future Prospects for Sorghum Improvement: A Review
Authors: Micheale Yifter Weldemichael, Hailay Mehari Gebremedhn, Teklehaimanot Hailesslasie Teklu
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Recent developments in targeted genome editing accelerated genetic research and opened new potentials to improve crops for better yields and quality. Given the significance of cereal crops as a primary source of food for the global population, the utilization of contemporary genome editing techniques like CRISPR/Cas9 is timely and crucial. CRISPR/Cas technology has enabled targeted genomic modifications, revolutionizing genetic research and exploration. Application of gene editing through CRISPR/Cas9 in enhancing sorghum is particularly vital given the current ecological, environmental, and agricultural challenges exacerbated by climate change. As sorghum is one of the main staple foods of our region and is known to be a resilient crop with a high potential to overcome the above challenges, the application of genome editing technology will enhance the investigation of gene functionality. CRISPR/Cas9 enables the improvement of desirable sorghum traits, including nutritional value, yield, resistance to pests and diseases, and tolerance to various abiotic stresses. Furthermore, CRISPR/Cas9 has the potential to perform intricate editing and reshape the existing elite sorghum varieties, and introduce new genetic variations. However, current research primarily focuses on improving the efficacy of the CRISPR/Cas9 system in successfully editing endogenous sorghum genes, making it a feasible and successful undertaking in sorghum improvement. Recent advancements and developments in CRISPR/Cas9 techniques have further empowered researchers to modify additional genes in sorghum with greater efficiency. Successful application and advancement of CRISPR techniques in sorghum will aid not only in gene discovery and the creation of novel traits that regulate gene expression and functional genomics but also in facilitating site-specific integration events. The purpose of this review is, therefore, to elucidate the current advances in sorghum genome editing and highlight its potential in addressing food security issues. It also assesses the efficiency of CRISPR-mediated improvement and its long-term effects on crop improvement and host resistance against parasites, including tissue-specific activity and the ability to induce resistance. This review ends by emphasizing the challenges and opportunities of CRISPR technology in combating parasitic plants and proposing directions for future research to safeguard global agricultural productivity.Keywords: CRISPR/Cas9, genome editing, quality, sorghum, stress, yield
Procedia PDF Downloads 3681 Biostimulant Activity of Chitooligomers: Effect of Different Degrees of Acetylation and Polymerization on Wheat Seedlings under Salt Stress
Authors: Xiaoqian Zhang, Ping Zou, Pengcheng Li
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Salt stress is one of the most serious abiotic stresses, and it can lead to the reduction of agricultural productivity. High salt concentration makes it more difficult for roots to absorb water and disturbs the homeostasis of cellular ions resulting in osmotic stress, ion toxicity and generation of reactive oxygen species (ROS). Compared with the normal physiological conditions, salt stress could inhibit the photosynthesis, break metabolic balance and damage cellular structures, and ultimately results in the reduction of crop yield. Therefore it is vital to develop practical methods for improving the salt tolerance of plants. Chitooligomers (COS) is partially depolymerized products of chitosan, which is consisted of D-glucosamine and N-acetyl-D-glucosamine. In agriculture, COS has the ability to promote plant growth and induce plant innate immunity. The bioactivity of COS closely related to its degree of polymerization (DP) and acetylation (DA). However, most of the previous reports fail to mention the function of COS with different DP and DAs in improving the capacity of plants against salt stress. Accordingly, in this study, chitooligomers (COS) with different degrees of DAs were used to test wheat seedlings response to salt stress. In addition, the determined degrees of polymerization (DPs) COS(DP 4-12) and a heterogeneous COS mixture were applied to explore the relationship between the DP of COSs and its effect on the growth of wheat seedlings in response to salt stress. It showed that COSs, the exogenous elicitor, could promote the growth of wheat seedling, reduce the malondialdehyde (MDA) concentration, and increase the activities of antioxidant enzymes. The results of mRNA expression level test for salt stress-responsive genes indicated that COS keep plants away from being hurt by the salt stress via the regulation of the concentration and the increased antioxidant enzymes activities. Moreover, it was found that the activities of COS was closely related to its Das and COS (DA: 50%) displayed the best salt resistance activity to wheat seedlings. The results also showed that COS with different DP could promote the growth of wheat seedlings under salt stress. COS with a DP (6-8) showed better activities than the other tested samples, implied its activity had a close relationship with its DP. After treatment with chitohexaose, chitoheptaose, and chitooctaose, the photosynthetic parameters were improved obviously. The soluble sugar and proline contents were improved by 26.7%-53.3% and 43.6.0%-70.2%, respectively, while the concentration of malondialdehyde (MDA) was reduced by 36.8% - 49.6%. In addition, the antioxidant enzymes activities were clearly activated. At the molecular level, the results revealed that they could obviously induce the expression of Na+/H+ antiporter genes. In general, these results were fundamental to the study of action mechanism of COS on promoting plant growth under salt stress and the preparation of plant growth regulator.Keywords: chitooligomers (COS), degree of polymerization (DP), degree of acetylation (DA), salt stress
Procedia PDF Downloads 17380 Identification of Candidate Gene for Root Development and Its Association With Plant Architecture and Yield in Cassava
Authors: Abiodun Olayinka, Daniel Dzidzienyo, Pangirayi Tongoona, Samuel Offei, Edwige Gaby Nkouaya Mbanjo, Chiedozie Egesi, Ismail Yusuf Rabbi
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Cassava (Manihot esculenta Crantz) is a major source of starch for various industrial applications. However, the traditional cultivation and harvesting methods of cassava are labour-intensive and inefficient, limiting the supply of fresh cassava roots for industrial starch production. To achieve improved productivity and quality of fresh cassava roots through mechanized cultivation, cassava cultivars with compact plant architecture and moderate plant height are needed. Plant architecture-related traits, such as plant height, harvest index, stem diameter, branching angle, and lodging tolerance, are critical for crop productivity and suitability for mechanized cultivation. However, the genetics of cassava plant architecture remain poorly understood. This study aimed to identify the genetic bases of the relationships between plant architecture traits and productivity-related traits, particularly starch content. A panel of 453 clones developed at the International Institute of Tropical Agriculture, Nigeria, was genotyped and phenotyped for 18 plant architecture and productivity-related traits at four locations in