Search results for: damage prediction
25 A Novel Paradigm in the Management of Pancreatic Trauma
Authors: E. Tan, O. McKay, T. Clarnette T., D. Croagh
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Background: Historically with pancreatic trauma, complete disruption of the main pancreatic duct (MPD), classified as Grade IV-V by the American Association for the Surgery of Trauma (AAST), necessitated a damage-control laparotomy. This was to avoid mortality, shorten diet upgrade timeframe, and hence shorter length of stay. However, acute pancreatic resection entailed complications of pancreatic fistulas and leaks. With the advance of imaging-guided interventions, non-operative management such as percutaneous and transpapillary drainage of traumatic peripancreatic collections have been trialled favourably. The aim of this case series is to evaluate the efficacy of endoscopic ultrasound-guided (EUS) transmural drainage in managing traumatic peripancreatic collections as a less invasive alternative to traditional approaches. This study also highlights the importance of anatomical knowledge regarding peripancreatic collection’s common location in the lesser sac, the pancreas relationship to adjacent organs, and the formation of the main pancreatic duct in regards to the feasibility of therapeutic internal drainage. Methodology: A retrospective case series was conducted at a single tertiary endoscopy unit, analysing patient data over a 5-year period. Inclusion criteria outlined patients age 5 to 80-years-old, traumatic pancreatic injury of at least Grade IV and haemodynamic stability. Exclusion criteria involved previous episodes of pancreatitis or abdominal trauma. Patient demographics and clinicopathological characteristics were retrospectively collected. Results: The study identified 7 patients with traumatic pancreatic injuries that were managed from 2018-2022; age ranging from 5 to 34 years old, with majority being female (n=5). Majority of the mechanisms of trauma were a handlebar injury (n=4). Diagnosis was confirmed with an elevated lipase and computerized tomotography (CT) confirmation of proximal pancreatic transection with MPD disruption. All patients sustained an isolated single organ grade IV pancreatic injury, except case 4 and 5 with other intra-abdominal visceral Grade 1 injuries. 6 patients underwent early ERCP-guided transpapillary drainage with 1 being unsuccessful for pancreatic duct stent insertion (case 1) and 1 complication of stent migration (case 2). Surveillance imaging post ERCP showed the stents were unable to bridge the disrupted duct and development of symptomatic collections with an average size of 9.9cm. Hence, all patients proceeded to EUS-guided transmural drainage, with 2/7 patients requiring repeat drainages (case 6 and 7). Majority (n=6) had a cystogastrostomy, whilst 1 (case 6) had a cystoenterostomy due to feasibility of the peripancreatic collection being adjacent to duodenum rather than stomach. However, case 6 subsequently required repeat EUS-guided drainage with cystogastrostomy for ongoing collections. Hence all patients avoided initial laparotomy with an average index length of stay of 11.7 days. Successful transmural drainage was demonstrated, with no long-term complications of pancreatic insufficiency; except for 1 patient requiring a distal pancreatectomy at 2 year follow-up due to chronic pain. Conclusion: The early results of this series support EUS-guided transmural drainage as a viable management option for traumatic peripancreatic collections, showcasing successful outcomes, minimal complications, and long-term efficacy in avoiding surgical interventions. More studies are required before the adoption of this procedure as a less invasive and complication-prone management approach for traumatic peripancreatic collections.Keywords: endoscopic ultrasound, cystogastrostomy, pancreatic trauma, traumatic peripancreatic collection, transmural drainage
Procedia PDF Downloads 4324 Impact of Elevated Temperature on Spot Blotch Development in Wheat and Induction of Resistance by Plant Growth Promoting Rhizobacteria
Authors: Jayanwita Sarkar, Usha Chakraborty, Bishwanath Chakraborty
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Plants are constantly interacting with various abiotic and biotic stresses. In changing climate scenario plants are continuously modifying physiological processes to adapt to changing environmental conditions which profoundly affect plant-pathogen interactions. Spot blotch in wheat is a fast-rising disease in the warmer plains of South Asia where the rise in minimum average temperature over most of the year already affecting wheat production. Hence, the study was undertaken to explore the role of elevated temperature in spot blotch disease development and modulation of antioxidative responses by plant growth promoting rhizobacteria (PGPR) for biocontrol of spot blotch at high temperature. Elevated temperature significantly increases the susceptibility of wheat plants to spot blotch causing pathogen Bipolaris sorokiniana. Two PGPR Bacillus safensis (W10) and Ochrobactrum pseudogrignonense (IP8) isolated from wheat (Triticum aestivum L.) and blady grass (Imperata cylindrical L.) rhizophere respectively, showing in vitro antagonistic activity against Bipolaris sorokiniana were tested for growth promotion and induction of resistance against spot blotch in wheat. GC-MS analysis showed that Bacillus safensis (W10) and Ochrobactrum pseudogrignonense (IP8) produced antifungal and antimicrobial compounds in culture. Seed priming with these two bacteria significantly increase growth, modulate antioxidative signaling and induce resistance and eventually reduce disease incidence in wheat plants at optimum as well as elevated temperature which was further confirmed by indirect immunofluorescence assay using polyclonal antibody raised against Bipolaris sorokiniana. Application of the PGPR led to enhancement in activities of plant defense enzymes- phenylalanine ammonia lyase, peroxidase, chitinase and β-1,3 glucanase in infected leaves. Immunolocalization of chitinase and β-1,3 glucanase in PGPR primed and pathogen inoculated leaf tissue was further confirmed by transmission electron microscopy using PAb of chitinase, β-1,3 glucanase and gold labelled conjugates. Activity of ascorbate-glutathione redox cycle related enzymes such as ascorbate peroxidase, superoxide dismutase and glutathione reductase along with antioxidants such as carotenoids, glutathione and ascorbate and osmolytes like proline and glycine betain accumulation were also increased during disease development in PGPR primed plant in comparison to unprimed plants at high temperature. Real-time PCR analysis revealed enhanced expression of defense genes- chalcone synthase and phenyl alanineammonia lyase. Over expression of heat shock proteins like HSP 70, small HSP 26.3 and heat shock factor HsfA3 in PGPR primed plants effectively protect plants against spot blotch infection at elevated temperature as compared with control plants. Our results revealed dynamic biochemical cross talk between elevated temperature and spot blotch disease development and furthermore highlight PGPR mediated array of antioxidative and molecular alterations responsible for induction of resistance against spot blotch disease at elevated temperature which seems to be associated with up-regulation of defense genes, heat shock proteins and heat shock factors, less ROS production, membrane damage, increased expression of redox enzymes and accumulation of osmolytes and antioxidants.Keywords: antioxidative enzymes, defense enzymes, elevated temperature, heat shock proteins, PGPR, Real-Time PCR, spot blotch, wheat
Procedia PDF Downloads 16323 Fold and Thrust Belts Seismic Imaging and Interpretation
Authors: Sunjay
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Plate tectonics is of very great significance as it represents the spatial relationships of volcanic rock suites at plate margins, the distribution in space and time of the conditions of different metamorphic facies, the scheme of deformation in mountain belts, or orogens, and the association of different types of economic deposit. Orogenic belts are characterized by extensive thrust faulting, movements along large strike-slip fault zones, and extensional deformation that occur deep within continental interiors. Within oceanic areas there also are regions of crustal extension and accretion in the backarc basins that are located on the landward sides of many destructive plate margins.Collisional orogens develop where a continent or island arc collides with a continental margin as a result of subduction. collisional and noncollisional orogens can be explained by differences in the strength and rheology of the continental lithosphere and by processes that influence these properties during orogenesis.Seismic Imaging Difficulties-In triangle zones, several factors reduce the effectiveness of seismic methods. The topography in the central part of the triangle zone is usually rugged and is associated with near-surface velocity inversions which degrade the quality of the seismic image. These characteristics lead to low signal-to-noise ratio, inadequate penetration of energy through overburden, poor geophone coupling with the surface and wave scattering. Depth Seismic Imaging Techniques-Seismic processing relates to the process of altering the seismic data to suppress noise, enhancing the desired signal (higher signal-to-noise ratio) and migrating seismic events to their appropriate location in space and depth. Processing steps generally include analysis of velocities, static corrections, moveout corrections, stacking and migration. Exploration seismology Bow-tie effect -Shadow Zones-areas with no reflections (dead areas). These are called shadow zones and are common in the vicinity of faults and other discontinuous areas in the subsurface. Shadow zones result when energy from a reflector is focused on receivers that produce other traces. As a result, reflectors are not shown in their true positions. Subsurface Discontinuities-Diffractions occur at discontinuities in the subsurface such as faults and velocity discontinuities (as at “bright spot” terminations). Bow-tie effect caused by the two deep-seated synclines. Seismic imaging of thrust faults and structural damage-deepwater thrust belts, Imaging deformation in submarine thrust belts using seismic attributes,Imaging thrust and fault zones using 3D seismic image processing techniques, Balanced structural cross sections seismic interpretation pitfalls checking, The seismic pitfalls can originate due to any or all of the limitations of data acquisition, processing, interpretation of the subsurface geology,Pitfalls and limitations in seismic attribute interpretation of tectonic features, Seismic attributes are routinely used to accelerate and quantify the interpretation of tectonic features in 3D seismic data. Coherence (or variance) cubes delineate the edges of megablocks and faulted strata, curvature delineates folds and flexures, while spectral components delineate lateral changes in thickness and lithology. Carbon capture and geological storage leakage surveillance because fault behave as a seal or a conduit for hydrocarbon transportation to a trap,etc.Keywords: tectonics, seismic imaging, fold and thrust belts, seismic interpretation
Procedia PDF Downloads 6822 Molecular Signaling Involved in the 'Benzo(a)Pyrene' Induced Germ Cell DNA Damage and Apoptosis: Possible Protection by Natural Aryl Hydrocarbon Receptor Antagonist and Anti-Tumor Agent
Authors: Kuladip Jana
