Search results for: 2)al harouge al aswad igneous complex.
1865 Alternative General Formula to Estimate and Test Influences of Early Diagnosis on Cancer Survival
Authors: Li Yin, Xiaoqin Wang
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Background and purpose: Cancer diagnosis is part of a complex stochastic process, in which patients' personal and social characteristics influence the choice of diagnosing methods, diagnosing methods, in turn, influence the initial assessment of cancer stage, the initial assessment, in turn, influences the choice of treating methods, and treating methods in turn influence cancer outcomes such as cancer survival. To evaluate diagnosing methods, one needs to estimate and test the causal effect of a regime of cancer diagnosis and treatments. Recently, Wang and Yin (Annals of statistics, 2020) derived a new general formula, which expresses these causal effects in terms of the point effects of treatments in single-point causal inference. As a result, it is possible to estimate and test these causal effects via point effects. The purpose of the work is to estimate and test causal effects under various regimes of cancer diagnosis and treatments via point effects. Challenges and solutions: The cancer stage has influences from earlier diagnosis as well as on subsequent treatments. As a consequence, it is highly difficult to estimate and test the causal effects via standard parameters, that is, the conditional survival given all stationary covariates, diagnosing methods, cancer stage and prognosis factors, treating methods. Instead of standard parameters, we use the point effects of cancer diagnosis and treatments to estimate and test causal effects under various regimes of cancer diagnosis and treatments. We are able to use familiar methods in the framework of single-point causal inference to accomplish the task. Achievements: we have applied this method to stomach cancer survival from a clinical study in Sweden. We have studied causal effects under various regimes, including the optimal regime of diagnosis and treatments and the effect moderation of the causal effect by age and gender.Keywords: cancer diagnosis, causal effect, point effect, G-formula, sequential causal effect
Procedia PDF Downloads 1971864 Investigating a Deterrence Function for Work Trips for Perth Metropolitan Area
Authors: Ali Raouli, Amin Chegenizadeh, Hamid Nikraz
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The Perth metropolitan area and its surrounding regions have been expanding rapidly in recent decades and it is expected that this growth will continue in the years to come. With this rapid growth and the resulting increase in population, consideration should be given to strategic planning and modelling for the future expansion of Perth. The accurate estimation of projected traffic volumes has always been a major concern for the transport modelers and planners. Development of a reliable strategic transport model depends significantly on the inputs data into the model and the calibrated parameters of the model to reflect the existing situation. Trip distribution is the second step in four-step modelling (FSM) which is complex due to its behavioral nature. Gravity model is the most common method for trip distribution. The spatial separation between the Origin and Destination (OD) zones will be reflected in gravity model by applying deterrence functions which provide an opportunity to include people’s behavior in choosing their destinations based on distance, time and cost of their journeys. Deterrence functions play an important role for distribution of the trips within a study area and would simulate the trip distances and therefore should be calibrated for any particular strategic transport model to correctly reflect the trip behavior within the modelling area. This paper aims to review the most common deterrence functions and propose a calibrated deterrence function for work trips within the Perth Metropolitan Area based on the information obtained from the latest available Household data and Perth and Region Travel Survey (PARTS) data. As part of this study, a four-step transport model using EMME software has been developed for Perth Metropolitan Area to assist with the analysis and findings.Keywords: deterrence function, four-step modelling, origin destination, transport model
Procedia PDF Downloads 1691863 Diagnostics and Explanation of the Current Status of the 40- Year Railway Viaduct
Authors: Jakub Zembrzuski, Bartosz Sobczyk, Mikołaj MIśkiewicz
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Besides designing new constructions, engineers all over the world must face another problem – maintenance, repairs, and assessment of the technical condition of existing bridges. To solve more complex issues, it is necessary to be familiar with the theory of finite element method and to have access to the software that provides sufficient tools which to enable create of sometimes significantly advanced numerical models. The paper includes a brief assessment of the technical condition, a description of the in situ non-destructive testing carried out and the FEM models created for global and local analysis. In situ testing was performed using strain gauges and displacement sensors. Numerical models were created using various software and numerical modeling techniques. Particularly noteworthy is the method of modeling riveted joints of the crossbeam of the viaduct. It is a simplified method that consists of the use of only basic numerical tools such as beam and shell finite elements, constraints, and simplified boundary conditions (fixed support and symmetry). The results of the numerical analyses were presented and discussed. It is clearly explained why the structure did not fail, despite the fact that the weld of the deck plate completely failed. A further research problem that was solved was to determine the cause of the rapid increase in values on the stress diagram in the cross-section of the transverse section. The problems were solved using the solely mentioned, simplified method of modeling riveted joints, which demonstrates that it is possible to solve such problems without access to sophisticated software that enables to performance of the advanced nonlinear analysis. Moreover, the obtained results are of great importance in the field of assessing the operation of bridge structures with an orthotropic plate.Keywords: bridge, diagnostics, FEM simulations, failure, NDT, in situ testing
Procedia PDF Downloads 751862 Plural Perspectives in Conservation Conflicts: The Role of Iconic Species
Authors: Jean Hugé, Francisco Benitez-Capistros, Giorgia Camperio-Ciani
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Addressing conservation conflicts requires the consideration of multiple stakeholders' perspectives and knowledge claims, in order to inform complex and possibly contentious decision-making dilemmas. Hence, a better understanding of why people in particular contexts act in a particular way in a conservation conflict is needed. First, this contribution aims at providing and applying an approach to map and interpret the diversity of subjective viewpoints with regard to iconic species in conservation conflicts. Secondly, this contribution aims to feed the reflection on the possible consequences of the diversity of perspectives for the future management of wildlife (in particular iconic species), based on case studies in Galapagos and Malaysia. The use of the semi-quantitative Q methodology allowed us to identify various perspectives on conservation in different social-ecological contexts. While the presence of iconic species may lead to a more passionate and emotional debate, it may also provide more opportunities for finding common ground and for jointly developing acceptable management solutions that will depolarize emergent, long-lasting or latent conservation conflicts. Based on the research team’s experience in the field, and on the integration of ecological and social knowledge, methodological and management recommendations are made with regard to conservation conflicts involving iconic wildlife. The mere presence of iconic wildlife does not guarantee its centrality in conservation conflicts, and comparisons will be drawn between the cases of the giant tortoises (Chelonoidis spec.) in Galapagos, Ecuador and the Milky Stork (Mycteria cinerea) in western peninsular Malaysia. Acknowledging the diversity of viewpoints, reflecting how different stakeholders see, act and talk about wildlife management, highlights the need to develop pro-active and resilient strategies to deal with these issues.Keywords: conservation conflicts, Q methodology, Galapagos, Malaysia, giant tortoise, milky stork
