Search results for: radial distribution network
Commenced in January 2007
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Edition: International
Paper Count: 9287

Search results for: radial distribution network

17 Salmon Diseases Connectivity between Fish Farm Management Areas in Chile

Authors: Pablo Reche

Abstract:

Since 1980’s aquaculture has become the biggest economic activity in southern Chile, being Salmo salar and Oncorhynchus mykiss the main finfish species. High fish density makes both species prone to contract diseases, what drives the industry to big losses, affecting greatly the local economy. Three are the most concerning infective agents, the infectious salmon anemia virus (ISAv), the bacteria Piscirickettsia salmonis and the copepod Caligus rogercresseyi. To regulate the industry the government arranged the salmon farms within management areas named as barrios, which coordinate the fallowing periods and antibiotics treatments of their salmon farms. In turn, barrios are gathered into larger management areas, named as macrozonas whose purpose is to minimize the risk of disease transmission between them and to enclose the outbreaks within their boundaries. However, disease outbreaks still happen and transmission to neighbor sites enlarges the initial event. Salmon disease agents are mostly transported passively by local currents. Thus, to understand how transmission occurs it must be firstly studied the physical environment. In Chile, salmon farming takes place in the inner seas of the southernmost regions of western Patagonia, between 41.5ºS-55ºS. This coastal marine system is characterised by western winds, latitudinally modulated by the position of the South-Eats Pacific high-pressure centre, high precipitation rates and freshwater inflows from the numerous glaciers (including the largest ice cap out of Antarctic and Greenland). All of these forcings meet in a complex bathymetry and coastline system - deep fjords, shallow sills, narrow straits, channels, archipelagos, inlets, and isolated inner seas- driving an estuarine circulation (fast outflows westwards on surface and slow deeper inflows eastwards). Such a complex system is modelled on the numerical model MIKE3, upon whose 3D current fields particle-track-biological models (one for each infective agent) are decoupled. Each agent biology is parameterized by functions for maturation and mortality (reproduction not included). Such parameterizations are depending upon environmental factors, like temperature and salinity, so their lifespan will depend upon the environmental conditions those virtual agents encounter on their way while passively transported. CLIC (Connectivity-Langrangian–IFOP-Chile) is a service platform that supports the graphical visualization of the connectivity matrices calculated from the particle trajectories files resultant of the particle-track-biological models. On CLIC users can select, from a high-resolution grid (~1km), the areas the connectivity will be calculated between them. These areas can be barrios and macrozonas. Users also can select what nodes of these areas are allowed to release and scatter particles from, depth and frequency of the initial particle release, climatic scenario (winter/summer) and type of particle (ISAv, Piscirickettsia salmonis, Caligus rogercresseyi plus an option for lifeless particles). Results include probabilities downstream (where the particles go) and upstream (where the particles come from), particle age and vertical distribution, all of them aiming to understand how currently connectivity works to eventually propose a minimum risk zonation for aquaculture purpose. Preliminary results in Chiloe inner sea shows that the risk depends not only upon dynamic conditions but upon barrios location with respect to their neighbors.

Keywords: aquaculture zonation, Caligus rogercresseyi, Chilean Patagonia, coastal oceanography, connectivity, infectious salmon anemia virus, Piscirickettsia salmonis

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16 Cardiac Hypertrophy in Diabetes; The Role of Factor Forkhead Box Class O-Regulation by O-GlcNAcylation

Authors: Mohammadjavad Sotoudeheian, Navid Farahmandian

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Cardiac hypertrophy arises in response to persistent increases in hemodynamic loads. In comparison, diabetic cardiomyopathy is defined by an abnormal myocardial changes without other cardiac-related risk factors. Pathological cardiac hypertrophy and myocardial remodeling are hallmarks of cardiovascular diseases and are risk factors for heart failure. The transcription factor forkhead box class O (FOXOs) can protect heart tissue by hostile oxidative stress and stimulating apoptosis and autophagy. FOXO proteins, as sensitive elements and mediators in response to environmental changes, have been revealed to prevent and inverse cardiac hypertrophy. FOXOs are inhibited by insulin and are critical mediators of insulin action. Insulin deficiency and uncontrolled diabetes lead to a catabolic state. FOXO1 acts downstream of the insulin-dependent pathways, which are dysregulated in diabetes. It regulates cardiomyocyte hypertrophy downstream of IGF1R/PI3K/Akt activation, which are critical regulators of cardiac hypertrophy. The complex network of signaling pathways comprising insulin/IGF-1 signaling, AMPK, JNK, and Sirtuins regulate the development of cardiovascular dysfunction by modulating the activity of FOXOs. Insulin receptors and IGF1R act via the PI3k/Akt and the MAPK/ERK pathways. Activation of Akt in response to insulin or IGF-1 induces phosphorylation of FOXOs. Increased protein synthesis induced by activation of the IGF-I/Akt/mTOR signaling pathway leads to hypertrophy. This pathway and the myostatin/Smad pathway are potent negative muscle development regulators. In cardiac muscle, insulin receptor substrates (IRS)-1 or IRS-2 activates the Akt signaling pathway and inactivate FOXO1. Under metabolic stress, p38 MAPK promotes degradation of IRS-1 and IRS-2 in cardiac myocytes and activates FOXO1, leading to cardiomyopathy. Sirt1 and FOXO1 interaction play an essential role in starvation-induced autophagy in cardiac metabolism. Inhibition of Angiotensin-II induced cardiomyocyte hypertrophy is associated with reduced FOXO1 acetylation and activation of Sirt1. The NF-κB, ERK, and FOXOs are de-acetylated by SIRT1. De-acetylation of FOXO1 induces the expression of genes involved in autophagy and stimulates autophagy flux. Therefore, under metabolic stress, FOXO1 can cause diabetic cardiomyopathy. The overexpression of FOXO1 leads to decreased cardiomyocyte size and suppresses cardiac hypertrophy through inhibition of the calcineurin–NFAT pathway. Diabetes mellitus is associated with elevation of O-GlcNAcylation. Some of its binding partners regulate the substrate selectivity of O-GlcNAc transferase (OGT). O-GlcNAcylation of essential contractile proteins may inhibit protein-protein interactions, reduce calcium sensitivity, and modulate contractile function. Uridine diphosphate (UDP)-GlcNAc is the obligatory substrate of OGT, which catalyzes a reversible post-translational protein modification. The increase of O-GlcNAcylation is accompanied by impaired cardiac hypertrophy in diabetic hearts. Inhibition of O-GlcNAcylation blocks activation of ERK1/2 and hypertrophic growth. O-GlcNAc modification on NFAT is required for its translocation from the cytosol to the nucleus, where NFAT stimulates the transcription of various hypertrophic genes. Inhibition of O-GlcNAcylation dampens NFAT-induced cardiac hypertrophic growth. Transcriptional activity of FOXO1 is enriched by improved O-GlcNAcylation upon high glucose stimulation or OGT overexpression. In diabetic conditions, the modification of FOXO1 by O-GlcNAc is promoted in cardiac troponin I and myosin light chain 2. Therefore targeting O-GlcNAcylation represents a potential therapeutic option to prevent hypertrophy in the diabetic heart.