Nigeria. A genome-wide association study (GWAS) was conducted using the phenotypic data from a panel of 453 clones and 61,238 high-quality Diversity Arrays Technology sequencing (DArTseq) derived Single Nucleotide Polymorphism (SNP) markers that are evenly distributed across the cassava genome. Five significant associations between ten SNPs and three plant architecture component traits were identified through GWAS. We found five SNPs on chromosomes 6 and 16 that were significantly associated with shoot weight, harvest index, and total yield through genome-wide association mapping. We also discovered an essential candidate gene that is co-located with peak SNPs linked to these traits in M. esculenta. A review of the cassava reference genome v7.1 revealed that the SNP on chromosome 6 is in proximity to Manes.06G101600.1, a gene that regulates endodermal differentiation and root development in plants. The findings of this study provide insights into the genetic basis of plant architecture and yield in cassava. Cassava breeders could leverage this knowledge to optimize plant architecture and yield in cassava through marker-assisted selection and targeted manipulation of the candidate gene.Keywords: manihot esculenta crantz, plant architecture, dartseq, snp markers, genome-wide association study
Procedia PDF Downloads 9479 Effect of Hypoxia on AOX2 Expression in Chlamydomonas reinhardtii
Authors: Maria Ostroukhova, Zhanneta Zalutskaya, Elena Ermilova
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The alternative oxidase (AOX) mediates cyanide-resistant respiration, which bypasses proton-pumping complexes III and IV of the cytochrome pathway to directly transfer electrons from reduced ubiquinone to molecular oxygen. In Chlamydomonas reinhardtii, AOX is a monomeric protein that is encoded by two genes of discrete subfamilies, AOX1 and AOX2. Although AOX has been proposed to play essential roles in stress tolerance of organisms, the role of subfamily AOX2 is largely unknown. In C. reinhardtii, AOX2 was initially identified as one of constitutively low expressed genes. Like other photosynthetic organisms C. reinhardtii cells frequently experience periods of hypoxia. To examine AOX2 transcriptional regulation and role of AOX2 in hypoxia adaptation, real-time PCR analysis and artificial microRNA method were employed. Two experimental approaches have been used to induce the anoxic conditions: dark-anaerobic and light-anaerobic conditions. C. reinhardtii cells exposed to the oxygen deprivation have shown increased AOX2 mRNA levels. By contrast, AOX1 was not an anoxia-responsive gene. In C. reinhardtii, a subset of genes is regulated by transcription factor CRR1 in anaerobic conditions. Notable, the AOX2 promoter region contains the potential motif for CRR1 binding. Therefore, the role of CRR1 in the control of AOX2 transcription was tested. The CRR1-underexpressing strains, that were generated and characterized in this work, exhibited low levels of AOX2 transcripts under anoxic conditions. However, the transformants still slightly induced AOX2 gene expression in the darkness. These confirmed our suggestions that darkness is a regulatory stimulus for AOX genes in C. reinhardtii. Thus, other factors must contribute to AOX2 promoter activity under dark-anoxic conditions. Moreover, knock-down of CRR1 caused a complete reduction of AOX2 expression under light-anoxic conditions. These results indicate that (1) CRR1 is required for AOX2 expression during hypoxia, and (2) AOX2 gene is regulated by CRR1 together with yet-unknown regulatory factor(s). In addition, the AOX2-underexpressing strains were generated. The analysis of amiRNA-AOX2 strains suggested a role of this alternative oxidase in hypoxia adaptation of the alga. In conclusion, the results reported here show that C. reinhardtii AOX2 gene is stress inducible. CRR1 transcriptional factor is involved in the regulation of the AOX2 gene expression in the absence of oxygen. Moreover, AOX2 but not AOX1 functions under oxygen deprivation. This work was supported by Russian Science Foundation (research grant № 16-14-10004).Keywords: alternative oxidase 2, artificial microRNA approach, chlamydomonas reinhardtii, hypoxia
Procedia PDF Downloads 24078 Autophagy in the Midgut Epithelium of Spodoptera exigua Hübner (Lepidoptera: Noctuidae) Larvae Exposed to Various Cadmium Concentration - 6-Generational Exposure
Authors: Magdalena Maria Rost-Roszkowska, Alina Chachulska-Żymełka, Monika Tarnawska, Maria Augustyniak, Alina Kafel, Agnieszka Babczyńska
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Autophagy is a form of cell remodeling in which an internalization of organelles into vacuoles that are called autophagosomes occur. Autophagosomes are the targets of lysosomes, thus causing digestion of cytoplasmic components. Eventually, it can lead to the death of the entire cell. However, in response to several stress factors, e.g., starvation, heavy metals (e.g., cadmium) autophagy can also act as a pro-survival factor, protecting the cell against its death. The main aim of our studies was to check if the process of autophagy, which could appear in the midgut epithelium after Cd treatment, can be fixed during the following generations of insects. As a model animal, we chose the beet armyworm Spodoptera exigua Hübner (Lepidoptera: Noctuidae), a well-known polyphagous pest of many vegetable crops. We analyzed specimens at final larval stage (5th larval stage), due to its hyperfagy, resulting in great amount of cadmium assimilate. The culture consisted of two strains: a control strain (K) fed a standard diet, and a cadmium strain (Cd), fed on standard diet supplemented with cadmium (44 mg Cd per kg of dry weight of food) for 146 generations, both strains. In addition, the control insects were transferred to the Cd supplemented diet (5 mg Cd per kg of dry weight of food, 10 mg Cd per kg of dry weight of food, 20 mg Cd per kg of dry weight of food, 44 mg Cd per kg of dry weight of food). Therefore, we obtained Cd1, Cd2, Cd3 and KCd experimental groups. Autophagy has been examined using transmission electron microscope. During this process, degenerated organelles were surrounded by a membranous phagophore and enclosed in an autophagosome. Eventually, after the autophagosome fused with a lysosome, an autolysosome was formed and the process of the digestion of organelles began. During the 1st year of the experiment, we analyzed specimens of 6 generations in all the lines. The intensity of autophagy depends significantly on the generation, tissue and cadmium concentration in the insect rearing medium. In the Ist, IInd, IIIrd, IVth, Vth and VIth generation the intensity of autophagy in the midguts from cadmium-exposed strains decreased gradually according to the following order of strains: Cd1, Cd2, Cd3 and KCd. The higher amount of cells with autophagy was observed in Cd1 and Cd2. However, it was still higher than the percentage of cells with autophagy in the same tissues of the insects from the control and multigenerational cadmium strain. This may indicate that during 6-generational exposure to various Cd concentration, a preserved tolerance to cadmium was not maintained. The study has been financed by the National Science Centre Poland, grant no 2016/21/B/NZ8/00831.Keywords: autophagy, cell death, digestive system, ultrastructure
Procedia PDF Downloads 23277 Food Consumption and Adaptation to Climate Change: Evidence from Ghana
Authors: Frank Adusah-Poku, John Bosco Dramani, Prince Boakye Frimpong