Procedia PDF Downloads 2871861 Comparison of an Anthropomorphic PRESAGE® Dosimeter and Radiochromic Film with a Commercial Radiation Treatment Planning System for Breast IMRT: A Feasibility Study
Authors: Khalid Iqbal
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This work presents a comparison of an anthropomorphic PRESAGE® dosimeter and radiochromic film measurements with a commercial treatment planning system to determine the feasibility of PRESAGE® for 3D dosimetry in breast IMRT. An anthropomorphic PRESAGE® phantom was created in the shape of a breast phantom. A five-field IMRT plan was generated with a commercially available treatment planning system and delivered to the PRESAGE® phantom. The anthropomorphic PRESAGE® was scanned with the Duke midsized optical CT scanner (DMOS-RPC) and the OD distribution was converted to dose. Comparisons were performed between the dose distribution calculated with the Pinnacle3 treatment planning system, PRESAGE®, and EBT2 film measurements. DVHs, gamma maps, and line profiles were used to evaluate the agreement. Gamma map comparisons showed that Pinnacle3 agreed with PRESAGE® as greater than 95% of comparison points for the PTV passed a ± 3%/± 3 mm criterion when the outer 8 mm of phantom data were discluded. Edge artifacts were observed in the optical CT reconstruction, from the surface to approximately 8 mm depth. These artifacts resulted in dose differences between Pinnacle3 and PRESAGE® of up to 5% between the surface and a depth of 8 mm and decreased with increasing depth in the phantom. Line profile comparisons between all three independent measurements yielded a maximum difference of 2% within the central 80% of the field width. For the breast IMRT plan studied, the Pinnacle3 calculations agreed with PRESAGE® measurements to within the ±3%/± 3 mm gamma criterion. This work demonstrates the feasibility of the PRESAGE® to be fashioned into anthropomorphic shape, and establishes the accuracy of Pinnacle3 for breast IMRT. Furthermore, these data have established the groundwork for future investigations into 3D dosimetry with more complex anthropomorphic phantoms.Keywords: 3D dosimetry, PRESAGE®, IMRT, QA, EBT2 GAFCHROMIC film
Procedia PDF Downloads 4181860 Structural Protein-Protein Interactions Network of Breast Cancer Lung and Brain Metastasis Corroborates Conformational Changes of Proteins Lead to Different Signaling
Authors: Farideh Halakou, Emel Sen, Attila Gursoy, Ozlem Keskin
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Protein–Protein Interactions (PPIs) mediate major biological processes in living cells. The study of PPIs as networks and analyze the network properties contribute to the identification of genes and proteins associated with diseases. In this study, we have created the sub-networks of brain and lung metastasis from primary tumor in breast cancer. To do so, we used seed genes known to cause metastasis, and produced their interactions through a network-topology based prioritization method named GUILDify. In order to have the experimental support for the sub-networks, we further curated them using STRING database. We proceeded by modeling structures for the interactions lacking complex forms in Protein Data Bank (PDB). The functional enrichment analysis shows that KEGG pathways associated with the immune system and infectious diseases, particularly the chemokine signaling pathway, are important for lung metastasis. On the other hand, pathways related to genetic information processing are more involved in brain metastasis. The structural analyses of the sub-networks vividly demonstrated their difference in terms of using specific interfaces in lung and brain metastasis. Furthermore, the topological analysis identified genes such as RPL5, MMP2, CCR5 and DPP4, which are already known to be associated with lung or brain metastasis. Additionally, we found 6 and 9 putative genes that are specific for lung and brain metastasis, respectively. Our analysis suggests that variations in genes and pathways contributing to these different breast metastasis types may arise due to change in tissue microenvironment. To show the benefits of using structural PPI networks instead of traditional node and edge presentation, we inspect two case studies showing the mutual exclusiveness of interactions and effects of mutations on protein conformation which lead to different signaling.Keywords: breast cancer, metastasis, PPI networks, protein conformational changes
Procedia PDF Downloads 2451859 Control of a Quadcopter Using Genetic Algorithm Methods
Authors: Mostafa Mjahed
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This paper concerns the control of a nonlinear system using two different methods, reference model and genetic algorithm. The quadcopter is a nonlinear unstable system, which is a part of aerial robots. It is constituted by four rotors placed at the end of a cross. The center of this cross is occupied by the control circuit. Its motions are governed by six degrees of freedom: three rotations around 3 axes (roll, pitch and yaw) and the three spatial translations. The control of such system is complex, because of nonlinearity of its dynamic representation and the number of parameters, which it involves. Numerous studies have been developed to model and stabilize such systems. The classical PID and LQ correction methods are widely used. If the latter represent the advantage to be simple because they are linear, they reveal the drawback to require the presence of a linear model to synthesize. It also implies the complexity of the established laws of command because the latter must be widened on all the domain of flight of these quadcopter. Note that, if the classical design methods are widely used to control aeronautical systems, the Artificial Intelligence methods as genetic algorithms technique receives little attention. In this paper, we suggest comparing two PID design methods. Firstly, the parameters of the PID are calculated according to the reference model. In a second phase, these parameters are established using genetic algorithms. By reference model, we mean that the corrected system behaves according to a reference system, imposed by some specifications: settling time, zero overshoot etc. Inspired from the natural evolution of Darwin's theory advocating the survival of the best, John Holland developed this evolutionary algorithm. Genetic algorithm (GA) possesses three basic operators: selection, crossover and mutation. We start iterations with an initial population. Each member of this population is evaluated through a fitness function. Our purpose is to correct the behavior of the quadcopter around three axes (roll, pitch and yaw) with 3 PD controllers. For the altitude, we adopt a PID controller.Keywords: quadcopter, genetic algorithm, PID, fitness, model, control, nonlinear system
Procedia PDF Downloads 4351858 Tax System Reform in Nepal: Analysis of Contemporary Issues, Challenges, and Ways Forward
Authors: Dilliram Paudyal
