Search results for: type II generalized logistic distribution

Authors: Dmitriy Berillo, Areej K. A. Al-Jwaid, Jonathan L. Caplin, Andrew Cundy, Irina Savina

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Chlorophenols (CPs) are used as a precursor in the production of higher CPs and dyestuffs, and as a preservative. Contamination by CPs of the ground water is located in the range from 0.15-100mg/L. The EU has set maximum concentration limits for pesticides and their degradation products of 0.1μg/L and 0.5μg/L, respectively. People working in industries which produce textiles, leather products, domestic preservatives, and petrochemicals are most heavily exposed to CPs. The International Agency for Research on Cancers categorized CPs as potential human carcinogens. Existing multistep water purification processes for CPs such as hydrogenation, ion exchange, liquid-liquid extraction, adsorption by activated carbon, forward and inverse osmosis, electrolysis, sonochemistry, UV irradiation, and chemical oxidation are not always cost effective and can cause the formation of even more toxic or mutagenic derivatives. Bioremediation of CPs derivatives utilizing microorganisms results in 60 to 100% decontamination efficiency and the process is more environmentally-friendly compared with existing physico-chemical methods. Microorganisms immobilized onto a substrate show many advantages over free bacteria systems, such as higher biomass density, higher metabolic activity, and resistance to toxic chemicals. They also enable continuous operation, avoiding the requirement for biomass-liquid separation. The immobilized bacteria can be reused several times, which opens the opportunity for developing cost-effective processes for wastewater treatment. In this study, we develop a bioremediation system for CPs based on macroporous materials, which can be efficiently used for wastewater treatment. Conditions for the preparation of the macroporous material from specific bacterial strains (Pseudomonas mendocina and Rhodococus koreensis) were optimized. The concentration of bacterial cells was kept constant; the difference was only the type of cross-linking agents used e.g. glutaraldehyde, novel polymers, which were utilized at concentrations of 0.5 to 1.5%. SEM images and rheology analysis of the material indicated a monolithic macroporous structure. Phenol was chosen as a model system to optimize the function of the cryogel material and to estimate its enzymatic activity, since it is relatively less toxic and harmful compared to CPs. Several types of macroporous systems comprising live bacteria were prepared. The viability of the cross-linked bacteria was checked using Live/Dead BacLight kit and Laser Scanning Confocal Microscopy, which revealed the presence of viable bacteria with the novel cross-linkers, whereas the control material cross-linked with glutaraldehyde(GA), contained mostly dead cells. The bioreactors based on bacteria were used for phenol degradation in batch mode at an initial concentration of 50mg/L, pH 7.5 and a temperature of 30°C. Bacterial strains cross-linked with GA showed insignificant ability to degrade phenol and for one week only, but a combination of cross-linking agents illustrated higher stability, viability and the possibility to be reused for at least five weeks. Furthermore, conditions for CPs degradation will be optimized, and the chlorophenol degradation rates will be compared to those for phenol. This is a cutting-edge bioremediation approach, which allows the purification of waste water from sustainable compounds without a separation step to remove free planktonic bacteria. Acknowledgments: Dr. Berillo D. A. is very grateful to Individual Fellowship Marie Curie Program for funding of the research.

Keywords: bioremediation, cross-linking agents, cross-linked microbial cell, chlorophenol degradation

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Authors: T. Heikkinen, J. Oksman, T. Bragge, A. Nurmi, O. Kontkanen, T. Ahtoniemi

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Motor impairment is an inherent phenotypic feature of several chronic neurodegenerative diseases, and pharmacological therapies aimed to counterbalance the motor disability have a great market potential. Animal models of chronic neurodegenerative diseases display a number deteriorating motor phenotype during the disease progression. There is a wide array of behavioral tools to evaluate motor functions in rodents. However, currently existing methods to study motor functions in rodents are often limited to evaluate gross motor functions only at advanced stages of the disease phenotype. The most commonly applied traditional motor assays used in CNS rodent models, lack the sensitivity to capture fine motor impairments or improvements. Fine motor skill characterization in rodents provides a more sensitive tool to capture more subtle motor dysfunctions and therapeutic effects. Importantly, similar approach, kinematic movement analysis, is also used in clinic, and applied both in diagnosis and determination of therapeutic response to pharmacological interventions. The aim of this study was to apply kinematic gait analysis, a novel and automated high precision movement analysis system, to characterize phenotypic deficits in three different chronic neurodegenerative animal models, a transgenic mouse model (SOD1 G93A) for amyotrophic lateral sclerosis (ALS), and R6/2 and Q175KI mouse models for Huntington’s disease (HD). The readouts from walking behavior included gait properties with kinematic data, and body movement trajectories including analysis of various points of interest such as movement and position of landmarks in the torso, tail and joints. Mice (transgenic and wild-type) from each model were analyzed for the fine motor kinematic properties at young ages, prior to the age when gross motor deficits are clearly pronounced. Fine motor kinematic Evaluation was continued in the same animals until clear motor dysfunction with conventional motor assays was evident. Time course analysis revealed clear fine motor skill impairments in each transgenic model earlier than what is seen with conventional gross motor tests. Motor changes were quantitatively analyzed for up to ~80 parameters, and the largest data sets of HD models were further processed with principal component analysis (PCA) to transform the pool of individual parameters into a smaller and focused set of mutually uncorrelated gait parameters showing strong genotype difference. Kinematic fine motor analysis of transgenic animal models described in this presentation show that this method isa sensitive, objective and fully automated tool that allows earlier and more sensitive detection of progressive neuromuscular and CNS disease phenotypes. As a result of the analysis a comprehensive set of fine motor parameters for each model is created, and these parameters provide better understanding of the disease progression and enhanced sensitivity of this assay for therapeutic testing compared to classical motor behavior tests. In SOD1 G93A, R6/2, and Q175KI mice, the alterations in gait were evident already several weeks earlier than with traditional gross motor assays. Kinematic testing can be applied to a wider set of motor readouts beyond gait in order to study whole body movement patterns such as with relation to joints and various body parts longitudinally, providing a sophisticated and translatable method for disseminating motor components in rodent disease models and evaluating therapeutic interventions.

Keywords: Gait analysis, kinematic, motor impairment, inherent feature

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Authors: Ching-Sung Lee, Wei-Chou Hsu, Han-Yin Liu, Hung-Hsi Huang, Si-Fu Chen, Yun-Jung Yang, Bo-Chun Chiang, Yu-Chuang Chen, Shen-Tin Yang

