Search results for: glucose level

Authors: Sarah Mueller-Saegebrecht, André Brendler

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Business model innovation (BMI) as an intentional change of an existing business model (BM) or the design of a new BM is essential to a firm's development in dynamic markets. The relevance of BMI is also evident in the ongoing COVID-19 pandemic, in which start-ups, in particular, are affected by limited access to resources. However, first studies also show that they react faster to the pandemic than established firms. A strategy to successfully handle such threatening dynamic changes represents BMI. Entrepreneurship literature shows how and when firms should utilize BMI in times of crisis and which barriers one can expect during the BMI process. Nevertheless, research merging BMI barriers and crises is still underexplored. Specifically, further knowledge about antecedents and the effect of moderators on the BMI process is necessary for advancing BMI research. The addressed research gap of this study is two-folded: First, foundations to the subject on how different crises impact BM change intention exist, yet their analysis lacks the inclusion of barriers. Especially, entrepreneurship literature lacks knowledge about the individual perception of BMI barriers, which is essential to predict managerial reactions. Moreover, internal BMI barriers have been the focal point of current research, while external BMI barriers remain virtually understudied. Second, to date, BMI research is based on qualitative methodologies. Thus, a lack of quantitative work can specify and confirm these qualitative findings. By focusing on the crisis context, this study contributes to BMI literature by offering a first quantitative attempt to embed BMI barriers into a structural equation model. It measures managers' perception of BMI development and implementation barriers in the BMI process, asking the following research question: How does a manager's perception of BMI barriers influence BMI development and implementation in times of crisis? Two distinct research streams in economic literature explain how individuals react when perceiving a threat. "Prospect Theory" claims that managers demonstrate risk-seeking tendencies when facing a potential loss, and opposing "Threat-Rigidity Theory" suggests that managers demonstrate risk-averse behavior when facing a potential loss. This study quantitively tests which theory can best predict managers' BM reaction to a perceived crisis. Out of three in-depth interviews in the German chemical industry, 60 past BMIs were identified. The participating start-up managers gave insights into their start-up's strategic and operational functioning. After, each interviewee described crises that had already affected their BM. The participants explained how they conducted BMI to overcome these crises, which development and implementation barriers they faced, and how severe they perceived them, assessed on a 5-point Likert scale. In contrast to current research, results reveal that a higher perceived threat level of a crisis harms BM experimentation. Managers seem to conduct less BMI in times of crisis, whereby BMI development barriers dampen this relation. The structural equation model unveils a mediating role of BMI implementation barriers on the link between the intention to change a BM and the concrete BMI implementation. In conclusion, this study confirms the threat-rigidity theory.

Keywords: barrier perception, business model innovation, business model innovation barriers, crises, prospect theory, start-ups, structural equation model, threat-rigidity theory

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Authors: Nalika S. Rajapaksha, James Airton, Amina Aboobakar, Nick Chappell, Andy Dyer