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The history of taxation in Nepal dates back to antiquity. However, the modern tax system gained its momentum after the establishment of democracy in 1951, which initially focused only land tax and tariff on foreign trade. In the due time, several taxes were introduced, such as direct taxes, indirect taxes, and non-taxes. However, the tax structure in Nepal is heavily dominated by indirect taxes that contribute more than 60 % of the total revenue. The government has been mobilizing revenues through a series of tax reforms during the Tenth Five-year Plan (2002 – 2007) and successive Three-year Interim Development Plans by introducing several tax measures. However, these reforms are regressive in nature, which does not lead the overall economy towards short-run stability as well as in the long run development. Based on the literature review and discussion among government officials and few taxpayers individually and groups, this paper aims to major issues and challenges that hinder the tax reform effective in Nepal. Additionally, this paper identifies potential way and process of tax reform in Nepal. The results of the study indicate that transparency in a major problem in Nepalese tax system in Nepal, where serious structural constraints with administrative and procedural complexities envisaged in the Income Tax Act and taxpayers are often unaware of the specific size of tax which is to comply them. Some other issues include high tax rate, limited tax base, leakages in tax collection, rigid and complex Income Tax Act, inefficient and corrupt tax administration, limited potentialities of direct taxes and negative responsiveness of land tax with higher administrative costs. In the context, modality of tax structure and mobilize additional resources is to be rectified on a greater quantum by establishing an effective, dynamic and highly power driven Autonomous Revenue Board.Keywords: corrupt, development, inefficient, taxation
Procedia PDF Downloads 1811857 Comparison between High Resolution Ultrasonography and Magnetic Resonance Imaging in Assessment of Musculoskeletal Disorders Causing Ankle Pain
Authors: Engy S. El-Kayal, Mohamed M. S. Arafa
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There are various causes of ankle pain including traumatic and non-traumatic causes. Various imaging techniques are available for assessment of AP. MRI is considered to be the imaging modality of choice for ankle joint evaluation with an advantage of its high spatial resolution, multiplanar capability, hence its ability to visualize small complex anatomical structures around the ankle. However, the high costs and the relatively limited availability of MRI systems, as well as the relatively long duration of the examination all are considered disadvantages of MRI examination. Therefore there is a need for a more rapid and less expensive examination modality with good diagnostic accuracy to fulfill this gap. HRU has become increasingly important in the assessment of ankle disorders, with advantages of being fast, reliable, of low cost and readily available. US can visualize detailed anatomical structures and assess tendinous and ligamentous integrity. The aim of this study was to compare the diagnostic accuracy of HRU with MRI in the assessment of patients with AP. We included forty patients complaining of AP. All patients were subjected to real-time HRU and MRI of the affected ankle. Results of both techniques were compared to surgical and arthroscopic findings. All patients were examined according to a defined protocol that includes imaging the tendon tears or tendinitis, muscle tears, masses, or fluid collection, ligament sprain or tears, inflammation or fluid effusion within the joint or bursa, bone and cartilage lesions, erosions and osteophytes. Analysis of the results showed that the mean age of patients was 38 years. The study comprised of 24 women (60%) and 16 men (40%). The accuracy of HRU in detecting causes of AP was 85%, while the accuracy of MRI in the detection of causes of AP was 87.5%. In conclusions: HRU and MRI are two complementary tools of investigation with the former will be used as a primary tool of investigation and the latter will be used to confirm the diagnosis and the extent of the lesion especially when surgical interference is planned.Keywords: ankle pain (AP), high-resolution ultrasound (HRU), magnetic resonance imaging (MRI) ultrasonography (US)
Procedia PDF Downloads 1931856 Development the Potential of Parking Tax and Parking Retribution Revenues: Case Study in Bekasi City
Authors: Ivan Yudianto
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The research objectives are to analyze the factors that impede the Parking Tax and Parking Retribution collection in Bekasi City Government, analyzing the factors that can increase local own revenue from the tax sector of parking tax and parking retribution, analyze monitoring the parking retribution collection by the Bekasi City Government, analyze strategies Bekasi City Government through the preparation of a roadmap and action plan to increase parking tax and parking retribution revenues. The approach used in this research is a qualitative approach. Qualitative research is used because the problem is not yet clear and the object to be studied will be holistic, complex, and dynamic, and the relationship will be interactive symptoms. Methods of data collection and technical analysis of the data was in-depth interviews, participant observation, documentary materials, literature, and triangulation, as well as new methods such as the methods of visual materials and internet browsing. The results showed that there are several factors that become an obstacle such as the parking taxpayer does not disclose the actual parking revenue, the parking taxpayer are late or do not pay Parking Tax, many parking locations controlled by illegal organizations, shortage of human resources in charge levy and supervise the parking tax and parking retribution collection in the Bekasi City Government, surveillance parking tax and parking retribution are not scheduled on a regular basis. Several strategic priorities in order to develop the potential of the Parking Tax and Parking Retribution in the Bekasi City Government, namely through increased controling and monitoring of the Parking Taxpayer, forming a team of auditors to audit the Parking Taxpayer, seek law enforcement persuasive and educative to reduce Parking Taxpayer wayward, providing strict sanctions against the Parking Taxpayer disobedient, revised regulations mayors about locations of parking in Bekasi City, rationalize revenues target of Parking Retribution, conducting takeover attempts parking location on the roadside of the individual or specific group, and drafting regional regulations on parking subscribe.Keywords: local own revenue, parking retribution, parking tax, parking taxpayer
Procedia PDF Downloads 3271855 Bacterial Interactions of Upper Respiratory Tract Microbiota
Authors: Sarah Almuhayya, Andrew Mcbain, Gavin Humphreys
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Background. The microbiome of the upper respiratory tract (URT) has received less research attention than other body sites. This study aims to investigate the microbial ecology of the human URT with a focus on the antagonism between the corynebacteria and staphylococci. Methods. Mucosal swabs were collected from the anterior nares and nasal turbinates of 20 healthy adult subjects. Genomic DNA amplification targeting the (V4) of the 16Sr RNA gene was conducted and analyzed using QIIME. Nasal swab isolates were cultured and identified using near full-length sequencing of the 16S rRNA gene. Isolates identified as corynebacteria or staphylococci were typed using (rep-PCR). Antagonism was determined using an agar-based inhibition assay. Results. Four major bacterial phyla (Actinobacteria, Bacteroidetes, Firmicutes, and Proteobacteria) were identified from all volunteers. The typing of cultured staphylococci and corynebacteria suggested that intra-individual strain diversity was limited. Analysis of generated nasal microbiota profiles suggested an inverse correlation in terms of relative abundance between staphylococci and corynebacteria. Despite the apparent antagonism between these genera, it was limited when investigated on agar. Of 1000 pairwise interactions, observable zones of inhibition were only reported between a single strain of C.pseudodiphtheriticum and S.aureus. Imaging under EM revealed this effect to be bactericidal with clear lytic effects on staphylococcal cell morphology. Conclusion. Nasal microbiota is complex, but culturable staphylococci and corynebacteria were limited in terms of clone type. Analysis of generated nasal microbiota profiles suggested an inverse correlation in terms of relative abundance between these genera suggesting an antagonism or competition between these taxonomic groups.Keywords: nasal, microbiota, S.aureus, microbioal interaction
Procedia PDF Downloads 1171854 Analytical Slope Stability Analysis Based on the Statistical Characterization of Soil Shear Strength
Authors: Bernardo C. P. Albuquerque, Darym J. F. Campos
