Search results for: project evaluation

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: 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: Justin Woulfe

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Siloed logistics and supply chain management systems throughout the Department of Defense (DOD) has led to disparate approaches to modeling and simulation (M&S), a lack of understanding of how one system impacts the whole, and issues with “optimal” solutions that are good for one organization but have dramatic negative impacts on another. Many different systems have evolved to try to understand and account for uncertainty and try to reduce the consequences of the unknown. As the DoD undertakes expansive digital transformation initiatives, there is an opportunity to fuse and leverage traditionally disparate data into a centrally hosted source of truth. With a streamlined process incorporating machine learning (ML) and artificial intelligence (AI), advanced M&S will enable informed decisions guiding program success via optimized operational readiness and improved mission success. One of the current challenges is to leverage the terabytes of data generated by monitored systems to provide actionable information for all levels of users. The implementation of a cloud-based application analyzing data transactions, learning and predicting future states from current and past states in real-time, and communicating those anticipated states is an appropriate solution for the purposes of reduced latency and improved confidence in decisions. Decisions made from an ML and AI application combined with advanced optimization algorithms will improve the mission success and performance of systems, which will improve the overall cost and effectiveness of any program. The Systecon team constructs and employs model-based simulations, cutting across traditional silos of data, aggregating maintenance, and supply data, incorporating sensor information, and applying optimization and simulation methods to an as-maintained digital twin with the ability to aggregate results across a system’s lifecycle and across logical and operational groupings of systems. This coupling of data throughout the enterprise enables tactical, operational, and strategic decision support, detachable and deployable logistics services, and configuration-based automated distribution of digital technical and product data to enhance supply and logistics operations. As a complete solution, this approach significantly reduces program risk by allowing flexible configuration of data, data relationships, business process workflows, and early test and evaluation, especially budget trade-off analyses. A true capability to tie resources (dollars) to weapon system readiness in alignment with the real-world scenarios a warfighter may experience has been an objective yet to be realized to date. By developing and solidifying an organic capability to directly relate dollars to readiness and to inform the digital twin, the decision-maker is now empowered through valuable insight and traceability. This type of educated decision-making provides an advantage over the adversaries who struggle with maintaining system readiness at an affordable cost. The M&S capability developed allows program managers to independently evaluate system design and support decisions by quantifying their impact on operational availability and operations and support cost resulting in the ability to simultaneously optimize readiness and cost. This will allow the stakeholders to make data-driven decisions when trading cost and readiness throughout the life of the program. Finally, sponsors are available to validate product deliverables with efficiency and much higher accuracy than in previous years.

Keywords: artificial intelligence, digital transformation, machine learning, predictive analytics

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Authors: Agman Gupta, Rajashekar Badam, Noriyoshi Matsumi