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Nutrient pollution and their impact on water quality is a key concern in England. Many water quality issues originate from multiple sources of pollution spread across the catchment. The river water quality in England has improved since 1990s and wastewater effluent discharges into rivers now contain less phosphorus than in the past. However, excess phosphorus is still recognised as the prevailing issue for rivers failing Water Framework Directive (WFD) good ecological status. To achieve WFD Phosphorus objectives, Wastewater Treatment Works (WwTW) permit limits are becoming increasingly stringent. Nevertheless, in some rural catchments, the apportionment of Phosphorus pollution can be greater from agricultural runoff and other sources such as septic tanks. Therefore, the challenge of meeting the requirements of watercourses to deliver WFD objectives often goes beyond water company activities, providing significant opportunities to co-deliver activities in wider catchments to reduce nutrient load at source. The aim of this study was to apply the United Utilities' Catchment Systems Thinking (CaST) strategy and pilot an innovative permitting approach - Catchment Nutrient Balancing (CNB) in a rural catchment in Cumbria (the River Petteril) in collaboration with the regulator and others to achieve WFD objectives and multiple benefits. The study area is mainly agricultural land, predominantly livestock farms. The local ecology is impacted by significant nutrient inputs which require intervention to meet WFD obligations. There are a range of Phosphorus inputs into the river, including discharges from wastewater assets but also significantly from agricultural contributions. Solely focusing on the WwTW discharges would not have resolved the problem hence in order to address this issue effectively, a CNB trial was initiated at a small WwTW, targeting the removal of a total of 150kg of Phosphorus load, of which 13kg were to be reduced through the use of catchment interventions. Various catchment interventions were implemented across selected farms in the upstream of the catchment and also an innovative polonite reactive filter media was implemented at the WwTW as an alternative to traditional Phosphorus treatment methods. During the 3 years of this trial, the impact of the interventions in the catchment and the treatment works were monitored. In 2020 and 2022, it respectively achieved a 69% and 63% reduction in the phosphorus level in the catchment against the initial reduction target of 9%. Phosphorus treatment at the WwTW had a significant impact on overall load reduction. The wider catchment impact, however, was seven times greater than the initial target when wider catchment interventions were also established. While it is unlikely that all the Phosphorus load reduction was delivered exclusively from the interventions implemented though this project, this trial evidenced the enhanced benefits that can be achieved with an integrated approach, that engages all sources of pollution within the catchment - rather than focusing on a one-size-fits-all solution. Primarily, the CNB approach and the act of collaboratively engaging others, particularly the agriculture sector is likely to yield improved farm and land management performance and better compliance, which can lead to improved river quality as well as wider benefits.

Keywords: agriculture, catchment nutrient balancing, phosphorus pollution, water quality, wastewater

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Authors: Kimberly Samaha

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The Bio-Hub Ecosystem model was developed to address a critical area of concern within the global energy market regarding biomass as a feedstock for power plants. Yet the lack of an economically-viable business model for bioenergy facilities has resulted in the continuation of idled and decommissioned plants. This study analyzed data and submittals to the Born Global Maine Innovation Challenge. The Innovation Challenge was a global innovation challenge to identify process innovations that could address a ‘whole-tree’ approach of maximizing the products, byproducts, energy value and process slip-streams into a circular zero-waste design. Participating companies were at various stages of developing bioproducts and included biofuels, lignin-based products, carbon capture platforms and biochar used as both a filtration medium and as a soil amendment product. This case study shows the QCA (Qualitative Comparative Analysis) methodology of the prequalification process and the resulting techno-economic model that was developed for the maximizing profitability of the Bio-Hub Ecosystem through continuous expansion of system waste streams into valuable process inputs for co-hosts. A full site plan for the integration of co-hosts (biorefinery, land-based shrimp and salmon aquaculture farms, a tomato green-house and a hops farm) at an operating forestry-based biomass to energy plant in West Enfield, Maine USA. This model and process for evaluating the profitability not only proposes models for integration of forestry, aquaculture and agriculture in cradle-to-cradle linkages of what have typically been linear systems, but the proposal also allows for the early measurement of the circularity and impact of resource use and investment risk mitigation, for these systems. In this particular study, profitability is assessed at two levels CAPEX (Capital Expenditures) and in OPEX (Operating Expenditures). Given that these projects start with repurposing facilities where the industrial level infrastructure is already built, permitted and interconnected to the grid, the addition of co-hosts first realizes a dramatic reduction in permitting, development times and costs. In addition, using the biomass energy plant’s waste streams such as heat, hot water, CO₂ and fly ash as valuable inputs to their operations and a significant decrease in the OPEX costs, increasing overall profitability to each of the co-hosts bottom line. This case study utilizes a proprietary techno-economic model to demonstrate how utilizing waste streams of a biomass energy plant and/or biorefinery, results in significant reduction in OPEX for both the biomass plants and the agriculture and aquaculture co-hosts. Economically viable Bio-Hubs with favorable environmental and community impacts may prove critical in garnering local and federal government support for pilot programs and more wide-scale adoption, especially for those living in severely economically depressed rural areas where aging industrial sites have been shuttered and local economies devastated.