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Increasing our ability to solve complex engineering problems is directly related to the processing capacity of computers. By means of such equipments, one is able to fast and accurately run numerical algorithms. Besides the increasing interest in numerical simulations, probabilistic approaches are also of great importance. This way, statistical tools have shown their relevance to the modelling of practical engineering problems. In general, statistical approaches to such problems consider that the random variables involved follow a normal distribution. This assumption tends to provide incorrect results when skew data is present since normal distributions are symmetric about their means. Thus, in order to visualize and quantify this aspect, 9 statistical distributions (symmetric and skew) have been considered to model a hypothetical slope stability problem. The data modeled is the friction angle of a superficial soil in Brasilia, Brazil. Despite the apparent universality, the normal distribution did not qualify as the best fit. In the present effort, data obtained in consolidated-drained triaxial tests and saturated direct shear tests have been modeled and used to analytically derive the probability density function (PDF) of the safety factor of a hypothetical slope based on Mohr-Coulomb rupture criterion. Therefore, based on this analysis, it is possible to explicitly derive the failure probability considering the friction angle as a random variable. Furthermore, it is possible to compare the stability analysis when the friction angle is modelled as a Dagum distribution (distribution that presented the best fit to the histogram) and as a Normal distribution. This comparison leads to relevant differences when analyzed in light of the risk management.Keywords: statistical slope stability analysis, skew distributions, probability of failure, functions of random variables
Procedia PDF Downloads 3401853 Facile Synthesis of Sulfur Doped TiO2 Nanoparticles with Enhanced Photocatalytic Activity
Authors: Vishnu V. Pillai, Sunil P. Lonkar, Akhil M. Abraham, Saeed M. Alhassan
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An effectual technology for wastewater treatment is a great demand now in order to encounter the water pollution caused by organic pollutants. Photocatalytic oxidation technology is widely used in removal of such unsafe contaminants. Among the semi-conducting metal oxides, robust and thermally stable TiO2 has emerged as a fascinating material for photocatalysis. Enhanced catalytic activity was observed for nanostructured TiO2 due to its higher surface, chemical stability and higher oxidation ability. However, higher charge carrier recombination and wide band gap of TiO2 limits its use as a photocatalyst in the UV region. It is desirable to develop a photocatalyst that can efficiently absorb the visible light, which occupies the main part of the solar spectrum. Hence, in order to extend its photocatalytic efficiency under visible light, TiO2 nanoparticles are often doped with metallic or non-metallic elements. Non-metallic doping of TiO2 has attracted much attention due to the low thermal stability and enhanced recombination of charge carriers endowed by metallic doping of TiO2. Amongst, sulfur doped TiO2 is most widely used photocatalyst in environmental purification. However, the most of S-TiO2 synthesis technique uses toxic chemicals and complex procedures. Hence, a facile, scalable and environmentally benign preparation process for S-TiO2 is highly desirable. In present work, we have demonstrated new and facile solid-state reaction method for S-TiO2 synthesis that uses abundant elemental sulfur as S source and moderate temperatures. The resulting nano-sized S-TiO2 has been successfully employed as visible light photocatalyst in methylene blue dye removal from aqueous media.Keywords: ecofriendly, nanomaterials, methylene blue, photocatalysts
Procedia PDF Downloads 3501852 Right Cerebellar Stroke with a Right Vertebral Artery Occlusion Following an Embolization of the Right Glomus Tympanicum Tumor
Authors: Naim Izet Kajtazi
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Context: Although rare, glomus tumor (i.e., nonchromaffin chemodectomas and paragan¬gliomas) is the most common middle ear tumor, with female predominance. Pre-operative embolization is often required to devascularize the hypervascular tumor for better surgical outcomes. Process: A 35-year-old female presented with episodes of frequent dizziness, ear fullness, and right ear tinnitus for 12 months. Head imaging revealed a right glomus tympanicum tumor. She underwent pre-operative endovascular embolization of the glomus tympanicum tumor with surgical, cyanoacrylate-based glue. Immediately after the procedure, she developed drowsiness and severe pain in the right temporal region. Further investigations revealed a right cerebellar stroke in the posterior inferior cerebellar artery territory. She was treated with intravenous heparin, followed by one year of oral anticoagulation. With rehabilitation, she significantly recovered from her post embolization stroke. However, the tumor was resected at another institution. Ten years later, follow-up imaging indicated a gradual increase in the size of the glomus jugulare tumor, compressing the nearby critical vascular structures. She subsequently received radiation therapy to treat the residual tumor. Outcome: Currently, she has no neurological deficit, but her mild dizziness, right ear tinnitus, and hearing impairment persist. Relevance: This case highlights the complex nature of these tumors, which often bring challenges to the patients as well as treatment teams. The multi-disciplinary team approach is necessary to tailor the management plan for individual tumors. Although embolization is a safe procedure, careful attention and thoughtful anatomic knowledge regarding dangerous anastomosis are essential to avoid devastating complications. Complications occur due to encountered vessel anomalies and new anastomoses formed during the gluing and changes in hemodynamics.Keywords: stroke, embolization, MRI brain, cerebral angiogram
Procedia PDF Downloads 731851 Incorporation of Growth Factors onto Hydrogels via Peptide Mediated Binding for Development of Vascular Networks
Authors: Katie Kilgour, Brendan Turner, Carly Catella, Michael Daniele, Stefano Menegatti
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In vivo, the extracellular matrix (ECM) provides biochemical and mechanical properties that are instructional to resident cells to form complex tissues with characteristics to develop and support vascular networks. In vitro, the development of vascular networks can be guided by biochemical patterning of substrates via spatial distribution and display of peptides and growth factors to prompt cell adhesion, differentiation, and proliferation. We have developed a technique utilizing peptide ligands that specifically bind vascular endothelial growth factor (VEGF), erythropoietin (EPO), or angiopoietin-1 (ANG1) to spatiotemporally distribute growth factors to cells. This allows for the controlled release of each growth factor, ultimately enhancing the formation of a vascular network. Our engineered tissue constructs (ETCs) are fabricated out of gelatin methacryloyl (GelMA), which is an ideal substrate for tailored stiffness and bio-functionality, and covalently patterned with growth factor specific peptides. These peptides mimic growth factor receptors, facilitating the non-covalent binding of the growth factors to the ETC, allowing for facile uptake by the cells. We have demonstrated in the absence of cells the binding affinity of VEGF, EPO, and ANG1 to their respective peptides and the ability for each to be patterned onto a GelMA substrate. The ability to organize growth factors on an ETC provides different functionality to develop organized vascular networks. Our results demonstrated a method to incorporate biochemical cues into ETCs that enable spatial and temporal control of growth factors. Future efforts will investigate the cellular response by evaluating gene expression, quantifying angiogenic activity, and measuring the speed of growth factor consumption.Keywords: growth factor, hydrogel, peptide, angiogenesis, vascular, patterning