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Climate change is considered a principal threat to human existence and livelihood. The persistence and intensity of droughts and floods in recent years have adversely affected food production systems and value chains, making it impossible to end global hunger by 2030. Thus, this study aims to examine the effect of climate change on food consumption for both farm and non-farm households in Ghana. An important focus of the analysis is to investigate how climate change affects alternative dimensions of food security, examine the extent to which these effects vary across heterogeneous groups, and explore the channels through which climate change affects food consumption. Finally, we conducted a pilot study to understand the significance of farm and non-farm diversification measures in reducing the harmful impact of climate change on farm households. The approach of this article is to use two secondary and one primary datasets. The first secondary dataset is the Ghana Socioeconomic Panel Survey (GSPS). The GSPS is a household panel dataset collected during the period 2009 to 2019. The second dataset is monthly district rainfall and temperature gridded data from the Ghana Meteorological Agency. This data was matched to the GSPS dataset at the district level. Finally, the primary data was obtained from a survey of farm and non-farm adaptation practices used by farmers in three regions in Northern Ghana. The study employed the household fixed effects model to estimate the effect of climate change (measured by temperature and rainfall) on food consumption in Ghana. Again, it used the spatial and temporal variation in temperature and rainfall across the districts in Ghana to estimate the household-level model. Evidence of potential mechanisms through which climate change affects food consumption was explored using two steps. First, the potential mechanism variables were regressed on temperature, rainfall, and the control variables. In the second and final step, the potential mechanism variables were included as extra covariates in the first model. The results revealed that extreme average temperature and drought had caused a decrease in food consumption as well as reduced the intake of important food nutrients such as carbohydrates, protein and vitamins. The results further indicated that low rainfall increased food insecurity among households with no education compared with those with primary and secondary education. Again, non-farm activity and silos have been revealed as the transmission pathways through which the effect of climate change on farm households can be moderated. Finally, the results indicated over 90% of the small-holder farmers interviewed had no farm diversification adaptation strategies for climate change, and a little over 50% of the farmers owned unskilled or manual non-farm economic ventures. This makes it very difficult for the majority of the farmers to withstand climate-related shocks. These findings suggest that achieving the Sustainable Development Goal of Zero Hunger by 2030 needs an integrated approach, such as reducing the over-reliance on rainfed agriculture, educating farmers, and implementing non-farm interventions to improve food consumption in Ghana.Keywords: climate change, food consumption, Ghana, non-farm activity
Procedia PDF Downloads 476 The Audiovisual Media as a Metacritical Ludicity Gesture in the Musical-Performatic and Scenic Works of Caetano Veloso and David Bowie
Authors: Paulo Da Silva Quadros
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This work aims to point out comparative parameters between the artistic production of two exponents of the contemporary popular culture scene: Caetano Veloso (Brazil) and David Bowie (England). Both Caetano Veloso and David Bowie were pioneers in establishing an aesthetic game between various artistic expressions at the service of the music-visual scene, that is, the conceptual interconnections between several forms of aesthetic processes, such as fine arts, theatre, cinema, poetry, and literature. There are also correlations in their expressive attitudes of art, especially regarding the dialogue between the fields of art and politics (concern with respect to human rights, human dignity, racial issues, tolerance, gender issues, and sexuality, among others); the constant tension and cunning game between market, free expression and critical sense; the sophisticated, playful mechanisms of metalanguage and aesthetic metacritique. Fact is that both of them almost came to cooperate with each other in the 1970s when Caetano was in exile in England, and when both had at the same time the same music producer, who tried to bring them closer, noticing similar aesthetic qualities in both artistic works, which was later glimpsed by some music critics. Among many of the most influential issues in Caetano's and Bowie's game of artistic-aesthetic expression are, for example, the ideas advocated by the sensation of strangeness (Albert Camus), art as transcendence (Friedrich Nietzsche), the deconstruction and reconstruction of auratic reconfiguration of artistic signs (Walter Benjamin and Andy Warhol). For deepen more theoretical issues, the following authors will be used as supportive interpretative references: Hans-Georg Gadamer, Immanuel Kant, Friedrich Schiller, Johan Huizinga. In addition to the aesthetic meanings of Ars Ludens characteristics of the two artists, the following supporting references will be also added: the question of technique (Martin Heidegger), the logic of sense (Gilles Deleuze), art as an event and the sense of the gesture of art ( Maria Teresa Cruz), the society of spectacle (Guy Debord), Verarbeitung and Durcharbeitung (Sigmund Freud), the poetics of interpretation and the sign of relation (Cremilda Medina). The purpose of such interpretative references is to seek to understand, from a cultural reading perspective (cultural semiology), some significant elements in the dynamics of aesthetic and media interconnections of both artists, which made them as some of the most influential interlocutors in contemporary music aesthetic thought, as a playful vivid experience of life and art.Keywords: Caetano Veloso, David Bowie, music aesthetics, symbolic playfulness, cultural reading
Procedia PDF Downloads 16475 Effect of Fermented Orange Juice Intake on Urinary 6‑Sulfatoxymelatonin in Healthy Volunteers
Authors: I. Cerrillo, A. Carrillo-Vico, M. A. Ortega, B. Escudero-López, N. Álvarez-Sánchez, F. Martín, M. S. Fernández-Pachón
