Search results for: evaluation of enterprise architecture implementation
Commenced in January 2007
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Paper Count: 11964

Search results for: evaluation of enterprise architecture implementation

24 A Comparative Evaluation of Cognitive Load Management: Case Study of Postgraduate Business Students

Authors: Kavita Goel, Donald Winchester

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In a world of information overload and work complexities, academics often struggle to create an online instructional environment enabling efficient and effective student learning. Research has established that students’ learning styles are different, some learn faster when taught using audio and visual methods. Attributes like prior knowledge and mental effort affect their learning. ‘Cognitive load theory’, opines learners have limited processing capacity. Cognitive load depends on the learner’s prior knowledge, the complexity of content and tasks, and instructional environment. Hence, the proper allocation of cognitive resources is critical for students’ learning. Consequently, a lecturer needs to understand the limits and strengths of the human learning processes, various learning styles of students, and accommodate these requirements while designing online assessments. As acknowledged in the cognitive load theory literature, visual and auditory explanations of worked examples potentially lead to a reduction of cognitive load (effort) and increased facilitation of learning when compared to conventional sequential text problem solving. This will help learner to utilize both subcomponents of their working memory. Instructional design changes were introduced at the case site for the delivery of the postgraduate business subjects. To make effective use of auditory and visual modalities, video recorded lectures, and key concept webinars were delivered to students. Videos were prepared to free up student limited working memory from irrelevant mental effort as all elements in a visual screening can be viewed simultaneously, processed quickly, and facilitates greater psychological processing efficiency. Most case study students in the postgraduate programs are adults, working full-time at higher management levels, and studying part-time. Their learning style and needs are different from other tertiary students. The purpose of the audio and visual interventions was to lower the students cognitive load and provide an online environment supportive to their efficient learning. These changes were expected to impact the student’s learning experience, their academic performance and retention favourably. This paper posits that these changes to instruction design facilitates students to integrate new knowledge into their long-term memory. A mixed methods case study methodology was used in this investigation. Primary data were collected from interviews and survey(s) of students and academics. Secondary data were collected from the organisation’s databases and reports. Some evidence was found that the academic performance of students does improve when new instructional design changes are introduced although not statistically significant. However, the overall grade distribution of student’s academic performance has changed and skewed higher which shows deeper understanding of the content. It was identified from feedback received from students that recorded webinars served as better learning aids than material with text alone, especially with more complex content. The recorded webinars on the subject content and assessments provides flexibility to students to access this material any time from repositories, many times, and this enhances students learning style. Visual and audio information enters student’s working memory more effectively. Also as each assessment included the application of the concepts, conceptual knowledge interacted with the pre-existing schema in the long-term memory and lowered student’s cognitive load.

Keywords: cognitive load theory, learning style, instructional environment, working memory

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23 Nurturing Minds, Shaping Futures: A Reflective Journey of 32 Years as a Teacher Educator

Authors: Mary Isobelle Mullaney

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The maxim "an unexamined life is not worth living," attributed to Socrates, prompts a contemplative reflection spanning over 32 years as a teacher educator in the Republic of Ireland. Taking time to contemplate the changes that have occurred and the current landscape provides valuable insights into the dynamic terrain of teacher preparation. The reflective journey traverses the impacts of global and societal shifts, responding to challenges, embracing advancements, and navigating the delicate balance between responsiveness to the world and the active shaping of it. The transformative events of the COVID-19 pandemic spotlighted the indispensable role of teachers in Ireland, reinforcing the critical nature of education for the well-being of pupils. Research solidifies the understanding that teachers matter and so it is worth exploring the pivotal role of the teacher educator. This reflective piece examines the changes in teacher education and explores the juxtapositions that have emerged in response to three decades of profound change. The attractiveness of teaching as a career is juxtaposed against the reality of the demands of the job, with conditions for public servants in Ireland undergoing a shift. High-level strategic discussions about increasing teacher numbers now contrast with a previous oversupply. The delicate balance between the imperative to increase enrolment (getting "bums on seats") and the gatekeeper role of teacher educators is explored, raising questions about maintaining high standards amid changing student profiles. Another poignant dichotomy involves the high demand for teachers versus the hurdles candidates face in becoming teachers. The rising cost and duration of teacher education courses raise concerns about attracting quality candidates. The perceived attractiveness of teaching as a career contends with the reality of increased demands on educators. One notable juxtaposition centres around the rapid evolution of Irish initial teacher education versus the potential risk of change overload. The Teaching Council of Ireland has spearheaded considerable changes, raising questions about the timing and evaluation of these changes. This reflection contemplates the vision of a professional teaching council versus its evolving reality and the challenges posed by the value placed on school placement in teacher preparation. The juxtapositions extend to the classroom, where theory may not seamlessly align with the lived experience. Inconsistencies between college expectations and the classroom reality prompt reflection on the effectiveness of teacher preparation programs. Addressing the changing demographic landscape of society and schools, there is a persistent incongruity between the diversity of Irish society and the profile of second-level teachers. As education undergoes a digital revolution, the enduring philosophies of education confront technological advances. This reflection highlights the tension between established practices and contemporary demands, acknowledging the irreplaceable value of face-to-face interaction while integrating technology into teacher training programs. In conclusion, this reflective journey encapsulates the intricate web of juxtapositions in Irish Initial Teacher Education. It emphasises the enduring commitment to fostering education, recognising the profound influence educators wield, and acknowledging the challenges and gratifications inherent in shaping the minds and futures of generations to come.

Keywords: Irish post primary teaching, juxtapositions, reflection, teacher education

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22 Immunostimulatory Response of Supplement Feed in Fish against Aeromonas hydrophila