Procedia PDF Downloads 1651850 Numerical Investigation of Multiphase Flow in Pipelines
Authors: Gozel Judakova, Markus Bause
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We present and analyze reliable numerical techniques for simulating complex flow and transport phenomena related to natural gas transportation in pipelines. Such kind of problems are of high interest in the field of petroleum and environmental engineering. Modeling and understanding natural gas flow and transformation processes during transportation is important for the sake of physical realism and the design and operation of pipeline systems. In our approach a two fluid flow model based on a system of coupled hyperbolic conservation laws is considered for describing natural gas flow undergoing hydratization. The accurate numerical approximation of two-phase gas flow remains subject of strong interest in the scientific community. Such hyperbolic problems are characterized by solutions with steep gradients or discontinuities, and their approximation by standard finite element techniques typically gives rise to spurious oscillations and numerical artefacts. Recently, stabilized and discontinuous Galerkin finite element techniques have attracted researchers’ interest. They are highly adapted to the hyperbolic nature of our two-phase flow model. In the presentation a streamline upwind Petrov-Galerkin approach and a discontinuous Galerkin finite element method for the numerical approximation of our flow model of two coupled systems of Euler equations are presented. Then the efficiency and reliability of stabilized continuous and discontinous finite element methods for the approximation is carefully analyzed and the potential of the either classes of numerical schemes is investigated. In particular, standard benchmark problems of two-phase flow like the shock tube problem are used for the comparative numerical study.Keywords: discontinuous Galerkin method, Euler system, inviscid two-fluid model, streamline upwind Petrov-Galerkin method, twophase flow
Procedia PDF Downloads 3331849 Phenolic Composition and Antioxidant Property of Honey with Dried Apricots
Authors: Jasna Čanadanović-Brunet, Gordana Ćetković, Sonja Djilas, Vesna Tumbas-Šaponjac, Jelena Vulić, Sladjana Stajčić
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Honey, produced by the honeybee, is a natural saturated sugar solution, which is mainly composed of a complex mixture of carbohydrates. Besides this, it also contains certain minor constituents, proteins, enzymes, amino and organic acids, lipids, vitamins, phenolic acids, flavonoids and carotenoids. Honey serves as a source of natural antioxidants, which are effective in reducing the risk of heart disease, cancer, immune-system decline, cataracts, and different inflammatory processes. Honey is consumed in its natural form alone, but also in combination with nuts and various kinds of dried fruits (plums, figs, cranberries, apricots etc.). The aim of this research was to investigate the contribution of dried apricot addition to polyphenols and flavonoids contents and antioxidant activities of honey. Some individual phenolic compounds in Serbian polyfloral honey (PH), linden honey (LH) and also in their mixtures with dried apricot, in 40% mass concentrations (PH40; LH40), were identified and quantified by HPLC. The most dominant phenolic compound was: gallic acid in LH (11.14 mg/100g), LH40 (42.65 mg/100g), PH (7.24 mg/100g) and catehin in PH40 (11.83 mg/100g). The antioxidant activity of PH, LH, PH40 and LH40 was tested by measuring their ability to scavenge hydroxyl radicals (OH) by electron spin resonance spectroscopy (ESR). Honey samples with 40% dried apricot exhibited better antioxidant activity measured by hydroxyl radical scavenging activity. The EC50 values, the amount of antioxidant necessary to decrease the initial concentration of OH radicals by 50%, were: EC50PH=3.36 mg/ml, EC50LH=13.36 mg/ml, EC50PH40=2.29 mg/ml, EC50 LH40=7.78 mg/ml. Our results indicate that supplementation of polyfloral honey and linden honey with dried apricots improves antioxidant activity of honey by enriching the phenolic composition.Keywords: honey, dried apricot, HPLC, hydroxyl radical
Procedia PDF Downloads 3591848 NLRP3-Inflammassome Participates in the Inflammatory Response Induced by Paracoccidioides brasiliensis
Authors: Eduardo Kanagushiku Pereira, Frank Gregory Cavalcante da Silva, Barbara Soares Gonçalves, Ana Lúcia Bergamasco Galastri, Ronei Luciano Mamoni
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The inflammatory response initiates after the recognition of pathogens by receptors expressed by innate immune cells. Among these receptors, the NLRP3 was associated with the recognition of pathogenic fungi in experimental models. NLRP3 operates forming a multiproteic complex called inflammasome, which actives caspase-1, responsible for the production of the inflammatory cytokines IL-1beta and IL-18. In this study, we aimed to investigate the involvement of NLRP3 in the inflammatory response elicited in macrophages against Paracoccidioides brasiliensis (Pb), the etiologic agent of PCM. Macrophages were differentiated from THP-1 cells by treatment with phorbol-myristate-acetate. Following differentiation, macrophages were stimulated by Pb yeast cells for 24 hours, after previous treatment with specific NLRP3 (3,4-methylenedioxy-beta-nitrostyrene) and/or caspase-1 (VX-765) inhibitors, or specific inhibitors of pathways involved in NLRP3 activation such as: Reactive Oxigen Species (ROS) production (N-Acetyl-L-cysteine), K+ efflux (Glibenclamide) or phagossome acidification (Bafilomycin). Quantification of IL-1beta and IL-18 in supernatants was performed by ELISA. Our results showed that the production of IL-1beta and IL-18 by THP-1-derived-macrophages stimulated with Pb yeast cells was dependent on NLRP3 and caspase-1 activation, once the presence of their specific inhibitors diminished the production of these cytokines. Furthermore, we found that the major pathways involved in NLRP3 activation, after Pb recognition, were dependent on ROS production and K+ efflux. In conclusion, our results showed that NLRP3 participates in the recognition of Pb yeast cells by macrophages, leading to the activation of the NLRP3-inflammasome and production of IL-1beta and IL-18. Together, these cytokines can induce an inflammatory response against P. brasiliensis, essential for the establishment of the initial inflammatory response and for the development of the subsequent acquired immune response.Keywords: inflammation, IL-1beta, IL-18, NLRP3, Paracoccidioidomycosis
Procedia PDF Downloads 2761847 The Image of Saddam Hussein and Collective Memory: The Semiotics of Ba'ath Regime's Mural in Iraq (1980-2003)
Authors: Maryam Pirdehghan
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During the Ba'ath Party's rule in Iraq, propaganda was utilized to justify and to promote Saddam Hussein's image in the collective memory as the greatest Arab leader. Consequently, urban walls were routinely covered with images of Saddam. Relying on these images, the regime aimed to provide a basis for evoking meanings in the public opinion, which would supposedly strengthen Saddam’s power and reconstruct facts to legitimize his political ideology. Nonetheless, Saddam was not always portrayed with common and explicit elements but in certain periods of his rule, the paintings depicted him in an unusual context, where various historical and contemporary elements were combined in a narrative background. Therefore, an understanding of the implied socio-political references of these elements is required to fully elucidate the impact of these images on forming the memory and collective unconscious of the Iraqi people. To obtain such understanding, one needs to address the following questions: a) How Saddam Hussein is portrayed in mural during his rule? b) What of elements and mythical-historical narratives are found in the paintings? c) Which Saddam's political views were subject to the collective memory through mural? Employing visual semiotics, this study reveals that during Saddam Hussein's regime, the paintings were initially simple portraits but gradually transformed into narrative images, characterized by a complex network of historical, mythical and religious elements. These elements demonstrate the transformation of a secular-nationalist politician into a Muslim ruler who tried to instill three major policies in domestic and international relations i.e. the arabization of Iraq, as well as the propagation of pan-arabism ideology (first period), the implementation of anti-Israel policy (second period) and the implementation of anti-American-British policy (last period).Keywords: Ba'ath Party, Saddam Hussein, mural, Iraq, propaganda, collective memory