Keywords: diabetes, cardiac hypertrophy, O-GlcNAcylation, FOXO1, Akt, PI3K, AMPK, insulin

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15 Flood Risk Management in the Semi-Arid Regions of Lebanon - Case Study “Semi Arid Catchments, Ras Baalbeck and Fekha”

Authors: Essam Gooda, Chadi Abdallah, Hamdi Seif, Safaa Baydoun, Rouya Hdeib, Hilal Obeid

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Floods are common natural disaster occurring in semi-arid regions in Lebanon. This results in damage to human life and deterioration of environment. Despite their destructive nature and their immense impact on the socio-economy of the region, flash floods have not received adequate attention from policy and decision makers. This is mainly because of poor understanding of the processes involved and measures needed to manage the problem. The current understanding of flash floods remains at the level of general concepts; most policy makers have yet to recognize that flash floods are distinctly different from normal riverine floods in term of causes, propagation, intensity, impacts, predictability, and management. Flash floods are generally not investigated as a separate class of event but are rather reported as part of the overall seasonal flood situation. As a result, Lebanon generally lacks policies, strategies, and plans relating specifically to flash floods. Main objective of this research is to improve flash flood prediction by providing new knowledge and better understanding of the hydrological processes governing flash floods in the East Catchments of El Assi River. This includes developing rainstorm time distribution curves that are unique for this type of study region; analyzing, investigating, and developing a relationship between arid watershed characteristics (including urbanization) and nearby villages flow flood frequency in Ras Baalbeck and Fekha. This paper discusses different levels of integration approach¬es between GIS and hydrological models (HEC-HMS & HEC-RAS) and presents a case study, in which all the tasks of creating model input, editing data, running the model, and displaying output results. The study area corresponds to the East Basin (Ras Baalbeck & Fakeha), comprising nearly 350 km2 and situated in the Bekaa Valley of Lebanon. The case study presented in this paper has a database which is derived from Lebanese Army topographic maps for this region. Using ArcMap to digitizing the contour lines, streams & other features from the topographic maps. The digital elevation model grid (DEM) is derived for the study area. The next steps in this research are to incorporate rainfall time series data from Arseal, Fekha and Deir El Ahmar stations to build a hydrologic data model within a GIS environment and to combine ArcGIS/ArcMap, HEC-HMS & HEC-RAS models, in order to produce a spatial-temporal model for floodplain analysis at a regional scale. In this study, HEC-HMS and SCS methods were chosen to build the hydrologic model of the watershed. The model then calibrated using flood event that occurred between 7th & 9th of May 2014 which considered exceptionally extreme because of the length of time the flows lasted (15 hours) and the fact that it covered both the watershed of Aarsal and Ras Baalbeck. The strongest reported flood in recent times lasted for only 7 hours covering only one watershed. The calibrated hydrologic model is then used to build the hydraulic model & assessing of flood hazards maps for the region. HEC-RAS Model is used in this issue & field trips were done for the catchments in order to calibrated both Hydrologic and Hydraulic models. The presented models are a kind of flexible procedures for an ungaged watershed. For some storm events it delivers good results, while for others, no parameter vectors can be found. In order to have a general methodology based on these ideas, further calibration and compromising of results on the dependence of many flood events parameters and catchment properties is required.

Keywords: flood risk management, flash flood, semi arid region, El Assi River, hazard maps

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14 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.