Authors: Shikha Rani, Neeta Sehgal, Vipin Kumar Verma, Om Prakash

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Introduction: Fish is an important protein source for humans and has great economic value. Fish cultures are affected due to various anthropogenic activities that lead to bacterial and viral infections. Aeromonas hydrophila is a fish pathogenic bacterium that causes several aquaculture outbreaks throughout the world and leads to huge mortalities. In this study, plants of no commercial value were used to investigate their immunostimulatory, antioxidant, anti-inflammatory, anti-bacterial, and disease resistance potential in fish against Aeromonas hydrophila, through fish feed fortification. Methods: The plant was dried at room temperature in the shade, dissolved in methanol, and analysed for biological compounds through GC-MS/MS. DPPH, FRAP, Phenolic, and flavonoids were estimated following standardized protocols. In silico molecular docking was also performed to validate its broad-spectrum activities based on binding affinity with specific proteins. Fish were divided into four groups (n=6; total 30 in a group): Group 1, non-challenged fish (fed on a non-supplemented diet); Group 2, fish challenged with bacteria (fed on a non-supplemented diet); Group 3 and 4, fish challenged with bacteria (A. hydrophila) and fed on plant supplemented feed at 2.5% and 5%. Blood was collected from the fish on 0, 7th, 14th, 21st, and 28th days. Serum was separated for glutamic-oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), alkaline phosphatase assay (ALP), lysozyme activity assay, superoxide dismutase assay (SOD), lipid peroxidation assay (LPO) and molecular parameters (including cytokine levels) were estimated through ELISA. The phagocytic activity of macrophages from the spleen and head kidney, along with quantitative analysis of immune-related genes, were analysed in different tissue samples. The digestive enzymes (Pepsin, Trypsin, and Chymotrypsin) were also measured to evaluate the effect of plant-supplemented feed on freshwater fish. Results and Discussion: GC-MS/MS analysis of a methanolic extract of plant validated the presence of key compounds having antioxidant, anti-inflammatory, anti-bacterial, anti-inflammatory, and immunomodulatory activities along with disease resistance properties. From biochemical investigations like ABTS, DPPH, and FRAP, the amount of total flavonoids, phenols, and promising binding affinities towards different proteins in molecular docking analysis helped us to realize the potential of this plant that can be used for investigation in the supplemented feed of fish. Measurement liver function tests, ALPs, oxidation-antioxidant enzyme concentrations, and immunoglobulin concentrations in the experimental groups (3 and 4) showed significant improvement as compared to the positive control group. The histopathological evaluation of the liver, spleen, and head kidney supports the biochemical findings. The isolated macrophages from the group fed on supplemented feed showed a higher percentage of phagocytosis and a phagocytic index, indicating an enhanced cell-mediated immune response. Significant improvements in digestive enzymes were also observed in fish fed on supplemented feed, even after weekly challenges with bacteria. Hence, the plant-fortified feed can be recommended as a regular feed to enhance fish immunity and disease resistance against the Aeromonas hydrophila infection after confirmation from the field trial.

Keywords: immunostimulation, antipathogen, plant fortified feed, macrophages, GC-MS/MS, in silico molecular docking

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21 The Use of Antioxidant and Antimicrobial Properties of Plant Extracts for Increased Safety and Sustainability of Dairy Products

Authors: Loreta Serniene, Dalia Sekmokiene, Justina Tomkeviciute, Lina Lauciene, Vaida Andruleviciute, Ingrida Sinkeviciene, Kristina Kondrotiene, Neringa Kasetiene, Mindaugas Malakauskas

Abstract:

One of the most important areas of product development and research in the dairy industry is the product enrichment with active ingredients as well as leading to increased product safety and sustainability. The most expanding field of the active ingredients is the various plants' CO₂ extracts with aromatic, antioxidant and antimicrobial properties. In this study, 15 plant extracts were evaluated based on their antioxidant, antimicrobial properties as well as sensory acceptance indicators for the development of new dairy products. In order to increase the total antioxidant capacity of the milk products, it was important to determine the content of phenolic compounds and antioxidant activity of CO₂ extract. The total phenolic content of fifteen different commercial CO₂ extracts was determined by the Folin-Ciocalteu reagent and expressed as milligrams of the Gallic acid equivalents (GAE) in gram of extract. The antioxidant activities were determined by 2.2′-azinobis-(3-ethylbenzthiazoline)-6-sulfonate (ABTS) methods. The study revealed that the antioxidant activities of investigated CO₂ extract vary from 4.478-62.035 µmole Trolox/g, while the total phenolic content was in the range of 2.021-38.906 mg GAE/g of extract. For the example, the estimated antioxidant activity of Chinese cinnamon (Cinammonum aromaticum) CO₂ extract was 62.023 ± 0.15 µmole Trolox/g and the total flavonoid content reached 17.962 ± 0.35 mg GAE/g. These two parameters suggest that cinnamon could be a promising supplement for the development of new cheese. The inhibitory effects of these essential oils were tested by using agar disc diffusion method against pathogenic bacteria, most commonly found in dairy products. The obtained results showed that essential oil of lemon myrtle (Backhousia citriodora) and cinnamon (Cinnamomum cassia) has antimicrobial activity against E. coli, S. aureus, B. cereus, P. florescens, L. monocytogenes, Br. thermosphacta, P. aeruginosa and S. typhimurium with the diameter of inhibition zones variation from 10 to 52 mm. The sensory taste acceptability of plant extracts in combination with a dairy product was evaluated by a group of sensory evaluation experts (31 individuals) by the criteria of overall taste acceptability in the scale of 0 (not acceptable) to 10 (very acceptable). Each of the tested samples included 200g grams of natural unsweetened greek yogurt without additives and 1 drop of single plant extract (essential oil). The highest average of overall taste acceptability was defined for the samples with essential oils of orange (Citrus sinensis) - average score 6.67, lemon myrtle (Backhousia citriodora) – 6.62, elderberry flower (Sambucus nigra flos.) – 6.61, lemon (Citrus limon) – 5.75 and cinnamon (Cinnamomum cassia) – 5.41, respectively. The results of this study indicate plant extracts of Cinnamomum cassia and Backhousia citriodora as a promising additive not only to increase the total antioxidant capacity of the milk products and as alternative antibacterial agent to combat pathogenic bacteria commonly found in dairy products but also as a desirable flavour for the taste pallet of the consumers with expressed need for safe, sustainable and innovative dairy products. Acknowledgment: This research was funded by the European Regional Development Fund according to the supported activity 'Research Projects Implemented by World-class Researcher Groups' under Measure No. 01.2.2-LMT-K-718.

Keywords: antioxidant properties, antimicrobial properties, cinnamon, CO₂ plant extracts, dairy products, essential oils, lemon myrtle

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20 'Go Baby Go'; Community-Based Integrated Early Childhood and Maternal Child Health Model Improving Early Childhood Stimulation, Care Practices and Developmental Outcomes in Armenia: A Quasi-Experimental Study

Authors: Viktorya Sargsyan, Arax Hovhannesyan, Karine Abelyan

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Introduction: During the last decade, scientific studies have proven the importance of Early Childhood Development (ECD) interventions. These interventions are shown to create strong foundations for children’s intellectual, emotional and physical well-being, as well as the impact they have on learning and economic outcomes for children as they mature into adulthood. Many children in rural Armenia fail to reach their full development potential due to lack of early brain stimulation (playing, singing, reading, etc.) from their parents, and lack of community tools and services to follow-up children’s neurocognitive development. This is exacerbated by high rates of stunting and anemia among children under 3(CU3). This research study tested the effectiveness of an integrated ECD and Maternal, Newborn and Childhood Health (MNCH) model, called “Go Baby, Go!” (GBG), against the traditional (MNCH) strategy which focuses solely on preventive health and nutrition interventions. The hypothesis of this quasi-experimental study was: Children exposed to GBG will have better neurocognitive and nutrition outcomes compared to those receiving only the MNCH intervention. The secondary objective was to assess the effect of GBG on parental child care and nutrition practices. Methodology: The 14 month long study, targeted all 1,300 children aged 0 to 23 months, living in 43 study communities the in Gavar and Vardenis regions (Gegharkunik province, Armenia). Twenty-three intervention communities, 680 children, received GBG, and 20 control communities, 630 children, received MCHN interventions only. Baseline and evaluation data on child development, nutrition status and parental child care and nutrition practices were collected (caregiver interview, direct child assessment). In the intervention sites, in addition to MNCH (maternity schools, supportive supervision for Health Care Providers (HCP), the trained GBG facilitators conducted six interactive group sessions for mothers (key messages, information, group discussions, role playing, video-watching, toys/books preparation, according to GBG curriculum), and two sessions (condensed GBG) for adult family members (husbands, grandmothers). The trained HCPs received quality supervision for ECD counseling and screening. Findings: The GBG model proved to be effective in improving ECD outcomes. Children in the intervention sites had 83% higher odd of total ECD composite score (cognitive, language, motor) compared to children in the control sites (aOR 1.83; 95 percent CI: 1.08-3.09; p=0.025). Caregivers also demonstrated better child care and nutrition practices (minimum dietary diversity in intervention site is 55 percent higher compared to control (aOR=1.55, 95 percent CI 1.10-2.19, p =0.013); support for learning and disciplining practices (aOR=2.22, 95 percent CI 1.19-4.16, p=0.012)). However, there was no evidence of stunting reduction in either study arm. he effect of the integrated model was more prominent in Vardenis, a community which is characterised by high food insecurity and limited knowledge of positive parenting skills. Conclusion: The GBG model is effective and could be applied in target areas with the greatest economic disadvantages and parenting challenges to improve ECD, care practices and developmental outcomes. Longitudinal studies are needed to view the long-term effects of GBG on learning and school readiness.