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AlGaN/GaN high electron mobility transistors (HEMTs) have been intensively studied due to their intrinsic advantages of high breakdown electric field, high electron saturation velocity, and excellent chemical stability. They are also suitable for ultra-violet (UV) photodetection due to the corresponding wavelengths of GaN bandgap. To improve the optical responsivity by decreasing the dark current due to gate leakage problems and limited Schottky barrier heights in GaN-based HEMT devices, various metal-oxide-semiconductor HEMTs (MOS-HEMTs) have been devised by using atomic layer deposition (ALD), molecular beam epitaxy (MBE), metal-organic chemical vapor deposition (MOCVD), liquid phase deposition (LPD), and RF sputtering. The gate dielectrics include MgO, HfO2, Al2O3, La2O3, and TiO2. In order to provide complementary circuit operation, enhancement-mode (E-mode) devices have been lately studied using techniques of fluorine treatment, p-type capper, piezoneutralization layer, and MOS-gate structure. This work reports an Al2O3-dielectric Al0.25Ga0.75N/GaN E-mode MOS-HEMT design by using a cost-effective ozone water oxidization technique. The present ozone oxidization method advantages of low cost processing facility, processing simplicity, compatibility to device fabrication, and room-temperature operation under atmospheric pressure. It can further reduce the gate-to-channel distance and improve the transocnductance (gm) gain for a specific oxide thickness, since the formation of the Al2O3 will consume part of the AlGaN barrier at the same time. The epitaxial structure of the studied devices was grown by using the MOCVD technique. On a Si substrate, the layer structures include a 3.9 m C-doped GaN buffer, a 300 nm GaN channel layer, and a 5 nm Al0.25Ga0.75N barrier layer. Mesa etching was performed to provide electrical isolation by using an inductively coupled-plasma reactive ion etcher (ICP-RIE). Ti/Al/Au were thermally evaporated and annealed to form the source and drain ohmic contacts. The device was immersed into the H2O2 solution pumped with ozone gas generated by using an OW-K2 ozone generator. Ni/Au were deposited as the gate electrode to complete device fabrication of MOS-HEMT. The formed Al2O3 oxide thickness 7 nm and the remained AlGaN barrier thickness is 2 nm. A reference HEMT device has also been fabricated in comparison on the same epitaxial structure. The gate dimensions are 1.2 × 100 µm 2 with a source-to-drain spacing of 5 μm for both devices. The dielectric constant (k) of Al2O3 was characterized to be 9.2 by using C-V measurement. Reduced interface state density after oxidization has been verified by the low-frequency noise spectra, Hooge coefficients, and pulse I-V measurement. Improved device characteristics at temperatures of 300 K-450 K have been achieved for the present MOS-HEMT design. Consequently, Al2O3-dielectric Al0.25Ga0.75N/GaN E-mode MOS-HEMTs by using the ozone water oxidization method are reported. In comparison with a conventional Schottky-gate HEMT, the MOS-HEMT design has demonstrated excellent enhancements of 138% (176%) in gm, max, 118% (139%) in IDS, max, 53% (62%) in BVGD, 3 (2)-order reduction in IG leakage at VGD = -60 V at 300 (450) K. This work is promising for millimeter-wave integrated circuit (MMIC) and three-terminal active UV photodetector applications.

Keywords: MOS-HEMT, enhancement mode, AlGaN/GaN, passivation, ozone water oxidation, gate leakage

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Authors: Marija Mihajlovic Pereira

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Teaching and learning a musical instrument is challenging for both teachers and students. Teachers generally use diverse strategies to resolve students' particular issues in a one-to-one context. Considering individual sessions as a supportive educational context, the teacher can play a decisive role in stimulating and promoting self-regulated learning strategies, especially with beginning learners. The teachers who promote self-controlling behaviors, strategic monitoring, and regulation of actions toward goals could expect their students to practice more qualitatively and consciously. When encouraged to adopt self-regulation habits, students' could benefit from greater productivity on a longer path. Founded on Bary Zimmerman's cyclical model that comprehends three phases - forethought, performance, and self-reflection, this work aims to articulate self-regulated and music learning. Self-regulated learning appeals to the individual's attitude in planning, controlling, and reflecting on their performance. Furthermore, this study aimed to present an observation grid for perceiving teaching instructions that encourage students' controlling cognitive behaviors in light of the belief that conscious promotion of self-regulation may motivate strategic actions toward goals in musical performance. The participants, two teachers, and two students have been involved in the social inclusion project in Lisbon (Portugal). The author and one independent inter-observer analyzed six video-recorded string instrument lessons. The data correspond to three sessions per teacher lectured to one (different) student. Violin (f) and violoncello (m) teachers hold a Master's degree in music education and approximately five years of experience. In their second year of learning an instrument, students have acquired reasonable skills in musical reading, posture, and sound quality until then. The students also manifest positive learning behaviors, interest in learning a musical instrument, although their study habits are still inconsistent. According to the grid's four categories (parent codes), in-class rehearsal frames were coded using MaxQda software, version 20, according to the grid's four categories (parent codes): self-regulated learning, teaching verbalizations, teaching strategies, and students' in-class performance. As a result, selected rehearsal frames qualitatively describe teaching instructions that might promote students' body and hearing awareness, such as "close the eyes while playing" or "sing to internalize the pitch." Another analysis type, coding the short video events according to the observation grid's subcategories (child codes), made it possible to perceive the time teachers dedicate to specific verbal or non-verbal strategies. Furthermore, a coding overlay analysis indicated that teachers tend to stimulate. (i) Forethought – explain tasks, offer feedback and ensure that students identify a goal, (ii) Performance – teach study strategies and encourage students to sing and use vocal abilities to ensure inner audition, (iii) Self-reflection – frequent inquiring and encouraging the student to verbalize their perception of performance. Although developed in the context of individual string instrument lessons, this classroom observation grid brings together essential variables in a one-to-one lesson. It may find utility in a broader context of music education due to the possibility to organize, observe and evaluate teaching practices. Besides that, this study contributes to cognitive development by suggesting a practical approach to fostering self-regulated learning.

Keywords: music education, observation grid, self-regulated learning, string instruments, teaching practices

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Authors: Dean Sinković, Tea Golja, Morena Paulišić

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Upon the end of the vicious war in former Yugoslavia in 1995, international development community widely promoted microfinance as the key development framework to eradicate poverty, create jobs, increase income. Widespread claims were made that microfinance institutions would play vital role in creating a bedrock for sustainable ‘bottom-up’ economic development trajectory, thus, helping newly formed states to find proper way from economic post-war depression. This uplifting neoliberal narrative has no empirical support in the Republic of Croatia. Firstly, the type of enterprises created via microfinance sector are small, unskilled, labor intensive, no technology and with huge debt burden. This results in extremely high failure rates of microenterprises and poor individuals plunging into even deeper poverty, acute indebtedness and social marginalization. Secondly, evidence shows that microcredit is exact reflection of dangerous and destructive sub-prime lending model with ‘boom-to-bust’ scenarios in which benefits are solely extracted by the tiny financial and political elite working around the microfinance sector. We argue that microcredit providers are not proper financial structures through which developing countries should look way out of underdevelopment and poverty. In order to achieve sustainable long-term growth goals, public policy needs to focus on creating, supporting and facilitating the small and mid-size enterprises development. These enterprises should be technically sophisticated, capable of creating new capabilities and innovations, with managerial expertise (skills formation) and inter-connected with other organizations (i.e. clusters, networks, supply chains, etc.). Evidence from South-East Europe suggest that such structures are not created via microfinance model but can be fostered through various forms of social enterprises. Various legal entities may operate as social enterprises: limited liability private company, limited liability public company, cooperative, associations, foundations, institutions, Mutual Insurances and Credit union. Our main hypothesis is that cooperatives are potential agents of social and economic transformation and community development in the region. Financial cooperatives are structures that can foster more efficient allocation of financial resources involving deeper democratic arrangements and more socially just outcomes. In Croatia, pioneers of the first social enterprises were civil society organizations whilst forming a separated legal entity. (i.e. cooperatives, associations, commercial companies working on the principles of returning the investment to the founder). Ever since 1995 cooperatives in Croatia have not grown by pursuing their own internal growth but mostly by relying on external financial support. The greater part of today’s registered cooperatives tend to be agricultural (39%), followed by war veterans cooperatives (38%) and others. There are no financial cooperatives in Croatia. Due to the above mentioned we look at the historical developments and the prevailing social enterprises forms and discuss their advantages and disadvantages as potential agents for social and economic transformation and community development in the region. There is an evident lack of understanding of this business model and of its potential for social and economic development followed by an unfavorable institutional environment. Thus, we discuss the role of governance and management in the formation of social enterprises in Croatia, stressing the challenges for the governance of the country’s social enterprise movement.