Procedia PDF Downloads 3281846 Ethical Considerations in In-Utero Gene Editing
Authors: Shruti Govindarajan
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In-utero gene editing with CRISPR-Cas9 opens up new possibilities for treating genetic disorders during pregnancy while still in mother’s womb. By targeting genetic mutations in the early stages of fetal development, this approach could potentially prevent severe conditions—like cystic fibrosis, sickle cell anemia, and muscular dystrophy—from causing harm. CRISPR-Cas9, which allows precise DNA edits, could be delivered into fetal cells through vectors such as adeno-associated viruses (AAVs) or nanoparticles, correcting disease-causing mutations and possibly offering lifelong relief from these disorders. For families facing severe genetic diagnoses, in-utero gene editing could provide a transformative option. However, technical challenges remain, including ensuring that gene editing only targets the intended cells and verifying long-term safety. Ethical considerations are also at the forefront of this technology. The editing of a fetus's genes brings up difficult questions about consent, especially since these genetic changes will affect the child’s entire life without their input. There's also concern over possible unintended side effects, or changes passed down to future generations. Moreover, if used beyond therapeutic purposes, this technology could be misused for ‘enhancements,’ like selecting for certain physical or cognitive traits, raising concerns about inequality and social pressures. In this way, in-utero gene editing brings both exciting potential and complex moral questions. As research progresses, addressing these scientific and ethical concerns will be key to ensuring that this technology is used responsibly, prioritizing safety, fairness, and a focus on alleviating genetic disease. A cautious and inclusive approach, along with clear regulations, will be essential to realizing the benefits of in-utero gene editing while protecting against unintended consequences.Keywords: in-utero gene editing, CRISPR, bioethics, genetic disorder
Procedia PDF Downloads 141845 Interorganizational Relationships in the Brazilian Milk Production Chain
Authors: Marcelo T. Okano, Oduvaldo Vendrametto, Osmildo S. Santos, Marcelo E. Fernandes, Heide Landi
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The literature on the interorganizational relationship between companies and organizations has increased in recent years, but there are still doubts about the various settings. The interorganizational networks are important in economic life, the fact facilitate the complex interdependence between transactional and cooperative organizations. A need identified in the literature is the lack of indicators to measure and identify the types of existing networks. The objective of this research is to examine the interorganizational relationships of two milk chains through indicators proposed by the theories of the four authors, characterizing them as network or not and what the benefits obtained by the chain organization. To achieve the objective of this work was carried out a survey of milk producers in two regions of the state of São Paulo. To collect the information needed for the analysis, exploratory research, qualitative nature was used. The research instrument of this work consists of a roadmap of semistructured interviews with open questions. Some of the answers were directed by the interviewer in the form of performance notes aimed at detecting the degree of importance, according to the perception of intensity to that regard. The results showed that interorganizational relationships are small and largely limited to the sale of milk or dairy cooperatives. These relationships relate only to trade relations between the owner and purchaser of milk. But when the producers are organized in associations or networks, interorganizational relationships and increase benefits for all participants in the network. The various visits and interviews in several dairy farms in the regions of São Pau-lo (indicated that the inter-relationships are small and largely limited to the sale of milk to cooperatives or dairy. These relationships refer only to trade relations between the owner and the purchaser of milk. But when the producers are organized in associations or networks, interorganizational relationships increase and bring benefits to all participants in the network.Keywords: interorganizational networks, dairy chain, interorganizational system, São Pau-lo
Procedia PDF Downloads 5811844 Analysis of Rock Cutting Progress with a New Axe-Shaped PDC Cutter to Improve PDC Bit Performance in Elastoplastic Formation
Authors: Fangyuan Shao, Wei Liu, Deli Gao
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Polycrystalline diamond compact (PDC) bits have occupied a large market of unconventional oil and gas drilling. The application of PDC bits benefits from the efficient rock breaking of PDC cutters. In response to increasingly complex formations, many shaped cutters have been invited, but many of them have not been solved by the mechanism of rock breaking. In this paper, two kinds of PDC cutters: a new axe-shaped (NAS) cutter and cylindrical cutter (benchmark) were studied by laboratory experiments. NAS cutter is obtained by optimizing two sides of axe-shaped cutter with curved surfaces. All the cutters were put on a vertical turret lathe (VTL) in the laboratory for cutting tests. According to the cutting distance, the VTL tests can be divided into two modes: single-turn rotary cutting and continuous cutting. The cutting depth of cutting (DOC) was set at 1.0 mm and 2.0 mm in the former mode. The later mode includes a dry VTL test for thermal stability and a wet VTL test for wear resistance. Load cell and 3D optical profiler were used to obtain the value of cutting forces and wear area, respectively. Based on the findings of the single-turn rotary cutting VTL tests, the performance of A NAS cutter was better than the benchmark cutter on elastoplastic material cutting. The cutting forces (normal forces, tangential force, and radial force) and special mechanical energy (MSE) of a NAS cutter were lower than that of the benchmark cutter under the same condition. It meant that a NAS cutter was more efficient on elastoplastic material breaking. However, the wear resistance of a new axe-shaped cutter was higher than that of a benchmark cutter. The results of the dry VTL test showed that the thermal stability of a NAS cutter was higher than that of a benchmark cutter. The cutting efficiency can be improved by optimizing the geometric structure of the PDC cutter. The change of thermal stability may be caused by the decrease of the contact area between cutter and rock at given DOC. The conclusions of this paper can be used as an important reference for PDC cutters designers.Keywords: axe-shaped cutter, PDC cutter, rotary cutting test, vertical turret lathe
Procedia PDF Downloads 2081843 3D Geological Modeling and Engineering Geological Characterization of Shallow Subsurface Soil and Rock of Addis Ababa, Ethiopia
Authors: Biruk Wolde, Atalay Ayele, Yonatan Garkabo, Trufat Hailmariam, Zemenu Germewu