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Melatonin is a bioactive compound involved in multiple biological activities such as glucose tolerance, circadian rhythm regulation, antioxidant defense or immune system action. In elderly subjects the intake of foods and drinks rich in melatonin is very important due to its endogenous level decreases with age. Alcoholic fermentation is a process carried out in fruits, vegetables and legumes to obtain new products with improved bioactive compounds profile in relation to original substrates. Alcoholic fermentation process carried out by Saccharomycetaceae var. Pichia kluyveri induces an important synthesis of melatonin in orange juice. A novel beverage derived of fermented orange juice could be a promising source of this bioactive compound. The aim of the present study was to determine whether the acute intake of fermented orange juice increase the levels of urinary 6-sulfatoxymelatonin in healthy humans. Nine healthy volunteers (7 women and 2 men), aged between 20 and 25 years old and BMI of 21.1 2.4 kg/m2, were recruited. On the study day, participants ingested 500 mL of fermented orange juice. The first urine collection was made before fermented orange juice consumption (basal). The rest of urine collections were made in the following time intervals after fermented orange juice consumption: 0-2, 2-5, 5-10, 10- 15 and 15-24 hours. During the experimental period only the consumption of water was allowed. At lunch time a meal was provided (60 g of white bread, two slices of ham, a slice of cheese, 125 g of sweetened natural yoghurt and water). The subjects repeated the protocol with orange juice following a 2-wk washout period between both types of beverages. The levels of 6-sulfatoxymelatonin (6-SMT) were measured in urine recollected at different time points using the Melatonin-Sulfate Urine ELISA (IBL International GMBH, Hamburg, Germany). Levels of 6-SMT were corrected to those of creatinine for each sample. A significant (p < 0.05) increase in urinary 6-SMT levels was observed between 2-5 hours after fermented orange juice ingestion with respect to basal values (increase of 67,8 %). The consumption of orange juice did not induce any significant change in urinary 6-SMT levels. In addition, urinary 6-SMT levels obtained between 2-5 hours after fermented orange juice ingestion (115,6 ng/mg) were significantly different (p < 0.05) from those of orange juice (42,4 ng/mg). The enhancement of urinary 6-SMT after the ingestion of 500 mL of fermented orange juice in healthy humans compared to orange juice could be an important advantage of this novel product as an excellent source of melatonin. Fermented orange juice could be a new functional food, and its consumption could exert a potentially positive effect on health in both the maintenance of health status and the prevention of chronic diseases.Keywords: fermented orange juice, functional beverage, healthy human, melatonin
Procedia PDF Downloads 40574 Coping with Incompatible Identities in Russia: Case of Orthodox Gays
Authors: Siuzan Uorner
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The era of late modernity is characterized, on the one hand, by social disintegration, values of personal freedom, tolerance, and self-expression. Boundaries between the accessible and the elitist, normal and abnormal are blurring. On the other hand, traditional social institutions, such as religion (especially Russian Orthodox Church), exist, criticizing lifestyle and worldview other than conventionally structured canons. Despite the declared values and opportunities in late modern society, people's freedom is ambivalent. Personal identity and its aspects are becoming a subject of choice. Hence, combinations of identity aspects can be incompatible. Our theoretical framework is based on P. Ricoeur's concept of narrative identity and hermeneutics, E. Goffman’s theory of social stigma, self-presentation, discrepant roles and W. James lectures about varieties of religious experience. This paper aims to reconstruct ways of coping with incompatible identities of Orthodox gays (an extreme sampling of a combination of sexual orientation and religious identity in a heteronormative society). This study focuses on the discourse of Orthodox gay parishioners and ROC gay priests in Russia (sampling ‘hard to reach’ populations because of the secrecy of gay community in ROC and sensitivity of the topic itself). We conducted a qualitative research design, using in-depth personal semi-structured online-interviews. Recruiting of informants took place in 'Nuntiare et Recreare' (Russian movement of religious LGBT) page in VKontakte through the post with an invitation to participate in the research. In this work, we analyzed interview transcripts using axial coding. We chose the Grounded Theory methodology to construct a theory from empirical data and contribute to the growing body of knowledge in ways of harmonizing incompatible identities in late modern societies. The research has found that there are two types of conflicts Orthodox gays meet with: canonic contradictions (postulates of Scripture and its interpretations) and problems in social interaction, mainly with ROC priests and Orthodox parishioners. We have revealed semantic meanings of most commonly used words that appear in the narratives (words such as ‘love’, ‘sin’, ‘religion’ etc.). Finally, we have reconstructed biographical patterns of LGBT social movements’ involvement. This paper argues that all incompatibilities are harmonizing in the narrative itself. As Ricoeur has suggested, the narrative configuration allows the speaker to gather facts and events together and to compose causal relationships between them. Sexual orientation and religious identity are getting along and harmonizing in the narrative.Keywords: gay priests, incompatible identities, narrative identity, Orthodox gays, religious identity, ROC, sexual orientation
Procedia PDF Downloads 13773 Effect of Salinity and Heavy Metal Toxicity on Gene Expression, and Morphological Characteristics in Stevia rebaudiana Plants
Authors: Umara Nissar Rafiqi, Irum Gul, Nazima Nasrullah, Monica Saifi, Malik Z. Abdin
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Background: Stevia rebaudiana, a member of Asteraceae family is an important medicinal plant and produces a commercially used non-caloric natural sweetener, which is also an alternate herbal cure for diabetes. Steviol glycosides are the main sweetening compounds present in these plants. Secondary metabolites are crucial to the adaption of plants to the environment and its overcoming stress conditions. In agricultural procedures, the abiotic stresses like salinity, high metal toxicity and drought, in particular, are responsible for the majority of the reduction that differentiates yield potential from harvestable yield. Salt stress and heavy metal toxicity lead to increased production of reactive oxygen species (ROS). To avoid oxidative damage due to ROS and osmotic stress, plants have a system of anti-oxidant enzymes along with several stress induced enzymes. This helps in scavenging the ROS and relieve the osmotic stress in different cell compartments. However, whether stress induced toxicity modulates the activity of these enzymes in Stevia rebaudiana is poorly understood. Aim: The present study focussed on the effect of salinity, heavy metal toxicity (lead and mercury) on physiological traits and transcriptional profiling of Stevia rebaudiana. Method: Stevia rebaudiana plants were collected from the Central Institute of Medicinal and Aromatic plants (CIMAP), Patnagar, India and maintained under controlled conditions in a greenhouse at Hamdard University, Delhi, India. The plants were subjected to different concentrations of salt (0, 25, 50 and 75 mM respectively) and heavy metals, lead and mercury (0, 100, 200 and 300 µM respectively). The physiological traits such as shoot length, root numbers, leaf growth were evaluated. The samples were collected at different developmental stages and analysed for transcription profiling by RT-PCR. Transcriptional studies in stevia rebaudiana involves important antioxidant enzymes: catalase (CAT), superoxide dismutase (SOD), cytochrome P450 monooxygenase (CYP) and stress induced aquaporin (AQU), auxin repressed protein (ARP-1), Ndhc gene. The data was analysed using GraphPad Prism and expressed as mean ± SD. Result: Low salinity and lower metal toxicity did not affect the fresh weight of the plant. However, this was substantially decreased by 55% at high salinity and heavy metal treatment. With increasing salinity and heavy metal toxicity, the values of all studied physiological traits were significantly decreased. Chlorosis in treated plants was also observed which could be due to changes in Fe:Zn ratio. At low concentrations (upto 25 mM) of NaCl and heavy metals, we did not observe any significant difference in the gene expressions of treated plants compared to control plants. Interestingly, at high salt concentration and high metal toxicity, a significant increase in the expression profile of stress induced genes was observed in treated plants compared to control (p < 0.005). Conclusion: Stevia rebaudiana is tolerant to lower salt and heavy metal concentration. This study also suggests that with the increase in concentrations of salt and heavy metals, harvest yield of S. rebaudiana was hampered.Keywords: Stevia rebaudiana, natural sweetener, salinity, heavy metal toxicity