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Benzo(a)pyrene [B(a)P] is an environmental toxicant present mostly in cigarette smoke and car exhaust, is an aryl hydrocarbon receptor (AhR) ligand that exerts its toxic effects on both male and female reproductive systems. In this study, the effect of B(a)P at different doses (0.1, 0.25, 0.5, 1 and 5 mg /kg body weight) was studied on male reproductive system of rat. A significant decrease in cauda epididymal sperm count and motility along with the presence of sperm head abnormalities and altered epididymal and testicular histology were documented following B(a)P treatment. B(a)P treatment resulted apoptotic sperm cells as observed by TUNEL and Annexin V-PI assay with increased ROS, altered sperm mitochondrial membrane potential (ΔΨm) with a simultaneous decrease in the activity of antioxidant enzymes and GSH status. TUNEL positive apoptotic cells also observed in testis as well as isolated germ and Leydig cells following B(a)P exposure. Western Blot analysis revealed the activation of p38MAPK, cytosolic translocation of cytochrome-c, up-regulation of Bax and inducible nitric oxide synthase (iNOS) with cleavage of PARP and down-regulation of BCl2 in testis upon B(a)P treatment. The protein and mRNA levels of testicular key steroidogenesis regulatory proteins like StAR, cytochrome P450 IIA1 (CYPIIA1), 3β HSD, 17β HSD showed a significant decrease in a dose dependent manner while an increase in the expression of cytochrome P450 1A1 (CYP1A1), Aryl hydrocarbon Receptor (AhR), active caspase- 9 and caspase- 3 following B(a)P exposure. We conclude that exposure of benzo(a)pyrene caused testicular gamatogenic and steroidogenic disorders by induction of oxidative stress, inhibition of StAR and other steroidogenic enzymes along with activation of p38MAPK and initiated caspase-3 mediated germ and Leydig cell apoptosis.The possible protective role of naturally occurring phytochemicals against B(a)P induced testicular toxicity needs immediate consideration. Curcumin and resveratrol separately were found to protect against B(a)P induced germ cell apoptosis, and their combinatorial effect was more significant. Our present study in isolated testicular germ cell population from adult male Wistar rats, highlighted their synergistic protective effect against B(a)P induced germ cell apoptosis. Curcumin-resveratrol co-treatment decreased the expression of pro-apoptotic proteins like cleaved caspase 3,8,9, cleaved PARP, Apaf1, FasL, tBid. Curcumin-resveratrol co-treatment decreased Bax/Bcl2 ratio, mitochondria to cytosolic translocation of cytochrome c and activated the survival protein Akt. Curcumin-resveratrol decreased the expression of p53 dependent apoptotic genes like Fas, FasL, Bax, Bcl2, Apaf1.Curcumin-resveratrol co-treatment thus prevented B(a)P induced germ cell apoptosis. B(a)P induced testicular ROS generation and oxidative stress were significantly ameliorated with curcumin and resveratrol. Curcumin-resveratrol co-treatment prevented B(a)P induced nuclear translocation of AhR and CYP1A1 production. The combinatorial treatment significantly inhibited B(a)P induced ERK 1/2, p38 MAPK and JNK 1/2 activation. B(a)P treatment increased the expression of p53 and its phosphorylation (p53 ser 15). Curcumin-resveratrol co-treatment significantly decreased p53 level and its phosphorylation (p53 ser 15). The study concludes that curcumin-resveratrol synergistically modulated MAPKs and p53, prevented oxidative stress, regulated the expression of pro and anti-apoptotic proteins as well as the proteins involved in B(a)P metabolism thus protected germ cells from B(a)P induced apoptosis.Keywords: benzo(a)pyrene, germ cell, apoptosis, oxidative stress, resveratrol, curcumin
Procedia PDF Downloads 25321 Pharmacophore-Based Modeling of a Series of Human Glutaminyl Cyclase Inhibitors to Identify Lead Molecules by Virtual Screening, Molecular Docking and Molecular Dynamics Simulation Study
Authors: Ankur Chaudhuri, Sibani Sen Chakraborty
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In human, glutaminyl cyclase activity is highly abundant in neuronal and secretory tissues and is preferentially restricted to hypothalamus and pituitary. The N-terminal modification of β-amyloids (Aβs) peptides by the generation of a pyro-glutamyl (pGlu) modified Aβs (pE-Aβs) is an important process in the initiation of the formation of neurotoxic plaques in Alzheimer’s disease (AD). This process is catalyzed by glutaminyl cyclase (QC). The expression of QC is characteristically up-regulated in the early stage of AD, and the hallmark of the inhibition of QC is the prevention of the formation of pE-Aβs and plaques. A computer-aided drug design (CADD) process was employed to give an idea for the designing of potentially active compounds to understand the inhibitory potency against human glutaminyl cyclase (QC). This work elaborates the ligand-based and structure-based pharmacophore exploration of glutaminyl cyclase (QC) by using the known inhibitors. Three dimensional (3D) quantitative structure-activity relationship (QSAR) methods were applied to 154 compounds with known IC50 values. All the inhibitors were divided into two sets, training-set, and test-sets. Generally, training-set was used to build the quantitative pharmacophore model based on the principle of structural diversity, whereas the test-set was employed to evaluate the predictive ability of the pharmacophore hypotheses. A chemical feature-based pharmacophore model was generated from the known 92 training-set compounds by HypoGen module implemented in Discovery Studio 2017 R2 software package. The best hypothesis was selected (Hypo1) based upon the highest correlation coefficient (0.8906), lowest total cost (463.72), and the lowest root mean square deviation (2.24Å) values. The highest correlation coefficient value indicates greater predictive activity of the hypothesis, whereas the lower root mean square deviation signifies a small deviation of experimental activity from the predicted one. The best pharmacophore model (Hypo1) of the candidate inhibitors predicted comprised four features: two hydrogen bond acceptor, one hydrogen bond donor, and one hydrophobic feature. The Hypo1 was validated by several parameters such as test set activity prediction, cost analysis, Fischer's randomization test, leave-one-out method, and heat map of ligand profiler. The predicted features were then used for virtual screening of potential compounds from NCI, ASINEX, Maybridge and Chembridge databases. More than seven million compounds were used for this purpose. The hit compounds were filtered by drug-likeness and pharmacokinetics properties. The selective hits were docked to the high-resolution three-dimensional structure of the target protein glutaminyl cyclase (PDB ID: 2AFU/2AFW) to filter these hits further. To validate the molecular docking results, the most active compound from the dataset was selected as a reference molecule. From the density functional theory (DFT) study, ten molecules were selected based on their highest HOMO (highest occupied molecular orbitals) energy and the lowest bandgap values. Molecular dynamics simulations with explicit solvation systems of the final ten hit compounds revealed that a large number of non-covalent interactions were formed with the binding site of the human glutaminyl cyclase. It was suggested that the hit compounds reported in this study could help in future designing of potent inhibitors as leads against human glutaminyl cyclase.Keywords: glutaminyl cyclase, hit lead, pharmacophore model, simulation
Procedia PDF Downloads 12820 The Proposal for a Framework to Face Opacity and Discrimination ‘Sins’ Caused by Consumer Creditworthiness Machines in the EU
Authors: Diogo José Morgado Rebelo, Francisco António Carneiro Pacheco de Andrade, Paulo Jorge Freitas de Oliveira Novais
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Not everything in AI-power consumer credit scoring turns out to be a wonder. When using AI in Creditworthiness Assessment (CWA), opacity and unfairness ‘sins’ must be considered to the task be deemed Responsible. AI software is not always 100% accurate, which can lead to misclassification. Discrimination of some groups can be exponentiated. A hetero personalized identity can be imposed on the individual(s) affected. Also, autonomous CWA sometimes lacks transparency when using black box models. However, for this intended purpose, human analysts ‘on-the-loop’ might not be the best remedy consumers are looking for in credit. This study seeks to explore the legality of implementing a Multi-Agent System (MAS) framework in consumer CWA to ensure compliance with the regulation outlined in Article 14(4) of the Proposal for an Artificial Intelligence Act (AIA), dated 21 April 2021 (as per the last corrigendum by the European Parliament on 19 April 2024), Especially with the adoption of Art. 18(8)(9) of the EU Directive 2023/2225, of 18 October, which will go into effect on 20 November 2026, there should be more emphasis on the need for hybrid oversight in AI-driven scoring to ensure fairness and transparency. In fact, the range of EU regulations on AI-based consumer credit will soon impact the AI lending industry locally and globally, as shown by the broad territorial scope of AIA’s Art. 2. Consequently, engineering the law of consumer’s CWA is imperative. Generally, the proposed MAS framework consists of several layers arranged in a specific sequence, as follows: firstly, the Data Layer gathers legitimate predictor sets from traditional sources; then, the Decision Support System Layer, whose Neural Network model is trained using k-fold Cross Validation, provides recommendations based on the feeder data; the eXplainability (XAI) multi-structure comprises Three-Step-Agents; and, lastly, the Oversight Layer has a 'Bottom Stop' for analysts to intervene in a timely manner. From the analysis, one can assure a vital component of this software is the XAY layer. It appears as a transparent curtain covering the AI’s decision-making process, enabling comprehension, reflection, and further feasible oversight. Local Interpretable Model-agnostic Explanations (LIME) might act as a pillar by offering counterfactual insights. SHapley Additive exPlanation (SHAP), another agent in the XAI layer, could address potential discrimination issues, identifying the contribution of each feature to the prediction. Alternatively, for thin or no file consumers, the Suggestion Agent can promote financial inclusion. It uses lawful alternative sources such as the share of wallet, among others, to search for more advantageous solutions to incomplete evaluation appraisals based on genetic programming. Overall, this research aspires to bring the concept of Machine-Centered Anthropocentrism to the table of EU policymaking. It acknowledges that, when put into service, credit analysts no longer exert full control over the data-driven entities programmers have given ‘birth’ to. With similar explanatory agents under supervision, AI itself can become self-accountable, prioritizing human concerns and values. AI decisions should not be vilified inherently. The issue lies in how they are integrated into decision-making and whether they align with non-discrimination principles and transparency rules.Keywords: creditworthiness assessment, hybrid oversight, machine-centered anthropocentrism, EU policymaking
Procedia PDF Downloads 2819 Artificial Intelligence Impact on the Australian Government Public Sector
Authors: Jessica Ho
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AI has helped government, businesses and industries transform the way they do things. AI is used in automating tasks to improve decision-making and efficiency. AI is embedded in sensors and used in automation to help save time and eliminate human errors in repetitive tasks. Today, we saw the growth in AI using the collection of vast amounts of data to forecast with greater accuracy, inform decision-making, adapt to changing market conditions and offer more personalised service based on consumer habits and preferences. Government around the world share the opportunity to leverage these disruptive technologies to improve productivity while reducing costs. In addition, these intelligent solutions can also help streamline government processes to deliver more seamless and intuitive user experiences for employees and citizens. This is a critical challenge for NSW Government as we are unable to determine the risk that is brought by the unprecedented pace of adoption of AI solutions in government. Government agencies must ensure that their use of AI complies with relevant laws and regulatory requirements, including those related to data privacy and security. Furthermore, there will always be ethical concerns surrounding the use of AI, such as the potential for bias, intellectual property rights and its impact on job security. Within NSW’s public sector, agencies are already testing AI for crowd control, infrastructure management, fraud compliance, public safety, transport, and police surveillance. Citizens are also attracted to the ease of use and accessibility of AI solutions without requiring specialised technical skills. This increased accessibility also comes with balancing a higher risk and exposure to the health and safety of citizens. On the other side, public agencies struggle with keeping up with this pace while minimising risks, but the low entry cost and open-source nature of generative AI led to a rapid increase in the development of AI powered apps organically – “There is an AI for That” in Government. Other challenges include the fact that there appeared to be no legislative provisions that expressly authorise the NSW Government to use an AI to make decision. On the global stage, there were too many actors in the regulatory space, and a sovereign response is needed to minimise multiplicity and regulatory burden. Therefore, traditional corporate risk and governance framework and regulation and legislation frameworks will need to be evaluated for AI unique challenges due to their rapidly evolving nature, ethical considerations, and heightened regulatory scrutiny impacting the safety of consumers and increased risks for Government. Creating an effective, efficient NSW Government’s governance regime, adapted to the range of different approaches to the applications of AI, is not a mere matter of overcoming technical challenges. Technologies have a wide range of social effects on our surroundings and behaviours. There is compelling evidence to show that Australia's sustained social and economic advancement depends on AI's ability to spur economic growth, boost productivity, and address a wide range of societal and political issues. AI may also inflict significant damage. If such harm is not addressed, the public's confidence in this kind of innovation will be weakened. This paper suggests several AI regulatory approaches for consideration that is forward-looking and agile while simultaneously fostering innovation and human rights. The anticipated outcome is to ensure that NSW Government matches the rising levels of innovation in AI technologies with the appropriate and balanced innovation in AI governance.Keywords: artificial inteligence, machine learning, rules, governance, government