Keywords: financial cooperatives, governance and management models, microfinance institutions, social enterprises

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Authors: Papakonstantinou Apostolos, Argyrios Moustakas, Panagiotis Zervos, Dimitrios Stefanakis, Manolis Tsapakis, Nektarios Spyridakis, Mary Paspaliari, Christos Kontos, Antonis Legakis, Sarantis Houzouris, Konstantinos Topouzelis

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For years unmanned and remotely operated robots have been used as tools in industry research and education. The rapid development and miniaturization of sensors that can be attached to remotely operated vehicles in recent years allowed industry leaders and researchers to utilize them as an affordable means for data acquisition in air, land, and sea. Despite the recent developments in the ground and unmanned airborne vehicles, a small number of Unmanned Surface Vehicle (USV) platforms are targeted for mapping and monitoring environmental parameters for research and industry purposes. The ARGO project is developed an open-design USV equipped with multi-level control hardware architecture and state-of-the-art sensors and payloads for the autonomous monitoring of environmental parameters in large sea areas. The proposed USV is a catamaran-type USV controlled over a wireless radio link (5G) for long-range mapping capabilities and control for a ground-based control station. The ARGO USV has a propulsion control using 2x fully redundant electric trolling motors with active vector thrust for omnidirectional movement, navigation with opensource autopilot system with high accuracy GNSS device, and communication with the 2.4Ghz digital link able to provide 20km of Line of Sight (Los) range distance. The 3-meter dual hull design and composite structure offer well above 80kg of usable payload capacity. Furthermore, sun and friction energy harvesting methods provide clean energy to the propulsion system. The design is highly modular, where each component or payload can be replaced or modified according to the desired task (industrial or research). The system can be equipped with Multiparameter Sonde, measuring up to 20 water parameters simultaneously, such as conductivity, salinity, turbidity, dissolved oxygen, etc. Furthermore, a high-end multibeam echo sounder can be installed in a specific boat datum for shallow water high-resolution seabed mapping. The system is designed to operate in the Aegean Sea. The developed USV is planned to be utilized as a system for autonomous data acquisition, mapping, and monitoring bathymetry and various environmental parameters. ARGO USV can operate in small or large ports with high maneuverability and endurance to map large geographical extends at sea. The system presents state of the art solutions in the following areas i) the on-board/real-time data processing/analysis capabilities, ii) the energy-independent and environmentally friendly platform entirely made using the latest aeronautical and marine materials, iii) the integration of advanced technology sensors, all in one system (photogrammetric and radiometric footprint, as well as its connection with various environmental and inertial sensors) and iv) the information management application. The ARGO web-based application enables the system to depict the results of the data acquisition process in near real-time. All the recorded environmental variables and indices are presented, allowing users to remotely access all the raw and processed information using the implemented web-based GIS application.

Keywords: monitor marine environment, unmanned surface vehicle, mapping bythometry, sea environmental monitoring

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Authors: Joel A. Gordon, Nazmiye Balta-Ozkan, Seyed Ali Nabavi

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Hydrogen-fueled technologies are rapidly advancing as a critical component of the low-carbon energy transition. In countries historically reliant on natural gas for home heating, such as the UK, hydrogen may prove fundamental for decarbonizing the residential sector, alongside other technologies such as heat pumps and district heat networks. While the UK government is set to take a long-term policy decision on the role of domestic hydrogen by 2026, there are considerable uncertainties regarding consumer preferences for ‘hydrogen homes’ (i.e., hydrogen-fueled appliances for space heating, hot water, and cooking. In comparison to other hydrogen energy technologies, such as road transport applications, to date, few studies have engaged with the social acceptance aspects of the domestic hydrogen transition, resulting in a stark knowledge deficit and pronounced risk to policymaking efforts. In response, this study aims to safeguard against undesirable policy measures by revealing the underlying relationships between the factors of domestic hydrogen acceptance and their respective dimensions: attitudinal, socio-political, community, market, and behavioral acceptance. The study employs an online survey (n=~2100) to gauge how different UK householders perceive the proposition of switching from natural gas to hydrogen-fueled appliances. In addition to accounting for housing characteristics (i.e., housing tenure, property type and number of occupants per dwelling) and several other socio-structural variables (e.g. age, gender, and location), the study explores the impacts of consumer heterogeneity on hydrogen acceptance by recruiting respondents from across five distinct groups: (1) fuel poor householders, (2) technology engaged householders, (3) environmentally engaged householders, (4) technology and environmentally engaged householders, and (5) a baseline group (n=~700) which filters out each of the smaller targeted groups (n=~350). This research design reflects the notion that supporting a socially fair and efficient transition to hydrogen will require parallel engagement with potential early adopters and demographic groups impacted by fuel poverty while also accounting strongly for public attitudes towards net zero. Employing a second-order multigroup confirmatory factor analysis (CFA) in Mplus, the proposed hydrogen acceptance model is tested to fit the data through a partial least squares (PLS) approach. In addition to testing differences between and within groups, the findings provide policymakers with critical insights regarding the significance of knowledge and awareness, safety perceptions, perceived community impacts, cost factors, and trust in key actors and stakeholders as potential explanatory factors of hydrogen acceptance. Preliminary results suggest that knowledge and awareness of hydrogen are positively associated with support for domestic hydrogen at the household, community, and national levels. However, with the exception of technology and/or environmentally engaged citizens, much of the population remains unfamiliar with hydrogen and somewhat skeptical of its application in homes. Knowledge and awareness present as critical to facilitating positive safety perceptions, alongside higher levels of trust and more favorable expectations for community benefits, appliance performance, and potential cost savings. Based on these preliminary findings, policymakers should be put on red alert about diffusing hydrogen into the public consciousness in alignment with energy security, fuel poverty, and net-zero agendas.

Keywords: hydrogen homes, social acceptance, consumer heterogeneity, heat decarbonization

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Authors: Chusit Apirumanekul, Chayanis Krittasudthacheewa, Ratchapat Ratanavaraha, Yanyong Inmuong

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Rapid economic development in the Lower Mekong region is leading to changes in water quantity and quality. Changes in land- and forest-use, infrastructure development, increasing urbanization, migration patterns and climate risks are increasing demands for water, within various sectors, placing pressure on scarce water resources. Appropriate policies, strategies, and planning are urgently needed for improved water resource management. Over the last decade, Thailand has experienced more frequent and intense drought situations, affecting the level of water storage in reservoirs along with insufficient water allocation for agriculture during the dry season. The Huay Saibat River Basin, one of the well-known water-scarce areas in the northeastern region of Thailand, is experiencing ongoing water scarcity that affects both farming livelihoods and household consumption. Drought management in Thailand mainly focuses on emergency responses, rather than advance preparation and mitigation for long-term solutions. Despite many efforts from local authorities to mitigate the drought situation, there is yet no long-term comprehensive water management strategy, that integrates climate risks alongside other uncertainties. This paper assesses the application in the Huay Saibat River Basin, of the Robust Decision Support framework, to explore the feasibility of multiple drought management policies; including a shift in cropping season, in crop changes, in infrastructural operations and in the use of groundwater, under a wide range of uncertainties, including climate and land-use change. A series of consultative meetings were organized with relevant agencies and experts at the local level, to understand and explore plausible water resources strategies and identify thresholds to evaluate the performance of those strategies. Three different climate conditions were identified (dry, normal and wet). Other non-climatic factors influencing water allocation were further identified, including changes from sugarcane to rubber, delaying rice planting, increasing natural retention storage and using groundwater to supply demands for household consumption and small-scale gardening. Water allocation and water use in various sectors, such as in agriculture, domestic, industry and the environment, were estimated by utilising the Water Evaluation And Planning (WEAP) system, under various scenarios developed from the combination of climatic and non-climatic factors mentioned earlier. Water coverage (i.e. percentage of water demand being successfully supplied) was defined as a threshold for water resource strategy assessment. Thresholds for different sectors (agriculture, domestic, industry, and environment) were specified during multi-stakeholder engagements. Plausible water strategies (e.g. increasing natural retention storage, change of crop type and use of groundwater as an alternative source) were evaluated based on specified thresholds in 4 sectors (agriculture, domestic, industry, and environment) under 3 climate conditions. 'Business as usual' was evaluated for comparison. The strategies considered robust, emerge when performance is assessed as successful, under a wide range of uncertainties across the river basin. Without adopting any strategy, the water scarcity situation is likely to escalate in the future. Among the strategies identified, the use of groundwater as an alternative source was considered a potential option in combating water scarcity for the basin. Further studies are needed to explore the feasibility for groundwater use as a potential sustainable source.