Keywords: bio-economy, biomass energy, financing, zero-waste

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Authors: Dana Zelicha

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A 6-week mindfulness programme was launched to improve the well being and performance of 20 managers (including the supervisor) of an international corporation in London. A unique assessment methodology was customised to the organisation’s needs, measuring four parameters: prioritising skills, listening skills, mindfulness levels and happiness levels. All parameters showed significant improvements (p < 0.01) post intervention, with a remarkable increase in listening skills and mindfulness levels. Although corporate mindfulness programmes have proven to be effective, the challenge remains the low engagement levels at home and the implementation of these tools beyond the scope of the intervention. This study has offered an innovative approach to enforce home engagement levels, which yielded promising results. The programme launched with a 2-day introduction intervention, which was followed by a 6-week training course (1 day a week; 2 hours each). Participants learned all basic principles of mindfulness such as mindfulness meditations, Mindfulness Based Stress Reduction (MBSR) techniques and Mindfulness Based Cognitive Therapy (MBCT) practices to incorporate into their professional and personal lives. The programme contained experiential mindfulness meditations and innovative mindfulness tools (OWBA-MT) created by OWBA - The Well Being Agency. Exercises included Mindful Meetings, Unitasking and Mindful Feedback. All sessions concluded with guided discussions and group reflections. One fundamental element of this programme was engagement level outside of the workshop. In the office, participants connected with a mindfulness buddy - a team member in the group with whom they could find support throughout the programme. At home, participants completed online daily mindfulness forms that varied according to weekly themes. These customised forms gave participants the opportunity to reflect on whether they made time for daily mindfulness practice, and to facilitate a sense of continuity and responsibility. At the end of the programme, the most engaged team member was crowned the ‘mindful maven’ and received a special gift. The four parameters were measured using online self-reported questionnaires, including the Listening Skills Inventory (LSI), Mindfulness Attention Awareness Scale (MAAS), Time Management Behaviour Scale (TMBS) and a modified version of the Oxford Happiness Questionnaire (OHQ). Pre-intervention questionnaires were collected at the start of the programme, and post-intervention data was collected 4-weeks following completion. Quantitative analysis using paired T-tests of means showed significant improvements, with a 23% increase in listening skills, a 22% improvement in mindfulness levels, a 12% increase in prioritising skills, and an 11% improvement in happiness levels. Participant testimonials exhibited high levels of satisfaction and the overall results indicate that the mindfulness programme substantially impacted the team. These results suggest that 6-week mindfulness programmes can improve employees’ capacities to listen and work well with others, to effectively manage time and to experience enhanced satisfaction both at work and in life. Limitations noteworthy to consider include the afterglow effect and lack of generalisability, as this study was conducted on a small and fairly homogenous sample.

Keywords: corporate mindfulness, listening skills, organisational well being, prioritising skills, mindful leadership

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Authors: Paola Clerici Maestosi