Keywords: early childhood development, integrated interventions, parental practices, quasi-experimental study

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19 Analysis Of Fine Motor Skills in Chronic Neurodegenerative Models of Huntington’s Disease and Amyotrophic Lateral Sclerosis

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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18 Anti-Infective Potential of Selected Philippine Medicinal Plant Extracts against Multidrug-Resistant Bacteria

Authors: Demetrio L. Valle Jr., Juliana Janet M. Puzon, Windell L. Rivera

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From the various medicinal plants available in the Philippines, crude ethanol extracts of twelve (12) Philippine medicinal plants, namely: Senna alata L. Roxb. (akapulko), Psidium guajava L. (bayabas), Piper betle L. (ikmo), Vitex negundo L. (lagundi), Mitrephora lanotan (Blanco) Merr. (Lanotan), Zingiber officinale Roscoe (luya), Curcuma longa L. (Luyang dilaw), Tinospora rumphii Boerl (Makabuhay), Moringga oleifera Lam. (malunggay), Phyllanthus niruri L. (sampa-sampalukan), Centella asiatica (L.) Urban (takip kuhol), and Carmona retusa (Vahl) Masam (tsaang gubat) were studied. In vitro methods of evaluation against selected Gram-positive and Gram-negative multidrug-resistant (MDR), bacteria were performed on the plant extracts. Although five of the plants showed varying antagonistic activities against the test organisms, only Piper betle L. exhibited significant activities against both Gram-negative and Gram-positive multidrug-resistant bacteria, exhibiting wide zones of growth inhibition in the disk diffusion assay, and with the lowest concentrations of the extract required to inhibit the growth of the bacteria, as supported by the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) assays. Further antibacterial studies of the Piper betle L. leaf, obtained by three extraction methods (ethanol, methanol, supercritical CO2), revealed similar inhibitory activities against a multitude of Gram-positive and Gram-negative MDR bacteria. Thin layer chromatography (TLC) assay of the leaf extract revealed a maximum of eight compounds with Rf values of 0.92, 0.86, 0.76, 0.53, 0.40, 0.25, 0.13, and 0.013, best visualized when inspected under UV-366 nm. TLC- agar overlay bioautography of the isolated compounds showed the compounds with Rf values of 0.86 and 0.13 having inhibitory activities against Gram-positive MDR bacteria (MRSA and VRE). The compound with an Rf value of 0.86 also possesses inhibitory activity against Gram-negative MDR bacteria (CRE Klebsiella pneumoniae and MBL Acinetobacter baumannii). Gas Chromatography-Mass Spectrometry (GC-MS) was able to identify six volatile compounds, four of which are new compounds that have not been mentioned in the medical literature. The chemical compounds isolated include 4-(2-propenyl)phenol and eugenol; and the new four compounds were ethyl diazoacetate, tris(trifluoromethyl)phosphine, heptafluorobutyrate, and 3-fluoro-2-propynenitrite. Phytochemical screening and investigation of its antioxidant, cytotoxic, possible hemolytic activities, and mechanisms of antibacterial activity were also done. The results showed that the local variant of Piper betle leaf extract possesses significant antioxidant, anti-cancer and antimicrobial properties, attributed to the presence of bioactive compounds, particularly of flavonoids (condensed tannin, leucoanthocyanin, gamma benzopyrone), anthraquinones, steroids/triterpenes and 2-deoxysugars. Piper betle L. is also traditionally known to enhance wound healing, which could be primarily due to its antioxidant, anti-inflammatory and antimicrobial activities. In vivo studies on mice using 2.5% and 5% of the ethanol leaf extract cream formulations in the excised wound models significantly increased the process of wound healing in the mice subjects, the results and values of which are at par with the current antibacterial cream (Mupirocin). From the results of the series of studies, we have definitely proven the value of Piper betle L. as a source of bioactive compounds that could be developed into therapeutic agents against MDR bacteria.

Keywords: Philippine herbal medicine, multidrug-resistant bacteria, Piper betle, TLC-bioautography

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17 Contactless Heart Rate Measurement System based on FMCW Radar and LSTM for Automotive Applications

Authors: Asma Omri, Iheb Sifaoui, Sofiane Sayahi, Hichem Besbes

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Future vehicle systems demand advanced capabilities, notably in-cabin life detection and driver monitoring systems, with a particular emphasis on drowsiness detection. To meet these requirements, several techniques employ artificial intelligence methods based on real-time vital sign measurements. In parallel, Frequency-Modulated Continuous-Wave (FMCW) radar technology has garnered considerable attention in the domains of healthcare and biomedical engineering for non-invasive vital sign monitoring. FMCW radar offers a multitude of advantages, including its non-intrusive nature, continuous monitoring capacity, and its ability to penetrate through clothing. In this paper, we propose a system utilizing the AWR6843AOP radar from Texas Instruments (TI) to extract precise vital sign information. The radar allows us to estimate Ballistocardiogram (BCG) signals, which capture the mechanical movements of the body, particularly the ballistic forces generated by heartbeats and respiration. These signals are rich sources of information about the cardiac cycle, rendering them suitable for heart rate estimation. The process begins with real-time subject positioning, followed by clutter removal, computation of Doppler phase differences, and the use of various filtering methods to accurately capture subtle physiological movements. To address the challenges associated with FMCW radar-based vital sign monitoring, including motion artifacts due to subjects' movement or radar micro-vibrations, Long Short-Term Memory (LSTM) networks are implemented. LSTM's adaptability to different heart rate patterns and ability to handle real-time data make it suitable for continuous monitoring applications. Several crucial steps were taken, including feature extraction (involving amplitude, time intervals, and signal morphology), sequence modeling, heart rate estimation through the analysis of detected cardiac cycles and their temporal relationships, and performance evaluation using metrics such as Root Mean Square Error (RMSE) and correlation with reference heart rate measurements. For dataset construction and LSTM training, a comprehensive data collection system was established, integrating the AWR6843AOP radar, a Heart Rate Belt, and a smart watch for ground truth measurements. Rigorous synchronization of these devices ensured data accuracy. Twenty participants engaged in various scenarios, encompassing indoor and real-world conditions within a moving vehicle equipped with the radar system. Static and dynamic subject’s conditions were considered. The heart rate estimation through LSTM outperforms traditional signal processing techniques that rely on filtering, Fast Fourier Transform (FFT), and thresholding. It delivers an average accuracy of approximately 91% with an RMSE of 1.01 beat per minute (bpm). In conclusion, this paper underscores the promising potential of FMCW radar technology integrated with artificial intelligence algorithms in the context of automotive applications. This innovation not only enhances road safety but also paves the way for its integration into the automotive ecosystem to improve driver well-being and overall vehicular safety.