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Introduction: Recently, silicon has been recognized as one of the potential alternatives as anode active material in Li-ion batteries (LIBs) to replace the conventionally used graphite anodes. Silicon is abundantly present in the nature, it can alloy with lithium metal, and has a higher theoretical capacity (~4200 mAhg-1) that is approximately 10 times higher than graphite. However, because of a large volume expansion (~400%) upon repeated de-/alloying, the pulverization of Si particles causes the exfoliation of electrode laminate leading to the loss of electrical contact and adversely affecting the formation of solid-electrolyte interface (SEI).1 Functional polymers as binders have emerged as a competitive strategy to mitigate these drawbacks and failure mechanism of silicon anodes.1 A variety of aqueous/non-aqueous polymer binders like sodium carboxy-methyl cellulose (CMC-Na), styrene butadiene rubber (SBR), poly(acrylic acid), and other variants like mussel inspired binders have been investigated to overcome these drawbacks.1 However, there are only a few reports that mention the attempt of addressing all the drawbacks associated with silicon anodes effectively using a single novel functional polymer system as a binder. In this regard, here, we report a novel highly robust n-type bisiminoacenaphthenequinone (BIAN)-paraphenylene-based crosslinked polymer as a binder for Si anodes in lithium-ion batteries (Fig. 1). On its application, crosslinked-BIAN binder was evaluated to provide mechanical robustness to the large volume expansion of Si particles, maintain electrical conductivity within the electrode laminate, and facilitate in the formation of a thin SEI by restricting the extent of electrolyte decomposition on the surface of anode. The fabricated anodic half-cells were evaluated electrochemically for their rate capability, cyclability, and discharge capacity. Experimental: The polymerized BIAN (P-BIAN) copolymer was synthesized as per the procedure reported by our group.2 The synthesis of crosslinked P-BIAN: a solution of P-BIAN copolymer (1.497 g, 10 mmol) in N-methylpyrrolidone (NMP) (150 ml) was set-up to stir under reflux in nitrogen atmosphere. To this, 1,6-dibromohexane (5 mmol, 0.77 ml) was added dropwise. The resultant reaction mixture was stirred and refluxed at 150 °C for 24 hours followed by refrigeration for 3 hours at 5 °C. The product was obtained by evaporating the NMP solvent under reduced pressure and drying under vacuum at 120 °C for 12 hours. The obtained product was a black colored sticky compound. It was characterized by 1H-NMR, XPS, and FT-IR techniques. Results and Discussion: The N 1s XPS spectrum of the crosslinked BIAN polymer showed two characteristic peaks corresponding to the sp2 hybridized nitrogen (-C=N-) at 399.6 eV of the diimine backbone in the BP and quaternary nitrogen at 400.7 eV corresponding to the crosslinking of BP via dibromohexane. The DFT evaluation of the crosslinked BIAN binder showed that it has a low lying lowest unoccupied molecular orbital (LUMO) that enables it to get doped in the reducing environment and influence the formation of a thin (SEI). Therefore, due to the mechanically robust crosslinked matrices as well as its influence on the formation of a thin SEI, the crosslinked BIAN binder stabilized the Si anode-based half-cell for over 1000 cycles with a reversible capacity of ~2500 mAhg-1 and ~99% capacity retention as shown in Fig. 2. The dynamic electrochemical impedance spectroscopy (DEIS) characterization of crosslinked BIAN-based anodic half-cell confirmed that the SEI formed was thin in comparison with the conventional binder-based anodes. Acknowledgement: We are thankful to the financial support provided by JST-Mirai Program, Grant Number: JP18077239

Keywords: self-healing binder, n-type binder, thin solid-electrolyte interphase (SEI), high-capacity silicon anodes, low-LUMO

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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

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Authors: Tianqiao Zhang, Ye Tian, Yanliang Yin, Yichao Tian, Suzhai Tian, Weige Sun, Shuhui Gong, Limei Tang, Ruoliang Tang