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Positive Energy District (PED) is a rather recent concept whose aim is to contribute to the main objectives of the Energy Union strategy. It is based on an integrated multi-sectoral approach in response to Europe's most complex challenges. PED integrates energy efficiency, renewable energy production, and energy flexibility in an integrated, multi-sectoral approach at the city level. The core idea behind Positive Energy Districts (PEDs) is to establish an urban area that can generate more energy than it consumes. Additionally, it should be flexible enough to adapt to changes in the energy market. This is crucial because a PED's goal is not just to achieve an annual surplus of net energy but also to help reduce the impact on the interconnected centralized energy networks. It achieves this by providing options to increase on-site load matching and self-consumption, employing technologies for short- and long-term energy storage, and offering energy flexibility through smart control. Thus, it seems that PEDs can encompass all types of buildings in the city environment. Given this which is the added value of having green buildings being constitutive part of PEDS? The paper will present a systematic literature review identifying the role of green building in Positive Energy District to provide answer to following questions: (RQ1) the state of the art of PEDs implementation; (RQ2) penetration of green building in Positive Energy District selected case studies. Methodological approach is based on a broad holistic study of bibliographic sources according to Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) further data will be analysed, mapped and text mining through VOSviewer. Main contribution of research is a cognitive framework on Positive Energy District in Europe and a selection of case studies where green building supported the transition to PED. The inclusion of green buildings within Positive Energy Districts (PEDs) adds significant value for several reasons. Firstly, green buildings are designed and constructed with a focus on environmental sustainability, incorporating energy-efficient technologies, materials, and design principles. As integral components of PEDs, these structures contribute directly to the district's overall ability to generate more energy than it consumes. Secondly, green buildings typically incorporate renewable energy sources, such as solar panels or wind turbines, further boosting the district's capacity for energy generation. This aligns with the PED objective of achieving a surplus of net energy. Moreover, green buildings often feature advanced systems for on-site energy management, load-matching, and self-consumption. This enhances the PED's capability to respond to variations in the energy market, making the district more agile and flexible in optimizing energy use. Additionally, the environmental considerations embedded in green buildings align with the broader sustainability goals of PEDs. By reducing the ecological footprint of individual structures, PEDs with green buildings contribute to minimizing the overall impact on centralized energy networks and promote a more sustainable urban environment. In summary, the incorporation of green buildings within PEDs not only aligns with the district's energy objectives but also enhances environmental sustainability, energy efficiency, and the overall resilience of the urban environment.

Keywords: positive energy district, renewables energy production, energy flexibility, energy efficiency

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Authors: Jessica Kate Simonds

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The last successful hijacking perpetrated by Somali pirates in 2012 represented a critical turning point for the identity and brand of Indian Ocean (IO) insecurity, coined in this paper as the era of the post-piratical. This paper explores the broadening of the PMSC business model to account and contribute to the design of a new IO security environment that prioritises foreign and insurgency drone activity and Houthi rebel operations as the main threat to merchant shipping in the post-2012 era. This study is situated within a longer history of analysing maritime insecurity and also contributes a bespoke conceptual framework that understands the sea as a space that is produced and reproduced relative to existing and emerging threats to merchant shipping based on bespoke models of information sharing and intelligence acquisition. This paper also makes a prominent empirical contribution by drawing on a post-positivist methodology, data drawn from original semi-structured interviews with senior maritime insurers and active merchant seafarers that is triangulated with industry-produced guidance such as the BMP series as primary data sources. Each set is analysed through qualitative discourse and content analysis and supported by the quantitative data sets provided by the IMB Piracy Reporting center and intelligence networks. This analysis reveals that mechanisms such as the IGP&I Maritime Security Committee and intelligence divisions of PMSC’s have driven the exchanges of knowledge between land and sea and thus the reproduction of the maritime security environment through new regulations and guidance to account dones, rebels and bombs as the key challenges in the IO, beyond piracy. A contribution of this paper is the argument that experts who may not be in the highest-profile jobs are the architects of maritime insecurity based on their detailed knowledge and connections to vessels in transit. This paper shares the original insights of those who have served in critical decision making spaces to demonstrate that the development and refinement of industry produced deterrence guidance that has been accredited to the mitigation of piracy, have shaped new editions such as BMP 5 that now serve to frame a new security environment that prioritises the mitigation of risks from drones and WBEID’s from both state and insurgency risk groups. By highlighting the experiences and perspectives of key players on both land and at sea, the key finding of this paper is outlining that as pirates experienced a financial boom by profiteering from their bespoke business model during the peak of successful hijackings, the private security market encountered a similar level of financial success and guaranteed risk environment in which to prospect business. Thus, the reproduction of the Indian Ocean as a maritime security environment reflects a new found purpose for PMSC’s as part of the broader conglomerate of maritime insurers, regulators, shipowners and managers who continue to redirect the security consciousness and IO brand of insecurity.

