Search results for: critical energy level
10 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 4919 Numerical Simulation of Von Karman Swirling Bioconvection Nanofluid Flow from a Deformable Rotating Disk
Authors: Ali Kadir, S. R. Mishra, M. Shamshuddin, O. Anwar Beg
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Motivation- Rotating disk bio-reactors are fundamental to numerous medical/biochemical engineering processes including oxygen transfer, chromatography, purification and swirl-assisted pumping. The modern upsurge in biologically-enhanced engineering devices has embraced new phenomena including bioconvection of micro-organisms (photo-tactic, oxy-tactic, gyrotactic etc). The proven thermal performance superiority of nanofluids i.e. base fluids doped with engineered nanoparticles has also stimulated immense implementation in biomedical designs. Motivated by these emerging applications, we present a numerical thermofluid dynamic simulation of the transport phenomena in bioconvection nanofluid rotating disk bioreactor flow. Methodology- We study analytically and computationally the time-dependent three-dimensional viscous gyrotactic bioconvection in swirling nanofluid flow from a rotating disk configuration. The disk is also deformable i.e. able to extend (stretch) in the radial direction. Stefan blowing is included. The Buongiorno dilute nanofluid model is adopted wherein Brownian motion and thermophoresis are the dominant nanoscale effects. The primitive conservation equations for mass, radial, tangential and axial momentum, heat (energy), nanoparticle concentration and micro-organism density function are formulated in a cylindrical polar coordinate system with appropriate wall and free stream boundary conditions. A mass convective condition is also incorporated at the disk surface. Forced convection is considered i.e. buoyancy forces are neglected. This highly nonlinear, strongly coupled system of unsteady partial differential equations is normalized with the classical Von Karman and other transformations to render the boundary value problem (BVP) into an ordinary differential system which is solved with the efficient Adomian decomposition method (ADM). Validation with earlier Runge-Kutta shooting computations in the literature is also conducted. Extensive computations are presented (with the aid of MATLAB symbolic software) for radial and circumferential velocity components, temperature, nanoparticle concentration, micro-organism density number and gradients of these functions at the disk surface (radial local skin friction, local circumferential skin friction, Local Nusselt number, Local Sherwood number, motile microorganism mass transfer rate). Main Findings- Increasing radial stretching parameter decreases radial velocity and radial skin friction, reduces azimuthal velocity and skin friction, decreases local Nusselt number and motile micro-organism mass wall flux whereas it increases nano-particle local Sherwood number. Disk deceleration accelerates the radial flow, damps the azimuthal flow, decreases temperatures and thermal boundary layer thickness, depletes the nano-particle concentration magnitudes (and associated nano-particle species boundary layer thickness) and furthermore decreases the micro-organism density number and gyrotactic micro-organism species boundary layer thickness. Increasing Stefan blowing accelerates the radial flow and azimuthal (circumferential flow), elevates temperatures of the nanofluid, boosts nano-particle concentration (volume fraction) and gyrotactic micro-organism density number magnitudes whereas suction generates the reverse effects. Increasing suction effect reduces radial skin friction and azimuthal skin friction, local Nusselt number, and motile micro-organism wall mass flux whereas it enhances the nano-particle species local Sherwood number. Conclusions - Important transport characteristics are identified of relevance to real bioreactor nanotechnological systems not discussed in previous works. ADM is shown to achieve very rapid convergence and highly accurate solutions and shows excellent promise in simulating swirling multi-physical nano-bioconvection fluid dynamics problems. Furthermore, it provides an excellent complement to more general commercial computational fluid dynamics simulations.Keywords: bio-nanofluids, rotating disk bioreactors, Von Karman swirling flow, numerical solutions
Procedia PDF Downloads 1618 General Evaluation of a Three-Year Holistic Physical Activity Interventions Program in Qatar Campuses: Step into Health (SIH) in Campuses 2013- 2016
Authors: Daniela Salih Khidir, Mohamed G. Al Kuwari, Mercia V. Walt, Izzeldin J. Ibrahim