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A comprehensive three-dimensional (3D) geological modeling and engineering geological characterization of shallow subsurface soils and rocks are essential for a wide range of geotechnical and seismological engineering applications, particularly in urban environments. The spatial distribution and geological variation of the shallow subsurface of Addis Ababa city have not been studied so far in terms of geological and geotechnical modeling. This study aims at the construction of a 3D geological model, as well as provides awareness into the engineering geological characteristics of shallow subsurface soil and rock of Addis Ababa city. The 3D geological model was constructed by using more than 1500 geotechnical boreholes, well-drilling data, and geological maps. A well-known geostatistical kriging 3D interpolation algorithm was applied to visualize the spatial distribution and geological variation of the shallow subsurface. Due to the complex nature of geological formations, vertical and lateral variation of the geological profiles horizons-solid command has been selected via the Groundwater Modelling System (GMS) graphical user interface software. For the engineering geological characterization of typical soils and rocks, both index and engineering laboratory tests have been used. The geotechnical properties of soil and rocks vary from place to place due to the uneven nature of subsurface formations observed in the study areas. The constructed model ascertains the thickness, extent, and 3D distribution of the important geological units of the city. This study is the first comprehensive research work on 3D geological modeling and subsurface characterization of soils and rocks in Addis Ababa city, and the outcomes will be important for further future research on subsurface conditions in the city. Furthermore, these findings provide a reference for developing a geo-database for the city.Keywords: 3d geological modeling, addis ababa, engineering geology, geostatistics, horizons-solid
Procedia PDF Downloads 1031842 Evaluation of Elements Impurities in Drugs According to Pharmacopoeia by use FESEM-EDS Technique
Authors: Rafid Doulab
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Elemental Impurities in the Pharmaceuticals industryis are indispensable to ensure pharmaceuticalssafety for 24 elements. Although atomic absorption and inductively coupled plasma are used in the U.S Pharmacopeia and the European Pharmacopoeia, FESEM with energy dispersive spectrometers can be applied as an alternative analysis method for quantitative and qualitative results for a variety of elements without chemical pretreatment, unlike other techniques. This technique characterizes by shortest time, with more less contamination, no reagent consumption, and generation of minimal residue or waste, as well as sample preparations time limiting, with minimal analysis error. Simple dilution for powder or direct analysis for liquid, we analyzed the usefulness of EDS method in testing with field emission scanning electron microscopy (FESEM, SUPRA 55 Carl Zeiss Germany) with an X-ray energy dispersion (XFlash6l10 Bruker Germany). The samples analyzed directly without coating by applied 5µ of known concentrated diluted sample on carbon stub with accelerated voltage according to sample thickness, the result for this spot was in atomic percentage, and by Avogadro converted factor, the final result will be in microgram. Conclusion and recommendation: The conclusion of this study is application of FESEM-EDS in US pharmacopeia and ICH /Q3D guideline to reach a high-precision and accurate method in element impurities analysis of drugs or bulk materials to determine the permitted daily exposure PDE in liquid or solid specimens, and to obtain better results than other techniques, by the way it does not require complex methods or chemicals for digestion, which interfere with the final results with the possibility of to keep the sample at any time for re analysis. The recommendation is to use this technique in pharmacopeia as standard methods like inductively coupled plasma both ICP-AES, ICP-OES, and ICP-MS.Keywords: pharmacopoeia, FESEM-EDS, element impurities, atomic concentration
Procedia PDF Downloads 1191841 Managing and Marketing a Modern Art Museum in a Small Town: A Case Study on Odunpazarı Modern Museum
Authors: Mehmet Sinan Erguven
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Modern art is relatively new but a popular area in Turkish art society. Modern art museums are mainly located in big cities like Istanbul and Ankara where cultural life is more dynamic. Odunpazarı Modern Museum (OMM) will open its doors on September 2019 and be the only modern art museum located in a small town in Turkey. OMM executives declare the mission of the museum as; art must go beyond the metropolises of the world, give a new lease of life to cities that make a difference with their cultural texture, and reach a greater audience through that expansion. So OMM will not only serve as a museum but a landmark for regenerating the city brand of Eskişehir like the Guggenheim in Bilbao. OMM is located in the Odunpazarı area, the heart of Eskişehir. Named after the historical timber market it once hosted, Odunpazarı is a nominated site for the UNESCO Intangible Cultural Heritage List, and is Eskişehir’s first area of settlement. This study focuses on the complex nature of opening a modern art museum in a small town. The management and marketing dynamics of OMM are discussed in the study. Content analysis technique is used on local and national news to display the perception differences before and after the opening of OMM. In depth interviews with the executives of the museum are conducted in order to enlighten the insights of opening a modern art museum in a small town. Early findings of the content analysis point out that, the comments on the national press are mostly positive. On the other hand, different views occur on the local press. The location OMM is constructed and grandness of the museum building are criticized by some of the local newspapers. OMM’s potential as a tourist attraction is agreed by most of the media. OMM executives stated the most challenging task as reaching the different target audiences on international, national and local levels. These early findings will be improved and compared shortly before and after the opening of the museum.Keywords: management, marketing, Odunpazarı modern museum, small town
Procedia PDF Downloads 2331840 Cable De-Commissioning of Legacy Accelerators at CERN
Authors: Adya Uluwita, Fernando Pedrosa, Georgi Georgiev, Christian Bernard, Raoul Masterson
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CERN is an international organisation funded by 23 countries that provide the particle physics community with excellence in particle accelerators and other related facilities. Founded in 1954, CERN has a wide range of accelerators that allow groundbreaking science to be conducted. Accelerators bring particles to high levels of energy and make them collide with each other or with fixed targets, creating specific conditions that are of high interest to physicists. A chain of accelerators is used to ramp up the energy of particles and eventually inject them into the largest and most recent one: the Large Hadron Collider (LHC). Among this chain of machines is, for instance the Proton Synchrotron, which was started in 1959 and is still in operation. These machines, called "injectors”, keep evolving over time, as well as the related infrastructure. Massive decommissioning of obsolete cables started in 2015 at CERN in the frame of the so-called "injectors de-cabling project phase 1". Its goal was to replace aging cables and remove unused ones, freeing space for new cables necessary for upgrades and consolidation campaigns. To proceed with the de-cabling, a project co-ordination team was assembled. The start of this project led to the investigation of legacy cables throughout the organisation. The identification of cables stacked over half a century proved to be arduous. Phase 1 of the injectors de-cabling was implemented for 3 years with success after overcoming some difficulties. Phase 2, started 3 years later, focused on improving safety and structure with the introduction of a quality assurance procedure. This paper discusses the implementation of this quality assurance procedure throughout phase 2 of the project and the transition between the two phases. Over hundreds of kilometres of cable were removed in the injectors complex at CERN from 2015 to 2023.Keywords: CERN, de-cabling, injectors, quality assurance procedure
Procedia PDF Downloads 961839 The Dynamic of Nₘᵢₙ in Clay Loam Cambisol in Alternative Farming
Authors: Danute Jablonskyte-Rasce, Laura Masilionyte