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13 Synthetic Method of Contextual Knowledge Extraction

Authors: Olga Kononova, Sergey Lyapin

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Global information society requirements are transparency and reliability of data, as well as ability to manage information resources independently; particularly to search, to analyze, to evaluate information, thereby obtaining new expertise. Moreover, it is satisfying the society information needs that increases the efficiency of the enterprise management and public administration. The study of structurally organized thematic and semantic contexts of different types, automatically extracted from unstructured data, is one of the important tasks for the application of information technologies in education, science, culture, governance and business. The objectives of this study are the contextual knowledge typologization, selection or creation of effective tools for extracting and analyzing contextual knowledge. Explication of various kinds and forms of the contextual knowledge involves the development and use full-text search information systems. For the implementation purposes, the authors use an e-library 'Humanitariana' services such as the contextual search, different types of queries (paragraph-oriented query, frequency-ranked query), automatic extraction of knowledge from the scientific texts. The multifunctional e-library «Humanitariana» is realized in the Internet-architecture in WWS-configuration (Web-browser / Web-server / SQL-server). Advantage of use 'Humanitariana' is in the possibility of combining the resources of several organizations. Scholars and research groups may work in a local network mode and in distributed IT environments with ability to appeal to resources of any participating organizations servers. Paper discusses some specific cases of the contextual knowledge explication with the use of the e-library services and focuses on possibilities of new types of the contextual knowledge. Experimental research base are science texts about 'e-government' and 'computer games'. An analysis of the subject-themed texts trends allowed to propose the content analysis methodology, that combines a full-text search with automatic construction of 'terminogramma' and expert analysis of the selected contexts. 'Terminogramma' is made out as a table that contains a column with a frequency-ranked list of words (nouns), as well as columns with an indication of the absolute frequency (number) and the relative frequency of occurrence of the word (in %% ppm). The analysis of 'e-government' materials showed, that the state takes a dominant position in the processes of the electronic interaction between the authorities and society in modern Russia. The media credited the main role in these processes to the government, which provided public services through specialized portals. Factor analysis revealed two factors statistically describing the used terms: human interaction (the user) and the state (government, processes organizer); interaction management (public officer, processes performer) and technology (infrastructure). Isolation of these factors will lead to changes in the model of electronic interaction between government and society. In this study, the dominant social problems and the prevalence of different categories of subjects of computer gaming in science papers from 2005 to 2015 were identified. Therefore, there is an evident identification of several types of contextual knowledge: micro context; macro context; dynamic context; thematic collection of queries (interactive contextual knowledge expanding a composition of e-library information resources); multimodal context (functional integration of iconographic and full-text resources through hybrid quasi-semantic algorithm of search). Further studies can be pursued both in terms of expanding the resource base on which they are held, and in terms of the development of appropriate tools.

Keywords: contextual knowledge, contextual search, e-library services, frequency-ranked query, paragraph-oriented query, technologies of the contextual knowledge extraction

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12 Cycleloop Personal Rapid Transit: An Exploratory Study for Last Mile Connectivity in Urban Transport

Authors: Suresh Salla

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In this paper, author explores for most sustainable last mile transport mode addressing present problems of traffic congestion, jams, pollution and travel stress. Development of energy-efficient sustainable integrated transport system(s) is/are must to make our cities more livable. Emphasis on autonomous, connected, electric, sharing system for effective utilization of systems (vehicles and public infrastructure) is on the rise. Many surface mobility innovations like PBS, Ride hailing, ride sharing, etc. are, although workable but if we analyze holistically, add to the already congested roads, difficult to ride in hostile weather, causes pollution and poses commuter stress. Sustainability of transportation is evaluated with respect to public adoption, average speed, energy consumption, and pollution. Why public prefer certain mode over others? How commute time plays a role in mode selection or shift? What are the factors play-ing role in energy consumption and pollution? Based on the study, it is clear that public prefer a transport mode which is exhaustive (i.e., less need for interchange – network is widespread) and intensive (i.e., less waiting time - vehicles are available at frequent intervals) and convenient with latest technologies. Average speed is dependent on stops, number of intersections, signals, clear route availability, etc. It is clear from Physics that higher the kerb weight of a vehicle; higher is the operational energy consumption. Higher kerb weight also demands heavier infrastructure. Pollution is dependent on source of energy, efficiency of vehicle, average speed. Mode can be made exhaustive when the unit infrastructure cost is less and can be offered intensively when the vehicle cost is less. Reliable and seamless integrated mobility till last ¼ mile (Five Minute Walk-FMW) is a must to encourage sustainable public transportation. Study shows that average speed and reliability of dedicated modes (like Metro, PRT, BRT, etc.) is high compared to road vehicles. Electric vehicles and more so battery-less or 3rd rail vehicles reduce pollution. One potential mode can be Cycleloop PRT, where commuter rides e-cycle in a dedicated path – elevated, at grade or underground. e-Bike with kerb weight per rider at 15 kg being 1/50th of car or 1/10th of other PRT systems makes it sustainable mode. Cycleloop tube will be light, sleek and scalable and can be modular erected, either on modified street lamp-posts or can be hanged/suspended between the two stations. Embarking and dis-embarking points or offline stations can be at an interval which suits FMW to mass public transit. In terms of convenience, guided e-Bike can be made self-balancing thus encouraging driverless on-demand vehicles. e-Bike equipped with smart electronics and drive controls can intelligently respond to field sensors and autonomously move reacting to Central Controller. Smart switching allows travel from origin to destination without interchange of cycles. DC Powered Batteryless e-cycle with voluntary manual pedaling makes it sustainable and provides health benefits. Tandem e-bike, smart switching and Platoon operations algorithm options provide superior through-put of the Cycleloop. Thus Cycleloop PRT will be exhaustive, intensive, convenient, reliable, speedy, sustainable, safe, pollution-free and healthy alternative mode for last mile connectivity in cities.