Keywords: climate change, robust decision support, scenarios, water resources management

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Authors: Kumar Satyam Das, Murali Raghunathan

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This note discusses the feasibility of field development of a challenging shallow offshore field in South East Asia and how its learnings can be applied to marginal field development across the world especially developing marginal fields in this low oil price world. The field was found to be economically challenging even during high oil prices and the project was put on hold. Shell started development study with the aim to significantly reduce cost through competitively scoping and revive stranded projects. The proposed strategy to achieve this involved Improve Per platform recovery and Reduction in CAPEX. Methodology: Based on various Benchmarking Tool such as Woodmac for similar projects in the region and economic affordability, a challenging target of 50% reduction in unit development cost (UDC) was set for the project. Technical scope was defined to the minimum as to be a wellhead platform with minimum functionality to ensure production. The evaluation of key project decisions like Well location and number, well design, Artificial lift methods and wellhead platform type under different development concept was carried out through integrated multi-discipline approach. Key elements influencing per platform recovery were Wellhead Platform (WHP) location, Well count, well reach and well productivity. Major Findings: Reservoir being shallow posed challenges in well design (dog-leg severity, casing size and the achievable step-out), choice of artificial lift and sand-control method. Integrated approach amongst relevant disciplines with challenging mind-set enabled to achieve optimized set of development decisions. This led to significant improvement in per platform recovery. It was concluded that platform recovery largely depended on the reach of the well. Choice of slim well design enabled designing of high inclination and better productivity wells. However, there is trade-off between high inclination Gas Lift (GL) wells and low inclination wells in terms of long term value, operational complexity, well reach, recovery and uptime. Well design element like casing size, well completion, artificial lift and sand control were added successively over the minimum technical scope design leading to a value and risk staircase. Logical combinations of options (slim well, GL) were competitively screened to achieve 25% reduction in well cost. Facility cost reduction was achieved through sourcing standardized Low Cost Facilities platform in combination with portfolio execution to maximizing execution efficiency; this approach is expected to reduce facilities cost by ~23% with respect to the development costs. Further cost reductions were achieved by maximizing use of existing facilities nearby; changing reliance on existing water injection wells and utilizing existing water injector (W.I.) platform for new injectors. Conclusion: The study provides a spectrum of technically feasible options. It also made clear that different drivers lead to different development concepts and the cost value trade off staircase made this very visible. Scoping of the project through competitive way has proven to be valuable for decision makers by creating a transparent view of value and associated risks/uncertainty/trade-offs for difficult choices: elements of the projects can be competitive, whilst other parts will struggle, even though contributing to significant volumes. Reduction in UDC through proper scoping of present projects and its benchmarking paves as a learning for the development of marginal fields across the world, especially in this low oil price scenario. This way of developing a field has on average a reduction of 40% of cost for the Shell projects.

Keywords: benchmarking, full field development, CAPEX, feasibility

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Authors: Almas Rajguru

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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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Authors: Kaori Nakamura, Shun Su, Yusak Sulio, Daisuke Fukuda

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Active modes of transportation, such as walking and cycling, are crucial in promoting healthy and sustainable urban environments. Encouraging the use of these modes requires a well-designed road environment that ensures safety and comfort. Understanding what constitutes a safe environment for these users is essential. While previous research mainly focuses on subjective safety or the likelihood of collisions, there needs to be more analysis of the real-time experiences of travelers and dynamic transitions of their discomfort perceptions. Post-ride surveys or pre-ride impressions, the typical evaluation methods in past studies, may not accurately capture the immediate reactions and discomforts experienced during their rides. Though past experimental studies may also use physiological and behavioral data to evaluate road designs, they evaluated road design by comparing time-average physiological and behavioral data across different designs. This study aims to investigate the effects of the dynamic riding environmental changes experienced by cyclists during their rides on their dynamic physiological and behavioral responses and then explore how these conditions contribute to cyclists' overall subjective safety and comfort. We conducted an experiment with 24 participants who cycled approximately 500 meters in a virtual reality (VR) environment designed to mimic a typical road environment of Japanese local towns where lanes for cyclists and regular cars are adjacent in limited road spaces. Participants experienced six road designs varying in width, separation type, and bike lane color. We measured their physiological data, such as heart rate and skin conductance, and behavioral data, including steering, acceleration, and coordination of bicycles. Questionnaires for eliciting subjective impressions were conducted before and after each ride. The data analysis results indicate that wider paths (i.e., 1.5m and 2m width) are preferred, enhancing perceived safety and reducing stress, as supported by lower heart rates and skin conductance levels over narrower ones (1m width). Designs with clear divisions from car lanes may enhance perceived safety and reduce stress. The analysis of the physiological data also supports these arguments, showing that lower heart rates and skin conductance levels are found in wider, clearly marked paths. Further, the drift-diffusion decision model was performed to reveal whether different road environment designs may impact dynamic decision-making processes and physiological attributes. Designing a 1.5m wide bike lane with clear divisions from car lanes showed the highest level of clarity and safety in decision-making parameters. In contrast, designs without clear separations from car lanes resulted in less favorable decision-making outcomes. These results coincide with previous primary research indicating a preference for bike lane widths more significant than 1.5m. In conclusion, the analysis using the drift-diffusion decision model showed that decision-making ease slightly differs from subjective safety perceptions, providing a comprehensive understanding of how different road designs impact users. This study offers a solid foundation for assessing the perceptions of active mode users and highlights the importance of considering both real-time physiological and subjective data in designing road environments that encourage active transportation modes.

Keywords: active transport modes, cognitive and decision-making modeling, road environment designs, virtual reality experiment

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Authors: S. Fadda, M. Fiori, C. Matzuzzi

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Mineralized formations in the bottom sediments of a Miocene transgression have been discovered in Sardinia. The mineral assemblage consists of copper sulphides and oxidates suggesting fluctuations of redox conditions in neutral to high-pH restricted shallow-water coastal basins. Azurite/malachite has been observed as authigenic and occurs as loose spheroidal crystalline particles associated with the transitional-littoral horizon forming the bottom of the marine transgression. Many field observations are consistent with a supergenic circulation of metals involving terrestrial groundwater-seawater mixing. Both clastic materials and metals come from Tertiary volcanic edifices while the main precipitating anions, carbonates, and sulphides species are of both continental and marine origin. Formation of Cu carbonates as a supergene secondary 'oxide' assemblage, does not agree with field evidences, petrographic observations along with textural evidences in the host-rock types. Samples were collected along the sedimentary sequence for different analyses: the majority of elements were determined by X-ray fluorescence and plasma-atomic emission spectroscopy. Mineral identification was obtained by X-ray diffractometry and scanning electron microprobe. Thin sections of the samples were examined in microscopy while porosity measurements were made using a mercury intrusion porosimeter. Cu-carbonates deposited at a temperature below 100 C° which is consistent with the clay minerals in the matrix of the host rock dominated by illite and montmorillonite. Azurite nodules grew during the early diagenetic stage through reaction of cupriferous solutions with CO₂ imported from the overlying groundwater and circulating through the sandstones during shallow burial. Decomposition of organic matter in the bottom anoxic waters released additional carbon dioxide to pore fluids for azurite stability. In this manner localized reducing environments were also generated in which Cu was fixed as Cu-sulphide and sulphosalts. Microscopic examinations of textural features of azurite nodules give evidence of primary malachite/azurite deposition rather than supergene oxidation in place of primary sulfides. Photomicrographs show nuclei of azurite and malachite surrounded by newly formed microcrystalline carbonates which constitute the matrix. The typical pleochroism of crystals can be observed also when this mineral fills microscopic fissures or cracks. Sedimentological evidence of transgression and regression indicates that the pore water would have been a variable mixture of marine water and groundwaters with a possible meteoric component in an alternatively exposed and subaqueous environment owing to water-level fluctuation. Salinity data of the pore fluids, assessed at random intervals along the mineralised strata confirmed the values between about 7000 and 30,000 ppm measured in coeval sediments at the base of Miocene falling in the range of a more or less diluted sea water. This suggests a variation in mean pore-fluids pH between 5.5 and 8.5, compatible with the oxidized and reduced mineral paragenesis described in this work. The results of stable isotopes studies reflect the marine transgressive-regressive cyclicity of events and are compatibile with carbon derivation from sea water. During the last oxidative stage of diagenesis, under surface conditions of higher activity of H₂O and O₂, CO₂ partial pressure decreased, and malachite becomes the stable Cu mineral. The potential for these small but high grade deposits does exist.