Procedia PDF Downloads 6618 Closing down the Loop Holes: How North Korea and Other Bad Actors Manipulate Global Trade in Their Favor
Authors: Leo Byrne, Neil Watts
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In the complex and evolving landscape of global trade, maritime sanctions emerge as a critical tool wielded by the international community to curb illegal activities and alter the behavior of non-compliant states and entities. These sanctions, designed to restrict or prohibit trade by sea with sanctioned jurisdictions, entities, or individuals, face continuous challenges due to the sophisticated evasion tactics employed by countries like North Korea. As the Democratic People's Republic of Korea (DPRK) diverts significant resources to circumvent these measures, understanding the nuances of their methodologies becomes imperative for maintaining the integrity of global trade systems. The DPRK, one of the most sanctioned nations globally, has developed an intricate network to facilitate its trade in illicit goods, ensuring the flow of revenue from designated activities continues unabated. Given its geographic and economic conditions, North Korea predominantly relies on maritime routes, utilizing foreign ports to route its illicit trade. This reliance on the sea is exploited through various sophisticated methods, including the use of front companies, falsification of documentation, commingling of bulk cargos, and physical alterations to vessels. These tactics enable the DPRK to navigate through the gaps in regulatory frameworks and lax oversight, effectively undermining international sanctions regimes Maritime sanctions carry significant implications for global trade, imposing heightened risks in the maritime domain. The deceptive practices employed not only by the DPRK but also by other high-risk jurisdictions, necessitate a comprehensive understanding of UN targeted sanctions. For stakeholders in the maritime sector—including maritime authorities, vessel owners, shipping companies, flag registries, and financial institutions serving the shipping industry—awareness and compliance are paramount. Violations can lead to severe consequences, including reputational damage, sanctions, hefty fines, and even imprisonment. To mitigate risks associated with these deceptive practices, it is crucial for maritime sector stakeholders to employ rigorous due diligence and regulatory compliance screening measures. Effective sanctions compliance serves as a protective shield against legal, financial, and reputational risks, preventing exploitation by international bad actors. This requires not only a deep understanding of the sanctions landscape but also the capability to identify and manage risks through informed decision-making and proactive risk management practices. As the DPRK and other sanctioned entities continue to evolve their sanctions evasion tactics, the international community must enhance its collective efforts to demystify and counter these practices. By leveraging more stringent compliance measures, stakeholders can safeguard against the illicit use of the maritime domain, reinforcing the effectiveness of maritime sanctions as a tool for global security. This paper seeks to dissect North Korea's adaptive strategies in the face of maritime sanctions. By examining up-to-date, geographically, and temporally relevant case studies, it aims to shed light on the primary nodes through which Pyongyang evades sanctions and smuggles goods via third-party ports. The goal is to propose multi-level interaction strategies, ranging from governmental interventions to localized enforcement mechanisms, to counteract these evasion tactics.Keywords: maritime, maritime sanctions, international sanctions, compliance, risk
Procedia PDF Downloads 6117 Stabilizing Additively Manufactured Superalloys at High Temperatures
Authors: Keivan Davami, Michael Munther, Lloyd Hackel
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The control of properties and material behavior by implementing thermal-mechanical processes is based on mechanical deformation and annealing according to a precise schedule that will produce a unique and stable combination of grain structure, dislocation substructure, texture, and dispersion of precipitated phases. The authors recently developed a thermal-mechanical technique to stabilize the microstructure of additively manufactured nickel-based superalloys even after exposure to high temperatures. However, the mechanism(s) that controls this stability is still under investigation. Laser peening (LP), also called laser shock peening (LSP), is a shock based (50 ns duration) post-processing technique used for extending performance levels and improving service life of critical components by developing deep levels of plastic deformation, thereby generating high density of dislocations and inducing compressive residual stresses in the surface and deep subsurface of components. These compressive residual stresses are usually accompanied with an increase in hardness and enhance the material’s resistance to surface-related failures such as creep, fatigue, contact damage, and stress corrosion cracking. While the LP process enhances the life span and durability of the material, the induced compressive residual stresses relax at high temperatures (>0.5Tm, where Tm is the absolute melting temperature), limiting the applicability of the technology. At temperatures above 0.5Tm, the compressive residual stresses relax, and yield strength begins to drop dramatically. The principal reason is the increasing rate of solid-state diffusion, which affects both the dislocations and the microstructural barriers. Dislocation configurations commonly recover by mechanisms such as climbing and recombining rapidly at high temperatures. Furthermore, precipitates coarsen, and grains grow; virtually all of the available microstructural barriers become ineffective.Our results indicate that by using “cyclic” treatments with sequential LP and annealing steps, the compressive stresses survive, and the microstructure is stable after exposure to temperatures exceeding 0.5Tm for a long period of time. When the laser peening process is combined with annealing, dislocations formed as a result of LPand precipitates formed during annealing have a complex interaction that provides further stability at high temperatures. From a scientific point of view, this research lays the groundwork for studying a variety of physical, materials science, and mechanical engineering concepts. This research could lead to metals operating at higher sustained temperatures enabling improved system efficiencies. The strengthening of metals by a variety of means (alloying, work hardening, and other processes) has been of interest for a wide range of applications. However, the mechanistic understanding of the often complex processes of interactionsbetween dislocations with solute atoms and with precipitates during plastic deformation have largely remained scattered in the literature. In this research, the elucidation of the actual mechanisms involved in the novel cyclic LP/annealing processes as a scientific pursuit is investigated through parallel studies of dislocation theory and the implementation of advanced experimental tools. The results of this research help with the validation of a novel laser processing technique for high temperature applications. This will greatly expand the applications of the laser peening technology originally devised only for temperatures lower than half of the melting temperature.Keywords: laser shock peening, mechanical properties, indentation, high temperature stability
Procedia PDF Downloads 14316 Investigation on Pull-Out-Behavior and Interface Critical Parameters of Polymeric Fibers Embedded in Concrete and Their Correlation with Particular Fiber Characteristics
Authors: Michael Sigruener, Dirk Muscat, Nicole Struebbe
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Fiber reinforcement is a state of the art to enhance mechanical properties in plastics. For concrete and civil engineering, steel reinforcements are commonly used. Steel reinforcements show disadvantages in their chemical resistance and weight, whereas polymer fibers' major problems are in fiber-matrix adhesion and mechanical properties. In spite of these facts, longevity and easy handling, as well as chemical resistance motivate researches to develop a polymeric material for fiber reinforced concrete. Adhesion and interfacial mechanism in fiber-polymer-composites are already studied thoroughly. For polymer fibers used as concrete reinforcement, the bonding behavior still requires a deeper investigation. Therefore, several differing polymers (e.g., polypropylene (PP), polyamide 6 (PA6) and polyetheretherketone (PEEK)) were spun into fibers via single screw extrusion and monoaxial stretching. Fibers then were embedded in a concrete matrix, and Single-Fiber-Pull-Out-Tests (SFPT) were conducted to investigate bonding characteristics and microstructural interface of the composite. Differences in maximum pull-out-force, displacement and slope of the linear part of force vs displacement-function, which depicts the adhesion strength and the ductility of the interfacial bond were studied. In SFPT fiber, debonding is an inhomogeneous process, where the combination of interfacial bonding and friction mechanisms add up to a resulting value. Therefore, correlations between polymeric properties and pull-out-mechanisms have to be emphasized. To investigate these correlations, all fibers were introduced to a series of analysis such as differential scanning calorimetry (DSC), contact angle measurement, surface roughness and hardness analysis, tensile testing and scanning electron microscope (SEM). Of each polymer, smooth and abraded fibers were tested, first to simulate the abrasion and damage caused by a concrete mixing process and secondly to estimate the influence of mechanical anchoring of rough surfaces. In general, abraded fibers showed a significant increase in maximum pull-out-force due to better mechanical anchoring. Friction processes therefore play a major role to increase the maximum pull-out-force. The polymer hardness affects the tribological behavior and polymers with high hardness lead to lower surface roughness verified by SEM and surface roughness measurements. This concludes into a decreased maximum pull-out-force for hard polymers. High surface energy polymers show better interfacial bonding strength in general, which coincides with the conducted SFPT investigation. Polymers such as PEEK or PA6 show higher bonding strength in smooth and roughened fibers, revealed through high pull-out-force and concrete particles bonded on the fiber surface pictured via SEM analysis. The surface energy divides into dispersive and polar part, at which the slope is correlating with the polar part. Only polar polymers increase their SFPT-function slope due to better wetting abilities when showing a higher bonding area through rough surfaces. Hence, the maximum force and the bonding strength of an embedded fiber is a function of polarity, hardness, and consequently surface roughness. Other properties such as crystallinity or tensile strength do not affect bonding behavior. Through the conducted analysis, it is now feasible to understand and resolve different effects in pull-out-behavior step-by-step based on the polymer properties itself. This investigation developed a roadmap on how to engineer high adhering polymeric materials for fiber reinforcement of concrete.Keywords: fiber-matrix interface, polymeric fibers, fiber reinforced concrete, single fiber pull-out test
Procedia PDF Downloads 10615 Drug Reaction with Eosinophilia and Systemic Symptoms (Dress) Syndrome Presenting as Multi-Organ Failure
Authors: Keshari Shrestha, Philip Vatterott