Keywords: ballistocardiogram, FMCW Radar, vital sign monitoring, LSTM

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16 Microencapsulation of Probiotic and Evaluation for Viability, Antimicrobial Property and Cytotoxic Activities of its Postbiotic Metabolites on MCF-7 Breast Cancer Cell Line

Authors: Nkechi V. Enwuru, Bullum Nkeki, Elizabeth A. Adekoya, Olumide A. Adebesin, Rebecca F. Peters, Victoria A. Aikhomu, Mendie E. U.

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Background: Probiotics are live microbial feed supplement beneficial for host. Probiotics and their postbiotic products have been used to prevent or treat various health conditions. However, the products cell viability is often low due to harsh conditions subjected during processing, handling, storage, and gastrointestinal transit. These strongly influence probiotics’ benefits; thus, viability is essential for probiotics to produce health benefits for the host. Microencapsulation is a promising technique with considerable effects on probiotic survival. The study is aimed to formulate a microencapsulated probiotic and evaluate its viability, antimicrobial efficacy, and cytotoxic activity of its postbiotic on the MCF-7 breast cancer cell line. Method: Human and animal raw milk were sampled for lactic acid bacteria. The isolated bacteria were identified using conventional and VITEK 2 systems. The identified lactic acid bacterium was encapsulated using spray-dried and extrusion methods. The free, encapsulated, and chitosan-coated encapsulated probiotics were tested for viability in simulated-gastric intestinal (SGI) fluid and different storage conditions at refrigerated (4oC) and room (25oC) temperatures. The disintegration time and weight uniformity of the spray-dried hard gelatin capsules were tested. The antimicrobial property of free and encapsulated probiotics was tested against enteric pathogenic isolates from antiretroviral therapy (ART) treated HIV-positive patients. The postbiotic of the free cells was extracted, and its cytotoxic effect on the MCF-7 breast cancer cell line was tested through an MTT assay. Result: The Lactobacillus plantarum was isolated from animal raw milk. Zero-size hard gelatin L. plantarum capsules with granules within a size range of 0.71–1.00 mm diameter was formulated. The disintegration time ranges from 2.14±0.045 to 2.91±0.293 minutes, while the average weight is 502.1mg. Simulated gastric solution significantly affected viability of both free and microcapsules. However, the encapsulated cells were more protected and viable due to impermeability in the microcapsules. Furthermore, the viability of free cells stored at 4oC and 25oC were less than 4 log CFU/g and 6 log CFU/g respectively after 12 weeks. However, the microcapsules stored at 4oC achieved the highest viability among the free and microcapsules stored at 25oC and the free cells stored at 4oC. Encapsulated cells were released in the simulated gastric fluid, viable and effective against the enteric pathogens tested. However, chitosan-coated calcium alginate encapsulated probiotics significantly inhibited Shigella flexneri, Candida albicans, and Escherichia coli. The Postbiotic Metabolites (PM) of L. plantarum produced a cytotoxic effect on the MCF-7 breast cancer cell line. The postbiotic showed significant cytotoxic activity similar to 5FU, a standard antineoplastic agent. The inhibition concentration of 50% growth (IC50) of postbiotic metabolite K3 is low and consistent with the IC50 of the positive control (Cisplatin). Conclusions: Lactobacillus plantarum postbiotic exhibited a cytotoxic effect on the MCF-7 breast cancer cell line and could be used as combined adjuvant therapy in breast cancer management. The microencapsulation technique protects the probiotics, improving their viability and delivery to the gastrointestinal tract. Chitosan enhances antibacterial efficacy; thus, chitosan-coated microencapsulated L. plantarum probiotics could be more effective and used as a combined therapy in HIV management of opportunistic enteric infection.

Keywords: probiotics, encapsulation, gastrointestinal conditions, antimicrobial effect, postbiotic, cytotoxicity effect

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15 Evaluation of Functional Properties of Protein Hydrolysate from the Fresh Water Mussel Lamellidens marginalis for Nutraceutical Therapy

Authors: Jana Chakrabarti, Madhushrita Das, Ankhi Haldar, Roshni Chatterjee, Tanmoy Dey, Pubali Dhar

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High incidences of Protein Energy Malnutrition as a consequence of low protein intake are quite prevalent among the children in developing countries. Thus prevention of under-nutrition has emerged as a critical challenge to India’s developmental Planners in recent times. Increase in population over the last decade has led to greater pressure on the existing animal protein sources. But these resources are currently declining due to persistent drought, diseases, natural disasters, high-cost of feed, and low productivity of local breeds and this decline in productivity is most evident in some developing countries. So the need of the hour is to search for efficient utilization of unconventional low-cost animal protein resources. Molluscs, as a group is regarded as under-exploited source of health-benefit molecules. Bivalve is the second largest class of phylum Mollusca. Annual harvests of bivalves for human consumption represent about 5% by weight of the total world harvest of aquatic resources. The freshwater mussel Lamellidens marginalis is widely distributed in ponds and large bodies of perennial waters in the Indian sub-continent and well accepted as food all over India. Moreover, ethno-medicinal uses of the flesh of Lamellidens among the rural people to treat hypertension have been documented. Present investigation thus attempts to evaluate the potential of Lamellidens marginalis as functional food. Mussels were collected from freshwater ponds and brought to the laboratory two days before experimentation for acclimatization in laboratory conditions. Shells were removed and fleshes were preserved at- 20oC until analysis. Tissue homogenate was prepared for proximate studies. Fatty acids and amino acids composition were analyzed. Vitamins, Minerals and Heavy metal contents were also studied. Mussel Protein hydrolysate was prepared using Alcalase 2.4 L and degree of hydrolysis was evaluated to analyze its Functional properties. Ferric Reducing Antioxidant Power (FRAP) and DPPH Antioxidant assays were performed. Anti-hypertensive property was evaluated by measuring Angiotensin Converting Enzyme (ACE) inhibition assay. Proximate analysis indicates that mussel meat contains moderate amount of protein (8.30±0.67%), carbohydrate (8.01±0.38%) and reducing sugar (4.75±0.07%), but less amount of fat (1.02±0.20%). Moisture content is quite high but ash content is very low. Phospholipid content is significantly high (19.43 %). Lipid constitutes, substantial amount of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) which have proven prophylactic values. Trace elements are found present in substantial amount. Comparative study of proximate nutrients between Labeo rohita, Lamellidens and cow’s milk indicates that mussel meat can be used as complementary food source. Functionality analyses of protein hydrolysate show increase in Fat absorption, Emulsification, Foaming capacity and Protein solubility. Progressive anti-oxidant and anti-hypertensive properties have also been documented. Lamellidens marginalis can thus be regarded as a functional food source as this may combine effectively with other food components for providing essential elements to the body. Moreover, mussel protein hydrolysate provides opportunities for utilizing it in various food formulations and pharmaceuticals. The observations presented herein should be viewed as a prelude to what future holds.