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Background: University-based physical activity interventions aim to establish durable social patterns during the transition to adulthood. This study is a comprehensive evaluation of a 3-year intervention-based program to increase the culture of physical activity (PA) routine in Qatar campuses community, using a holistic approach. Methodology: General assessment methods: formative evaluation-SIH Campuses logic model design, stakeholders’ identification; process evaluation-members’ step counts analyze and qualitative Appreciative Inquiry session (4-D model); daily steps categorized as: ≤5,000, inactive; 5,000-7,499 low active; ≥7,500, physically active; outcome evaluation - records 3 years interventions. Holistic PA interventions methods: walking interventions - pedometers distributions and walking competitions for students and staff; educational interventions - in campuses implementation of bilingual educational materials, lectures, video related to PA in prevention of non-communicable diseases (NCD); articles published online; monthly emails and sms notifications for pedometer use; mass media campaign - radio advertising, yearly pre/post press releases; community stakeholders interventions-biyearly planning/reporting/achievements rewarding/ qualitative meetings; continuous follow-up communication, biweekly steps reports. Findings: Results formative evaluation - SIH in Campuses logic model identified the need of PA awareness and education within universities, resources, activities, health benefits, program continuity. Results process evaluation: walking interventions: Phase 1: 5 universities recruited, 2352 members, 3 months competition; Phase 2: 6 new universities recruited, 1328 members in addition, 4 months competition; Phase 3: 4 new universities recruited in addition, 1210 members, 6 months competition. Results phase 1 and 2: 1,299 members eligible for analyzes: 800 females (62%), 499 males (38%); 86% non-Qataris, 14% Qatari nationals, daily step count 5,681 steps, age groups 18–24 (n=841; 68%) students, 25–64; (n=458; 35.3%) staff; 38% - low active, 37% physically active and 25% inactive. The AI main themes engaging stakeholders: awareness/education - 5 points (100%); competition, multi levels of involvement in SIH, community-based program/motivation - 4 points each (80%). The AI points represent themes’ repetition within stakeholders’ discussions. Results education interventions: 2 videos implementation, 35 000 educational materials, 3 online articles, 11 walking benefits lectures, 40 emails and sms notifications. Results community stakeholders’ interventions: 6 stakeholders meetings, 3 rewarding gatherings, 1 focus meeting, 40 individual reports, 18 overall reports. Results mass media campaign: 1 radio campaign, 7 press releases, 52 campuses newsletters. Results outcome evaluation: overall 2013-2016, the study used: 1 logic model, 3 PA holistic interventions, partnerships 15 universities, registered 4890 students and staff (aged 18-64 years), engaged 30 campuses stakeholders and 14 internal stakeholders; Total registered population: 61.5% female (2999), 38.5% male (1891), 20.2% (988) Qatari nationals, 79.8% (3902) non-Qataris, 55.5% (2710) students aged 18 – 25 years, 44.5% (2180) staff aged 26 - 64 years. Overall campaign 1,558 members eligible for analyzes: daily step count 7,923; 37% - low active, 43% physically active and 20% inactive. Conclusion: The study outcomes confirm program effectiveness and engagement of young campuses community, specifically female, in PA. The authors recommend implementations of 'holistic PA intervention program approach in Qatar' aiming to impact the community at national level for PA guidelines achievement in support of NCD prevention.Keywords: campuses, evaluation, Qatar, step-count
Procedia PDF Downloads 3137 Influence of Oil Prices on the Central Caucasus State of Georgia
Authors: Charaia Vakhtang
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Global oil prices are seeing new bottoms every day. The prices have already collapsed beneath the psychological verge of 30 USD. This tendency would be fully acceptable for the Georgian consumers, but there is one detail: two our neighboring countries (one friendly and one hostile) largely depend on resources of these hydrocarbons. Namely, the ratio of Azerbaijan in Georgia’s total FDI inflows in 2014 marked 20%. The ratio reached 40% in the January to September 2015. Azerbaijan is Georgia’s leading exports market. Namely, in 2014 Georgia’s exports to Azerbaijan constituted 544 million USD, i.e. 19% in Georgia’s total experts. In the January to November period of 2015, the ratio exceeded 11%. Moreover, Azerbaijan