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Introduction: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare and potentially fatal drug-related syndrome. DRESS classically presents with a diffuse maculopapular rash, fevers, and eosinophilia more than three weeks after drug exposure. DRESS can present with multi-organ involvement, with liver damage being the most common and severe. Pulmonary involvement is a less common manifestation and is associated with poor clinical outcomes. Chest imaging is often nonspecific, and symptoms can range from mild cough to acute respiratory distress syndrome (ARDS) . This is a case of a 49-year-old female with a history of recent clostridium difficile colitis status post treatment with oral vancomycin who presented with rash, acute liver and kidney failure, as well as diffuse nodular alveolar lung opacities concerning for DRESS syndrome with multi-organ involvement. Clinical Course: This patient initially presented to an outside hospital with clostridium difficile colitis, acute liver injury, and acute kidney injury. She developed a desquamating maculopapular rash in the setting of recent oral vancomycin, meloxicam, and furosemide initiation. She was hospitalized on two additional occasions with worsening altered mental status, liver injury, and acute kidney injury and was initiated on intermittent hemodialysis. Notably, she was found to have systemic eosinophilia (4100 cells/microliter) several weeks prior. She was transferred to this institution for further management where she was found to have encephalopathy, jaundice, lower extremity edema, and diffuse bilateral rhonchorous breath sounds on pulmonary examination. The patient was started on methylprednisolone for suspected DRESS syndrome. She underwent an evaluation for alternative causes of her organ failure. Her workup included a negative infectious, autoimmune, metabolic, toxic, and malignant work-up. Abdominal computed tomography (CT) and ultrasound were remarkable for evidence of hepatic steatosis and possible cirrhotic morphology. Additionally, a chest CT demonstrated diffuse and symmetric nodular alveolar lung opacities with peripheral sparing not consistent with acute respiratory distress syndrome or edema. Ultimately, her condition continued to decline, and she required intubation on several occasions. On hospital day 25 she succumbed to distributive shock in the setting of probable sepsis and multi-organ failure. Discussion: DRESS syndrome occurs in 1 in 1,000 to 10,000 patients with a mortality rate of around 10%. Anti-convulsant, anti-bacterial, anti-viral, and sulfonamide drugs are the most common drugs implicated in the development of DRESS syndrome; however, the list of offending agents is extensive . The diagnosis of DRESS syndrome is made after excluding other causes of disease such as infectious and autoimmune etiologies. The RegiSCAR scoring system is used to diagnose DRESS syndrome with 2-3 points indicating possible disease, 4-5 probable disease, and >5 definite disease. This patient scored a 7 on the RegiSCAR scale for eosinophilia, rash, organ involvement, and exclusion of other causes (infectious and autoimmune). While the pharmacologic trigger in this case is unknown, it is speculated to be caused by vancomycin, meloxicam, or furosemide due to the favorable timeline of initiation. Despite aggressive treatment, DRESS syndrome can often be fatal. Because of this, early diagnosis and treatment of patients with suspected DRESS syndrome is imperative.Keywords: drug reaction with eosinophilia and systemic symptoms, multi-organ failure, pulmonary involvement, renal failure
Procedia PDF Downloads 16514 Radioprotective Effects of Super-Paramagnetic Iron Oxide Nanoparticles Used as Magnetic Resonance Imaging Contrast Agent for Magnetic Resonance Imaging-Guided Radiotherapy
Authors: Michael R. Shurin, Galina Shurin, Vladimir A. Kirichenko
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Background. Visibility of hepatic malignancies is poor on non-contrast imaging for daily verification of liver malignancies prior to radiation therapy on MRI-guided Linear Accelerators (MR-Linac). Ferumoxytol® (Feraheme, AMAG Pharmaceuticals, Waltham, MA) is a SPION agent that is increasingly utilized off-label as hepatic MRI contrast. This agent has the advantage of providing a functional assessment of the liver based upon its uptake by hepatic Kupffer cells proportionate to vascular perfusion, resulting in strong T1, T2 and T2* relaxation effects and enhanced contrast of malignant tumors, which lack Kupffer cells. The latter characteristic has been recently utilized for MRI-guided radiotherapy planning with precision targeting of liver malignancies. However potential radiotoxicity of SPION has never been addressed for its safe use as an MRI-contrast agent during liver radiotherapy on MRI-Linac. This study defines the radiomodulating properties of SPIONs in vitro on human monocyte and macrophage cell lines exposed to 60Go gamma-rays within clinical radiotherapy dose range. Methods. Human monocyte and macrophages cell line in cultures were loaded with a clinically relevant concentration of Ferumoxytol (30µg/ml) for 2 and 24 h and irradiated to 3Gy, 5Gy and 10Gy. Cells were washed and cultured for additional 24 and 48 h prior to assessing their phenotypic activation by flow cytometry and function, including viability (Annexin V/PI assay), proliferation (MTT assay) and cytokine expression (Luminex assay). Results. Our results reveled that SPION affected both human monocytes and macrophages in vitro. Specifically, iron oxide nanoparticles decreased radiation-induced apoptosis and prevented radiation-induced inhibition of human monocyte proliferative activity. Furthermore, Ferumoxytol protected monocytes from radiation-induced modulation of phenotype. For instance, while irradiation decreased polarization of monocytes to CD11b+CD14+ and CD11bnegCD14neg phenotype, Ferumoxytol prevented these effects. In macrophages, Ferumoxytol counteracted the ability of radiation to up-regulate cell polarization to CD11b+CD14+ phenotype and prevented radiation-induced down-regulation of expression of HLA-DR and CD86 molecules. Finally, Ferumoxytol uptake by human monocytes down-regulated expression of pro-inflammatory chemokines MIP-1α (Macrophage inflammatory protein 1α), MIP-1β (CCL4) and RANTES (CCL5). In macrophages, Ferumoxytol reversed the expression of IL-1RA, IL-8, IP-10 (CXCL10) and TNF-α, and up-regulates expression of MCP-1 (CCL2) and MIP-1α in irradiated macrophages. Conclusion. SPION agent Ferumoxytol increases resistance of human monocytes to radiation-induced cell death in vitro and supports anti-inflammatory phenotype of human macrophages under radiation. The effect is radiation dose-dependent and depends on the duration of Feraheme uptake. This study also finds strong evidence that SPIONs reversed the effect of radiation on the expression of pro-inflammatory cytokines involved in initiation and development of radiation-induced liver damage. Correlative translational work at our institution will directly assess the cyto-protective effects of Ferumoxytol on human Kupfer cells in vitro and ex vivo analysis of explanted liver specimens in a subset of patients receiving Feraheme-enhanced MRI-guided radiotherapy to the primary liver tumors as a bridge to liver transplant.Keywords: superparamagnetic iron oxide nanoparticles, radioprotection, magnetic resonance imaging, liver
Procedia PDF Downloads 6913 Case Study Hyperbaric Oxygen Therapy for Idiopathic Sudden Sensorineural Hearing Loss
Authors: Magdy I. A. Alshourbagi
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Background: The National Institute for Deafness and Communication Disorders defines idiopathic sudden sensorineural hearing loss as the idiopathic loss of hearing of at least 30 dB across 3 contiguous frequencies occurring within 3 days.The most common clinical presentation involves an individual experiencing a sudden unilateral hearing loss, tinnitus, a sensation of aural fullness and vertigo. The etiologies and pathologies of ISSNHL remain unclear. Several pathophysiological mechanisms have been described including: vascular occlusion, viral infections, labyrinthine membrane breaks, immune associated disease, abnormal cochlear stress response, trauma, abnormal tissue growth, toxins, ototoxic drugs and cochlear membrane damage. The rationale for the use of hyperbaric oxygen to treat ISSHL is supported by an understanding of the high metabolism and paucity of vascularity to the cochlea. The cochlea and the structures within it require a high oxygen supply. The direct vascular supply, particularly to the organ of Corti, is minimal. Tissue oxygenation to the structures within the cochlea occurs via oxygen diffusion from cochlear capillary networks into the perilymph and the cortilymph. . The perilymph is the primary oxygen source for these intracochlear structures. Unfortunately, perilymph oxygen tension is decreased significantly in patients with ISSHL. To achieve a consistent rise of perilymph oxygen content, the arterial-perilymphatic oxygen concentration difference must be extremely high. This can be restored with hyperbaric oxygen therapy. Subject and Methods: A 37 year old man was presented at the clinic with a five days history of muffled hearing and tinnitus of the right ear. Symptoms were sudden onset, with no associated pain, dizziness or otorrhea and no past history of hearing problems or medical illness. Family history was negative. Physical examination was normal. Otologic examination revealed normal tympanic membranes bilaterally, with no evidence of cerumen or middle ear effusion. Tuning fork examination showed positive Rinne test bilaterally but with lateralization of Weber test to the left side, indicating right ear sensorineural hearing loss. Audiometric analysis confirmed sensorineural hearing loss across all frequencies of about 70- dB in the right ear. Routine lab work were all within normal limits. Clinical diagnosis of idiopathic sudden sensorineural hearing loss of the right ear was made and the patient began a medical treatment (corticosteroid, vasodilator and HBO therapy). The recommended treatment profile consists of 100% O2 at 2.5 atmospheres absolute for 60 minutes daily (six days per week) for 40 treatments .The optimal number of HBOT treatments will vary, depending on the severity and duration of symptomatology and the response to treatment. Results: As HBOT is not yet a standard for idiopathic sudden sensorineural hearing loss, it was introduced to this patient as an adjuvant therapy. The HBOT program was scheduled for 40 sessions, we used a 12-seat multi place chamber for the HBOT, which was started at day seven after the hearing loss onset. After the tenth session of HBOT, improvement of both hearing (by audiogram) and tinnitus was obtained in the affected ear (right). Conclusions: In conclusion, HBOT may be used for idiopathic sudden sensorineural hearing loss as an adjuvant therapy. It may promote oxygenation to the inner ear apparatus and revive hearing ability. Patients who fail to respond to oral and intratympanic steroids may benefit from this treatment. Further investigation is warranted, including animal studies to understand the molecular and histopathological aspects of HBOT and randomized control clinical studies.Keywords: idiopathic sudden sensorineural hearing loss (issnhl), hyperbaric oxygen therapy (hbot), the decibel (db), oxygen (o2)
Procedia PDF Downloads 42712 The Impact of Right to Repair Initiatives on Environmental and Financial Performance in European Consumer Electronics Firms: An Econometric Analysis
Authors: Daniel Stabler, Anne-Laure Mention, Henri Hakala, Ahmad Alaassar
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In Europe, 2.2 billion tons of waste annually generate severe environmental damage and economic burdens, and negatively impact human health. A stark illustration of the problem is found within the consumer electronics industry, which reflects one of the most complex global waste streams. Of the 5.3 billion globally discarded mobile phones in 2022, only 17% were properly recycled. To address these pressing issues, Europe has made significant strides in developing waste management strategies, Circular Economy initiatives, and Right to Repair policies. These endeavors aim to make product repair and maintenance more accessible, extend product lifespans, reduce waste, and promote sustainable resource use. European countries have introduced Right to Repair policies, often in conjunction with extended producer responsibility legislation, repair subsidies, and consumer repair indices, to varying degrees of regulatory rigor. Changing societal trends emphasizing sustainability and environmental responsibility have driven consumer demand for more sustainable and repairable products, benefiting repair-focused consumer electronics businesses. In academic research, much of the literature in Management studies has examined the European Circular Economy and the Right to Repair from firm-level perspectives. These studies frequently employ a business-model lens, emphasizing innovation and strategy frameworks. However, this study takes an institutional perspective, aiming to understand the adoption of Circular Economy and repair-focused business models within the European consumer electronics market. The concepts of the Circular Economy and the Right to Repair align with institutionalism as they reflect evolving societal norms favoring sustainability and consumer empowerment. Regulatory institutions play a pivotal role in shaping and enforcing these concepts through legislation, influencing the behavior of businesses and individuals. Compliance and enforcement mechanisms are essential for their success, compelling actors to adopt sustainable practices and consider product life extension. Over time, these mechanisms create a path for more sustainable choices, underscoring the influence of institutions and societal values on behavior and decision-making. Institutionalism, particularly 'neo-institutionalism,' provides valuable insights into the factors driving the adoption of Circular and repair-focused business models. Neo-institutional pressures can manifest through coercive regulatory initiatives or normative standards shaped by socio-cultural trends. The Right to Repair movement has emerged as a prominent and influential idea within academic discourse and sustainable development initiatives. Therefore, understanding how macro-level societal shifts toward the Circular Economy and the Right to Repair trigger firm-level responses is imperative. This study aims to answer a crucial question about the impact of European Right to Repair initiatives had on the financial and environmental performance of European consumer electronics companies at the firm level. A quantitative and statistical research design will be employed. The study will encompass an extensive sample of consumer electronics firms in Northern and Western Europe, analyzing their financial and environmental performance in relation to the implementation of Right to Repair mechanisms. The study's findings are expected to provide valuable insights into the broader implications of the Right to Repair and Circular Economy initiatives on the European consumer electronics industry.Keywords: circular economy, right to repair, institutionalism, environmental management, european union