Keywords: maritime security, private security, risk intelligence, political geography, international relations, political economy, maritime law, security studies

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Authors: Prabhjot Kaur, B.K. Kang, Balwinder Singh

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The tobacco caterpillar, Spodoptera litura (Fabricius) (Lepidoptera: Noctuidae) is an agricultural important pest species. S. litura has a wide host range of approximately recorded 150 plant species worldwide. In Punjab, this pest attains sporadic status primarily on cauliflower, Brassica oleracea (L.). This pest destroys vegetable crop and particularly prefers the cruciferae family. However, it is also observed feeding on other crops such as arbi, Colocasia esculenta (L.), mung bean, Vigna radiata (L.), sunflower, Helianthus annuus (L.), cotton, Gossypium hirsutum (L.), castor, Ricinus communis (L.), etc. Larvae of this pest completely devour the leaves of infested plant resulting in huge crop losses which ranges from 50 to 70 per cent. Indiscriminate and continuous use of insecticides has contributed in development of insecticide resistance in insects and caused the environmental degradation as well. Moreover, a base line data regarding the toxicity of the newer insecticides would help in understanding the level of resistance developed in this pest and any possible cross-resistance there in, which could be assessed in advance. Therefore, present studies on development of resistance in S. litura against four new chemistry insecticides (emamectin benzoate, chlorantraniliprole, indoxacarb and spinosad) were carried out in the Toxicology laboratory, Department of Entomology, Punjab Agricultural University, Ludhiana, Punjab, India during the year 2011-12. Various stages of S. litura (eggs, larvae) were collected from four different locations (Malerkotla, Hoshiarpur, Amritsar and Samrala) of Punjab. Resistance is developed in third instars of lepidopterous pests. Therefore, larval bioassays were conducted to estimate the response of field populations of thirty third-instar larvae of S. litura under laboratory conditions at 25±2°C and 65±5 per cent relative humidity. Leaf dip bioassay technique with diluted insecticide formulations recommended by Insecticide Resistance Action Committee (IRAC) was performed in the laboratory with seven to ten treatments depending on the insecticide class, respectively. LC50 values were estimated by probit analysis after correction to record control mortality data which was used to calculate the resistance ratios (RR). The LC50 values worked out for emamectin benzoate, chlorantraniliprole, indoxacarb, spinosad are 0.081, 0.088, 0.380, 4.00 parts per million (ppm) against pest populations collected from Malerkotla; 0.051, 0.060, 0.250, 3.00 (ppm) of Amritsar; 0.002, 0.001, 0.0076, 0.10 ppm for Samrala and 0.000014, 0.00001, 0.00056, 0.003 ppm against pest population of Hoshiarpur, respectively. The LC50 values for populations collected from these four locations were in the order Malerkotla>Amritsar>Samrala>Hoshiarpur for the insecticides (emamectin benzoate, chlorantraniliprole, indoxacarb and spinosad) tested. Based on LC50 values obtained, emamectin benzoate (0.000014 ppm) was found to be the most toxic among all the tested populations, followed by chlorantraniliprole (0.00001 ppm), indoxacarb (0.00056 ppm) and spinosad (0.003 ppm), respectively. The pairwise correlation coefficients of LC50 values indicated that there was lack of cross resistance for emamectin benzoate, chlorantraniliprole, spinosad, indoxacarb in populations of S. litura from Punjab. These insecticides may prove to be promising substitutes for the effective control of insecticide resistant populations of S. litura in Punjab state, India.