is Georgia’s strategic partner country as part of many regional projects that are designated for long-term perspectives. For example, the Baku-Tbilisi-Karsi railroad, the Black Sea terminal, preferential gas tariffs for Georgia and so on. The Russian economic contribution to the Georgian economy is also considerable, despite the losses the Russian hostile policy has inflicted to our country. Namely, Georgian emigrants are mainly employed in the Russian Federation and this category of Georgian citizens transfers considerable funds to Georgia every year. These transfers account for about 1 billion USD and consequently, these funds previously equalized to total FDI inflows. Moreover, despite the difficulties in the Russian market, Russia still remains a leader in terms of money transfers to Georgia. According to the last reports, money transfers from Russia to Georgia slipped by 276 million USD in 2015 compared to 2014 (-39%). At the same time, the total money transfers to Georgia in 2015 marked 1.08 billion USD, down 25% from 1.44 billion USD in 2014. This signifies the contraction in money transfers is by ¾ dependent on the Russian factor (in this case, contraction in oil prices and the Russian Ruble devaluation directly make negative impact on money transfers to Georgia). As to other countries, it is interesting that money transfers have also slipped from Italy (to 109 million USD from 121 million USD). Nevertheless, the country’s ratio in total money transfers to Georgia has increased to 10% from 8%. Money transfers to Georgia have increased by 22% (+18 million USD) from the USA. Money transfers have halved from Greece to 117 million USD from 205 million USD. As to Turkey, money transfers to Georgia from Turkey have increased by 1% to 69 million USD. Moreover, the problems with the national currencies of Russia and Azerbaijan, along with the above-mentioned developments, outline unfavorable perspectives for the Georgian economy. The depreciation of the national currencies of Azerbaijan and Russia is expected to bring unfavorable results for the Georgian economy. Even more so, the statement released by the Russian Finance Ministry on expected default is in direct relation to the welfare of the whole region and these tendencies will make direct and indirect negative impacts on Georgia’s economic indicators. Amid the economic slowdown in Armenia, Turkey and Ukraine, Georgia should try to enhance economic ties with comparatively stronger and flexible economies such as EU and USA. In other case, the Georgian economy will enter serious turbulent zone. We should make maximum benefit from the EU association agreement. It should be noted that the Russian economy slowdown that causes both regretful and happy moods in Georgia, will make negative impact on the Georgian economy. The same forecasts are made in relation to Azerbaijan. However, Georgia has many partner countries. Enhancement and development of the economic relations with these countries may maximally alleviate negative impacts from the declining economies. First of all, the EU association agreement should be mentioned as a main source for Georgia’s economic stabilization. It is the Georgian government‘s responsibility to successfully fulfill the EU association agreement requirements. In any case the imports must be replaced by domestic products and the exports should be stimulated through government support programs. The Authorities should ensure drawing more foreign investments and money resources, accumulating more tourism revenues and reducing external debts, budget expenditures should be balanced and the National Bank should carry out strict monetary policy. Moreover, the Government should develop a long-term state economic policy and carry out this policy at various Ministries. It is also of crucial importance to carry out constitutive policy and promote perspective directions on the domestic level.Keywords: oil prices, economic growth, foreign direct investments, international trade
Procedia PDF Downloads 2726 Mapping the Neurotoxic Effects of Sub-Toxic Manganese Exposure: Behavioral Outcomes, Imaging Biomarkers, and Dopaminergic System Alterations
Authors: Katie M. Clark, Adriana A. Tienda, Krista C. Paffenroth, Lindsey N. Brigante, Daniel C. Colvin, Jose Maldonado, Erin S. Calipari, Fiona E. Harrison