Keywords: cycleloop PRT, five-minute walk, lean modular infrastructure, self-balanced intelligent e-cycle

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11 Saving Lives from a Laptop: How to Produce a Live Virtual Media Briefing That Will Inform, Educate, and Protect Communities in Crisis

Authors: Cory B. Portner, Julie A. Grauert, Lisa M. Stromme, Shelby D. Anderson, Franji H. Mayes

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Introduction: WASHINGTON state in the Pacific Northwest of the United States is internationally known for its technology industry, fisheries, agriculture, and vistas. On January 21, 2020, Washington state also became known as the first state with a confirmed COVID-19 case in the United States, thrusting the state into the international spotlight as the world came to grips with the global threat of this disease presented. Tourism is Washington state’s fourth-largest industry. Tourism to the state generates over 1.8 billion dollars (USD) in local and state tax revenue and employs over 180,000 people. Communicating with residents, stakeholders, and visitors on the status of disease activity, prevention measures, and response updates was vital to stopping the pandemic and increasing compliance and awareness. Significance: In order to communicate vital public health updates, guidance implementation, and safety measures to the public, the Washington State Department of Health established routine live virtual media briefings to reach audiences via social media, internet television, and broadcast television. Through close partnership with regional broadcast news stations and the state public affairs news network, the Washington State Department of Health hosted 95 media briefings from January 2020 through September 2022 and continues to regularly host live virtual media briefings to accommodate the needs of the public and media. Methods: Our methods quickly evolved from hosting briefings in the cement closet of a military base to being able to produce and stream the briefings live from any home-office location. The content was tailored to the hot topic of the day and to the reporter's questions and needs. Virtual media briefings hosted through inexpensive or free platforms online are extremely cost-effective: the only mandatory components are WiFi, a laptop, and a monitor. There is no longer a need for a fancy studio or expensive production software to achieve the goal of communicating credible, reliable information promptly. With minimal investment and a small learning curve, facilitators and panelists are able to host highly produced and engaging media availabilities from their living rooms. Results: The briefings quickly developed a reputation as the best source for local and national journalists to get the latest and most factually accurate information about the pandemic. In the height of the COVID-19 response, 135 unique media outlets logged on to participate in the briefing. The briefings typically featured 4-5 panelists, with as many as 9 experts in attendance to provide information and respond to media questions. Preparation was always a priority: Public Affairs staff for the Washington State Department of Health produced over 170 presenter remarks, including guidance on talking points for 63 expert guest panelists. Implication For Practice: Information is today’s most valuable currency. The ability to disseminate correct information urgently and on a wide scale is the most effective tool in crisis communication. Due to our role as the first state with a confirmed COVID-19 case, we were forced to develop the most accurate and effective way to get life-saving information to the public. The cost-effective, web-based methods we developed can be applied in any crisis to educate and protect communities under threat, ultimately saving lives from a laptop.

Keywords: crisis communications, public relations, media management, news media

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10 Light Sensitive Plasmonic Nanostructures for Photonic Applications

Authors: Istvan Csarnovics, Attila Bonyar, Miklos Veres, Laszlo Himics, Attila Csik, Judit Kaman, Julia Burunkova, Geza Szanto, Laszlo Balazs, Sandor Kokenyesi

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In this work, the performance of gold nanoparticles were investigated for stimulation of photosensitive materials for photonic applications. It was widely used for surface plasmon resonance experiments, not in the last place because of the manifestation of optical resonances in the visible spectral region. The localized surface plasmon resonance is rather easily observed in nanometer-sized metallic structures and widely used for measurements, sensing, in semiconductor devices and even in optical data storage. Firstly, gold nanoparticles on silica glass substrate satisfy the conditions for surface plasmon resonance in the green-red spectral range, where the chalcogenide glasses have the highest sensitivity. The gold nanostructures influence and enhance the optical, structural and volume changes and promote the exciton generation in gold nanoparticles/chalcogenide layer structure. The experimental results support the importance of localized electric fields in the photo-induced transformation of chalcogenide glasses as well as suggest new approaches to improve the performance of these optical recording media. Results may be utilized for direct, micrometre- or submicron size geometrical and optical pattern formation and used also for further development of the explanations of these effects in chalcogenide glasses. Besides of that, gold nanoparticles could be added to the organic light-sensitive material. The acrylate-based materials are frequently used for optical, holographic recording of optoelectronic elements due to photo-stimulated structural transformations. The holographic recording process and photo-polymerization effect could be enhanced by the localized plasmon field of the created gold nanostructures. Finally, gold nanoparticles widely used for electrochemical and optical sensor applications. Although these NPs can be synthesized in several ways, perhaps one of the simplest methods is the thermal annealing of pre-deposited thin films on glass or silicon surfaces. With this method, the parameters of the annealing process (time, temperature) and the pre-deposited thin film thickness influence and define the resulting size and distribution of the NPs on the surface. Localized surface plasmon resonance (LSPR) is a very sensitive optical phenomenon and can be utilized for a large variety of sensing purposes (chemical sensors, gas sensors, biosensors, etc.). Surface-enhanced Raman spectroscopy (SERS) is an analytical method which can significantly increase the yield of Raman scattering of target molecules adsorbed on the surface of metallic nanoparticles. The sensitivity of LSPR and SERS based devices is strongly depending on the used material and also on the size and geometry of the metallic nanoparticles. By controlling these parameters the plasmon absorption band can be tuned and the sensitivity can be optimized. The technological parameters of the generated gold nanoparticles were investigated and influence on the SERS and on the LSPR sensitivity was established. The LSPR sensitivity were simulated for gold nanocubes and nanospheres with MNPBEM Matlab toolbox. It was found that the enhancement factor (which characterize the increase in the peak shift for multi-particle arrangements compared to single-particle models) depends on the size of the nanoparticles and on the distance between the particles. This work was supported by GINOP- 2.3.2-15-2016-00041 project, which is co-financed by the European Union and European Social Fund. Istvan Csarnovics is grateful for the support through the New National Excellence Program of the Ministry of Human Capacities, supported by the ÚNKP-17-4 Attila Bonyár and Miklós Veres are grateful for the support of the János Bolyai Research Scholarship of the Hungarian Academy of Sciences.