Keywords: sedimentary, Cu-carbonates, authigenic, tertiary, Sardinia

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Authors: Paul J. McKay

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Large-scale genome-wide association studies (GWAS) investigating genetic contributions to sexual orientation and gender identity are largely lacking and may reduce stigma experienced in the LGBTQ+ community by providing an underlying biological explanation for queerness. While there is a growing consensus within the scientific community that genetic makeup contributes – at least in part – to sexual orientation and gender identity, there is a marked lack of genomics research exploring polygenic contributions to queerness. Based on recent (2019) findings from a large-scale GWAS investigating the genetic architecture of same-sex sexual behavior, and various additional peer-reviewed publications detailing novel insights into the molecular mechanisms of sexual orientation and gender identity, we hypothesize that sexual orientation and gender identity are complex, multifactorial, and polygenic; meaning that many genetic factors contribute to these phenomena, and environmental factors play a possible role through epigenetic modulation. In recent years, large-scale GWAS studies have been paramount to our modern understanding of many other complex human traits, such as in the case of autism spectrum disorder (ASD). Despite possible benefits of such research, including reduced stigma towards queer people, improved outcomes for LGBTQ+ in familial, socio-cultural, and political contexts, and improved access to healthcare (particularly for trans populations); important risks and considerations remain surrounding this type of research. To mitigate possibilities such as invalidation of the queer identities of existing LGBTQ+ individuals, genetic discrimination, or the possibility of euthanasia of embryos with a genetic predisposition to queerness (through reproductive technologies like IVF and/or gene-editing in utero), we propose a community-engaged research (CER) framework which emphasizes the privacy and confidentiality of research participants. Importantly, the historical legacy of scientific research attempting to pathologize queerness (in particular, falsely equating gender variance to mental illness) must be acknowledged to ensure any future research conducted in this realm does not propagate notions of homophobia, transphobia or stigma against queer people. Ultimately, in a world where same-sex sexual activity is criminalized in 69 UN member states, with 67 of these states imposing imprisonment, 8 imposing public flogging, 6 (Brunei, Iran, Mauritania, Nigeria, Saudi Arabia, Yemen) invoking the death penalty, and another 5 (Afghanistan, Pakistan, Qatar, Somalia, United Arab Emirates) possibly invoking the death penalty, the importance of this research cannot be understated, as finding a biological basis for queerness would directly oppose the harmful rhetoric that “being LGBTQ+ is a choice.” Anti-trans legislation is similarly widespread: In the United States in 2022 alone (as of Oct. 13), 155 anti-trans bills have been introduced preventing trans girls and women from playing on female sports teams, barring trans youth from using bathrooms and locker rooms that align with their gender identity, banning access to gender affirming medical care (e.g., hormone-replacement therapy, gender-affirming surgeries), and imposing legal restrictions on name changes. Understanding that a general lack of knowledge about the biological basis of queerness may be a contributing factor to the societal stigma faced by gender and sexual orientation minorities, we propose the initiation of large-scale GWAS studies investigating the genetic basis of gender identity and sexual orientation.

Keywords: genome-wide association studies (GWAS), sexual and gender minorities (SGM), polygenicity, community-engaged research (CER)

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

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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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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 57

Authors: A. Aceranti, L. Moretti, S. Vernocchi, M. Colorato, P. Caristia

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Irritable bowel syndrome (IBS) is the association between abdominal pain, abdominal distension and intestinal dysfunction for recurring periods. About 10% of the world's population has IBS at any given time in their life, and about 200 people per 100,000 receive an initial diagnosis of IBS each year. Persistent pain is recognized as one of the most pervasive and challenging problems facing the medical community today. Persistent pain is considered more as a complex pathophysiological, diagnostic and therapeutic situation rather than as a persistent symptom. The low efficiency of conventional drug treatments has led many doctors to become interested in the non-drug alternative treatment of IBS, especially for more severe cases. Patients and providers are often dissatisfied with the available drug remedies and often seek complementary and alternative medicine (CAM), a unique and holistic approach to treatment that is not a typical component of conventional medicine. Osteopathic treatment may be of specific interest in patients with IBS. Osteopathy is a complementary health approach that emphasizes the role of the musculoskeletal system in health and promotes optimal function of the body's tissues using a variety of manual techniques to improve body function. Osteopathy has been defined as a patient-centered health discipline based on the principles of interrelation between body structure and function, the body's innate capacity for self-healing and the adoption of a whole person health approach. mainly by practicing manual processing. Studies reported that osteopathic manual treatment (OMT) reduced IBS symptoms, such as abdominal pain, constipation, diarrhea, and improved general well-being. The focus in the treatment of IBS with osteopathy has gone beyond simple spinal alignment, to directly address the abnormal physiology of the body using a series of direct and indirect techniques. The topic of this study was chosen for different reasons: due to the large number of people involved who suffer from this disorder and for the dysfunction itself, since nowadays there is still little clarity about the best type of treatment and, above all, to its origin. The visceral component in the osteopathic field is still a world to be discovered, although it is related to a large part of patient series, it has contents that affect numerous disciplines and this makes it an enigma yet to be solved. The study originated in the didactic practice where the curiosity of a topic is marked that, even today, no one is able to explain and, above all, cure definitively. The main purpose of this study is to try to create a good basis on the osteopathic discipline for subsequent studies that can be exhaustive in the best possible way, resolving some doubts about which treatment modality can be used with more relevance. The path was decided to structure it in such a way that 3 types of osteopathic treatment are used on 3 groups of people who will be selected after completing a questionnaire, which will deem them suitable for the study. They will, in fact, be divided into three groups where: - the first group was given a visceral osteopathic treatment. - The second group was given a manual osteopathic treatment of neurological stimulation. - The third group received a placebo treatment. At the end of the treatment, questionnaires will be re-proposed respectively one week after the session and one month after the treatment from which any data will be collected that will demonstrate the effectiveness or otherwise of the treatment received. The sample of 50 patients examined underwent an oral interview to evaluate the inclusion and exclusion criteria to participate in the study. Of the 50 patients questioned, 17 people who underwent different osteopathic techniques were eligible for the study. Comparing the data related to the first assessment of tenderness and frequency of symptoms with the data related to the first follow-up shows a significant improvement in the score assigned to the different questions, especially in the neurogenic and visceral groups. We are aware of the fact that it is a study performed on a small sample of patients, and this is a penalizing factor. We remain, however, convinced that having obtained good results in terms of subjective improvement in the quality of life of the subjects, it would be very interesting to re-propose the study on a larger sample and fill the gaps.