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Manganese (Mn) is an essential trace element required for human health and is important in antioxidant defenses, as well as in the development and function of dopaminergic neurons. However, chronic low-level Mn exposure, such as through contaminated drinking water, poses risks that may contribute to neurodevelopmental and neurodegenerative conditions, including attention deficit hyperactivity disorder (ADHD). Pharmacological inhibition of the dopamine transporter (DAT) blocks reuptake, elevates synaptic dopamine, and alleviates ADHD symptoms. This study aimed to determine whether Mn exposure in juvenile mice modifies their response to DAT blockers, amphetamine, and methylphenidate and utilize neuroimaging methods to visualize and quantify Mn distribution across dopaminergic brain regions. Male and female heterozygous DATᵀ³⁵⁶ᴹ and wild-type littermates were randomly assigned to receive control (2.5% Stevia) or high Manganese (2.5 mg/ml Mn + 2.5% Stevia) via water ad libitum from weaning (21-28 days) for 4-5 weeks. Mice underwent repeated testing in locomotor activity chambers for three consecutive days (60 mins.) to ensure that they were fully habituated to the environments. On the fourth day, a 3-hour activity session was conducted following treatment with amphetamine (3 mg/kg) or methylphenidate (5 mg/kg). The second drug was administered in a second 3-hour activity session following a 1-week washout period. Following the washout, the mice were given one last injection of amphetamine and euthanized one hour later. Using the ex-vivo brains, magnetic resonance relaxometry (MRR) was performed on a 7Telsa imaging system to map T1- and T2-weighted (T1W, T2W) relaxation times. Mn inherent paramagnetic properties shorten both T1W and T2W times, which enhances the signal intensity and contrast, enabling effective visualization of Mn accumulation in the entire brain. A subset of mice was treated with amphetamine 1 hour before euthanasia. SmartSPIM light sheet microscopy with cleared whole brains and cFos and tyrosine hydroxylase (TH) labeling enabled an unbiased automated counting and densitometric analysis of TH and cFos positive cells. Immunohistochemistry was conducted to measure synaptic protein markers and quantify changes in neurotransmitter regulation. Mn exposure elevated Mn brain levels and potentiated stimulant effects in males. The globus pallidus, substantia nigra, thalamus, and striatum exhibited more pronounced T1W shortening, indicating regional susceptibility to Mn accumulation (p<0.0001, 2-Way ANOVA). In the cleared whole brains, initial analyses suggest that TH and c-Fos co-staining mirrors behavioral data with decreased co-staining in DATT356M+/- mice. Ongoing studies will identify the molecular basis of the effect of Mn, including changes to DAergic metabolism and transport and post-translational modification to the DAT. These findings demonstrate that alterations in T1W relaxation times, as measured by MRR, may serve as an early biomarker for Mn neurotoxicity. This neuroimaging approach exhibits remarkable accuracy in identifying Mn-susceptible brain regions, with a spatial resolution and sensitivity that surpasses current conventional dissection and mass spectrometry approaches. The capability to label and map TH and cFos expression across the entire brain provides insights into whole-brain neuronal activation and its connections to functional neural circuits and behavior following amphetamine and methylphenidate administration.Keywords: manganese, environmental toxicology, dopamine dysfunction, biomarkers, drinking water, light sheet microscopy, magnetic resonance relaxometry (MRR)
Procedia PDF Downloads 245 Acute Severe Hyponatremia in Patient with Psychogenic Polydipsia, Learning Disability and Epilepsy
Authors: Anisa Suraya Ab Razak, Izza Hayat
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Introduction: The diagnosis and management of severe hyponatremia in neuropsychiatric patients present a significant challenge to physicians. Several factors contribute, including diagnostic shadowing and attributing abnormal behavior to intellectual disability or psychiatric conditions. Hyponatraemia is the commonest electrolyte abnormality in the inpatient population, ranging from mild/asymptomatic, moderate to severe levels with life-threatening symptoms such as seizures, coma and death. There are several documented fatal case reports in the literature of severe hyponatremia secondary to psychogenic polydipsia, often diagnosed only in autopsy. This paper presents a case study of acute severe hyponatremia in a neuropsychiatric patient with early diagnosis and admission to intensive care. Case study: A 21-year old Caucasian male with known epilepsy and learning disability was admitted from residential living with generalized tonic-clonic self-terminating seizures after refusing medications for several weeks. Evidence of superficial head injury was detected on physical examination. His laboratory data demonstrated