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Introduction: Healthcare workers, especially the nurses all over the world, are highly vulnerable to work-related musculoskeletal disorders (WMSDs), experiencing high rates of neck, shoulder, and low back injuries, due to the unfavorable working conditions. To reduce WMSDs among nursing personnel, many workplace interventions have been developed and implemented. Unfortunately, the ongoing Covid-19 (SARS-CoV-2) pandemic has posed great challenges to the ergonomic practices and interventions in healthcare facilities, particularly the hospitals, since current Covid-19 mitigation measures, such as social distancing and working remotely, has substantially minimized in-person gatherings and trainings. On the other hand, hospitals throughout the world have been short-staffed, resulting in disturbance of shift scheduling and more importantly, the increased job demand among the available caregivers, particularly the doctors and nurses. With the latest development in communication technology, remote intervention measures have been developed as an alternative, without the necessity of in-person meetings. The Omaha System (OS) is a standardized classification system for nursing practices, including a problem classification system, an intervention system, and an outcome evaluation system. This paper describes the development of an OS-based ergonomic intervention program. Methods: First, a comprehensive literature search was performed among worldwide electronic databases, including PubMed, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), between journal inception to May 2020, resulting in a total of 1,418 scientific articles. After two independent screening processes, the final knowledge pool included eleven randomized controlled trial studies to develop the draft of the intervention program with Omaha intervention subsystem as the framework. After the determination of sample size needed for statistical power and the potential loss to follow-up, a total of 94 nurses from eight clinical departments agreed to provide written, informed consent to participate in the study, which were subsequently assigned into two random groups (i.e., intervention vs. control). A subgroup of twelve nurses were randomly selected to participate in a semi-structured interview, during which their general understanding and awareness of musculoskeletal disorders and potential interventions was assessed. Then, the first draft was modified to reflect the findings from these interviews. Meanwhile, the tentative program schedule was also assessed. Next, two rounds of consultation were conducted among experts in nursing management, occupational health, psychology, and rehabilitation, to further adjust and finalize the intervention program. The control group had access to all the information and exercise modules at baseline, while an interdisciplinary research team was formed and supervised the implementation of the on-line intervention program through multiple social media groups. Outcome measures of this comparative study included biomechanical load assessed by the Quick Exposure Check and stresses due to awkward body postures. Results and Discussion: Modification to the draft included (1) supplementing traditional Chinese medicine practices, (2) adding the use of assistive patient handling equipment, and (3) revising the on-line training method. Information module should be once a week, lasting about 20 to 30 minutes, for a total of 6 weeks, while the exercise module should be 5 times a week, each lasting about 15 to 20 minutes, for a total of 6 weeks.

Keywords: ergonomic interventions, musculoskeletal disorders (MSDs), omaha system, nurses, Covid-19

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Authors: Joanna Szymanska, Paulina Wawulska-Marek, Jaroslaw Mizera

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Nowadays, the rapid growth of global energy consumption and uncontrolled depletion of natural resources become a serious problem. Shale rocks are the largest and potential global basins containing hydrocarbons, trapped in closed pores of the shale matrix. Regardless of the shales origin, mining conditions are extremely unfavourable due to high reservoir pressure, great depths, increased clay minerals content and limited permeability (nanoDarcy) of the rocks. Taking into consideration such geomechanical barriers, effective extraction of natural gas from shales with plastic zones demands effective operations. Actually, hydraulic fracturing is the most developed technique based on the injection of pressurized fluid into a wellbore, to initiate fractures propagation. However, a rapid drop of pressure after fluid suction to the ground induces a fracture closure and conductivity reduction. In order to minimize this risk, proppants should be applied. They are solid granules transported with hydraulic fluids to locate inside the rock. Proppants act as a prop for the closing fracture, thus gas migration to a borehole is effective. Quartz sands are commonly applied proppants only at shallow deposits (USA). Whereas, ceramic proppants are designed to meet rigorous downhole conditions to intensify output. Ceramic granules predominate with higher mechanical strength, stability in strong acidic environment, spherical shape and homogeneity as well. Quality of ceramic proppants is conditioned by raw materials selection. Aim of this study was to obtain the proppants from aluminosilicates (the kaolinite subgroup) and mix of minerals with a high alumina content. These loamy minerals contain a tubular and platy morphology that improves mechanical properties and reduces their specific weight. Moreover, they are distinguished by well-developed surface area, high porosity, fine particle size, superb dispersion and nontoxic properties - very crucial for particles consolidation into spherical and crush-resistant granules in mechanical granulation process. The aluminosilicates were mixed with water and natural organic binder to improve liquid-bridges and pores formation between particles. Afterward, the green proppants were subjected to sintering at high temperatures. Evaluation of the minerals utility was based on their particle size distribution (laser diffraction study) and thermal stability (thermogravimetry). Scanning Electron Microscopy was useful for morphology and shape identification combined with specific surface area measurement (BET). Chemical composition was verified by Energy Dispersive Spectroscopy and X-ray Fluorescence. Moreover, bulk density and specific weight were measured. Such comprehensive characterization of loamy materials confirmed their favourable impact on the proppants granulation. The sintered granules were analyzed by SEM to verify the surface topography and phase transitions after sintering. Pores distribution was identified by X-Ray Tomography. This method enabled also the simulation of proppants settlement in a fracture, while measurement of bulk density was essential to predict their amount to fill a well. Roundness coefficient was also evaluated, whereas impact on mining environment was identified by turbidity and solubility in acid - to indicate risk of the material decay in a well. The obtained outcomes confirmed a positive influence of the loamy minerals on ceramic proppants properties with respect to the strict norms. This research is perspective for higher quality proppants production with costs reduction.