Procedia PDF Downloads 19472 Development and Characterization of Topical 5-Fluorouracil Solid Lipid Nanoparticles for the Effective Treatment of Non-Melanoma Skin Cancer
Authors: Sudhir Kumar, V. R. Sinha
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Background: The topical and systemic toxicity associated with present nonmelanoma skin cancer (NMSC) treatment therapy using 5-Fluorouracil (5-FU) make it necessary to develop a novel delivery system having lesser toxicity and better control over drug release. Solid lipid nanoparticles offer many advantages like: controlled and localized release of entrapped actives, nontoxicity, and better tolerance. Aim:-To investigate safety and efficacy of 5-FU loaded solid lipid nanoparticles as a topical delivery system for the treatment of nonmelanoma skin cancer. Method: Topical solid lipid nanoparticles of 5-FU were prepared using Compritol 888 ATO (Glyceryl behenate) as lipid component and pluronic F68 (Poloxamer 188), Tween 80 (Polysorbate 80), Tyloxapol (4-(1,1,3,3-Tetramethylbutyl) phenol polymer with formaldehyde and oxirane) as surfactants. The SLNs were prepared with emulsification method. Different formulation parameters viz. type and ratio of surfactant, ratio of lipid and ratio of surfactant:lipid were investigated on particle size and drug entrapment efficiency. Results: Characterization of SLNs like–Transmission Electron Microscopy (TEM), Differential Scannig calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), Particle size determination, Polydispersity index, Entrapment efficiency, Drug loading, ex vivo skin permeation and skin retention studies, skin irritation and histopathology studies were performed. TEM results showed that shape of SLNs was spherical with size range 200-500nm. Higher encapsulation efficiency was obtained for batches having higher concentration of surfactant and lipid. It was found maximum 64.3% for SLN-6 batch with size of 400.1±9.22 nm and PDI 0.221±0.031. Optimized SLN batches and marketed 5-FU cream were compared for flux across rat skin and skin drug retention. The lesser flux and higher skin retention was obtained for SLN formulation in comparison to topical 5-FU cream, which ensures less systemic toxicity and better control of drug release across skin. Chronic skin irritation studies lacks serious erythema or inflammation and histopathology studies showed no significant change in physiology of epidermal layers of rat skin. So, these studies suggest that the optimized SLN formulation is efficient then marketed cream and safer for long term NMSC treatment regimens. Conclusion: Topical and systemic toxicity associated with long-term use of 5-FU, in the treatment of NMSC, can be minimized with its controlled release with significant drug retention with minimal flux across skin. The study may provide a better alternate for effective NMSC treatment.Keywords: 5-FU, topical formulation, solid lipid nanoparticles, non melanoma skin cancer
Procedia PDF Downloads 51571 Salmonella Emerging Serotypes in Northwestern Italy: Genetic Characterization by Pulsed-Field Gel Electrophoresis
Authors: Clara Tramuta, Floris Irene, Daniela Manila Bianchi, Monica Pitti, Giulia Federica Cazzaniga, Lucia Decastelli
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This work presents the results obtained by the Regional Reference Centre for Salmonella Typing (CeRTiS) in a retrospective study aimed to investigate, through Pulsed-field Gel Electrophoresis (PFGE) analysis, the genetic relatedness of emerging Salmonella serotypes of human origin circulating in North-West of Italy. Furthermore, the goal of this work was to create a Regional database to facilitate foodborne outbreak investigation and to monitor them at an earlier stage. A total of 112 strains, isolated from 2016 to 2018 in hospital laboratories, were included in this study. The isolates were previously identified as Salmonella according to standard microbiological techniques and serotyping was performed according to ISO 6579-3 and the Kaufmann-White scheme using O and H antisera (Statens Serum Institut®). All strains were characterized by PFGE: analysis was conducted according to a standardized PulseNet protocol. The restriction enzyme XbaI was used to generate several distinguishable genomic fragments on the agarose gel. PFGE was performed on a CHEF Mapper system, separating large fragments and generating comparable genetic patterns. The agarose gel was then stained with GelRed® and photographed under ultraviolet transillumination. The PFGE patterns obtained from the 112 strains were compared using Bionumerics version 7.6 software with the Dice coefficient with 2% band tolerance and 2% optimization. For each serotype, the data obtained with the PFGE were compared according to the geographical origin and the year in which they were isolated. Salmonella strains were identified as follow: S. Derby n. 34; S. Infantis n. 38; S. Napoli n. 40. All the isolates had appreciable restricted digestion patterns ranging from approximately 40 to 1100 kb. In general, a fairly heterogeneous distribution of pulsotypes has emerged in the different provinces. Cluster analysis indicated high genetic similarity (≥ 83%) among strains of S. Derby (n. 30; 88%), S. Infantis (n. 36; 95%) and S. Napoli (n. 38; 95%) circulating in north-western Italy. The study underlines the genomic similarities shared by the emerging Salmonella strains in Northwest Italy and allowed to create a database to detect outbreaks in an early stage. Therefore, the results confirmed that PFGE is a powerful and discriminatory tool to investigate the genetic relationships among strains in order to monitoring and control Salmonellosis outbreak spread. Pulsed-field gel electrophoresis (PFGE) still represents one of the most suitable approaches to characterize strains, in particular for the laboratories for which NGS techniques are not available.Keywords: emerging Salmonella serotypes, genetic characterization, human strains, PFGE
Procedia PDF Downloads 10570 Nutritional Education in Health Resort Institutions in the Face of Demographic and Epidemiological Changes in Poland
Authors: J. Woźniak-Holecka, T. Holecki, S. Jaruga