Procedia PDF Downloads 7211 Managing Crowds at Sports Mega Events: Examining the Impact of ‘Fan Parks’ at International Football Tournaments between 2002 and 2016
Authors: Joel Rookwood
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Sports mega events have become increasingly significant in sporting, political and economic terms, with analysis often focusing on issues including resource expenditure, development, legacy and sustainability. Transnational tournaments can inspire interest from a variety of demographics, and the operational management of such events can involve contributions from a range of personnel. In addition to television audiences events also attract attending spectators, and in football contexts the temporary migration of fans from potentially rival nations and teams can present event organising committees and security personnel with various challenges in relation to crowd management. The behaviour, interaction and control of supporters has previously led to incidents of disorder and hooliganism, with damage to property as well as injuries and deaths proving significant consequences. The Heysel tragedy at the 1985 European Cup final in Brussels is a notable example, where 39 fans died following crowd disorder and mismanagement. Football disasters and disorder, particularly in the context of international competition, have inspired responses from police, law makers, event organisers, clubs and associations, including stadium improvements, legislative developments and crowd management practice to improve the effectiveness of spectator safety. The growth and internationalisation of fandom and developments in event management and tourism have seen various responses to the evolving challenges associated with hosting large numbers of visiting spectators at mega events. In football contexts ‘fan parks’ are a notable example. Since the first widespread introduction in European football competitions at the 2006 World Cup finals in Germany, these facilities have become a staple element of such mega events. This qualitative, longitudinal, multi-continent research draws on extensive semi-structured interview and observation data. As a frame of reference, this work considers football events staged before and after the development of fan parks. Research was undertaken at four World Cup finals (Japan 2002, Germany 2006, South Africa 2010 and Brazil 2014), four European Championships (Portugal 2004, Switzerland/Austria 2008, Poland/Ukraine 2012 and France 2016), four other confederation tournaments (Ghana 2008, Qatar 2011, USA 2011 and Chile 2015), and four European club finals (Istanbul 2005, Athens 2007, Rome 2009 and Basle 2016). This work found that these parks are typically temporarily erected, specifically located zones where supporters congregate together irrespective of allegiances to watch matches on large screens, and partake in other forms of organised on-site entertainment. Such facilities can also allow organisers to control the behaviour, confine the movement and monitor the alcohol consumption of supporters. This represents a notable shift in policy from previous football tournaments, when the widely assumed causal link between alcohol and hooliganism which frequently shaped legislative and police responses to disorder, also dissuaded some authorities from permitting fans to consume alcohol in and around stadia. It also reflects changing attitudes towards modern football fans. The work also found that in certain contexts supporters have increasingly engaged with such provision which impacts fan behaviour, but that this is relative to factors including location, facilities, management and security.Keywords: event, facility, fan, management, park
Procedia PDF Downloads 31010 Design of DNA Origami Structures Using LAMP Products as a Combined System for the Detection of Extended Spectrum B-Lactamases
Authors: Kalaumari Mayoral-Peña, Ana I. Montejano-Montelongo, Josué Reyes-Muñoz, Gonzalo A. Ortiz-Mancilla, Mayrin Rodríguez-Cruz, Víctor Hernández-Villalobos, Jesús A. Guzmán-López, Santiago García-Jacobo, Iván Licona-Vázquez, Grisel Fierros-Romero, Rosario Flores-Vallejo
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The group B-lactamic antibiotics include some of the most frequently used small drug molecules against bacterial infections. Nevertheless, an alarming decrease in their efficacy has been reported due to the emergence of antibiotic-resistant bacteria. Infections caused by bacteria expressing extended Spectrum B-lactamases (ESBLs) are difficult to treat and account for higher morbidity and mortality rates, delayed recovery, and high economic burden. According to the Global Report on Antimicrobial Resistance Surveillance, it is estimated that mortality due to resistant bacteria will ascend to 10 million cases per year worldwide. These facts highlight the importance of developing low-cost and readily accessible detection methods of drug-resistant ESBLs bacteria to prevent their spread and promote accurate and fast diagnosis. Bacterial detection is commonly done using molecular diagnostic techniques, where PCR stands out for its high performance. However, this technique requires specialized equipment not available everywhere, is time-consuming, and has a high cost. Loop-Mediated Isothermal Amplification (LAMP) is an alternative technique that works at a constant temperature, significantly decreasing the equipment cost. It yields double-stranded DNA of several lengths with repetitions of the target DNA sequence as a product. Although positive and negative results from LAMP can be discriminated by colorimetry, fluorescence, and turbidity, there is still a large room for improvement in the point-of-care implementation. DNA origami is a technique that allows the formation of 3D nanometric structures by folding a large single-stranded DNA (scaffold) into a determined shape with the help of short DNA sequences (staples), which hybridize with the scaffold. This research aimed to generate DNA origami structures using LAMP products as scaffolds to improve the sensitivity to detect ESBLs in point-of-care diagnosis. For this study, the coding sequence of the CTM-X-15 ESBL of E. coli was used to generate the LAMP products. The set of LAMP primers were designed using PrimerExplorerV5. As a result, a target sequence of 200 nucleotides from CTM-X-15 ESBL was obtained. Afterward, eight different DNA origami structures were designed using the target sequence in the SDCadnano and analyzed with CanDo to evaluate the stability of the 3D structures. The designs were constructed minimizing the total number of staples to reduce costs and complexity for point-of-care applications. After analyzing the DNA origami designs, two structures were selected. The first one was a zig-zag flat structure, while the second one was a wall-like shape. Given the sequence repetitions in the scaffold sequence, both were able to be assembled with only 6 different staples each one, ranging between 18 to 80 nucleotides. Simulations of both structures were performed using scaffolds of different sizes yielding stable structures in all the cases. The generation of the LAMP products were tested by colorimetry and electrophoresis. The formation of the DNA structures was analyzed using electrophoresis and colorimetry. The modeling of novel detection methods through bioinformatics tools allows reliable control and prediction of results. To our knowledge, this is the first study that uses LAMP products and DNA-origami in combination to delect ESBL-producing bacterial strains, which represent a promising methodology for diagnosis in the point-of-care.Keywords: beta-lactamases, antibiotic resistance, DNA origami, isothermal amplification, LAMP technique, molecular diagnosis
Procedia PDF Downloads 2119 Towards Dynamic Estimation of Residential Building Energy Consumption in Germany: Leveraging Machine Learning and Public Data from England and Wales
Authors: Philipp Sommer, Amgad Agoub
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The construction sector significantly impacts global CO₂ emissions, particularly through the energy usage of residential buildings. To address this, various governments, including Germany's, are focusing on reducing emissions via sustainable refurbishment initiatives. This study examines the application of machine learning (ML) to estimate energy demands dynamically in residential buildings and enhance the potential for large-scale sustainable refurbishment. A major challenge in Germany is the lack of extensive publicly labeled datasets for energy performance, as energy performance certificates, which provide critical data on building-specific energy requirements and consumption, are not available for all buildings or require on-site inspections. Conversely, England and other countries in the European Union (EU) have rich public datasets, providing a viable alternative for analysis. This research adapts insights from these English datasets to the German context by developing a comprehensive data schema and calibration dataset capable of predicting building energy demand effectively. The study proposes a minimal feature set, determined through feature importance analysis, to optimize the ML model. Findings indicate that ML significantly improves the scalability and accuracy of energy demand forecasts, supporting more effective emissions reduction strategies in the construction industry. Integrating energy performance certificates into municipal heat planning in Germany highlights the transformative impact of data-driven approaches on environmental sustainability. The goal is to identify and utilize key features from open data sources that significantly influence energy demand, creating an efficient forecasting model. Using Extreme Gradient Boosting (XGB) and data from energy performance certificates, effective features such as building type, year of construction, living space, insulation level, and building materials were incorporated. These were supplemented by data derived from descriptions of roofs, walls, windows, and floors, integrated into three datasets. The emphasis was on features accessible via remote sensing, which, along with other correlated characteristics, greatly improved the model's accuracy. The model was further validated using SHapley Additive exPlanations (SHAP) values and aggregated feature importance, which quantified the effects of individual features on the predictions. The refined model using remote sensing data showed a coefficient of determination (R²) of 0.64 and a mean absolute error (MAE) of 4.12, indicating predictions based on efficiency class 1-100 (G-A) may deviate by 4.12 points. This R² increased to 0.84 with the inclusion of more samples, with wall type emerging as the most predictive feature. After optimizing and incorporating related features like estimated primary energy consumption, the R² score for the training and test set reached 0.94, demonstrating good generalization. The study concludes that ML models significantly improve prediction accuracy over traditional methods, illustrating the potential of ML in enhancing energy efficiency analysis and planning. This supports better decision-making for energy optimization and highlights the benefits of developing and refining data schemas using open data to bolster sustainability in the building sector. The study underscores the importance of supporting open data initiatives to collect similar features and support the creation of comparable models in Germany, enhancing the outlook for environmental sustainability.Keywords: machine learning, remote sensing, residential building, energy performance certificates, data-driven, heat planning