Keywords: light sensitive nanocomposites, metallic nanoparticles, photonic application, plasmonic nanostructures

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9 Introducing Global Navigation Satellite System Capabilities into IoT Field-Sensing Infrastructures for Advanced Precision Agriculture Services

Authors: Savvas Rogotis, Nikolaos Kalatzis, Stergios Dimou-Sakellariou, Nikolaos Marianos

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As precision holds the key for the introduction of distinct benefits in agriculture (e.g., energy savings, reduced labor costs, optimal application of inputs, improved products, and yields), it steadily becomes evident that new initiatives should focus on rendering Precision Agriculture (PA) more accessible to the average farmer. PA leverages on technologies such as the Internet of Things (IoT), earth observation, robotics and positioning systems (e.g., the Global Navigation Satellite System – GNSS - as well as individual positioning systems like GPS, Glonass, Galileo) that allow: from simple data georeferencing to optimal navigation of agricultural machinery to even more complex tasks like Variable Rate Applications. An identified customer pain point is that, from one hand, typical triangulation-based positioning systems are not accurate enough (with errors up to several meters), while on the other hand, high precision positioning systems reaching centimeter-level accuracy, are very costly (up to thousands of euros). Within this paper, a Ground-Based Augmentation System (GBAS) is introduced, that can be adapted to any existing IoT field-sensing station infrastructure. The latter should cover a minimum set of requirements, and in particular, each station should operate as a fixed, obstruction-free towards the sky, energy supplying unit. Station augmentation will allow them to function in pairs with GNSS rovers following the differential GNSS base-rover paradigm. This constitutes a key innovation element for the proposed solution that encompasses differential GNSS capabilities into an IoT field-sensing infrastructure. Integrating this kind of information supports the provision of several additional PA beneficial services such as spatial mapping, route planning, and automatic field navigation of unmanned vehicles (UVs). Right at the heart of the designed system, there is a high-end GNSS toolkit with base-rover variants and Real-Time Kinematic (RTK) capabilities. The GNSS toolkit had to tackle all availability, performance, interfacing, and energy-related challenges that are faced for a real-time, low-power, and reliable in the field operation. Specifically, in terms of performance, preliminary findings exhibit a high rover positioning precision that can even reach less than 10-centimeters. As this precision is propagated to the full dataset collection, it enables tractors, UVs, Android-powered devices, and measuring units to deal with challenging real-world scenarios. The system is validated with the help of Gaiatrons, a mature network of agro-climatic telemetry stations with presence all over Greece and beyond ( > 60.000ha of agricultural land covered) that constitutes part of “gaiasense” (www.gaiasense.gr) smart farming (SF) solution. Gaiatrons constantly monitor atmospheric and soil parameters, thus, providing exact fit to operational requirements asked from modern SF infrastructures. Gaiatrons are ultra-low-cost, compact, and energy-autonomous stations with a modular design that enables the integration of advanced GNSS base station capabilities on top of them. A set of demanding pilot demonstrations has been initiated in Stimagka, Greece, an area with a diverse geomorphological landscape where grape cultivation is particularly popular. Pilot demonstrations are in the course of validating the preliminary system findings in its intended environment, tackle all technical challenges, and effectively highlight the added-value offered by the system in action.

Keywords: GNSS, GBAS, precision agriculture, RTK, smart farming

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8 A Study of the Trap of Multi-Homing in Customers: A Comparative Case Study of Digital Payments

Authors: Shari S. C. Shang, Lynn S. L. Chiu

Abstract:

In the digital payment market, some consumers use only one payment wallet while many others play multi-homing with a variety of payment services. With the diffusion of new payment systems, we examined the determinants of the adoption of multi-homing behavior. This study aims to understand how a digital payment provider dynamically expands business touch points with cross-business strategies to enrich the digital ecosystem and avoid the trap of multi-homing in customers. By synthesizing platform ecosystem literature, we constructed a two-dimensional research framework with one determinant of user digital behavior from offline to online intentions and the other determinant of digital payment touch points from convenient accessibility to cross-business platforms. To explore on a broader scale, we selected 12 digital payments from 5 countries of UK, US, Japan, Korea, and Taiwan. With the interplays of user digital behaviors and payment touch points, we group the study cases into four types: (1) Channel Initiated: users originated from retailers with high access to in-store shopping with face-to-face guidance for payment adoption. Providers offer rewards for customer loyalty and secure the retailer’s efficient cash flow management. (2) Social Media Dependent: users usually are digital natives with high access to social media or the internet who shop and pay digitally. Providers might not own physical or online shops but are licensed to aggregate money flows through virtual ecosystems. (3) Early Life Engagement: digital banks race to capture the next generation from popularity to profitability. This type of payment aimed to give children a taste of financial freedom while letting parents track their spending. Providers are to capitalize on the digital payment and e-commerce boom and hold on to new customers into adulthood. (4) Traditional Banking: plastic credit cards are purposely designed as a control group to track the evolvement of business strategies in digital payments. Traditional credit card users may follow the bank’s digital strategy to land on different types of digital wallets or mostly keep using plastic credit cards. This research analyzed business growth models and inter-firms’ coopetition strategies of the selected cases. Results of the multiple case analysis reveal that channel initiated payments bundled rewards with retailer’s business discount for recurring purchases. They also extended other financial services, such as insurance, to fulfill customers’ new demands. Contrastively, social media dependent payments developed new usages and new value creation, such as P2P money transfer through network effects among the virtual social ties, while early life engagements offer virtual banking products to children who are digital natives but overlooked by incumbents. It has disrupted the banking business domains in preparation for the metaverse economy. Lastly, the control group of traditional plastic credit cards has gradually converted to a BaaS (banking as a service) model depending on customers’ preferences. The multi-homing behavior is not avoidable in digital payment competitions. Payment providers may encounter multiple waves of a multi-homing threat after a short period of success. A dynamic cross-business collaboration strategy should be explored to continuously evolve the digital ecosystems and allow users for a broader shopping experience and continual usage.

Keywords: digital payment, digital ecosystems, multihoming users, cross business strategy, user digital behavior intentions

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7 Hybrid GNN Based Machine Learning Forecasting Model For Industrial IoT Applications

Authors: Atish Bagchi, Siva Chandrasekaran

Abstract:

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

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6 From Core to Hydrocarbon: Reservoir Sedimentology, Facies Analysis and Depositional Model of Early Oligocene Mahuva Formation in Tapti Daman Block, Western Offshore Basin, India

Authors: Almas Rajguru

Abstract:

The Oligocene succession of the Tapti- Daman area is one of the established petroleum plays in Tapti-Daman block of the Mumbai Offshore Basin. Despite good control and production history, the sand geometry and continuity of reservoir character of these sediments are less understood as most reservoirs are thin and fall below seismic resolution. The present work focuses on a detailed analysis of the Early Oligocene Mahuva Formation at the reservoir scale through laboratory studies (sedimentology and biostratigraphy) of core and sidewall cores in integration with electro logs for firming up facies’ distribution, micro-depositional environment and sequence stratigraphy, diagenesis and reservoir characterization from seventeen wells from North Tapti-C-37 area in Tapti Daman Block, WOB. The thick shale/claystone with thin interbeds of sandstone and siltstones of deeper marine in the lower part of Mahuva Fm represents deposition in a transgressive regime. The overlying interbedded sandstone, glauconitic-siltstone/fine-grained sandstone, and thin beds of packstone/grainstone within highly fissile shale were deposited in a prograding tide-dominated delta during late-rise normal regression. Nine litho facies (F1-F9) representing deposition in various microenvironments of the tide-dominated delta are identified based on their characteristic sediment texture, structure and microfacies. Massive, gritty sandstone (F1) with poorly sorted sands lithic fragments with calcareous and Fe-rich matrix represents channel fill sediments. High-angle cross-stratified sandstone (F2) deposited in rapidly shifting/migrating bars under strong tidal currents. F3 records the laterally accreted tidal-channel point bars. F3 (low-angle cross-stratified to parallel bedded sandstone) and F4 (Clean sandstone) are often associated with F2 in a tidal bar complex. F5 (interbedded thin sand and mud) and F6 (bioturbated sandstone) represent tidal flat deposits. High energy open marine carbonate shoals (F8) and fossiliferous sandstone in offshore bars (F7) represent deepening up facies. Shallow marine standstill conditions facilitated the deposition of thick shale (F9) beds. The reservoir facies (F1-F6) are commonly poorly to moderately sorted; bimodal, immature sandstone represented by quartz-wacke. The framework grains are sub-angular to sub-rounded, medium to coarse-grained (occasionally gritty) embedded within argillaceous (kaolinite/chlorite/chamosite) to highly Fe-rich matrix (sideritic). The facies F7 and F8, representing the sandy packstone and grainstone facies, respectively, exhibit poor reservoir characteristics due to sanitization, diagenetic compaction and matrix-filled intergranular spaces. The various diagenetic features such as the presence of authigenic clays (kaolinite/dickite/smectite); ferruginous minerals like siderite, pyrite, hematite and other iron oxides; bioturbations; glauconite; calcite and quartz cementation, precipitation of gypsum, pressure solution and other compaction effects are identified. These diagenetic features, wherever present, have reduced porosity and permeability thereby adversely affecting reservoir quality. Tidal bar sandstones possess good reservoir characteristics such as moderate to good sorting, fair to good porosity and geometry that facilitates efficient lateral extension and vertical thickness of reservoir. The sand bodies of F2, F3 and F4 facies of Well L, M and Q deposited in a tidal bar complex exhibit good reservoir quality represented by relatively cleaner, poorly burrowed, loose, friable sandstone with good porosity. Sandstone facies around these wells could prove a potential hydrocarbon reservoir and could be considered for further exploration.