Keywords: functional food, functional properties, Lamellidens marginalis, protein hydrolysate

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14 Drug Reaction with Eosinophilia and Systemic Symptoms (Dress) Syndrome Presenting as Multi-Organ Failure

Authors: Keshari Shrestha, Philip Vatterott

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Introduction: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare and potentially fatal drug-related syndrome. DRESS classically presents with a diffuse maculopapular rash, fevers, and eosinophilia more than three weeks after drug exposure. DRESS can present with multi-organ involvement, with liver damage being the most common and severe. Pulmonary involvement is a less common manifestation and is associated with poor clinical outcomes. Chest imaging is often nonspecific, and symptoms can range from mild cough to acute respiratory distress syndrome (ARDS) . This is a case of a 49-year-old female with a history of recent clostridium difficile colitis status post treatment with oral vancomycin who presented with rash, acute liver and kidney failure, as well as diffuse nodular alveolar lung opacities concerning for DRESS syndrome with multi-organ involvement. Clinical Course: This patient initially presented to an outside hospital with clostridium difficile colitis, acute liver injury, and acute kidney injury. She developed a desquamating maculopapular rash in the setting of recent oral vancomycin, meloxicam, and furosemide initiation. She was hospitalized on two additional occasions with worsening altered mental status, liver injury, and acute kidney injury and was initiated on intermittent hemodialysis. Notably, she was found to have systemic eosinophilia (4100 cells/microliter) several weeks prior. She was transferred to this institution for further management where she was found to have encephalopathy, jaundice, lower extremity edema, and diffuse bilateral rhonchorous breath sounds on pulmonary examination. The patient was started on methylprednisolone for suspected DRESS syndrome. She underwent an evaluation for alternative causes of her organ failure. Her workup included a negative infectious, autoimmune, metabolic, toxic, and malignant work-up. Abdominal computed tomography (CT) and ultrasound were remarkable for evidence of hepatic steatosis and possible cirrhotic morphology. Additionally, a chest CT demonstrated diffuse and symmetric nodular alveolar lung opacities with peripheral sparing not consistent with acute respiratory distress syndrome or edema. Ultimately, her condition continued to decline, and she required intubation on several occasions. On hospital day 25 she succumbed to distributive shock in the setting of probable sepsis and multi-organ failure. Discussion: DRESS syndrome occurs in 1 in 1,000 to 10,000 patients with a mortality rate of around 10%. Anti-convulsant, anti-bacterial, anti-viral, and sulfonamide drugs are the most common drugs implicated in the development of DRESS syndrome; however, the list of offending agents is extensive . The diagnosis of DRESS syndrome is made after excluding other causes of disease such as infectious and autoimmune etiologies. The RegiSCAR scoring system is used to diagnose DRESS syndrome with 2-3 points indicating possible disease, 4-5 probable disease, and >5 definite disease. This patient scored a 7 on the RegiSCAR scale for eosinophilia, rash, organ involvement, and exclusion of other causes (infectious and autoimmune). While the pharmacologic trigger in this case is unknown, it is speculated to be caused by vancomycin, meloxicam, or furosemide due to the favorable timeline of initiation. Despite aggressive treatment, DRESS syndrome can often be fatal. Because of this, early diagnosis and treatment of patients with suspected DRESS syndrome is imperative.

Keywords: drug reaction with eosinophilia and systemic symptoms, multi-organ failure, pulmonary involvement, renal failure

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13 Optical Coherence Tomography in Differentiation of Acute and Non-Healing Wounds

Authors: Ananya Barui, Provas Banerjee, Jyotirmoy Chatterjee

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Application of optical technology in medicine and biology has a long track-record. In this endeavor, OCT is able to attract both engineers and biologists to work together in the field of photonics for establishing a striking non-invasive imaging technology. In contrast to other in vivo imaging modalities like Raman imaging, confocal imaging, two-photon microscopy etc. which can perform in vivo imaging upto 100-200 micron depth due to limitation in numerical aperture or scattering, however, OCT can achieve high-resolution imaging upto few millimeters of tissue structures depending on their refractive index in different anatomical location. This tomographic system depends on interference of two light waves in an interferometer to produce a depth profile of specimen. In wound healing, frequent collection of biopsies for follow-up of repair process could be avoided by such imaging technique. Real time skin OCT (the optical biopsy) has efficacy in deeper and faster illumination of cutaneou tissue to acquire high resolution cross sectional images of their internal micro-structure. Swept Source-OCT (SS-OCT), a novel imaging technique, can generate high-speed depth profile (~ 2 mm) of wound at a sweeping rate of laser with micron level resolution and optimum coherent length of 5-6 mm. Normally multi-layered skin tissue depicts different optical properties along with variation in thickness, refractive index and composition (i.e. keratine layer, water, fat etc.) according to their anatomical location. For instance, stratum corneum, the upper-most and relatively dehydrated layer of epidermis reflects more light and produces more lucid and a sharp demarcation line with rest of the hydrated epidermal region. During wound healing or regeneration, optical properties of cutaneous tissue continuously altered with maturation of wound bed. More mature and less hydrated tissue component reflects more light and becomes visible as a brighter area in comparison to immature region which content higher amount water or fat that depicts as a darker area in OCT image. Non-healing wound possess prolonged inflammation and inhibits nascent proliferative stage. Accumulation of necrotic tissues also prevents the repair of non-healing wounds. Due to high resolution and potentiality to reflect the compositional aspects of tissues in terms of their optical properties, this tomographic method may facilitate in differentiating non-healing and acute wounds in addition to clinical observations. Non-invasive OCT offers better insight regarding specific biological status of tissue in health and pathological conditions, OCT images could be associated with histo-pathological ‘gold standard’. This correlated SS-OCT and microscopic evaluation of the wound edges can provide information regarding progressive healing and maturation of the epithelial components. In the context of searching analogy between two different imaging modalities, their relative performances in imaging of healing bed were estimated for probing an alternative approach. Present study validated utility of SS-OCT in revealing micro-anatomic structure in the healing bed with newer information. Exploring precise correspondence of OCT images features with histo-chemical findings related to epithelial integrity of the regenerated tissue could have great implication. It could establish the ‘optical biopsy’ as a potent non-invasive diagnostic tool for cutaneous pathology.