Procedia PDF Downloads 488 Investigation of Delamination Process in Adhesively Bonded Hardwood Elements under Changing Environmental Conditions
Authors: M. M. Hassani, S. Ammann, F. K. Wittel, P. Niemz, H. J. Herrmann
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Application of engineered wood, especially in the form of glued-laminated timbers has increased significantly. Recent progress in plywood made of high strength and high stiffness hardwoods, like European beech, gives designers in general more freedom by increased dimensional stability and load-bearing capacity. However, the strong hygric dependence of basically all mechanical properties renders many innovative ideas futile. The tendency of hardwood for higher moisture sorption and swelling coefficients lead to significant residual stresses in glued-laminated configurations, cross-laminated patterns in particular. These stress fields cause initiation and evolution of cracks in the bond-lines resulting in: interfacial de-bonding, loss of structural integrity, and reduction of load-carrying capacity. Subsequently, delamination of glued-laminated timbers made of hardwood elements can be considered as the dominant failure mechanism in such composite elements. In addition, long-term creep and mechano-sorption under changing environmental conditions lead to loss of stiffness and can amplify delamination growth over the lifetime of a structure even after decades. In this study we investigate the delamination process of adhesively bonded hardwood (European beech) elements subjected to changing climatic conditions. To gain further insight into the long-term performance of adhesively bonded elements during the design phase of new products, the development and verification of an authentic moisture-dependent constitutive model for various species is of great significance. Since up to now, a comprehensive moisture-dependent rheological model comprising all possibly emerging deformation mechanisms was missing, a 3D orthotropic elasto-plastic, visco-elastic, mechano-sorptive material model for wood, with all material constants being defined as a function of moisture content, was developed. Apart from the solid wood adherends, adhesive layer also plays a crucial role in the generation and distribution of the interfacial stresses. Adhesive substance can be treated as a continuum layer constructed from finite elements, represented as a homogeneous and isotropic material. To obtain a realistic assessment on the mechanical performance of the adhesive layer and a detailed look at the interfacial stress distributions, a generic constitutive model including all potentially activated deformation modes, namely elastic, plastic, and visco-elastic creep was developed. We focused our studies on the three most common adhesive systems for structural timber engineering: one-component polyurethane adhesive (PUR), melamine-urea-formaldehyde (MUF), and phenol-resorcinol-formaldehyde (PRF). The corresponding numerical integration approaches, with additive decomposition of the total strain are implemented within the ABAQUS FEM environment by means of user subroutine UMAT. To predict the true stress state, we perform a history dependent sequential moisture-stress analysis using the developed material models for both wood substrate and adhesive layer. Prediction of the delamination process is founded on the fracture mechanical properties of the adhesive bond-line, measured under different levels of moisture content and application of the cohesive interface elements. Finally, we compare the numerical predictions with the experimental observations of de-bonding in glued-laminated samples under changing environmental conditions.Keywords: engineered wood, adhesive, material model, FEM analysis, fracture mechanics, delamination
Procedia PDF Downloads 4257 Assessing the Utility of Unmanned Aerial Vehicle-Borne Hyperspectral Image and Photogrammetry Derived 3D Data for Wetland Species Distribution Quick Mapping
Authors: Qiaosi Li, Frankie Kwan Kit Wong, Tung Fung
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Lightweight unmanned aerial vehicle (UAV) loading with novel sensors offers a low cost approach for data acquisition in complex environment. This study established a framework for applying UAV system in complex environment quick mapping and assessed the performance of UAV-based hyperspectral image and digital surface model (DSM) derived from photogrammetric point clouds for 13 species classification in wetland area Mai Po Inner Deep Bay Ramsar Site, Hong Kong. The study area was part of shallow bay with flat terrain and the major species including reedbed and four mangroves: Kandelia obovata, Aegiceras corniculatum, Acrostichum auerum and Acanthus ilicifolius. Other species involved in various graminaceous plants, tarbor, shrub and invasive species Mikania micrantha. In particular, invasive species climbed up to the mangrove canopy caused damage and morphology change which might increase species distinguishing difficulty. Hyperspectral images were acquired by Headwall Nano sensor with spectral range from 400nm to 1000nm and 0.06m spatial resolution image. A sequence of multi-view RGB images was captured with 0.02m spatial resolution and 75% overlap. Hyperspectral image was corrected for radiative and geometric distortion while high resolution RGB images were matched to generate maximum dense point clouds. Furtherly, a 5 cm grid digital surface model (DSM) was derived from dense point clouds. Multiple feature reduction methods were compared to identify the efficient method and to explore the significant spectral bands in distinguishing different species. Examined methods including stepwise discriminant analysis (DA), support vector machine (SVM) and minimum noise fraction (MNF) transformation. Subsequently, spectral subsets composed of the first 20 most importance bands extracted by SVM, DA and MNF, and multi-source subsets adding extra DSM to 20 spectrum bands were served as input in maximum likelihood classifier (MLC) and SVM classifier to compare the classification result. Classification results showed that feature reduction methods from best to worst are MNF transformation, DA and SVM. MNF transformation accuracy was even higher than all bands input result. Selected bands frequently laid along the green peak, red edge and near infrared. Additionally, DA found that chlorophyll absorption red band and yellow band were also important for species classification. In terms of 3D data, DSM enhanced the discriminant capacity among low plants, arbor and mangrove. Meanwhile, DSM largely reduced misclassification due to the shadow effect and morphological variation of inter-species. In respect to classifier, nonparametric SVM outperformed than MLC for high dimension and multi-source data in this study. SVM classifier tended to produce higher overall accuracy and reduce scattered patches although it costs more time than MLC. The best result was obtained by combining MNF components and DSM in SVM classifier. This study offered a precision species distribution survey solution for inaccessible wetland area with low cost of time and labour. In addition, findings relevant to the positive effect of DSM as well as spectral feature identification indicated that the utility of UAV-borne hyperspectral and photogrammetry deriving 3D data is promising in further research on wetland species such as bio-parameters modelling and biological invasion monitoring.Keywords: digital surface model (DSM), feature reduction, hyperspectral, photogrammetric point cloud, species mapping, unmanned aerial vehicle (UAV)
Procedia PDF Downloads 2536 Climate Change Threats to UNESCO-Designated World Heritage Sites: Empirical Evidence from Konso Cultural Landscape, Ethiopia
Authors: Yimer Mohammed Assen, Abiyot Legesse Kura, Engida Esyas Dube, Asebe Regassa Debelo, Girma Kelboro Mensuro, Lete Bekele Gure
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Climate change has posed severe threats to many cultural landscapes of UNESCO world heritage sites recently. The UNESCO State of Conservation (SOC) reports categorized flooding, temperature increment, and drought as threats to cultural landscapes. This study aimed to examine variations and trends of rainfall and temperature extreme events and their threats to the UNESCO-designated Konso Cultural Landscape in southern Ethiopia. The study used dense merged satellite-gauge station rainfall data (1981-2020) with spatial resolution of 4km by 4km and observed maximum and minimum temperature data (1987-2020). Qualitative data were also gathered from cultural leaders, local administrators, and religious leaders using structured interview checklists. The spatial patterns, coefficient of variation, standardized anomalies, trends, and magnitude of change of rainfall and temperature extreme events both at annual and seasonal levels were computed using the Mann-Kendall trend test and Sen’s slope estimator under the CDT package. The standard precipitation index (SPI) was also used to calculate drought severity, frequency, and trend maps. The data gathered from key informant interviews and focus group discussions were coded and analyzed thematically to complement statistical findings. Thematic areas that explain the impacts of extreme events on the cultural landscape were chosen for coding. The thematic analysis was conducted using Nvivo software. The findings revealed that rainfall was highly variable and unpredictable, resulting in extreme drought and flood. There were significant (P<0.05) increasing trends of heavy rainfall (R10mm and R20mm) and the total amount of rain on wet days (PRCPTOT), which might have resulted in flooding. The study also confirmed that absolute temperature extreme indices (TXx, TXn, and TNx) and the percentile-based temperature extreme indices (TX90p, TN90p, TX10p, and TN10P) showed significant (P<0.05) increasing trends which are signals for warming of the study area. The results revealed that the frequency as well as the severity of drought at 3-months (katana/hageya seasons) was more pronounced than the 12-months (annual) time scale. The highest number of droughts in 100 years is projected at a 3-months timescale across the study area. The findings also showed that frequent drought has led to loss of grasses which are used for making traditional individual houses and multipurpose communal houses (pafta), food insecurity, migration, loss of biodiversity, and commodification of stones from terrace. On the other hand, the increasing trends of rainfall extreme indices resulted in destruction of terraces, soil erosion, loss of life and damage of properties. The study shows that a persistent decline in farmland productivity, due to erratic and extreme rainfall and frequent drought occurrences, forced the local people to participate in non-farm activities and retreat from daily preservation and management of their landscape. Overall, the increasing rainfall and temperature extremes coupled with prevalence of drought are thought to have an impact on the sustainability of cultural landscape through disrupting the ecosystem services and livelihood of the community. Therefore, more localized adaptation and mitigation strategies to the changing climate are needed to maintain the sustainability of Konso cultural landscapes as a global cultural treasure and to strengthen the resilience of smallholder farmers.Keywords: adaptation, cultural landscape, drought, extremes indices
Procedia PDF Downloads 175 An Integrated Multisensor/Modeling Approach Addressing Climate Related Extreme Events
Authors: H. M. El-Askary, S. A. Abd El-Mawla, M. Allali, M. M. El-Hattab, M. El-Raey, A. M. Farahat, M. Kafatos, S. Nickovic, S. K. Park, A. K. Prasad, C. Rakovski, W. Sprigg, D. Struppa, A. Vukovic