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The field experiments of different farming systems were conducted at Joniškėlis Experimental Station of the Lithuanian Research Centre for Agriculture and Forestry in 2006–2016. The soil of the experimental site was Endocalcari-Endohypogleyic Cambisol (CMg-n-w-can). The research was designed to identify the effects of dry matter and nitrogen accumulated in the above-ground biomass of various catch crops grown after winter wheat on soil mineral nitrogen variation during the autumn and spring period in the presence of intensive leaching complex. Research was done in the soil differing in humus status in the organic and sustainable cropping systems by growing various plant mixtures as catch crops: narrow-leafed lupine (Lupinus angustifolius L.) and oil radish (Raphanus sativus var. Oleifera L.), white mustard (Sinapis alba L.) and buckwheat (Fagopyrum exculentum Moench.) and white mustard as a sole crop. All crop and soil management practices have shown optimal efficiency in late autumn – stubble breaking, catch crops and straw used during the post-harvest period of the main crops, reduced Nmin migration into deeper (40–80 cm) soil layer. The greatest Nmin reduction in the 0–40 cm soil layer during the period from late autumn to early spring was identified in the sustainable cropping system having applied N30 for the promotion of straw mineralization and with no catch crops cultivation. The sustainable cropping system, having applied N30 for straw mineralization and growing white mustard in combination with buckwheat as catch crops, Nmin difference in the spring compared with its status in the autumn in the soil low and moderate in humus was lower by 70.1% and 34.2%, respectively.Keywords: soil nitrogen, catch crops, ecological and sustainable farming systems, Cambisol
Procedia PDF Downloads 2611838 Unfolding Global Biodiversity Patterns of Marine Planktonic Diatom Communities across the World's Oceans
Authors: Shruti Malviya, Chris Bowler
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Analysis of microbial eukaryotic diversity is fundamental to understanding ecosystems’ structure, biology, and ecology. Diatoms (Stramenopiles, Bacillariophyceae) are one of the most diverse and ecologically prominent groups of phytoplankton. This study was performed to enhance the understanding of global biodiversity patterns and structure of planktonic diatom communities across the world's oceans. We used the metabarcoding data set generated from the biological samples and associated environmental data collected during the Tara Oceans (2009-2013) global circumnavigation covering all major oceanic provinces. A total of ~18 million diatom V9-18S rDNA tags from 126 sampling stations, constituting 631 size-fractionated plankton communities were generated. Using ~250,000 unique diatom metabarcodes, the global diatom distribution and diversity across size classes, genus and ecological niches was assessed. Notably, our analysis revealed: (i) a new estimate of the total number of planktonic diatom species, (ii) a considerable unknown diversity and exceptionally high diversity in the open ocean, and (iii) complex diversity patterns across oceanic provinces. Also, co-occurrence of several ribotypes in locations separated by great geographic distances (equatorial stations) demonstrated a widespread but not ubiquitous distribution. This work provides a comprehensive perspective on diatom distribution and diversity in the world’s oceans and elaborates interconnections between associated theories and underlying drivers. It shows how meta-barcoding approaches can provide a framework to investigate environmental diversity at a global scale, which is deemed as an essential step in answering various ecological research questions. Consequently, this work also provides a reference point to explore how microbial communities will respond to environmental conditions.Keywords: diatoms, Tara Oceans, biodiversity, metabarcoding
Procedia PDF Downloads 1551837 Free Energy Computation of A G-Quadruplex-Ligand Structure: A Classical Molecular Dynamics and Metadynamics Simulation Study
Authors: Juan Antonio Mondragon Sanchez, Ruben Santamaria
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The DNA G-quadruplex is a four-stranded DNA structure formed by stacked planes of four base paired guanines (G-quartet). Guanine rich DNA sequences appear in many sites of genomic DNA and can potential form G-quadruplexes, such as those occurring at 3'-terminus of the human telomeric DNA. The formation and stabilization of a G-quadruplex by small ligands at the telomeric region can inhibit the telomerase activity. In turn, the ligands can be used to down regulate oncogene expression making G-quadruplex an attractive target for anticancer therapy. Many G-quadruplex ligands have been proposed with a planar core to facilitate the pi–pi stacking and electrostatic interactions with the G-quartets. However, many drug candidates are impossibilitated to discriminate a G-quadruplex from a double helix DNA structure. In this context, it is important to investigate the site topology for the interaction of a G-quadruplex with a ligand. In this work, we determine the free energy surface of a G-quadruplex-ligand to study the binding modes of the G-quadruplex (TG4T) with the daunomycin (DM) drug. The complex TG4T-DM is studied using classical molecular dynamics in combination with metadynamics simulations. The metadynamics simulations permit an enhanced sampling of the conformational space with a modest computational cost and obtain free energy surfaces in terms of the collective variables (CV). The free energy surfaces of TG4T-DM exhibit other local minima, indicating the presence of additional binding modes of daunomycin that are not observed in short MD simulations without the metadynamics approach. The results are compared with similar calculations on a different structure (the mutated mu-G4T-DM where the 5' thymines on TG4T-DM have been deleted). The results should be of help to design new G-quadruplex drugs, and understand the differences in the recognition topology sites of the duplex and quadruplex DNA structures in their interaction with ligands.Keywords: g-quadruplex, cancer, molecular dynamics, metadynamics
Procedia PDF Downloads 4601836 War Heritage: Different Perceptions of the Dominant Discourse among Visitors to the “Adem Jashari” Memorial Complex in Prekaz
Authors: Zana Llonçari Osmani, Nita Llonçari
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In Kosovo, public rhetoric and popular sentiment position the War of 1998-99 (the war) as central to the formation of contemporary Kosovo's national identity. This period was marked by the forced massive displacement of Kosovo Albanians, the destruction of entire settlements, the loss of family members, and the profound emotional trauma experienced by civilians, particularly those who actively participated in the war as members of the Kosovo Liberation Army (KLA). Amidst these profound experiences, the Prekaz Massacre (The Massacre) is widely regarded as the defining event that preceded the final struggles of 1999 and the long-awaited attainment of independence. This study aims to explore how different visitors perceive the dominant discourse at The Memorial, a site dedicated to commemorating the Prekaz Massacre, and to identify the factors that influence their perceptions. The research employs a comprehensive mixed-method approach, combining online surveys, critical discourse analysis of visitor impressions, and content analysis of media representations. The findings of the study highlight the significant role played by original material remains in shaping visitor perceptions of The Memorial in comparison to the curated symbols and figurative representations interspersed throughout the landscape. While the design elements and physical layout of the memorial undeniably hold significance in conveying the memoryscape, there are notable shortcomings in enhancing the overall visitor experience. Visitors are still primarily influenced by the tangible remnants of the war, suggesting that there is room for improvement in how design elements can more effectively contribute to the memorial's narrative and the collective memory of the Prekaz Massacre.Keywords: critical discourse analysis, memorialisation, national discourse, public rhetoric, war tourism
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