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Spa treatment is an important area of the health care system in Poland due to the increasing needs of the population and the context of historical conditions for this form of therapy. It extends the range of financing possibilities of the outlets and increases the potential of spa services, which is very important in the context of demographic and epidemiological changes. The main advantages of spa treatment services include its relatively wide availability, low risk of side effects, good patient tolerance, long-lasting curative effect and a relatively low cost. In addition, patients should be provided with a proper diet and enable participation in health education and health promotion classes aimed at health problems consistent with the treatment profile. Challenges for global health care systems include a sharp increase in spending on benefits, dynamic development of health technologies and growing social expectations. This requires extending the competences of health resort facilities for health promotion. Within each type of health resort institutions in Poland, nutritional education services are implemented, aimed at creating and consolidating proper eating habits. Choosing the right diet can speed up recovery or become one of the methods to alleviate the symptoms of chronic diseases. During spa treatment patient learns the principles of rational nutrition and adequate dietotherapy to his diseases. The aim of the project is to assess the frequency and quality of nutritional education provided to patients in health resort facilities in a nationwide perspective. The material for the study will be data obtained as part of an in-depth interview conducted among Heads of Nutrition Departments of selected institutions. The use of nutritional education in a health resort may be an important goal of implementing the state health policy as a useful tool to reduce the risk of diet-related diseases. Recognizing nutritional education in health resort institutions as a type of full-value health service can be effective system support for health policy, including seniors, due to demographic changes currently occurring in the Polish population. Furthermore, it is necessary to increase the interest and motivation of patients to follow the recommendations of nutritional education, because it will bring tangible benefits for the long-term effects of therapy and care should be taken for the form and methodology of nutrition education implemented in health resort institutions. Finally it is necessary to construct an educational offer in terms of selected groups of patients with the highest health needs: the elderly and the disabled. In conclusion, it can be said that the system of nutritional education implemented in polish health resort institutions should be subjected to global changes and strong systemic correction.Keywords: health care system, nutritional education, public health, spa and treatment
Procedia PDF Downloads 11469 Modulation of Receptor-Activation Due to Hydrogen Bond Formation
Authors: Sourav Ray, Christoph Stein, Marcus Weber
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A new class of drug candidates, initially derived from mathematical modeling of ligand-receptor interactions, activate the μ-opioid receptor (MOR) preferentially at acidic extracellular pH-levels, as present in injured tissues. This is of commercial interest because it may preclude the adverse effects of conventional MOR agonists like fentanyl, which include but are not limited to addiction, constipation, sedation, and apnea. Animal studies indicate the importance of taking the pH value of the chemical environment of MOR into account when designing new drugs. Hydrogen bonds (HBs) play a crucial role in stabilizing protein secondary structure and molecular interaction, such as ligand-protein interaction. These bonds may depend on the pH value of the chemical environment. For the MOR, antagonist naloxone and agonist [D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (DAMGO) form HBs with ionizable residue HIS 297 at physiological pH to modulate signaling. However, such interactions were markedly reduced at acidic pH. Although fentanyl-induced signaling is also diminished at acidic pH, HBs with HIS 297 residue are not observed at either acidic or physiological pH for this strong agonist of the MOR. Molecular dynamics (MD) simulations can provide greater insight into the interaction between the ligand of interest and the HIS 297 residue. Amino acid protonation states are adjusted to the model difference in system acidity. Unbiased and unrestrained MD simulations were performed, with the ligand in the proximity of the HIS 297 residue. Ligand-receptor complexes were embedded in 1-palmitoyl-2-oleoyl-sn glycero-3-phosphatidylcholine (POPC) bilayer to mimic the membrane environment. The occurrence of HBs between the different ligands and the HIS 297 residue of MOR at acidic and physiological pH values were tracked across the various simulation trajectories. No HB formation was observed between fentanyl and HIS 297 residue at either acidic or physiological pH. Naloxone formed some HBs with HIS 297 at pH 5, but no such HBs were noted at pH 7. Interestingly, DAMGO displayed an opposite yet more pronounced HB formation trend compared to naloxone. Whereas a marginal number of HBs could be observed at even pH 5, HBs with HIS 297 were more stable and widely present at pH 7. The HB formation plays no and marginal role in the interaction of fentanyl and naloxone, respectively, with the HIS 297 residue of MOR. However, HBs play a significant role in the DAMGO and HIS 297 interaction. Post DAMGO administration, these HBs might be crucial for the remediation of opioid tolerance and restoration of opioid sensitivity. Although experimental studies concur with our observations regarding the influence of HB formation on the fentanyl and DAMGO interaction with HIS 297, the same could not be conclusively stated for naloxone. Therefore, some other supplementary interactions might be responsible for the modulation of the MOR activity by naloxone binding at pH 7 but not at pH 5. Further elucidation of the mechanism of naloxone action on the MOR could assist in the formulation of cost-effective naloxone-based treatment of opioid overdose or opioid-induced side effects.Keywords: effect of system acidity, hydrogen bond formation, opioid action, receptor activation
Procedia PDF Downloads 17468 Rational Approach to Analysis and Construction of Curved Composite Box Girders in Bridges
Authors: Dongming Feng, Fangyin Zhang, Liling Cao
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Horizontally curved steel-concrete composite box girders are extensively used in highway bridges. They consist of reinforced concrete deck on top of prefabricated steel box section beam which exhibits a high torsional rigidity to resist torsional effects induced by the curved structural geometry. This type of structural system is often constructed in two stages. The composite section will take the tension mainly by the steel box and, the compression by the concrete deck. The steel girders are delivered in large pre-fabricated U-shaped sections that are designed for ease of construction. They are then erected on site and overlaid by cast-in-place reinforced concrete deck. The functionality of the composite section is not achieved until the closed section is formed by fully cured concrete. Since this kind of composite section is built in two stages, the erection of the open steel box presents some challenges to contractors. When the reinforced concrete slab is cast-in-place, special care should be taken on bracings that can prevent the open U-shaped steel box from global and local buckling. In the case of multiple steel boxes, the design detailing should pay enough attention to the installation requirement of the bracings connecting adjacent steel boxes to prevent the global buckling. The slope in transverse direction and grade in