Keywords: histo-pathology, non invasive imaging, OCT, wound healing

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12 Robust Decision Support Framework for Addressing Uncertainties in Water Resources Management in the Mekong

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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11 Successful Optimization of a Shallow Marginal Offshore Field and Its Applications

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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10 Highly Robust Crosslinked BIAN-based Binder to Stabilize High-Performance Silicon Anode in Lithium-Ion Secondary Battery

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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9 Damages of Highway Bridges in Thailand during the 2014-Chiang Rai Earthquake

Authors: Rajwanlop Kumpoopong, Sukit Yindeesuk, Pornchai Silarom

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On May 5, 2014, an earthquake of magnitude 6.3 Richter hit the Northern part of Thailand. The epicenter was in Phan District, Chiang Rai Province. This earthquake or the so-called 2014-Chiang Rai Earthquake is the strongest ground shaking that Thailand has ever been experienced in her modern history. The 2014-Chiang Rai Earthquake confirms the geological evidence, which has previously been ignored by most engineers, that earthquakes of considerable magnitudes 6 to 7 Richter can occurr within the country. This promptly stimulates authorized agencies to pay more attention at the safety of their assets and promotes the comprehensive review of seismic resistance design of their building structures. The focus of this paper is to summarize the damages of highway bridges as a result of the 2014-Chiang Rai ground shaking, the remedy actions, and the research needs. The 2014-Chiang Rai Earthquake caused considerable damages to nearby structures such as houses, schools, and temples. The ground shaking, however, caused damage to only one highway bridge, Mae Laos Bridge, located several kilometers away from the epicenter. The damage of Mae Laos Bridge was in the form of concrete spalling caused by pounding of cap beam on the deck structure. The damage occurred only at the end or abutment span. The damage caused by pounding is not a surprise, but the pounding by only one bridge requires further investigation and discussion. Mae Laos Bridge is a river crossing bridge with relatively large approach structure. In as much, the approach structure is confined by strong retaining walls. This results in a rigid-like approach structure which vibrates at the acceleration approximately equal to the ground acceleration during the earthquake and exerts a huge force to the abutment causing the pounding of cap beam on the deck structure. Other bridges nearby have relatively small approach structures, and therefore have no capability to generate pounding. The effect of mass of the approach structure on pounding of cap beam on the deck structure is also evident by the damage of one pedestrian bridge in front of Thanthong Wittaya School located 50 meters from Mae Laos Bridge. The width of the approach stair of this bridge is wider than the typical one to accommodate the stream of students during pre- and post-school times. This results in a relatively large mass of the approach stair which in turn exerts a huge force to the pier causing pounding of cap beam on the deck structure during ground shaking. No sign of pounding was observed for a typical pedestrian bridge located at another end of Mae Laos Bridge. Although pounding of cap beam on the deck structure of the above mentioned bridges does not cause serious damage to bridge structure, this incident promotes the comprehensive review of seismic resistance design of highway bridges in Thailand. Given a proper mass and confinement of the approach structure, the pounding of cap beam on the deck structure can be easily excited even at the low to moderate ground shaking. In as much, if the ground shaking becomes stronger, the pounding is certainly more powerful. This may cause the deck structure to be unseated and fall off in the case of unrestrained bridge. For the bridge with restrainer between cap beam and the deck structure, the restrainer may prevent the deck structure from falling off. However, preventing free movement of the pier by the restrainer may damage the pier itself. Most highway bridges in Thailand have dowel bars embedded connecting cap beam and the deck structure. The purpose of the existence of dowel bars is, however, not intended for any seismic resistance. Their ability to prevent the deck structure from unseating and their effect on the potential damage of the pier should be evaluated. In response to this expected situation, Thailand Department of Highways (DOH) has set up a team to revise the standard practices for the seismic resistance design of highway bridges in Thailand. In addition, DOH has also funded the research project 'Seismic Resistance Evaluation of Pre- and Post-Design Modifications of DOH’s Bridges' with the scope of full-scale tests of single span bridges under reversed cyclic static loadings for both longitudinal and transverse directions and computer simulations to evaluate the seismic performance of the existing bridges and the design modification bridges. The research is expected to start in October, 2015.

Keywords: earthquake, highway bridge, Thailand, damage, pounding, seismic resistance

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8 Assessing Diagnostic and Evaluation Tools for Use in Urban Immunisation Programming: A Critical Narrative Review and Proposed Framework

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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7 Gamification Beyond Competition: the Case of DPG Lab Collaborative Learning Program for High-School Girls by GameLab KBTU and UNICEF in Kazakhstan

Authors: Nazym Zhumabayeva, Aleksandr Mezin, Alexandra Knysheva

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Women's underrepresentation in STEM is critical, worsened by ineffective engagement in educational practices. UNICEF Kazakhstan and GameLab KBTU's collaborative initiatives aim to enhance female STEM participation by fostering an inclusive environment. Learning from LEVEL UP's 2023 program, which featured a hackathon, the 2024 strategy pivots towards non-competitive gamification. Although the data from last year's project showed higher than average student engagement, observations and in-depth interviews with participants showed that the format was stressful for the girls, making them focus on points rather than on other values. This study presents a gamified educational system, DPG Lab, aimed at incentivizing young women's participation in STEM through the development of digital public goods (DPGs). By prioritizing collaborative gamification elements, the project seeks to create an inclusive learning environment that increases engagement and interest in STEM among young women. The DPG Lab aims to find a solution to minimize competition and support collaboration. The project is designed to motivate female participants towards the development of digital solutions through an introduction to the concept of DPGs. It consists of a short online course, a simulation videogame, and a real-time online quest with an offline finale at the KBTU campus. The online course offers short video lectures on open-source development and DPG standards. The game facilitates the practical application of theoretical knowledge, enriching the learning experience. Learners can also participate in a quest that encourages participants to develop DPG ideas in teams by choosing missions throughout the quest path. At the offline quest finale, the participants will meet in person to exchange experiences and accomplishments without engaging in comparative assessments: the quest ensures that each team’s trajectory is distinct by design. This marks a shift from competitive hackathons to a collaborative format, recognizing the unique contributions and achievements of each participant. The pilot batch of students is scheduled to commence in April 2024, with the finale anticipated in June. It is projected that this group will comprise 50 female high-school students from various regions across Kazakhstan. Expected outcomes include increased engagement and interest in STEM fields among young female participants, positive emotional and psychological impact through an emphasis on collaborative learning environments, and improved understanding and skills in DPG development. GameLab KBTU intends to undertake a hypothesis evaluation, employing a methodology similar to that utilized in the preceding LEVEL UP project. This approach will encompass the compilation of quantitative metrics (conversion funnels, test results, and surveys) and qualitative data from in-depth interviews and observational studies. For comparative analysis, a select group of participants from the previous year's project will be recruited to engage in the DPG Lab. By developing and implementing a gamified framework that emphasizes inclusion, engagement, and collaboration, the study seeks to provide practical knowledge about effective gamification strategies for promoting gender diversity in STEM. The expected outcomes of this initiative can contribute to the broader discussion on gamification in education and gender equality in STEM by offering a replicable and scalable model for similar interventions around the world.