Keywords: Spodoptera litura, insecticides, toxicity, resistance

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Authors: Khelladi Hadj Mostefa, Krouf Djamil, Taleb-Dida Nawel

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Background: Obesity results from a prolonged imbalance between energy intake and energy expenditure, as depending on basal metabolic rate. Oils and proteins from sea have important therapeutic (such as obesity and hypercholesterolemia) and antioxidant effects. Sardine are a widely consumed fish in the Mediterranean region. Its consumption provides humans with various nutrients such as oils (rich in omega 3 plyunsaturated fatty acids)) and proteins. Methods: Sardine oil (SO) and sardine proteins (SP) were extracted and purified. Mixture of vegetable oils (olive-walnut-sunflower) were prepared from oils produced in Algeria. Eighteen wistar rats are fed a high fat diet enriched with 1% cholesterol for 30 days to induce obesity and hypercholesterolemia. The rats are divided into 3 groups. The first group consumes 20% sardine protein combined with 5% sardine oil (38% SFA (saturated fatty acids), 31% MIFA (monounsaturated fatty acids) and 31% PIFA (polyunsaturated fatty acids)) (SPso). The second group consumes 20% sardine protein combined with 5% of a mixture of vegetable oils (VO) containing 13% SFA, 58% MIFA and 29% PIFA (PSvo), and the third group consuming 20% casein combined with 5% of the mixture of vegetable oils and serves as a semi-synthetic reference (CASvo). Body weights and glycaemia are measured weekly After 28 days of experimentation, the rats are sacrificed, the blood and the liver removed. Serum assays of total cholesterol (TC) and triglycerides (TG) were performed by enzymatic colorimetric methods. Evaluation of lipid peroxidation was performed by assaying thiobarbituric acid reactive species (TBARS) and hydroperoxides values. The protein oxidation was performed by assaying carbonyl derivatives values. Finally, evaluation of antioxidant defense is made by measuring the activity of antioxidant enzymes, the superoxide dismutase (SOD) and the catalase (CAT).Results: After 28 days, the body weight (BW) of the rats increased significantly in SPso and SPvo groups compared to CAS group, by +11% and 7%, respectively. Cholesterolemia (TC) increased significantly in the SPso and SPvo groups compared to the CAS group (P<0.01), while triglyceridemia (TG) decreased significantly in the SPso group compared to SPvo and CAS groups (P<0.01). Albumin (marker of inflammation) increased in the PSs group compared to SPvo and CAS groups by +35% and +13%, respectively. The serum TBARS levels are -40% lower in SPso group compared to SPvo group, and they are -80% and -76% lower in SPso compared to SPvo and CAS groups, respectively. The level of carbonyls derivatives in the serum and liver are significantly reduced in the SPso group compared to the SPvo and CAS groups. Superoxide dismutase (SOD) activity decreased in liver of SPso group compared to SPvo group (P<0.01). While that of CAT is increased in liver tissue of SPso group compared to SPvo group (P<0.01). Conclusion: Sardine oil combined with sardine protein has a hypotriglyceridemic effect, reduces body weight, attenuates inflammation and seems to protect against lipid peroxidation and protein oxidation and increases antioxidant defense in hypercholesterolemic and obese rats. This could be in favor of a protective effect against obesity and cardiovascular diseases.

Keywords: rat, obesity, hypercholesterolemia, sardine protein, sardine oil, vegetable oils mixture, lipid peroxidation, protein oxidation, antioxidant defense

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Authors: Omarova Gulnara, Assubayeva Saltanat, Tugambay Symbat, Bulegenov Kanat