longitudinal direction will result in some local deformation of the steel boxes that affect the connection of the bracings. During the design phase, it is common for engineers to model the curved composite box girder using one-dimensional beam elements. This is adequate to analyze the global behavior, however, it is unable to capture the local deformation which affects the installation of the field bracing connection. The presence of the local deformation may become a critical component to control the construction tolerance, and overlooking this deformation will produce inadequate structural details that eventually cause misalignment in field and erection failure. This paper will briefly describe the construction issues we encountered in real structures, investigate the difference between beam element modeling and shell/solid element modeling, and their impact on the different construction stages. P-delta effect due to the slope and curvature of the composite box girder is analyzed, and the secondary deformation is compared to the first-order response and evaluated for its impact on installation of lateral bracings. The paper will discuss the rational approach to prepare construction documents and recommendations are made on the communications between engineers, erectors, and fabricators to smooth out construction process.Keywords: buckling, curved composite box girder, stage construction, structural detailing
Procedia PDF Downloads 12067 Climate Change Adaptation Success in a Low Income Country Setting, Bangladesh
Authors: Tanveer Ahmed Choudhury
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Background: Bangladesh is one of the largest deltas in the world, with high population density and high rates of poverty and illiteracy. 80% of the country is on low-lying floodplains, leaving the country one of the most vulnerable to the adverse effects of climate change: sea level rise, cyclones and storms, salinity intrusion, rising temperatures and heavy monsoon downpours. Such climatic events already limit Economic Development in the country. Although Bangladesh has had little responsibility in contributing to global climatic change, it is vulnerable to both its direct and indirect impacts. Real threats include reduced agricultural production, worsening food security, increased incidence of flooding and drought, spreading disease and an increased risk of conflict over scarce land and water resources. Currently, 8.3 million Bangladeshis live in cyclone high risk areas. However, by 2050 this is expected to grow to 20.3 million people, if proper adaptive actions are not taken. Under a high emissions scenario, an additional 7.6 million people will be exposed to very high salinity by 2050 compared to current levels. It is also projected that, an average of 7.2 million people will be affected by flooding due to sea level rise every year between 2070-2100 and If global emissions decrease rapidly and adaptation interventions are taken, the population affected by flooding could be limited to only about 14,000 people. To combat the climate change adverse effects, Bangladesh government has initiated many adaptive measures specially in infrastructure and renewable energy sector. Government is investing huge money and initiated many projects which have been proved very success full. Objectives: The objective of this paper is to describe some successful measures initiated by Bangladesh government in its effort to make the country a Climate Resilient. Methodology: Review of operation plan and activities of different relevant Ministries of Bangladesh government. Result: The following initiative projects, programs and activities are considered as best practices for Climate Change adaptation successes for Bangladesh: 1. The Infrastructure Development Company Limited (IDCOL); 2. Climate Change and Health Promotion Unit (CCHPU); 3. The Climate Change Trust Fund (CCTF); 4. Community Climate Change Project (CCCP); 5. Health, Population, Nutrition Sector Development Program (HPNSDP, 2011-2016)- "Climate Change and Environmental Issues"; 6. Ministry of Health and Family Welfare, Bangladesh and WHO Collaboration; - National Adaptation Plan. -"Building adaptation to climate change in health in least developed countries through resilient WASH". 7. COP-21 “Climate and health country profile -2015 Bangladesh. Conclusion: Due to a vast coastline, low-lying land and abundance of rivers, Bangladesh is highly vulnerable to climate change. Having extensive experience with facing natural disasters, Bangladesh has developed a successful adaptation program, which led to a significant reduction in casualties from extreme weather events. In a low income country setting, Bangladesh had successfully adapted various projects and initiatives to combat future Climate Change challenges.Keywords: climate, change, success, Bangladesh
Procedia PDF Downloads 24866 Genetics of Pharmacokinetic Drug-Drug Interactions of Most Commonly Used Drug Combinations in the UK: Uncovering Unrecognised Associations
Authors: Mustafa Malki, Ewan R. Pearson
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Tools utilized by health care practitioners to flag potential adverse drug reactions secondary to drug-drug interactions ignore individual genetic variation, which has the potential to markedly alter the severity of these interactions. To our best knowledge, there have been limited published studies on the impact of genetic variation on drug-drug interactions. Therefore, our aim in this project is the discovery of previously unrecognized, clinically important drug-drug-gene interactions (DDGIs) within the list of most commonly used drug combinations in the UK. The UKBB database was utilized to identify the top most frequently prescribed drug combinations in the UK with at least one route of interaction (over than 200 combinations were identified). We have recognised 37 common and unique interacting genes considering all of our drug combinations. Out of around 600 potential genetic variants found in these 37 genes, 100 variants have met the selection criteria (common variant with minor allele frequency ≥ 5%, independence, and has passed HWE test). The association between these variants and the use of each of our top drug combinations has been tested with a case-control analysis under the log-additive model. As the data is cross-sectional, drug intolerance has been identified from the genotype distribution as presented by the lower percentage of patients carrying the risky allele and on the drug combination compared to those free of these risk factors and vice versa with drug tolerance. In GoDARTs database, the same list of common drug combinations identified by the UKBB was utilized here with the same list of candidate genetic variants but with the addition of 14 new SNPs so that we have a total of 114 variants which have met the selection criteria in GoDARTs. From the list of the top 200 drug combinations, we have selected 28 combinations where the two drugs in each combination are known to be used chronically. For each of our 28 combinations, three drug response phenotypes have been identified (drug stop/switch, dose decrease, or dose increase of any of the two drugs during their interaction). The association between each of the three phenotypes belonging to each of our 28 drug combinations has been tested against our 114 candidate genetic variants. The results show replication of four findings between both databases : (1) Omeprazole +Amitriptyline +rs2246709 (A > G) variant in CYP3A4 gene (p-values and ORs with the UKBB and GoDARTs respectively = 0.048,0.037,0.92,and 0.52 (dose increase phenotype)) (2) Simvastatin + Ranitidine + rs9332197 (T > C) variant in CYP2C9 gene (0.024,0.032,0.81, and 5.75 (drug stop/switch phenotype)) (3) Atorvastatin + Doxazosin + rs9282564 (T > C) variant in ABCB1 gene (0.0015,0.0095,1.58,and 3.14 (drug stop/switch phenotype)) (4) Simvastatin + Nifedipine + rs2257401 (C > G) variant in CYP3A7 gene (0.025,0.019,0.77,and 0.30 (drug stop/switch phenotype)). In addition, some other non-replicated, but interesting, significant findings were detected. Our work also provides a great source of information for researchers interested in DD, DG, or DDG interactions studies as it has highlighted the top common drug combinations in the UK with recognizing 114 significant genetic variants related to drugs' pharmacokinetic.Keywords: adverse drug reactions, common drug combinations, drug-drug-gene interactions, pharmacogenomics