Keywords: collaborative learning, competitive learning, digital public goods, educational gamification, emerging regions, STEM, underprivileged groups

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6 Characterization of Aluminosilicates and Verification of Their Impact on Quality of Ceramic Proppants Intended for Shale Gas Output

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

Procedia PDF Downloads 136
5 Numerical Simulation of Von Karman Swirling Bioconvection Nanofluid Flow from a Deformable Rotating Disk

Authors: Ali Kadir, S. R. Mishra, M. Shamshuddin, O. Anwar Beg

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Motivation- Rotating disk bio-reactors are fundamental to numerous medical/biochemical engineering processes including oxygen transfer, chromatography, purification and swirl-assisted pumping. The modern upsurge in biologically-enhanced engineering devices has embraced new phenomena including bioconvection of micro-organisms (photo-tactic, oxy-tactic, gyrotactic etc). The proven thermal performance superiority of nanofluids i.e. base fluids doped with engineered nanoparticles has also stimulated immense implementation in biomedical designs. Motivated by these emerging applications, we present a numerical thermofluid dynamic simulation of the transport phenomena in bioconvection nanofluid rotating disk bioreactor flow. Methodology- We study analytically and computationally the time-dependent three-dimensional viscous gyrotactic bioconvection in swirling nanofluid flow from a rotating disk configuration. The disk is also deformable i.e. able to extend (stretch) in the radial direction. Stefan blowing is included. The Buongiorno dilute nanofluid model is adopted wherein Brownian motion and thermophoresis are the dominant nanoscale effects. The primitive conservation equations for mass, radial, tangential and axial momentum, heat (energy), nanoparticle concentration and micro-organism density function are formulated in a cylindrical polar coordinate system with appropriate wall and free stream boundary conditions. A mass convective condition is also incorporated at the disk surface. Forced convection is considered i.e. buoyancy forces are neglected. This highly nonlinear, strongly coupled system of unsteady partial differential equations is normalized with the classical Von Karman and other transformations to render the boundary value problem (BVP) into an ordinary differential system which is solved with the efficient Adomian decomposition method (ADM). Validation with earlier Runge-Kutta shooting computations in the literature is also conducted. Extensive computations are presented (with the aid of MATLAB symbolic software) for radial and circumferential velocity components, temperature, nanoparticle concentration, micro-organism density number and gradients of these functions at the disk surface (radial local skin friction, local circumferential skin friction, Local Nusselt number, Local Sherwood number, motile microorganism mass transfer rate). Main Findings- Increasing radial stretching parameter decreases radial velocity and radial skin friction, reduces azimuthal velocity and skin friction, decreases local Nusselt number and motile micro-organism mass wall flux whereas it increases nano-particle local Sherwood number. Disk deceleration accelerates the radial flow, damps the azimuthal flow, decreases temperatures and thermal boundary layer thickness, depletes the nano-particle concentration magnitudes (and associated nano-particle species boundary layer thickness) and furthermore decreases the micro-organism density number and gyrotactic micro-organism species boundary layer thickness. Increasing Stefan blowing accelerates the radial flow and azimuthal (circumferential flow), elevates temperatures of the nanofluid, boosts nano-particle concentration (volume fraction) and gyrotactic micro-organism density number magnitudes whereas suction generates the reverse effects. Increasing suction effect reduces radial skin friction and azimuthal skin friction, local Nusselt number, and motile micro-organism wall mass flux whereas it enhances the nano-particle species local Sherwood number. Conclusions - Important transport characteristics are identified of relevance to real bioreactor nanotechnological systems not discussed in previous works. ADM is shown to achieve very rapid convergence and highly accurate solutions and shows excellent promise in simulating swirling multi-physical nano-bioconvection fluid dynamics problems. Furthermore, it provides an excellent complement to more general commercial computational fluid dynamics simulations.

Keywords: bio-nanofluids, rotating disk bioreactors, Von Karman swirling flow, numerical solutions

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4 Revolutionizing Financial Forecasts: Enhancing Predictions with Graph Convolutional Networks (GCN) - Long Short-Term Memory (LSTM) Fusion

Authors: Ali Kazemi

Abstract:

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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3 Sustainable Agricultural and Soil Water Management Practices in Relation to Climate Change and Disaster: A Himalayan Country Experience

Authors: Krishna Raj Regmi

Abstract:

A “Climate change adaptation and disaster risk management for sustainable agriculture” project was implemented in Nepal, a Himalayan country during 2008 to 2013 sponsored jointly by Food and Agriculture Organization (FAO) and United Nations Development Programme (UNDP), Nepal. The paper is based on the results and findings of this joint pilot project. The climate change events such as increased intensity of erratic rains in short spells, trend of prolonged drought, gradual rise in temperature in the higher elevations and occurrence of cold and hot waves in Terai (lower plains) has led to flash floods, massive erosion in the hills particularly in Churia range and drying of water sources. These recurring natural and climate-induced disasters are causing heavy damages through sedimentation and inundation of agricultural lands, crops, livestock, infrastructures and rural settlements in the downstream plains and thus reducing agriculture productivity and food security in the country. About 65% of the cultivated land in Nepal is rainfed with drought-prone characteristics and stabilization of agricultural production and productivity in these tracts will be possible through adoption of rainfed and drought-tolerant technologies as well as efficient soil-water management by the local communities. The adaptation and mitigation technologies and options identified by the project for soil erosion, flash floods and landslide control are on-farm watershed management, sloping land agriculture technologies (SALT), agro-forestry practices, agri-silvi-pastoral management, hedge-row contour planting, bio-engineering along slopes and river banks, plantation of multi-purpose trees and management of degraded waste land including sandy river-bed flood plains. The stress tolerant technologies with respect to drought, floods and temperature stress for efficient utilization of nutrient, soil, water and other resources for increased productivity are adoption of stress tolerant crop varieties and breeds of animals, indigenous proven technologies, mixed and inter-cropping systems, system of rice/wheat intensification (SRI), direct rice seeding, double transplanting of rice, off-season vegetable production and regular management of nurseries, orchards and animal sheds. The alternate energy use options and resource conservation practices for use by local communities are installation of bio-gas plants and clean stoves (Chulla range) for mitigation of green house gas (GHG) emissions, use of organic manures and bio-pesticides, jatropha cultivation, green manuring in rice fields and minimum/zero tillage practices for marshy lands. The efficient water management practices for increasing productivity of crops and livestock are use of micro-irrigation practices, construction of water conservation and water harvesting ponds, use of overhead water tanks and Thai jars for rain water harvesting and rehabilitation of on-farm irrigation systems. Initiation of some works on community-based early warning system, strengthening of met stations and disaster database management has made genuine efforts in providing disaster-tailored early warning, meteorological and insurance services to the local communities. Contingent planning is recommended to develop coping strategies and capacities of local communities to adopt necessary changes in the cropping patterns and practices in relation to adverse climatic and disaster risk conditions. At the end, adoption of awareness raising and capacity development activities (technical and institutional) and networking on climate-induced disaster and risks through training, visits and knowledge sharing workshops, dissemination of technical know-how and technologies, conduct of farmers' field schools, development of extension materials and their displays are being promoted. However, there is still need of strong coordination and linkage between agriculture, environment, forestry, meteorology, irrigation, climate-induced pro-active disaster preparedness and research at the ministry, department and district level for up-scaling, implementation and institutionalization of climate change and disaster risk management activities and adaptation mitigation options in agriculture for sustainable livelihoods of the communities.