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The article discusses the problem of developing a methodology for studying thin and nanoscale gold in ores and placers of primary deposits, which will allow us to develop schemes for revealing dispersed gold inclusions and thus improve its recovery rate to increase the gold reserves of the Republic of Kazakhstan. The type of studied gold, is characterized by a number of features. In connection with this, the conditions of its concentration and distribution in ore bodies and formations, as well as the possibility of reliably determining it by "traditional" methods, differ significantly from that of fine gold (less than 0.25 microns) and even more so from that of larger grains. The mineral composition of rocks (metasomatites) and gold ore and the mineralization associated with them were studied in detail on the Kalba ore field in Kazakhstan. Mineralized zones were identified, and samples were taken from them for analytical studies. The research revealed paragenetic relationships of newly formed mineral formations at the nanoscale, which makes it possible to clarify the conditions for the formation of deposits with a particular type of mineralization. This will provide significant assistance in developing a scheme for study. Typomorphic features of gold were revealed, and mechanisms of formation and aggregation of gold nanoparticles were proposed. The presence of a large number of particles isolated at the laboratory stage from concentrates of gravitational enrichment can serve as an indicator of the presence of even smaller particles in the object. Even the most advanced devices based on gravitational methods for gold concentration provide extraction of metal at a level of around 50%, while pulverized metal is extracted much worse, and gold of less than 1 micron size is extracted at only a few percent. Therefore, when particles of gold smaller than 10 microns are detected, their actual numbers may be significantly higher than expected. In particular, at the studied sites, enrichment of slurry and samples with volumes up to 1 m³ was carried out using a screw lock or separator to produce a final concentrate weighing up to several kilograms. Free gold particles were extracted from the concentrates in the laboratory using a number of processes (magnetic and electromagnetic separation, washing with bromoform in a cup to obtain an ultracontentrate, etc.) and examined under electron microscopes to investigate the nature of their surface and chemical composition. The main result of the study was the detection of gold nanoparticles located on the surface of loose metal grains. The most characteristic forms of gold secretions are individual nanoparticles and aggregates of different configurations. Sometimes, aggregates form solid dense films, deposits, and crusts, all of which are confined to the negative forms of the nano- and microrelief on the surfaces of golden. The results will provide significant knowledge about the prevalence and conditions for the distribution of fine and nanoscale gold in Kazakhstan deposits, as well as the development of methods for studying it, which will minimize losses of this type of gold during extraction. Acknowledgments: This publication has been produced within the framework of the Grant "Development of methodology for studying fine and nanoscale gold in ores of primary deposits, placers and products of their processing" (АР23485052, №235/GF24-26).

Keywords: electron microscopy, microminerology, placers, thin and nanoscale gold

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Authors: Yuliya Y. Gavrichenko

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Background and Aims: The increasing bacterial resistance to almost all the available antibiotics has encouraged scientists to search for alternative sources of antibacterial agents. Nowadays, it is known that many plant secondary metabolites have diverse biological activity. These compounds can be potentially active against human bacterial and viral infections. Extended research has been carried out to explore the use of the luminescent bacterial test as a rapid, accurate and inexpensive method to assess the antibacterial properties and to predict the biological activity spectra for plant origin substances. Method: Botanical material of fifteen species was collected from their natural and cultural habitats on the Crimean peninsula. The aqueous extracts of following plants were tested: Robinia pseudoacacia L., Sideritis comosa, Cotinus coggygria Scop., Thymus serpyllum L., Juglans regia L., Securigera varia L., Achillea millefolium L., Phlomis taurica, Corylus avellana L., Sambucus nigra L., Helichrysum arenarium L., Glycyrrhiza glabra L., Elytrigia repens L., Echium vulgare L., Conium maculatum L. The test was carried out using luminous strains of marine bacteria Photobacterium leiognathi, which was isolated from the Sea of Azov as well as four Escherichia coli MG1655 recombinant strains harbouring Vibrio fischeri luxCDABE genes. Results: The bactericidal capacity of plant extracts showed significant differences in the study. Cotinus coggygria, Phlomis taurica, Juglans regia L. proved to be the most toxic to P. leiognathi. (EC50 = 0.33 g dried plant/l). Glycyrrhiza glabra L., Robinia pseudoacacia L., Sideritis comosa and Helichrysum arenarium L. had moderate inhibitory effects (EC50 = 3.3 g dried plant/l). The rest of the aqueous extracts have decreased the luminescence of no more than 50% at the lowest concentration (16.5 g dried plant/l). Antibacterial activity of herbal extracts against constitutively luminescent E. coli MG1655 (pXen7-lux) strain was observed at approximately the same level as for P. leiognathi. Cotinus coggygria and Conium maculatum L. extracts have increased light emission in the mutant E. coli MG1655 (pFabA-lux) strain which is associated with cell membranes damage. Sideritis comosa, Phlomis taurica, Juglans regia induced SOS response in E. coli (pColD-lux) strain. Glycyrrhiza glabra L. induced protein damage response in E. coli MG1655 (pIbpA-lux) strain. Conclusion: The received results have shown that the plants’ extracts had nonspecific antimicrobial effects against both E. coli (pXen7-lux) and P. leiognathi biosensors. Mutagenic, cytotoxic and protein damage effects have been observed. In general, the bioluminescent inhibition test result correlated with the traditional use of screened plants. It leads to the following conclusion that whole-cell luminescent biosensors could be the indicator of overall plants antibacterial capacity. The results of the investigation have shown a possibility of bioluminescent method in medicine and pharmacy as an approach to research the antibacterial properties of medicinal plants.