Procedia PDF Downloads 16265 Influence of Dryer Autumn Conditions on Weed Control Based on Soil Active Herbicides
Authors: Juergen Junk, Franz Ronellenfitsch, Michael Eickermann
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An appropriate weed management in autumn is a prerequisite for an economically successful harvest in the following year. In Luxembourg oilseed rape, wheat and barley is sown from August until October, accompanied by a chemical weed control with soil active herbicides, depending on the state of the weeds and the meteorological conditions. Based on regular ground and surface water-analysis, high levels of contamination by transformation products of respective herbicide compounds have been found in Luxembourg. The most ideal conditions for incorporating soil active herbicides are single rain events. Weed control may be reduced if application is made when weeds are under drought stress or if repeated light rain events followed by dry spells, because the herbicides tend to bind tightly to the soil particles. These effects have been frequently reported for Luxembourg throughout the last years. In the framework of a multisite long-term field experiment (EFFO) weed monitoring, plants observations and corresponding meteorological measurements were conducted. Long-term time series (1947-2016) from the SYNOP station Findel-Airport (WMO ID = 06590) showed a decrease in the number of days with precipitation. As the total precipitation amount has not significantly changed, this indicates a trend towards rain events with higher intensity. All analyses are based on decades (10-day periods) for September and October of each individual year. To assess the future meteorological conditions for Luxembourg, two different approaches were applied. First, multi-model ensembles from the CORDEX experiments (spatial resolution ~12.5 km; transient projections until 2100) were analysed for two different Representative Concentration Pathways (RCP8.5 and RCP4.5), covering the time span from 2005 until 2100. The multi-model ensemble approach allows for the quantification of the uncertainties and also to assess the differences between the two emission scenarios. Second, to assess smaller scale differences within the country a high resolution model projection using the COSMO-LM model was used (spatial resolution 1.3 km). To account for the higher computational demands, caused by the increased spatial resolution, only 10-year time slices have been simulated (reference period 1991-2000; near future 2041-2050 and far future 2091-2100). Statistically significant trends towards higher air temperatures, +1.6 K for September (+5.3 K far future) and +1.3 K for October (+4.3 K), were predicted for the near future compared to the reference period. Precipitation simultaneously decreased by 9.4 mm (September) and 5.0 mm (October) for the near future and -49 mm (September) and -10 mm (October) in the far future. Beside the monthly values also decades were analyzed for the two future time periods of the CLM model. For all decades of September and October the number of days with precipitation decreased for the projected near and far future. Changes in meteorological variables such as air temperature and precipitation did already induce transformations in weed societies (composition, late-emerging etc.) of arable ecosystems in Europe. Therefore, adaptations of agronomic practices as well as effective weed control strategies must be developed to maintain crop yield.Keywords: CORDEX projections, dry spells, ensembles, weed management
Procedia PDF Downloads 23464 Synthesis, Molecular Modeling and Study of 2-Substituted-4-(Benzo[D][1,3]Dioxol-5-Yl)-6-Phenylpyridazin-3(2H)-One Derivatives as Potential Analgesic and Anti-Inflammatory Agents
Authors: Jyoti Singh, Ranju Bansal
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Fighting pain and inflammation is a common problem faced by physicians while dealing with a wide variety of diseases. Since ancient time nonsteroidal anti-inflammatory agents (NSAIDs) and opioids have been the cornerstone of treatment therapy, however, the usefulness of both these classes is limited due to severe side effects. NSAIDs, which are mainly used to treat mild to moderate inflammatory pain, induce gastric irritation and nephrotoxicity whereas opioids show an array of adverse reactions such as respiratory depression, sedation, and constipation. Moreover, repeated administration of these drugs induces tolerance to the analgesic effects and physical dependence. Further discovery of selective COX-2 inhibitors (coxibs) suggested safety without any ulcerogenic side effects; however, long-term use of these drugs resulted in kidney and hepatic toxicity along with an increased risk of secondary cardiovascular effects. The basic approaches towards inflammation and pain treatment are constantly changing, and researchers are continuously trying to develop safer and effective anti-inflammatory drug candidates for the treatment of different inflammatory conditions such as osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, psoriasis and multiple sclerosis. Synthetic 3(2H)-pyridazinones constitute an important scaffold for drug discovery. Structure-activity relationship studies on pyridazinones have shown that attachment of a lactam at N-2 of the pyridazinone ring through a methylene spacer results in significantly increased anti-inflammatory and analgesic properties of the derivatives. Further introduction of the heterocyclic ring at lactam nitrogen results in improvement of biological activities. Keeping in mind these SAR studies, a new series of compounds were synthesized as shown in scheme 1 and investigated for anti-inflammatory, analgesic, anti-platelet activities and docking studies. The structures of newly synthesized compounds have been established by various spectroscopic techniques. All the synthesized pyridazinone derivatives exhibited potent anti-inflammatory and analgesic activity. Homoveratryl substituted derivative was found to possess highest anti-inflammatory and analgesic activity displaying 73.60 % inhibition of edema at 40 mg/kg with no ulcerogenic activity when compared to standard drugs indomethacin. Moreover, 2-substituted-4-benzo[d][1,3]dioxole-6-phenylpyridazin-3(2H)-ones derivatives did not produce significant changes in bleeding time and emerged as safe agents. Molecular docking studies also illustrated good binding interactions at the active site of the cyclooxygenase-2 (hCox-2) enzyme.Keywords: anti-inflammatory, analgesic, pyridazin-3(2H)-one, selective COX-2 inhibitors
Procedia PDF Downloads 199