Keywords: aluminosilicates, ceramic proppants, mechanical granulation, shale gas

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Authors: Ali Kazemi

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Those within the volatile and interconnected international economic markets, appropriately predicting market trends, hold substantial fees for traders and financial establishments. Traditional device mastering strategies have made full-size strides in forecasting marketplace movements; however, monetary data's complicated and networked nature calls for extra sophisticated processes. This observation offers a groundbreaking method for monetary marketplace prediction that leverages the synergistic capability of Graph Convolutional Networks (GCNs) and Long Short-Term Memory (LSTM) networks. Our suggested algorithm is meticulously designed to forecast the traits of inventory market indices and cryptocurrency costs, utilizing a comprehensive dataset spanning from January 1, 2015, to December 31, 2023. This era, marked by sizable volatility and transformation in financial markets, affords a solid basis for schooling and checking out our predictive version. Our algorithm integrates diverse facts to construct a dynamic economic graph that correctly reflects market intricacies. We meticulously collect opening, closing, and high and low costs daily for key inventory marketplace indices (e.g., S&P 500, NASDAQ) and widespread cryptocurrencies (e.g., Bitcoin, Ethereum), ensuring a holistic view of marketplace traits. Daily trading volumes are also incorporated to seize marketplace pastime and liquidity, providing critical insights into the market's shopping for and selling dynamics. Furthermore, recognizing the profound influence of the monetary surroundings on financial markets, we integrate critical macroeconomic signs with hobby fees, inflation rates, GDP increase, and unemployment costs into our model. Our GCN algorithm is adept at learning the relational patterns amongst specific financial devices represented as nodes in a comprehensive market graph. Edges in this graph encapsulate the relationships based totally on co-movement styles and sentiment correlations, enabling our version to grasp the complicated community of influences governing marketplace moves. Complementing this, our LSTM algorithm is trained on sequences of the spatial-temporal illustration discovered through the GCN, enriched with historic fee and extent records. This lets the LSTM seize and expect temporal marketplace developments accurately. Inside the complete assessment of our GCN-LSTM algorithm across the inventory marketplace and cryptocurrency datasets, the version confirmed advanced predictive accuracy and profitability compared to conventional and opportunity machine learning to know benchmarks. Specifically, the model performed a Mean Absolute Error (MAE) of 0.85%, indicating high precision in predicting day-by-day charge movements. The RMSE was recorded at 1.2%, underscoring the model's effectiveness in minimizing tremendous prediction mistakes, which is vital in volatile markets. Furthermore, when assessing the model's predictive performance on directional market movements, it achieved an accuracy rate of 78%, significantly outperforming the benchmark models, averaging an accuracy of 65%. This high degree of accuracy is instrumental for techniques that predict the course of price moves. This study showcases the efficacy of mixing graph-based totally and sequential deep learning knowledge in economic marketplace prediction and highlights the fee of a comprehensive, records-pushed evaluation framework. Our findings promise to revolutionize investment techniques and hazard management practices, offering investors and economic analysts a powerful device to navigate the complexities of cutting-edge economic markets.