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A clear distinction between weather and climate is a necessity because while they are closely related, there are still important differences. Climate change is identified when we compute the statistics of the observed changes in weather over space and time. In this work we will show how the changing climate contribute to the frequency, magnitude and extent of different extreme events using a multi sensor approach with some synergistic modeling activities. We are exploring satellite observations of dust over North Africa, Gulf Region and the Indo Gangetic basin as well as dust versus anthropogenic pollution events over the Delta region in Egypt and Seoul through remote sensing and utilize the behavior of the dust and haze on the aerosol optical properties. Dust impact on the retreat of the glaciers in the Himalayas is also presented. In this study we also focus on the identification and monitoring of a massive dust plume that blew off the western coast of Africa towards the Atlantic on October 8th, 2012 right before the development of Hurricane Sandy. There is evidence that dust aerosols played a non-trivial role in the cyclogenesis process of Sandy. Moreover, a special dust event "An American Haboob" in Arizona is discussed as it was predicted hours in advance because of the great improvement we have in numerical, land–atmosphere modeling, computing power and remote sensing of dust events. Therefore we performed a full numerical simulation to that event using the coupled atmospheric-dust model NMME–DREAM after generating a mask of the potentially dust productive regions using land cover and vegetation data obtained from satellites. Climate change also contributes to the deterioration of different marine habitats. In that regard we are also presenting some work dealing with change detection analysis of Marine Habitats over the city of Hurghada, Red Sea, Egypt. The motivation for this work came from the fact that coral reefs at Hurghada have undergone significant decline. They are damaged, displaced, polluted, stepped on, and blasted off, in addition to the effects of climate change on the reefs. One of the most pressing issues affecting reef health is mass coral bleaching that result from an interaction between human activities and climatic changes. Over another location, namely California, we have observed that it exhibits highly-variable amounts of precipitation across many timescales, from the hourly to the climate timescale. Frequently, heavy precipitation occurs, causing damage to property and life (floods, landslides, etc.). These extreme events, variability, and the lack of good, medium to long-range predictability of precipitation are already a challenge to those who manage wetlands, coastal infrastructure, agriculture and fresh water supply. Adding on to the current challenges for long-range planning is climate change issue. It is known that La Niña and El Niño affect precipitation patterns, which in turn are entwined with global climate patterns. We have studied ENSO impact on precipitation variability over different climate divisions in California. On the other hand the Nile Delta has experienced lately an increase in the underground water table as well as water logging, bogging and soil salinization. Those impacts would pose a major threat to the Delta region inheritance and existing communities. There has been an undergoing effort to address those vulnerabilities by looking into many adaptation strategies.Keywords: remote sensing, modeling, long range transport, dust storms, North Africa, Gulf Region, India, California, climate extremes, sea level rise, coral reefs
Procedia PDF Downloads 4794 Hybrid GNN Based Machine Learning Forecasting Model For Industrial IoT Applications
Authors: Atish Bagchi, Siva Chandrasekaran
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Background: According to World Bank national accounts data, the estimated global manufacturing value-added output in 2020 was 13.74 trillion USD. These manufacturing processes are monitored, modelled, and controlled by advanced, real-time, computer-based systems, e.g., Industrial IoT, PLC, SCADA, etc. These systems measure and manipulate a set of physical variables, e.g., temperature, pressure, etc. Despite the use of IoT, SCADA etc., in manufacturing, studies suggest that unplanned downtime leads to economic losses of approximately 864 billion USD each year. Therefore, real-time, accurate detection, classification and prediction of machine behaviour are needed to minimise financial losses. Although vast literature exists on time-series data processing using machine learning, the challenges faced by the industries that lead to unplanned downtimes are: The current algorithms do not efficiently handle the high-volume streaming data from industrial IoTsensors and were tested on static and simulated datasets. While the existing algorithms can detect significant 'point' outliers, most do not handle contextual outliers (e.g., values within normal range but happening at an unexpected time of day) or subtle changes in machine behaviour. Machines are revamped periodically as part of planned maintenance programmes, which change the assumptions on which original AI models were created and trained. Aim: This research study aims to deliver a Graph Neural Network(GNN)based hybrid forecasting model that interfaces with the real-time machine control systemand can detect, predict machine behaviour and behavioural changes (anomalies) in real-time. This research will help manufacturing industries and utilities, e.g., water, electricity etc., reduce unplanned downtimes and consequential financial losses. Method: The data stored within a process control system, e.g., Industrial-IoT, Data Historian, is generally sampled during data acquisition from the sensor (source) and whenpersistingin the Data Historian to optimise storage and query performance. The sampling may inadvertently discard values that might contain subtle aspects of behavioural changes in machines. This research proposed a hybrid forecasting and classification model which combines the expressive and extrapolation capability of GNN enhanced with the estimates of entropy and spectral changes in the sampled data and additional temporal contexts to reconstruct the likely temporal trajectory of machine behavioural changes. The proposed real-time model belongs to the Deep Learning category of machine learning and interfaces with the sensors directly or through 'Process Data Historian', SCADA etc., to perform forecasting and classification tasks. Results: The model was interfaced with a Data Historianholding time-series data from 4flow sensors within a water treatment plantfor45 days. The recorded sampling interval for a sensor varied from 10 sec to 30 min. Approximately 65% of the available data was used for training the model, 20% for validation, and the rest for testing. The model identified the anomalies within the water treatment plant and predicted the plant's performance. These results were compared with the data reported by the plant SCADA-Historian system and the official data reported by the plant authorities. The model's accuracy was much higher (20%) than that reported by the SCADA-Historian system and matched the validated results declared by the plant auditors. Conclusions: The research demonstrates that a hybrid GNN based approach enhanced with entropy calculation and spectral information can effectively detect and predict a machine's behavioural changes. The model can interface with a plant's 'process control system' in real-time to perform forecasting and classification tasks to aid the asset management engineers to operate their machines more efficiently and reduce unplanned downtimes. A series of trialsare planned for this model in the future in other manufacturing industries.Keywords: GNN, Entropy, anomaly detection, industrial time-series, AI, IoT, Industry 4.0, Machine Learning
Procedia PDF Downloads 1393 Hydrocarbon Source Rocks of the Maragh Low
Authors: Elhadi Nasr, Ibrahim Ramadan
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Biostratigraphical analyses of well sections from the Maragh Low in the Eastern Sirt Basin has allowed high resolution correlations to be undertaken. Full integration of this data with available palaeoenvironmental, lithological, gravity, seismic, aeromagnetic, igneous, radiometric and wireline log information and a geochemical analysis of source rock quality and distribution has led to a more detailed understanding of the geological and the structural history of this area. Pre Sirt Unconformity two superimposed rifting cycles have been identified. The oldest is represented by the Amal Group of sediments and is of Late Carboniferous, Kasimovian / Gzelian to Middle Triassic, Anisian age. Unconformably overlying is a younger rift cycle which is represented the Sarir Group of sediments and is of Early Cretaceous, late Neocomian to Aptian in age. Overlying the Sirt Unconformity is the marine Late Cretaceous section. An assessment of pyrolysis results and a palynofacies analysis has allowed hydrocarbon source facies and quality to be determined. There are a number of hydrocarbon source rock horizons in the Maragh Low, these are sometimes vertically stacked and they are of fair to excellent quality. The oldest identified source rock is the Triassic Shale, this unit is unconformably overlain by sandstones belonging to the Sarir Group and conformably overlies a Triassic Siltstone unit. Palynological dating of the Triassic Shale unit indicates a Middle Triassic, Anisian age. The Triassic Shale is interpreted to have been deposited in a lacustrine palaeoenvironment. This particularly is evidenced by the dark, fine grained, organic rich nature of the sediment and is supported by palynofacies analysis and by the recovery of fish fossils. Geochemical analysis of the Triassic Shale indicates total organic carbon varying between 1.37 and 3.53. S2 pyrolysate yields vary between 2.15 mg/g and 6.61 mg/g and hydrogen indices vary between 156.91 and 278.91. The source quality of the Triassic Shale varies from being of fair to very good / rich. Linked to thermal maturity it is now a very good source for light oil and gas. It was once a very good to rich oil source. The Early Barremian Shale was also deposited in a lacustrine palaeoenvironment. Recovered palynomorphs indicate an Early Cretaceous, late Neocomian to early Barremian age. The Early Barremian Shale is conformably underlain and overlain by sandstone units belonging to the Sarir Group of sediments which are also of Early Cretaceous age. Geochemical analysis of the Early Barremian Shale indicates that it is a good oil source and was originally very good. Total organic carbon varies between 3.59% and 7%. S2 varies between 6.30 mg/g and 10.39 mg/g and the hydrogen indices vary between 148.4 and 175.5. A Late Barremian Shale unit of this age has also been identified in the central Maragh Low. Geochemical analyses indicate that total organic carbon varies between 1.05 and 2.38%, S2 pyrolysate between 1.6 and 5.34 mg/g and the hydrogen index between 152.4 and 224.4. It is a good oil source rock which is now mature. In addition to the non marine hydrocarbon source rocks pre Sirt Unconformity, three formations in the overlying Late Cretaceous section also provide hydrocarbon quality source rocks. Interbedded shales within the Rachmat Formation of Late Cretaceous, early Campanian age have total organic carbon ranging between, 0.7 and 1.47%, S2 pyrolysate varying between 1.37 and 4.00 mg/g and hydrogen indices varying between 195.7 and 272.1. The indication is that this unit would provide a fair gas source to a good oil source. Geochemical analyses of the overlying Tagrifet Limestone indicate that total organic carbon varies between 0.26% and 1.01%. S2 pyrolysate varies between 1.21 and 2.16 mg/g and hydrogen indices vary between 195.7 and 465.4. For the overlying Sirt Shale Formation of Late Cretaceous, late Campanian age, total organic carbon varies between 1.04% and 1.51%, S2 pyrolysate varies between 4.65 mg/g and 6.99 mg/g and the hydrogen indices vary between 151 and 462.9. The study has proven that both the Sirt Shale Formation and the Tagrifet Limestone are good to very good and rich sources for oil in the Maragh Low. High resolution biostratigraphical interpretations have been integrated and calibrated with thermal maturity determinations (Vitrinite Reflectance (%Ro), Spore Colour Index (SCI) and Tmax (ºC) and the determined present day geothermal gradient of 25ºC / Km for the Maragh Low. Interpretation of generated basin modelling profiles allows a detailed prediction of timing of maturation development of these source horizons and leads to a determination of amounts of missing section at major unconformities. From the results the top of the oil window (0.72% Ro) is picked as high as 10,700’ and the base of the oil window (1.35% Ro) assuming a linear trend and by projection is picked as low as 18,000’ in the Maragh Low. For the Triassic Shale the early phase of oil generation was in the Late Palaeocene / Early to Middle Eocene and the main phase of oil generation was in the Middle to Late Eocene. The Early Barremian Shale reached the main phase of oil generation in the Early Oligocene with late generation being reached in the Middle Miocene. For the Rakb Group section (Rachmat Formation, Tagrifet Limestone and Sirt Shale Formation) the early phase of oil generation started in the Late Eocene with the main phase of generation being between the Early Oligocene and the Early Miocene. From studying maturity profiles and from regional considerations it can be predicted that up to 500’ of sediment may have been deposited and eroded by the Sirt Unconformity in the central Maragh Low while up to 2000’ of sediment may have been deposited and then eroded to the south of the trough.Keywords: Geochemical analysis of the source rocks from wells in Eastern Sirt Basin.