Keywords: reservoir sedimentology, facies analysis, HST, tide dominated delta, tidal bars

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5 Supply Side Readiness for Universal Health Coverage: Assessing the Availability and Depth of Essential Health Package in Rural, Remote and Conflict Prone District

Authors: Veenapani Rajeev Verma

Abstract:

Context: Assessing facility readiness is paramount as it can indicate capacity of facilities to provide essential care for resilience to health challenges. In the context of decentralization, estimation of supply side readiness indices at sub national level is imperative for effective evidence based policy but remains a colossal challenge due to lack of dependable and representative data sources. Setting: District Poonch of Jammu and Kashmir was selected for this study. It is remote, rural district with unprecedented topographical barriers and is identified as high priority by government. It is also a fragile area as is bounded by Line of Control with Pakistan bearing the brunt of cease fire violations, military skirmishes and sporadic militant attacks. Hilly geographical terrain, rudimentary/absence of road network and impoverishment are quintessential to this area. Objectives: Objective of the study is to a) Evaluate the service readiness of health facilities and create a concise index subsuming plethora of discrete indicators and b) Ascertain supply side barriers in service provisioning via stakeholder’s analysis. Study also strives to expand analytical domain unravelling context and area specific intricacies associated with service delivery. Methodology: Mixed method approach was employed to triangulate quantitative analysis with qualitative nuances. Facility survey encompassing 90 Subcentres, 44 Primary health centres, 3 Community health centres and 1 District hospital was conducted to gauge general service availability and service specific availability (depth of coverage). Compendium of checklist was designed using Indian Public Health Standards (IPHS) in form of standard core questionnaire and scorecard generated for each facility. Information was collected across dimensions of amenities, equipment, medicines, laboratory and infection control protocols as proposed in WHO’s Service Availability and Readiness Assesment (SARA). Two stage polychoric principal component analysis employed to generate a parsimonious index by coalescing an array of tracer indicators. OLS regression method used to determine factors explaining composite index generated from PCA. Stakeholder analysis was conducted to discern qualitative information. Myriad of techniques like observations, key informant interviews and focus group discussions using semi structured questionnaires on both leaders and laggards were administered for critical stakeholder’s analysis. Results: General readiness score of health facilities was found to be 0.48. Results indicated poorest readiness for subcentres and PHC’s (first point of contact) with composite score of 0.47 and 0.41 respectively. For primary care facilities; principal component was characterized by basic newborn care as well as preparedness for delivery. Results revealed availability of equipment and surgical preparedness having lowest score (0.46 and 0.47) for facilities providing secondary care. Presence of contractual staff, more than 1 hr walk to facility, facilities in zone A (most vulnerable) to cross border shelling and facilities inaccessible due to snowfall and thick jungles was negatively associated with readiness index. Nonchalant staff attitude, unavailability of staff quarters, leakages and constraint in supply chain of drugs and consumables were other impediments identified. Conclusions/Policy Implications: It is pertinent to first strengthen primary care facilities in this setting. Complex dimensions such as geographic barriers, user and provider behavior is not under precinct of this methodology.

Keywords: effective coverage, principal component analysis, readiness index, universal health coverage

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4 Reassembling a Fragmented Border Landscape at Crossroads: Indigenous Rights, Rural Sustainability, Regional Integration and Post-Colonial Justice in Hong Kong

Authors: Chiu-Yin Leung

Abstract:

This research investigates a complex assemblage among indigenous identities, socio-political organization and national apparatus in the border landscape of post-colonial Hong Kong. This former British colony had designated a transient mode of governance in its New Territories and particularly the northernmost borderland in 1951-2012. With a discriminated system of land provisions for the indigenous villagers, the place has been inherited with distinctive village-based culture, historic monuments and agrarian practices until its sovereignty return into the People’s Republic of China. In its latest development imperatives by the national strategic planning, the frontier area of Hong Kong has been identified as a strategy site for regional economic integration in South China, with cross-border projects of innovation and technology zones, mega-transport infrastructure and inter-jurisdictional arrangement. Contemporary literature theorizes borders as the material and discursive production of territoriality, which manifest in state apparatus and the daily lives of its citizens and condense in the contested articulations of power, security and citizenship. Drawing on the concept of assemblage, this paper attempts to tract how the border regime and infrastructure in Hong Kong as a city are deeply ingrained in the everyday lived spaces of the local communities but also the changing urban and regional strategies across different longitudinal moments. Through an intensive ethnographic fieldwork among the borderland villages since 2008 and the extensive analysis of colonial archives, new development plans and spatial planning frameworks, the author navigates the genealogy of the border landscape in Ta Kwu Ling frontier area and its implications as the milieu for new state space, covering heterogeneous fields particularly in indigenous rights, heritage preservation, rural sustainability and regional economy. Empirical evidence suggests an apparent bias towards indigenous power and colonial representation in classifying landscape values and conserving historical monuments. Squatter and farm tenants are often deprived of property rights, statutory participation and livelihood option in the planning process. The postcolonial bureaucracies have great difficulties in mobilizing resources to catch up with the swift, political-first approach of the mainland counterparts. Meanwhile, the cultural heritage, lineage network and memory landscape are not protected altogether with any holistic view or collaborative effort across the border. The enactment of land resumption and compensation scheme is furthermore disturbed by lineage-based customary law, technocratic bureaucracy, intra-community conflicts and multi-scalar political mobilization. As many traces of colonial misfortune and tyranny have been whitewashed without proper management, the author argues that postcolonial justice is yet reconciled in this fragmented border landscape. The assemblage of border in mainstream representation has tended to oversimplify local struggles as a collective mist and setup a wider production of schizophrenia experiences in the discussion of further economic integration among Hong Kong and other mainland cities in the Pearl River Delta Region. The research is expected to shed new light on the theorizing of border regions and postcolonialism beyond Eurocentric perspectives. In reassembling the borderland experiences with other arrays in state governance, village organization and indigenous identities, the author also suggests an alternative epistemology in reconciling socio-spatial differences and opening up imaginaries for positive interventions.