Keywords: IBS, osteopathy, colon, intestinal inflammation

Procedia PDF Downloads 80

Authors: Tim Crocker-Buque, Sandra Mounier-Jack, Natasha Howard

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Background: Due to both the increasing scale and speed of urbanisation, urban areas in low and middle-income countries (LMICs) host increasingly large populations of under-immunized children, with the additional associated risks of rapid disease transmission in high-density living environments. Multiple interdependent factors are associated with these coverage disparities in urban areas and most evidence comes from relatively few countries, e.g., predominantly India, Kenya, Nigeria, and some from Pakistan, Iran, and Brazil. This study aimed to identify, describe, and assess the main tools used to measure or improve coverage of immunisation services in poor urban areas. Methods: Authors used a qualitative review design, including academic and non-academic literature, to identify tools used to improve coverage of public health interventions in urban areas. Authors selected and extracted sources that provided good examples of specific tools, or categories of tools, used in a context relevant to urban immunization. Diagnostic (e.g., for data collection, analysis, and insight generation) and programme tools (e.g., for investigating or improving ongoing programmes) and interventions (e.g., multi-component or stand-alone with evidence) were selected for inclusion to provide a range of type and availability of relevant tools. These were then prioritised using a decision-analysis framework and a tool selection guide for programme managers developed. Results: Authors reviewed tools used in urban immunisation contexts and tools designed for (i) non-immunization and/or non-health interventions in urban areas, and (ii) immunisation in rural contexts that had relevance for urban areas (e.g., Reaching every District/Child/ Zone). Many approaches combined several tools and methods, which authors categorised as diagnostic, programme, and intervention. The most common diagnostic tools were cross-sectional surveys, key informant interviews, focus group discussions, secondary analysis of routine data, and geographical mapping of outcomes, resources, and services. Programme tools involved multiple stages of data collection, analysis, insight generation, and intervention planning and included guidance documents from WHO (World Health Organisation), UNICEF (United Nations Children's Fund), USAID (United States Agency for International Development), and governments, and articles reporting on diagnostics, interventions, and/or evaluations to improve urban immunisation. Interventions involved service improvement, education, reminder/recall, incentives, outreach, mass-media, or were multi-component. The main gaps in existing tools were an assessment of macro/policy-level factors, exploration of effective immunization communication channels, and measuring in/out-migration. The proposed framework uses a problem tree approach to suggest tools to address five common challenges (i.e. identifying populations, understanding communities, issues with service access and use, improving services, improving coverage) based on context and available data. Conclusion: This study identified many tools relevant to evaluating urban LMIC immunisation programmes, including significant crossover between tools. This was encouraging in terms of supporting the identification of common areas, but problematic as data volumes, instructions, and activities could overwhelm managers and tools are not always suitably applied to suitable contexts. Further research is needed on how best to combine tools and methods to suit local contexts. Authors’ initial framework can be tested and developed further.

Keywords: health equity, immunisation, low and middle-income countries, poverty, urban health

Procedia PDF Downloads 127

Authors: P. J. Sweeney, T. Ahtoniemi, J. Puoliväli, T. Laitinen, K.Lehtimäki, A. Nurmi, D. Wells

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Duchenne muscular dystrophy (DMD) is an X-linked, lethal muscle wasting disease for which there are currently no treatment that effectively prevents the muscle necrosis and progressive muscle loss. DMD is among the most common of inherited diseases affecting around 1/3500 live male births. MDX (X-linked muscular dystrophy) mice only partially encapsulate the disease in humans and display weakness in muscles, muscle damage and edema during a period deemed the “critical period” when these mice go through cycles of muscular degeneration and regeneration. Although the MDX mutant mouse model has been extensively studied as a model for DMD, to-date an extensive temporal, non-invasive imaging profile that utilizes magnetic resonance imaging (MRI) and 1H-magnetic resonance spectroscopy (1H-MRS) has not been performed.. In addition, longitudinal imaging characterization has not coincided with attempts to exacerbate the progressive muscle damage by exercise. In this study we employed an 11.7 T small animal MRI in order to characterize the MRI and MRS profile of MDX mice longitudinally during a 12 month period during which MDX mice were subjected to exercise. Male mutant MDX mice (n=15) and male wild-type mice (n=15) were subjected to a chronic exercise regime of treadmill walking (30 min/ session) bi-weekly over the whole 12 month follow-up period. Mouse gastrocnemius and tibialis anterior muscles were profiled with baseline T2-MRI and 1H-MRS at 6 weeks of age. Imaging and spectroscopy was repeated again at 3 months, 6 months, 9 months and 12 months of age. Plasma creatine kinase (CK) level measurements were coincided with time-points for T2-MRI and 1H-MRS, but also after the “critical period” at 10 weeks of age. The results obtained from this study indicate that chronic exercise extends dystrophic phenotype of MDX mice as evidenced by T2-MRI and1H-MRS. T2-MRI revealed extent and location of the muscle damage in gastrocnemius and tibialis anterior muscles as hyperintensities (lesions and edema) in exercised MDX mice over follow-up period.. The magnitude of the muscle damage remained stable over time in exercised mice. No evident fat infiltration or cumulation to the muscle tissues was seen at any time-point in exercised MDX mice. Creatine, choline and taurine levels evaluated by 1H-MRS from the same muscles were found significantly decreased in each time-point, Extramyocellular (EMCL) and intramyocellular lipids (IMCL) did not change in exercised mice supporting the findings from anatomical T2-MRI scans for fat content. Creatine kinase levels were found to be significantly higher in exercised MDX mice during the follow-up period and importantly CK levels remained stable over the whole follow-up period. Taken together, we have described here longitudinal prophile for muscle damage and muscle metabolic changes in MDX mice subjected to chronic exercised. The extent of the muscle damage by T2-MRI was found to be stable through the follow-up period in muscles examined. In addition, metabolic profile, especially creatine, choline and taurine levels in muscles, was found to be sustained between time-points. The anatomical muscle damage evaluated by T2-MRI was supported by plasma CK levels which remained stable over the follow-up period. These findings show that non-invasive imaging and spectroscopy can be used effectively to evaluate chronic muscle pathology. These techniques can be also used to evaluate the effect of various manipulations, like here exercise, on the phenotype of the mice. Many of the findings we present here are translatable to clinical disease, such as decreased creatine, choline and taurine levels in muscles. Imaging by T2-MRI and 1H-MRS also revealed that fat content or extramyocellar and intramyocellular lipids, respectively, are not changed in MDX mice, which is in contrast to clinical manifestation of the Duchenne’s muscle dystrophy. Findings show that non-invasive imaging can be used to characterize the phenotype of a MDX model and its translatability to clinical disease, and to study events that have traditionally been not examined, like here rigorous exercise related sustained muscle damage after the “critical period”. The ability for this model to display sustained damage beyond the spontaneous “critical period“ and in turn to study drug effects on this extended phenotype will increase the value of the MDX mouse model as a tool to study therapies and treatments aimed at DMD and associated diseases.