Procedia PDF Downloads 4022 “MaxSALIVA-II” Advancing a Nano-Sized Dual-Drug Delivery System for Salivary Gland Radioprotection, Regeneration and Repair in a Head and Neck Cancer Pre-Clinical Murine Model
Authors: Ziyad S. Haidar
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Background: Saliva plays a major role in maintaining oral, dental, and general health and well-being; where it normally bathes the oral cavity acting as a clearing agent. This becomes more apparent when the amount and quality of saliva are significantly reduced due to medications, salivary gland neoplasms, disorders such as Sjögren’s syndrome, and especially ionizing radiation therapy for tumors of the head and neck, the 5th most common malignancy worldwide, during which the salivary glands are included within the radiation field/zone. Clinically, patients affected by salivary gland dysfunction often opt to terminate their radiotherapy course prematurely as they become malnourished and experience a significant decrease in their QoL. Accordingly, the formulation of a radio-protection/-prevention modality and development of an alternative Rx to restore damaged salivary gland tissue is eagerly awaited and highly desirable. Objectives: Assess the pre-clinical radio-protective effect and reparative/regenerative potential of layer-by-layer self-assembled lipid-polymer-based core-shell nanocapsules designed and fine-tuned for the sequential (ordered) release of dual cytokines, following a single local administration (direct injection) into a murine sub-mandibular salivary gland model of irradiation. Methods: The formulated core-shell nanocapsules were characterized by physical-chemical-mechanically pre-/post-loading with the drugs, followed by optimizing the pharmaco-kinetic profile. Then, nanosuspensions were administered directly into the salivary glands, 24hrs pre-irradiation (PBS, un-loaded nanocapsules, and individual and combined vehicle-free cytokines were injected into the control glands for an in-depth comparative analysis). External irradiation at an elevated dose of 18Gy was exposed to the head-and-neck region of C57BL/6 mice. Salivary flow rate (un-stimulated) and salivary protein content/excretion were regularly assessed using an enzyme-linked immunosorbent assay (3-month period). Histological and histomorphometric evaluation and apoptosis/proliferation analysis followed by local versus systemic bio-distribution and immuno-histochemical assays were then performed on all harvested major organs (at the distinct experimental end-points). Results: Monodisperse, stable, and cytocompatible nanocapsules capable of maintaining the bioactivity of the encapsulant within the different compartments with the core and shell and with controlled/customizable pharmaco-kinetics, resulted, as is illustrated in the graphical abstract (Figure) below. The experimental animals demonstrated a significant increase in salivary flow rates when compared to the controls. Herein, salivary protein content was comparable to the pre-irradiation (baseline) level. Histomorphometry further confirmed the biocompatibility and localization of the nanocapsules, in vivo, into the site of injection. Acinar cells showed fewer vacuoles and nuclear aberration in the experimental group, while the amount of mucin was higher in controls. Overall, fewer apoptotic activities were detected by a Terminal deoxynucleotidyl Transferase (TdT) dUTP Nick-End Labeling (TUNEL) assay and proliferative rates were similar to the controls, suggesting an interesting reparative and regenerative potential of irradiation-damaged/-dysfunctional salivary glands. The Figure below exemplifies some of these findings. Conclusions: Biocompatible, reproducible, and customizable self-assembling layer-by-layer core-shell delivery system is formulated and presented. Our findings suggest that localized sequential bioactive delivery of dual cytokines (in specific dose and order) can prevent irradiation-induced damage via reducing apoptosis and also has the potential to promote in situ proliferation of salivary gland cells; maxSALIVA is scalable (Good Manufacturing Practice or GMP production for human clinical trials) and patent-pending.Keywords: cancer, head and neck, oncology, drug development, drug delivery systems, nanotechnology, nanoncology
Procedia PDF Downloads 721 Glycyrrhizic Acid Inhibits Lipopolysaccharide-Stimulated Bovine Fibroblast-Like Synoviocyte, Invasion through Suppression of TLR4/NF-κB-Mediated Matrix Metalloproteinase-9 Expression
Authors: Hosein Maghsoudi
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Rheumatois arthritis (RA) is progressive inflammatory autoimmune diseases that primarily affect the joints, characterized by synovial hyperplasia and inflammatory cell infiltration, deformed and painful joints, which can lead tissue destruction, functional disability systemic complications, and early dead and socioeconomic costs. The cause of rheumatoid arthritis is unknown, but genetic and environmental factors are contributory and the prognosis is guarded. However, advances in understanding the pathogenesis of the disease have fostered the development of new therapeutics, with improved outcomes. The current treatment strategy, which reflects this progress, is to initiate aggressive therapy soon after diagnosis and to escalate the therapy, guided by an assessment of disease activity, in pursuit of clinical remission. The pathobiology of RA is multifaceted and involves T cells, B cells, fibroblast-like synoviocyte (FLSc) and the complex interaction of many pro-inflammatory cytokine. Novel biologic agents that target tumor necrosis or interlukin (IL)-1 and Il-6, in addition T- and B-cells inhibitors, have resulted in favorable clinical outcomes in patients with RA. Despite this, at least 30% of RA patients are résistance to available therapies, suggesting novel mediators should be identified that can target other disease-specific pathway or cell lineage. Among the inflammatory cell population that might participated in RA pathogenesis, FLSc are crucial in initiaing and driving RA in concert of cartilage and bone by secreting metalloproteinase (MMPs) into the synovial fluid and by direct invasion into extracellular matrix (ECM), further exacerbating joint damage. Invasion of fibroblast-like synoviocytes (FLSc) is critical in the pathogenesis of rheumatoid-arthritis. The metalloproteinase (MMPs) and activator of Toll-like receptor 4 (TLR4)/nuclear factor- κB pthway play a critical role in RA-FLS invasion induced by lipopolysaccharide (LPS). The present study aimed to explore the anti-invasion activity of Glycyrrhizic Acid as a pharmacologically safe phytochemical agent with potent anti-inflammatory properties on IL-1beta and TNF-alpha signalling pathways in Bovine fibroblast-like synoviocyte ex- vitro, on LPS-stimulated bovine FLS migration and invasion as well as MMP expression and explored the upstream signal transduction. Results showed that Glycyrrhizic Acid suppressed LPS-stimulated bovine FLS migration and invasion by inhibition MMP-9 expression and activity. In addition our results revealed that Glycyrrhizic Acid inhibited the transcriptional activity of MMP-9 by suppression the nbinding activity of NF- κB in the MMP-9 promoter pathway. The extract of licorice (Glycyrrhiza glabra L.) has been widely used for many centuries in the traditional Chinese medicine as native anti-allergic agent. Glycyrrhizin (GL), a triterpenoidsaponin, extracted from the roots of licorice is the most effective compound for inflammation and allergic diseases in human body. The biological and pharmacological studies revealed that GL possesses many pharmacological effects, such as anti-inflammatory, anti-viral and liver protective effects, and the biological effects, such as induction of cytokines (interferon-γ and IL-12), chemokines as well as extrathymic T and anti-type 2 T cells. GL is known in the traditional Chinese medicine for its anti-inflammatory effect, which is originally described by Finney in 1959. The mechanism of the GL-induced anti-inflammatory effect is based on different pathways of the GL-induced selective inhibition of the prostaglandin E2 production, the CK-II- mediated activation of both GL-binding lipoxygenas (gbLOX; 17) and PLA2, an anti-thrombin action of GL and production of the reactive oxygen species (ROS; GL exerts liver protection properties by inhibiting PLA2 or by the hydroxyl radical trapping action, leading to the lowering of serum alanine and aspartate transaminase levels. The present study was undertaken to examine the possible mechanism of anti-inflammatory properties GL on IL-1beta and TNF-alpha signalling pathways in bovine fibroblast-like synoviocyte ex-vivo, on LPS-stimulated bovine FLS migration and invasion as well as MMP expression and explored the upstream signal transduction. Our results clearly showed that treatment of bovine fibroblast-like synoviocyte with GL suppressed LPS-induced cell migration and invasion. Furthermore, it revealed that GL inhibited the transcription activity of MMP-9 by suppressing the binding activity of NF-κB in the MM-9 promoter. MMP-9 is an important ECM-degrading enzyme and overexpression of MMPs in important of RA-FLSs. LPS can stimulate bovine FLS to secret MMPs, and this induction is regulated at the transcription and translational levels. In this study, LPS treatment of bovine FLS caused an increase in MMP-2 and MMP-9 levels. The increase in MMP-9 expression and secretion was inhibited by ex- vitro. Furthermore, these effects were mimicked by MMP-9 siRNA. These result therefore indicate the the inhibition of LPS-induced bovine FLS invasion by GL occurs primarily by inhibiting MMP-9 expression and activity. Next we analyzed the functional significance of NF-κB transcription of MMP-9 activation in Bovine FLSs. Results from EMSA showed that GL suppressed LPS-induced NF-κB binding to the MMP-9 promotor, as NF-κB regulates transcriptional activation of multiple inflammatory cytokines, we predicted that GL might target NF-κB to suppress MMP-9 transcription by LPS. Myeloid differentiation-factor 88 (MyD88) and TIR-domain containing adaptor protein (TIRAP) are critical proteins in the LPS-induced NF-κB and apoptotic signaling pathways, GL inhibited the expression of TLR4 and MYD88. These results demonstrated that GL suppress LPS-induced MMP-9 expression through the inhibition of the induced TLR4/NFκB signaling pathway. Taken together, our results provide evidence that GL exerts anti-inflammatory effects by inhibition LPS-induced bovine FLSs migration and invasion, and the mechanisms may involve the suppression of TLR4/NFκB –mediated MMP-9 expression. Although further work is needed to clarify the complicated mechanism of GL-induced anti-invasion of bovine FLSs, GL might be used as a further anti-invasion drug with therapeutic efficacy in the treatment of immune-mediated inflammatory disease such as RA.Keywords: glycyrrhizic acid, bovine fibroblast-like synoviocyte, tlr4/nf-κb, metalloproteinase-9
Procedia PDF Downloads 382