Keywords: financial market prediction, graph convolutional networks (GCNs), long short-term memory (LSTM), cryptocurrency forecasting

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Authors: Maria João Ferreira, Natalia Sierra-Garcia, Javier Cremades, Carla António, Ana M. Rodrigues, Helena Silva, Ângela Cunha

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Salicornia ramosissima, a halophyte that grows naturally in coastal areas of the northern hemisphere, is often considered the most promising halophyte candidate for extensive crop cultivation and saline agriculture practices. The expanding interest in this plant surpasses its use as gourmet food and includes their potential application as a source of bioactive compounds for the pharmaceutical industry. Despite growing well in saline soils, sustainable and ecologically friendly techniques to enhance crop production and the nutritional value of this plant are still needed. The root microbiome of S. ramosissima proved to be a source of taxonomically diverse plant growth-promoting bacteria (PGPB). Halotolerant strains of Bacillus, Salinicola, Pseudomonas, and Brevibacterium, among other genera, exhibit a broad spectrum of plant-growth promotion traits [e.g., 3-indole acetic acid (IAA), 1-aminocyclopropane-1-carboxylic acid (ACC) deaminase, siderophores, phosphate solubilization, Nitrogen fixation] and express a wide range of extracellular enzyme activities. In this work, three plant growth-promoting bacteria strains (Brevibacterium casei EB3, Pseudomonas oryzihabitans RL18, and Bacillus aryabhattai SP20) isolated from the rhizosphere and the endosphere of S. ramosissima roots from different saltmarshes along the Portuguese coast were inoculated in S. ramosissima seeds. Plants germinated from inoculated seeds were grown for three months in pots filled with a mixture of perlite and estuarine sediment (1:1) in greenhouse conditions and later transferred to a growth chamber, where they were maintained two months with controlled photoperiod, temperature, and humidity. Pots were placed on trays containing the irrigation solution (Hoagland’s solution 20% added with 10‰ marine salt). Before reaching the flowering stage, plants were collected, and the fresh and dry weight of aerial parts was determined. Non-inoculated seeds were used as a negative control. Selected dried stems from the most promising treatments were later analyzed by GC-TOF-MS for primary metabolite composition. The efficiency of inoculation and persistence of the inoculum was assessed by Next Generation Sequencing. Inoculations with single strain EB3 and co-inoculations with EB3+RL18 and EB3+RL18+SP20 (All treatment) resulted in significantly higher biomass production (fresh and dry weight) compared to non-inoculated plants. Considering fresh weight alone, inoculation with isolates SP20 and RL18 also caused a significant positive effect. Combined inoculation with the consortia SP20+EB3 or SP20+RL18 did not significantly improve biomass production. The analysis of the profile of primary metabolites will provide clues on the mechanisms by which the growth-enhancement effect of the inoculants operates in the plants. These results sustain promising prospects for the use of rhizospheric and endophytic PGPB as biofertilizers, reducing environmental impacts and operational costs of agrochemicals and contributing to the sustainability and cost-effectiveness of saline agriculture. Acknowledgments: This work was supported by project Rhizomis PTDC/BIA-MIC/29736/2017 financed by Fundação para a Ciência e Tecnologia (FCT) through the Regional Operational Program of the Center (02/SAICT/2017) with FEDER funds (European Regional Development Fund, FNR, and OE) and by FCT through CESAM (UIDP/50017/2020 + UIDB/50017/2020), LAQV-REQUIMTE (UIDB/50006/2020). We also acknowledge FCT/FSE for the financial support to Maria João Ferreira through a PhD grant (PD/BD/150363/2019). We are grateful to Horta dos Peixinhos for their help and support during sampling and seed collection. We also thank Glória Pinto for her collaboration providing us the use of the growth chambers during the final months of the experiment and Enrique Mateos-Naranjo and Jennifer Mesa-Marín of the Departamento de Biología Vegetal y Ecología, the University of Sevilla for their advice regarding the growth of salicornia plants in greenhouse conditions.

Keywords: halophytes, PGPB, rhizosphere engineering, biofertilizers, primary metabolite profiling, plant inoculation, Salicornia ramosissima

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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

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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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