mild hyponatremia (125 mmol/L). Computed tomography imaging of his brain demonstrated no acute bleed or space-occupying lesion. He exhibited abnormal behavior - restlessness, drinking water from bathroom taps, inability to engage, paranoia, and hypersexuality. No collateral history was available to establish his baseline behavior. He was loaded with intravenous sodium valproate and leveritircaetam. Three hours later, he developed vomiting and a generalized tonic-clonic seizure lasting forty seconds. He remained drowsy for several hours and regained minimal recovery of consciousness. A repeat set of blood tests demonstrated profound hyponatremia (117 mmol/L). Outcomes: He was referred to intensive care for peripheral intravenous infusion of 2.7% sodium chloride solution with two-hourly laboratory monitoring of sodium concentration. Laboratory monitoring identified dangerously rapid correction of serum sodium concentration, and hypertonic saline was switched to a 5% dextrose solution to reduce the risk of acute large-volume fluid shifts from the cerebral intracellular compartment to the extracellular compartment. He underwent urethral catheterization and produced 8 liters of urine over 24 hours. Serum sodium concentration remained stable after 24 hours of correction fluids. His GCS recovered to baseline after 48 hours with improvement in behavior -he engaged with healthcare professionals, understood the importance of taking medications, admitted to illicit drug use and drinking massive amounts of water. He was transferred from high-dependency care to ward level and was initiated on multiple trials of anti-epileptics before achieving seizure-free days two weeks after resolution of acute hyponatremia. Conclusion: Psychogenic polydipsia is often found in young patients with intellectual disability or psychiatric disorders. Patients drink large volumes of water daily ranging from ten to forty liters, resulting in acute severe hyponatremia with mortality rates as high as 20%. Poor outcomes are due to challenges faced by physicians in making an early diagnosis and treating acute hyponatremia safely. A low index of suspicion of water intoxication is required in this population, including patients with known epilepsy. Monitoring urine output proved to be clinically effective in aiding diagnosis. Early referral and admission to intensive care should be considered for safe correction of sodium concentration while minimizing risk of fatal complications e.g. central pontine myelinolysis.Keywords: epilepsy, psychogenic polydipsia, seizure, severe hyponatremia
Procedia PDF Downloads 1264 Revealing Celtic and Norse Mythological Depths through Dragon Age’s Tattoos and Narratives
Authors: Charles W. MacQuarrie, Rachel R. Tatro Duarte
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This paper explores the representation of medieval identity within the world of games such as Dragon Age, Elden Ring, Hellblade: Senua’s sacrifice, fantasy role-playing games that draw effectively and problematically on Celtic and Norse mythologies. Focusing on tattoos, onomastics, and accent as visual and oral markers of status and ethnicity, this study analyzes how the game's interplay between mythology, character narratives, and visual storytelling enriches the themes and offers players an immersive, but sometimes baldly ahistorical, connection to ancient mythologies and contemporary digital storytelling. Dragon Age is a triple a game series, Hellblade Senua’s Sacrifice, and Elden Ring of gamers worldwide with its presentation of an idealized medieval world, inspired by the lore of Celtic and Norse mythologies. This paper sets out to explore the intricate relationships between tattoos, accent, and character narratives in the game, drawing parallels to themes,heroic figures and gods from Celtic and Norse mythologies. Tattoos as Mythic and Ethnic Markers: This study analyzes how tattoos in Dragon Age visually represent mythological elements from both Celtic and Norse cultures, serving as conduits of cultural identity and narratives. The nature of these tattoos reflects the slave, criminal, warrior associations made in classical and medieval literature, and some of the episodes concerning tattoos in the games have either close analogs or sources in literature. For example the elvish character Solas, in Dragon Age Inquisition, removes a slave tattoo from the face of a lower status elf in an episode that is reminiscent of Bridget removing the stigmata from Connallus in the Vita Prima of Saint Bridget Character Narratives: The paper examines how characters' personal narratives in the game parallel the archetypal journeys of Celtic heroes and Norse gods, with a focus