Keywords: climate change adaptation, disaster risk management, soil-water management practices, sustainable agriculture

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2 “MaxSALIVA-II” Advancing a Nano-Sized Dual-Drug Delivery System for Salivary Gland Radioprotection, Regeneration and Repair in a Head and Neck Cancer Pre-Clinical Murine Model

Authors: Ziyad S. Haidar

Abstract:

Background: Saliva plays a major role in maintaining oral, dental, and general health and well-being; where it normally bathes the oral cavity acting as a clearing agent. This becomes more apparent when the amount and quality of saliva are significantly reduced due to medications, salivary gland neoplasms, disorders such as Sjögren’s syndrome, and especially ionizing radiation therapy for tumors of the head and neck, the 5th most common malignancy worldwide, during which the salivary glands are included within the radiation field/zone. Clinically, patients affected by salivary gland dysfunction often opt to terminate their radiotherapy course prematurely as they become malnourished and experience a significant decrease in their QoL. Accordingly, the formulation of a radio-protection/-prevention modality and development of an alternative Rx to restore damaged salivary gland tissue is eagerly awaited and highly desirable. Objectives: Assess the pre-clinical radio-protective effect and reparative/regenerative potential of layer-by-layer self-assembled lipid-polymer-based core-shell nanocapsules designed and fine-tuned for the sequential (ordered) release of dual cytokines, following a single local administration (direct injection) into a murine sub-mandibular salivary gland model of irradiation. Methods: The formulated core-shell nanocapsules were characterized by physical-chemical-mechanically pre-/post-loading with the drugs, followed by optimizing the pharmaco-kinetic profile. Then, nanosuspensions were administered directly into the salivary glands, 24hrs pre-irradiation (PBS, un-loaded nanocapsules, and individual and combined vehicle-free cytokines were injected into the control glands for an in-depth comparative analysis). External irradiation at an elevated dose of 18Gy was exposed to the head-and-neck region of C57BL/6 mice. Salivary flow rate (un-stimulated) and salivary protein content/excretion were regularly assessed using an enzyme-linked immunosorbent assay (3-month period). Histological and histomorphometric evaluation and apoptosis/proliferation analysis followed by local versus systemic bio-distribution and immuno-histochemical assays were then performed on all harvested major organs (at the distinct experimental end-points). Results: Monodisperse, stable, and cytocompatible nanocapsules capable of maintaining the bioactivity of the encapsulant within the different compartments with the core and shell and with controlled/customizable pharmaco-kinetics, resulted, as is illustrated in the graphical abstract (Figure) below. The experimental animals demonstrated a significant increase in salivary flow rates when compared to the controls. Herein, salivary protein content was comparable to the pre-irradiation (baseline) level. Histomorphometry further confirmed the biocompatibility and localization of the nanocapsules, in vivo, into the site of injection. Acinar cells showed fewer vacuoles and nuclear aberration in the experimental group, while the amount of mucin was higher in controls. Overall, fewer apoptotic activities were detected by a Terminal deoxynucleotidyl Transferase (TdT) dUTP Nick-End Labeling (TUNEL) assay and proliferative rates were similar to the controls, suggesting an interesting reparative and regenerative potential of irradiation-damaged/-dysfunctional salivary glands. The Figure below exemplifies some of these findings. Conclusions: Biocompatible, reproducible, and customizable self-assembling layer-by-layer core-shell delivery system is formulated and presented. Our findings suggest that localized sequential bioactive delivery of dual cytokines (in specific dose and order) can prevent irradiation-induced damage via reducing apoptosis and also has the potential to promote in situ proliferation of salivary gland cells; maxSALIVA is scalable (Good Manufacturing Practice or GMP production for human clinical trials) and patent-pending.

Keywords: cancer, head and neck, oncology, drug development, drug delivery systems, nanotechnology, nanoncology

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

Authors: Ziyad S. Haidar

Abstract:

Background: Saliva plays a major role in maintaining oral and dental health (consequently, general health and well-being). Where it normally bathes the oral cavity and acts as a clearing agent. This becomes more apparent when the amount and quality of salivare significantly reduced due to medications, salivary gland neoplasms, disorders such as Sjögren’s syndrome, and especially ionizing radiation therapy for tumors of the head and neck, the fifth most common malignancy worldwide, during which the salivary glands are included within the radiation field or zone. Clinically, patients affected by salivary gland dysfunction often opt to terminate their radiotherapy course prematurely because they become malnourished and experience a significant decrease in their quality of life. Accordingly, the development of an alternative treatment to restore or regenerate damaged salivary gland tissue is eagerly awaited. Likewise, the formulation of a radioprotection modality and early damage prevention strategy is also highly desirable. Objectives: To assess the pre-clinical radio-protective effect as well as the reparative/regenerative potential of layer-by-layer self-assembled lipid-polymer-based core-shell nanocapsules designed and fine-tuned in this experimental work for the sequential (ordered) release of dual cytokines, following a single local administration (direct injection) into a murine sub-mandibular salivary gland model of irradiation. Methods: The formulated core-shell nanocapsules were characterized by physical-chemical-mechanically pre-/post-loading with the drugs (in solution and powder formats), followed by optimizing the pharmaco-kinetic profile. Then, nanosuspensions were administered directly into the salivary glands, 24hrs pre-irradiation (PBS, un-loaded nanocapsules, and individual and combined vehicle-free cytokines were injected into the control glands for an in-depth comparative analysis). External irradiation at an elevated dose of 18Gy (revised from our previous 15Gy model) was exposed to the head-and-neck region of C57BL/6 mice. Salivary flow rate (un-stimulated) and salivary protein content/excretion were regularly assessed using an enzyme-linked immunosorbent assay (3-month period). Histological and histomorphometric evaluation and apoptosis/proliferation analysis followed by local versus systemic bio-distribution and immuno-histochemical assays were then performed on all harvested major organs (at the distinct experimental end-points). Results: Monodisperse, stable, and cytocompatible nanocapsules capable of maintaining the bioactivity of the encapsulant within the different compartments with the core and shell and with controlled/customizable pharmaco-kinetics, resulted, as is illustrated in the graphical abstract (Figure) below. The experimental animals demonstrated a significant increase in salivary flow rates when compared to the controls. Herein, salivary protein content was comparable to the pre-irradiation (baseline) level. Histomorphometry further confirmed the biocompatibility and localization of the nanocapsules, in vivo, into the site of injection. Acinar cells showed fewer vacuoles and nuclear aberration in the experimental group, while the amount of mucin was higher in controls. Overall, fewer apoptotic activities were detected by a Terminal deoxynucleotidyl Transferase (TdT) dUTP Nick-End Labeling (TUNEL) assay and proliferative rates were similar to the controls, suggesting an interesting reparative and regenerative potential of irradiation-damaged/-dysfunctional salivary glands. The Figure below exemplifies some of these findings. Conclusions: Biocompatible, reproducible, and customizable self-assembling layer-by-layer core-shell delivery system is formulated and presented. Our findings suggest that localized sequential bioactive delivery of dual cytokines (in specific dose and order) can prevent irradiation-induced damage via reducing apoptosis and also has the potential to promote in situ proliferation of salivary gland cells; maxSALIVA is scalable (Good Manufacturing Practice or GMP production for human clinical trials) and patent-pending.

Keywords: saliva, head and neck cancer, nanotechnology, controlled drug delivery, xerostomia, mucositis, biopolymers, innovation

Procedia PDF Downloads 55