Keywords: 1H-MRS, MRI, muscular dystrophy, mouse model

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Authors: Rohini Das, Subhasish Das, Smruti Rekha Sahoo, Shagupta Yesmin

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The Paleoproterozoic Kolhan Group (Purana) ensemble constitutes the youngest lithostratigraphic 'outlier' in the Singhbhum Archaean craton. The Kolhan unconformably overlies both the Singhbhum granite and the Iron Ore Group (IOG). Representing a typical sandstone-shale ( +/- carbonates) sequence, the Kolhan is characterized by the development of thin and discontinuous patches of basal conglomerates draped by sandstone beds. The IOG-fault limits the western 'distal' margin of the Kolhan basin showing evidence of passive subsidence subsequent to the initial rifting stage. The basin evolved as a half-graben under the influence of an extensional stress regime. The assumption of a tectonic setting for the NE-SW trending Kolhan basin possibly relates to the basin opening to the E-W extensional stress system that prevailed during the development of the Newer Dolerite dyke. The Paleoproterozoic age of the Kolhan basin is based on the consideration of the conformable stress pattern responsible both for the basin opening and the development of the conjugate fracture system along which the Newer Dolerite dykes intruded the Singhbhum Archaean craton. The Kolhan sandstones show progressive change towards greater textural and mineralogical maturity in its upbuilding. The trend of variations in different mineralogical and textural attributes, however, exhibits inflections at different lithological levels. Petrological studies collectively indicate that the sandstones were dominantly derived from a weathered granitic crust under a humid climatic condition. Provenance-derived variations in sandstone compositions are therefore a key in unraveling regional tectonic histories. The basin axis controlled the progradation direction which was likely driven by climatically induced sediment influx, a eustatic fall, or both. In the case of the incongruent shift, increased sediment supply permitted the rivers to cross the basinal deep. Temporal association of the Kolhan with tectonic structures in the belt indicates that syn-tectonic thrust uplift, not isostatic uplift or climate, caused the influx of quartz. The sedimentation pattern in the Kolhan reflects a change from braided fluvial-ephemeral pattern to a fan-delta-lacustrine type. The channel geometries and the climate exerted a major control on the processes of sediment transfer. Repeated fault controlled uplift of the source followed by subsidence and forced regression, generated multiple sediment cyclicity that led to the fluvial-fan delta sedimentation pattern. Intermittent uplift of the faulted blocks exposed fresh bedrock to mechanical weathering that generated a large amount of detritus and resulted to forced regressions, repeatedly disrupting the cycles which may reflect a stratigraphic response of connected rift basins at the early stage of extension. The marked variations in the thickness of the fan delta succession and the stacking pattern in different measured profiles reflect the overriding tectonic controls on fan delta evolution. The accumulated fault displacement created higher accommodation and thicker delta sequences. Intermittent uplift of fault blocks exposed fresh bedrock to mechanical weathering, generated a large amount of detritus, and resulted in forced closure of the land-locked basin, repeatedly disrupting the fining upward pattern. The control of source rock lithology or climate was of secondary importance to tectonic effects. Such a retrograding fan delta could be a stratigraphic response of connected rift basins at the early stage of extension.

Keywords: Kolhan basin, petrology, sandstone, tectonics

Procedia PDF Downloads 481

Authors: Riccardo Fratini, Riccardo Santini, Jacopo Serafini, Massimo Gennaretti, Stefano Panzieri

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This paper presents a nonlinear differential model, for a three-bladed horizontal axis wind turbine (HAWT) suited for control applications. It is based on a 8-dofs, lumped parameters structural dynamics coupled with a quasi-steady sectional aerodynamics. In particular, using the Euler-Lagrange Equation (Energetic Variation approach), the authors derive, and successively validate, such model. For the derivation of the aerodynamic model, the Greenbergs theory, an extension of the theory proposed by Theodorsen to the case of thin airfoils undergoing pulsating flows, is used. Specifically, in this work, the authors restricted that theory under the hypothesis of low perturbation reduced frequency k, which causes the lift deficiency function C(k) to be real and equal to 1. Furthermore, the expressions of the aerodynamic loads are obtained using the quasi-steady strip theory (Hodges and Ormiston), as a function of the chordwise and normal components of relative velocity between flow and airfoil Ut, Up, their derivatives, and section angular velocity ε˙. For the validation of the proposed model, the authors carried out open and closed-loop simulations of a 5 MW HAWT, characterized by radius R =61.5 m and by mean chord c = 3 m, with a nominal angular velocity Ωn = 1.266rad/sec. The first analysis performed is the steady state solution, where a uniform wind Vw = 11.4 m/s is considered and a collective pitch angle θ = 0.88◦ is imposed. During this step, the authors noticed that the proposed model is intrinsically periodic due to the effect of the wind and of the gravitational force. In order to reject this periodic trend in the model dynamics, the authors propose a collective repetitive control algorithm coupled with a PD controller. In particular, when the reference command to be tracked and/or the disturbance to be rejected are periodic signals with a fixed period, the repetitive control strategies can be applied due to their high precision, simple implementation and little performance dependency on system parameters. The functional scheme of a repetitive controller is quite simple and, given a periodic reference command, is composed of a control block Crc(s) usually added to an existing feedback control system. The control block contains and a free time-delay system eτs in a positive feedback loop, and a low-pass filter q(s). It should be noticed that, while the time delay term reduces the stability margin, on the other hand the low pass filter is added to ensure stability. It is worth noting that, in this work, the authors propose a phase shifting for the controller and the delay system has been modified as e^(−(T−γk)), where T is the period of the signal and γk is a phase shifting of k samples of the same periodic signal. It should be noticed that, the phase shifting technique is particularly useful in non-minimum phase systems, such as flexible structures. In fact, using the phase shifting, the iterative algorithm could reach the convergence also at high frequencies. Notice that, in our case study, the shifting of k samples depends both on the rotor angular velocity Ω and on the rotor azimuth angle Ψ: we refer to this controller as a spatial repetitive controller. The collective repetitive controller has also been coupled with a C(s) = PD(s), in order to dampen oscillations of the blades. The performance of the spatial repetitive controller is compared with an industrial PI controller. In particular, starting from wind speed velocity Vw = 11.4 m/s the controller is asked to maintain the nominal angular velocity Ωn = 1.266rad/s after an instantaneous increase of wind speed (Vw = 15 m/s). Then, a purely periodic external disturbance is introduced in order to stress the capabilities of the repetitive controller. The results of the simulations show that, contrary to a simple PI controller, the spatial repetitive-PD controller has the capability to reject both external disturbances and periodic trend in the model dynamics. Finally, the nominal value of the angular velocity is reached, in accordance with results obtained with commercial software for a turbine of the same type.

Keywords: wind turbines, aeroelasticity, repetitive control, periodic systems

Procedia PDF Downloads 230

Authors: Ziyad S. Haidar

Abstract:

Millions of teeth are removed annually, and dental extraction is one of the most commonly performed surgical procedures globally. Whether due to caries, periodontal disease or trauma, exodontia and the ensuing wound healing and bone remodeling processes of the resultant socket (hole in the jaw bone) usually result in serious deformities of the residual alveolar osseous ridge and surrounding soft tissues (reduced height/width). Such voluminous changes render the placement of a proper conventional bridge, denture or even an implant-supported prosthesis extremely challenging. Further, most extractions continue to be performed with no regard for preventing the onset of alveolar osteitis (also known as dry socket, a painful and difficult-to-treat/-manage condition post-exodontia). Hence, such serious resorptive morphological changes often result in significant facial deformities and a negative impact on the overall Quality of Life (QoL) of patients (and oral health-related QoL), alarming, particularly for the geriatric with compromised healing and in light of the thriving longevity statistics. Opportunity: Despite advances in tissue/wound grafting, serious limitations continue to exist, including efficacy and clinical outcome predictability, cost, treatment time, expertise and risk of immune reactions. For cases of dry sockets, specifically, the commercially-available and often-prescribed home remedies are highly lacking. Indeed, most are not recommended for use anymore. Alveogyl is a fine example. Hence, there is a great market demand and need for alternative solutions. Solution: Herein, SockGEL/PLUG (patent pending), an all-natural, drug-free and injectable stimuli-responsive hydrogel, was designed, formulated, characterized and evaluated as an osteogenic, angiogenic, anti-microbial and pain-soothing suture-free intra-alveolar dressing, safe and efficacious for use in several oro-dental and cranio-maxillo-facial interventional applications; for example: in fresh dental extraction sockets, immediately post-exodontia. It is composed of FDA-approved, biocompatible and biodegradable polymers, self-assembled electro-statically to formulate a scaffolding matrix to (a) prevent the onset of alveolar osteitis via securing the fibrin-clot in situ and protecting/sealing the socket from contamination/infection; and (b) endogenously promote/accelerate wound healing and bone remodeling to preserve the volume of the alveolus. Findings: The intrinsic properties of the SockGEL/PLUG hydrogel were evaluated physico-chemico-mechanically for safety (cell viability), viscosity, rheology, bio-distribution and essentially, capacity to induce wound healing and osteogenesis (small defect, in vivo) without any signaling cues from exogenous cells, growth factors or drugs. The performed animal model of cranial critical-sized and non-vascularized bone defects shall provide vitally critical insights into the role and mechanism of the employed natural bio-polymer blend and gel product in endogenous reparative regeneration of soft tissues and bone morphogenesis. Alongside, the fine-tuning of our modified formulation method will further tackle appropriateness, reproducibility, scalability, ease and speed in producing stable, biodegradable and sterilizable stimuli (thermo-sensitive and photo-responsive) matrices (3-dimensional interpenetrating yet porous polymeric network) suitable for an intra-socket application, and beyond. Conclusions and Perspective: Findings are anticipated to provide sufficient evidence to translate into pilot clinical trials and validate the bionanomaterial before engaging the market for feasibility, acceptance and cost-effectiveness studies. The SockGEL/PLUG platform is patent pending: SockGEL is a bio-inspired drug-free hydrogel; SockPLUG is a drug-loaded hydrogel designed for complex indications.