Keywords: heritage conservation, indigenous communities, post-colonial borderland, regional development, rural sustainability

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3 Evaluation of Academic Research Projects Using the AHP and TOPSIS Methods

Authors: Murat Arıbaş, Uğur Özcan

Abstract:

Due to the increasing number of universities and academics, the fund of the universities for research activities and grants/supports given by government institutions have increased number and quality of academic research projects. Although every academic research project has a specific purpose and importance, limited resources (money, time, manpower etc.) require choosing the best ones from all (Amiri, 2010). It is a pretty hard process to compare and determine which project is better such that the projects serve different purposes. In addition, the evaluation process has become complicated since there are more than one evaluator and multiple criteria for the evaluation (Dodangeh, Mojahed and Yusuff, 2009). Mehrez and Sinuany-Stern (1983) determined project selection problem as a Multi Criteria Decision Making (MCDM) problem. If a decision problem involves multiple criteria and objectives, it is called as a Multi Attribute Decision Making problem (Ömürbek & Kınay, 2013). There are many MCDM methods in the literature for the solution of such problems. These methods are AHP (Analytic Hierarchy Process), ANP (Analytic Network Process), TOPSIS (Technique for Order Preference by Similarity to Ideal Solution), PROMETHEE (Preference Ranking Organization Method for Enrichment Evaluation), UTADIS (Utilities Additives Discriminantes), ELECTRE (Elimination et Choix Traduisant la Realite), MAUT (Multiattribute Utility Theory), GRA (Grey Relational Analysis) etc. Teach method has some advantages compared with others (Ömürbek, Blacksmith & Akalın, 2013). Hence, to decide which MCDM method will be used for solution of the problem, factors like the nature of the problem, types of choices, measurement scales, type of uncertainty, dependency among the attributes, expectations of decision maker, and quantity and quality of the data should be considered (Tavana & Hatami-Marbini, 2011). By this study, it is aimed to develop a systematic decision process for the grant support applications that are expected to be evaluated according to their scientific adequacy by multiple evaluators under certain criteria. In this context, project evaluation process applied by The Scientific and Technological Research Council of Turkey (TÜBİTAK) the leading institutions in our country, was investigated. Firstly in the study, criteria that will be used on the project evaluation were decided. The main criteria were selected among TÜBİTAK evaluation criteria. These criteria were originality of project, methodology, project management/team and research opportunities and extensive impact of project. Moreover, for each main criteria, 2-4 sub criteria were defined, hence it was decided to evaluate projects over 13 sub-criterion in total. Due to superiority of determination criteria weights AHP method and provided opportunity ranking great number of alternatives TOPSIS method, they are used together. AHP method, developed by Saaty (1977), is based on selection by pairwise comparisons. Because of its simple structure and being easy to understand, AHP is the very popular method in the literature for determining criteria weights in MCDM problems. Besides, the TOPSIS method developed by Hwang and Yoon (1981) as a MCDM technique is an alternative to ELECTRE method and it is used in many areas. In the method, distance from each decision point to ideal and to negative ideal solution point was calculated by using Euclidian Distance Approach. In the study, main criteria and sub-criteria were compared on their own merits by using questionnaires that were developed based on an importance scale by four relative groups of people (i.e. TUBITAK specialists, TUBITAK managers, academics and individuals from business world ) After these pairwise comparisons, weight of the each main criteria and sub-criteria were calculated by using AHP method. Then these calculated criteria’ weights used as an input in TOPSİS method, a sample consisting 200 projects were ranked on their own merits. This new system supported to opportunity to get views of the people that take part of project process including preparation, evaluation and implementation on the evaluation of academic research projects. Moreover, instead of using four main criteria in equal weight to evaluate projects, by using weighted 13 sub-criteria and decision point’s distance from the ideal solution, systematic decision making process was developed. By this evaluation process, new approach was created to determine importance of academic research projects.

Keywords: Academic projects, Ahp method, Research projects evaluation, Topsis method.

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2 “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

Abstract:

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

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1 “MaxSALIVA”: A Nano-Sized Dual-Drug Delivery System for Salivary Gland Radioprotection and Repair in Head and Neck Cancer

Authors: Ziyad S. Haidar

Abstract:

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 56