on their relationships to mythic themes. In these games the Elves usually have Welsh or Irish accents, are close to nature, magically powerful, oppressed by apparently Anglo-Saxon humans and Norse dwarves, and these elves wear facial tattoos. The Welsh voices of fairies and demons is older than the reference in Shakespeare’s Merry Wives of Windsor or even the Anglo-Saxon Life of Saint Guthlac. The English speaking world, and the fantasy genre of literature and gaming, undoubtedly driven by Tolkien, see Elves as Welsh speakers, and as having Welsh accents when speaking English Comparative Analysis: A comparative approach is employed to reveal connections, adaptations, and unique interpretations of the motifs of tattoos and narrative themes in Dragon Age, compared to those found in Celtic and Norse mythologies. Methodology: The study uses a comparative approach to examine the similarities and distinctions between Celtic and Norse mythologies and their counterparts in video games. The analysis encompasses character studies, narrative exploration, visual symbolism, and the historical context of Celtic and Norse cultures. Mythic Visuals: This study showcases how tattoos, as visual symbols, encapsulate mythic narratives, beliefs, and cultural identity, echoing Celtic and Norse visual motifs. Archetypal Journeys: The paper analyzes how character arcs mirror the heroic journeys of Celtic and Norse mythological figures, allowing players to engage with mythic narratives on a personal level. Cultural Interplay: The study discusses how the game's portrayal of tattoos and narratives both preserves and reinterprets elements from Celtic and Norse mythologies, fostering a connection between ancient cultures and modern digital storytelling. Conclusion: By exploring the interconnectedness of tattoos and character narratives in Dragon Age, this paper reveals the game series' ability to act as a bridge between ancient mythologies and contemporary gaming. By drawing inspiration from Celtic heroes and Norse gods and translating them into digital narratives and visual motifs, Dragon Age offers players a multi-dimensional engagement with mythic themes and a unique lens through which to appreciate the enduring allure of these cultures.Keywords: comparative analysis, character narratives, video games and literature, tattoos, immersive storytelling, character development, mythological influences, Celtic mythology, Norset mythology
Procedia PDF Downloads 773 “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 842 “MaxSALIVA”: A Nano-Sized Dual-Drug Delivery System for Salivary Gland Radioprotection and Repair in Head and Neck Cancer
Authors: Ziyad S. Haidar
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Background: Saliva plays a major role in maintaining oral and dental health (consequently, general health and well-being). Where it normally bathes the oral cavity and acts as a clearing agent. This becomes more apparent when the amount and quality of salivare 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 fifth most common malignancy worldwide, during which the salivary glands are included within the radiation field or zone. Clinically, patients affected by salivary gland dysfunction often opt to terminate their radiotherapy course prematurely because they become malnourished and experience a significant decrease in their quality of life. Accordingly, the development of an alternative treatment to restore or regenerate damaged salivary gland tissue is eagerly awaited. Likewise, the formulation of a radioprotection modality and early damage prevention strategy is also highly desirable. Objectives: To assess the pre-clinical radio-protective effect as well as the reparative/regenerative potential of layer-by-layer self-assembled lipid-polymer-based core-shell nanocapsules designed and fine-tuned in this experimental work 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 (in solution and powder formats), 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 (revised from our previous 15Gy model) 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: saliva, head and neck cancer, nanotechnology, controlled drug delivery, xerostomia, mucositis, biopolymers, innovation
Procedia PDF Downloads 921 Impacts of Transformational Leadership: Petronas Stations in Sabah, Malaysia
Authors: Lizinis Cassendra Frederick Dony, Jirom Jeremy Frederick Dony, Cyril Supain Christopher
Abstract:
The purpose of this paper is to improve the devotion to leadership through HR practices implementation at the PETRONAS stations. This emphasize the importance of personal grooming and Customer Care hospitality training for their front line working individuals and teams’ at PETRONAS stations in Sabah. Based on Thomas Edison, International Leadership Journal, theory, research, education and development practice and application to all organizational phenomena may affect or be affected by leadership. FINDINGS – PETRONAS in short called Petroliam Nasional Berhad is a Malaysian oil and gas company that was founded on August 17, 1974. Wholly owned by the Government of Malaysia, the corporation is vested with the entire oil and gas resources in Malaysia and is entrusted with the responsibility of developing and adding value to these resources. Fortune ranks PETRONAS as the 68th largest company in the world in 2012. It also ranks PETRONAS as the 12th most profitable company in the world and the most profitable in Asia. As of the end of March 2005, the PETRONAS Group comprised 103 wholly owned subsidiaries, 19 partly owned outfits and 57 associated companies. The group is engaged in a wide spectrum of petroleum activities, including upstream exploration and production of oil and gas to downstream oil refining, marketing and distribution of petroleum products, trading, gas processing and liquefaction, gas transmission pipeline network operations, marketing of liquefied natural gas; petrochemical manufacturing and marketing; shipping; automotive engineering and property investment. PETRONAS has growing their marketing channel in a competitive market. They have combined their resources to pursue common goals. PETRONAS provides opportunity to carry out Industrial Training Job Placement to the University students in Malaysia for 6-8 months. The effects of the Industrial Training have exposed them to the real working environment experience acting representing on behalf of General Manager for almost one year. Thus, the management education and reward incentives schemes have aspire the working teams transformed to gain their good leadership. Furthermore, knowledge and experiences are very important in the human capital development transformation. SPSS extends the accurate analysis PETRONAS achievement through 280 questionnaires and 81 questionnaires through excel calculation distributed to interview face to face with the customers, PETRONAS dealers and front desk staffs stations in the 17 stations in Kota Kinabalu, Sabah. Hence, this research study will improve its service quality innovation and business sustainability performance optimization. ORIGINALITY / VALUE – The impact of Transformational Leadership practices have influenced the working team’s behaviour as a Brand Ambassadors of PETRONAS. Finally, the findings correlation indicated that PETRONAS stations needs more HR resources practices to deploy more customer care retention resources in mitigating the business challenges in oil and gas industry. Therefore, as the business established at stiff competition globally (Cooper, 2006; Marques and Simon, 2006), it is crucial for the team management should be capable to minimize noises risk, financial risk and mitigating any other risks as a whole at the optimum level. CONCLUSION- As to conclude this research found that both transformational and transactional contingent reward leadership4 were positively correlated with ratings of platoon potency and ratings of leadership for the platoon leader and sergeant were moderately inter correlated. Due to this identification, we recommended that PETRONAS management should offers quality team management in PETRONAS stations in a broader variety of leadership training specialization in the operation efficiency at the front desk Customer Care hospitality. By having the reliability and validity of job experiences, it leverages diversity teamwork and cross collaboration. Other than leveraging factor, PETRONAS also will strengthen the interpersonal front liners effectiveness and enhance quality of interaction through effective communication. Finally, through numerous CSR correlation studies regression PETRONAS performance on Corporate Social Performance and several control variables.1 CSR model activities can be mis-specified if it is not controllable under R & D which evident in various feedbacks collected from the local communities and younger generation is inclined to higher financial expectation from PETRONAS. But, however, it created a huge impact on the nation building as part of its social adaptability overreaching their business stakeholders’ satisfaction in Sabah.Keywords: human resources practices implementation (hrpi), source of competitive advantage in people’s development (socaipd), corporate social responsibility (csr), service quality at front desk stations (sqafd), impacts of petronas leadership (iopl)
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