Keywords: hydrogel, injectable, dentistry, craniomaxillofacial complex, bioinspired, nanobiotechnology, biopolymer, sol-gel, stimuli-responsive, matrix, tissue engineering, regenerative medicine

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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

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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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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)

Procedia PDF Downloads 331

Authors: Hosein Maghsoudi

Abstract:

Rheumatois arthritis (RA) is progressive inflammatory autoimmune diseases that primarily affect the joints, characterized by synovial hyperplasia and inflammatory cell infiltration, deformed and painful joints, which can lead tissue destruction, functional disability systemic complications, and early dead and socioeconomic costs. The cause of rheumatoid arthritis is unknown, but genetic and environmental factors are contributory and the prognosis is guarded. However, advances in understanding the pathogenesis of the disease have fostered the development of new therapeutics, with improved outcomes. The current treatment strategy, which reflects this progress, is to initiate aggressive therapy soon after diagnosis and to escalate the therapy, guided by an assessment of disease activity, in pursuit of clinical remission. The pathobiology of RA is multifaceted and involves T cells, B cells, fibroblast-like synoviocyte (FLSc) and the complex interaction of many pro-inflammatory cytokine. Novel biologic agents that target tumor necrosis or interlukin (IL)-1 and Il-6, in addition T- and B-cells inhibitors, have resulted in favorable clinical outcomes in patients with RA. Despite this, at least 30% of RA patients are résistance to available therapies, suggesting novel mediators should be identified that can target other disease-specific pathway or cell lineage. Among the inflammatory cell population that might participated in RA pathogenesis, FLSc are crucial in initiaing and driving RA in concert of cartilage and bone by secreting metalloproteinase (MMPs) into the synovial fluid and by direct invasion into extracellular matrix (ECM), further exacerbating joint damage. Invasion of fibroblast-like synoviocytes (FLSc) is critical in the pathogenesis of rheumatoid-arthritis. The metalloproteinase (MMPs) and activator of Toll-like receptor 4 (TLR4)/nuclear factor- κB pthway play a critical role in RA-FLS invasion induced by lipopolysaccharide (LPS). The present study aimed to explore the anti-invasion activity of Glycyrrhizic Acid as a pharmacologically safe phytochemical agent with potent anti-inflammatory properties on IL-1beta and TNF-alpha signalling pathways in Bovine fibroblast-like synoviocyte ex- vitro, on LPS-stimulated bovine FLS migration and invasion as well as MMP expression and explored the upstream signal transduction. Results showed that Glycyrrhizic Acid suppressed LPS-stimulated bovine FLS migration and invasion by inhibition MMP-9 expression and activity. In addition our results revealed that Glycyrrhizic Acid inhibited the transcriptional activity of MMP-9 by suppression the nbinding activity of NF- κB in the MMP-9 promoter pathway. The extract of licorice (Glycyrrhiza glabra L.) has been widely used for many centuries in the traditional Chinese medicine as native anti-allergic agent. Glycyrrhizin (GL), a triterpenoidsaponin, extracted from the roots of licorice is the most effective compound for inflammation and allergic diseases in human body. The biological and pharmacological studies revealed that GL possesses many pharmacological effects, such as anti-inflammatory, anti-viral and liver protective effects, and the biological effects, such as induction of cytokines (interferon-γ and IL-12), chemokines as well as extrathymic T and anti-type 2 T cells. GL is known in the traditional Chinese medicine for its anti-inflammatory effect, which is originally described by Finney in 1959. The mechanism of the GL-induced anti-inflammatory effect is based on different pathways of the GL-induced selective inhibition of the prostaglandin E2 production, the CK-II- mediated activation of both GL-binding lipoxygenas (gbLOX; 17) and PLA2, an anti-thrombin action of GL and production of the reactive oxygen species (ROS; GL exerts liver protection properties by inhibiting PLA2 or by the hydroxyl radical trapping action, leading to the lowering of serum alanine and aspartate transaminase levels. The present study was undertaken to examine the possible mechanism of anti-inflammatory properties GL on IL-1beta and TNF-alpha signalling pathways in bovine fibroblast-like synoviocyte ex-vivo, on LPS-stimulated bovine FLS migration and invasion as well as MMP expression and explored the upstream signal transduction. Our results clearly showed that treatment of bovine fibroblast-like synoviocyte with GL suppressed LPS-induced cell migration and invasion. Furthermore, it revealed that GL inhibited the transcription activity of MMP-9 by suppressing the binding activity of NF-κB in the MM-9 promoter. MMP-9 is an important ECM-degrading enzyme and overexpression of MMPs in important of RA-FLSs. LPS can stimulate bovine FLS to secret MMPs, and this induction is regulated at the transcription and translational levels. In this study, LPS treatment of bovine FLS caused an increase in MMP-2 and MMP-9 levels. The increase in MMP-9 expression and secretion was inhibited by ex- vitro. Furthermore, these effects were mimicked by MMP-9 siRNA. These result therefore indicate the the inhibition of LPS-induced bovine FLS invasion by GL occurs primarily by inhibiting MMP-9 expression and activity. Next we analyzed the functional significance of NF-κB transcription of MMP-9 activation in Bovine FLSs. Results from EMSA showed that GL suppressed LPS-induced NF-κB binding to the MMP-9 promotor, as NF-κB regulates transcriptional activation of multiple inflammatory cytokines, we predicted that GL might target NF-κB to suppress MMP-9 transcription by LPS. Myeloid differentiation-factor 88 (MyD88) and TIR-domain containing adaptor protein (TIRAP) are critical proteins in the LPS-induced NF-κB and apoptotic signaling pathways, GL inhibited the expression of TLR4 and MYD88. These results demonstrated that GL suppress LPS-induced MMP-9 expression through the inhibition of the induced TLR4/NFκB signaling pathway. Taken together, our results provide evidence that GL exerts anti-inflammatory effects by inhibition LPS-induced bovine FLSs migration and invasion, and the mechanisms may involve the suppression of TLR4/NFκB –mediated MMP-9 expression. Although further work is needed to clarify the complicated mechanism of GL-induced anti-invasion of bovine FLSs, GL might be used as a further anti-invasion drug with therapeutic efficacy in the treatment of immune-mediated inflammatory disease such as RA.

Keywords: glycyrrhizic acid, bovine fibroblast-like synoviocyte, tlr4/nf-κb, metalloproteinase-9

Procedia PDF Downloads 367