Keywords: antibacterial property, bioluminescence, medicinal plants, whole-cell biosensors

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Authors: Babak Forouraghi

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A genetic circuit is a collection of interacting genes and proteins that enable individual cells to implement and perform vital biological functions such as cell division, growth, death, and signaling. In cell engineering, synthetic gene circuits are engineered networks of genes specifically designed to implement functionalities that are not evolved by nature. These engineered networks enable scientists to tackle complex problems such as engineering cells to produce therapeutics within the patient's body, altering T cells to target cancer-related antigens for treatment, improving antibody production using engineered cells, tissue engineering, and production of genetically modified plants and livestock. Construction of computational models to realize genetic circuits is an especially challenging task since it requires the discovery of flow of genetic information in complex biological systems. Building synthetic biological models is also a time-consuming process with relatively low prediction accuracy for highly complex genetic circuits. The primary goal of this study was to investigate the utility of a pre-trained bidirectional encoder transformer that can accurately predict gene expressions in genetic circuit designs. The main reason behind using transformers is their innate ability (attention mechanism) to take account of the semantic context present in long DNA chains that are heavily dependent on spatial representation of their constituent genes. Previous approaches to gene circuit design, such as CNN and RNN architectures, are unable to capture semantic dependencies in long contexts as required in most real-world applications of synthetic biology. For instance, RNN models (LSTM, GRU), although able to learn long-term dependencies, greatly suffer from vanishing gradient and low-efficiency problem when they sequentially process past states and compresses contextual information into a bottleneck with long input sequences. In other words, these architectures are not equipped with the necessary attention mechanisms to follow a long chain of genes with thousands of tokens. To address the above-mentioned limitations of previous approaches, a transformer model was built in this work as a variation to the existing DNA Bidirectional Encoder Representations from Transformers (DNABERT) model. It is shown that the proposed transformer is capable of capturing contextual information from long input sequences with attention mechanism. In a previous work on genetic circuit design, the traditional approaches to classification and regression, such as Random Forrest, Support Vector Machine, and Artificial Neural Networks, were able to achieve reasonably high R2 accuracy levels of 0.95 to 0.97. However, the transformer model utilized in this work with its attention-based mechanism, was able to achieve a perfect accuracy level of 100%. Further, it is demonstrated that the efficiency of the transformer-based gene expression classifier is not dependent on presence of large amounts of training examples, which may be difficult to compile in many real-world gene circuit designs.

Keywords: transformers, generative ai, gene expression design, classification

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Authors: Swadha Singh

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International Solar Alliance is the foremost treaty-based global organization concerned with tapping the potential of sun-abundant nations between the Tropics of Cancer and Capricorn and enables co-operation among them. As a founding member of the International Solar Alliance, India exhibits its positioning as an upcoming leader in clean energy. India has set ambitious goals and targets to expand the share of solar in its energy mix and is playing a proactive role both at the regional and global levels. ISA aims to serve multiple goals- bring about scale commercialization of solar power, boost domestic manufacturing, and leverage solar diplomacy in African countries, amongst others. Against this backdrop, this paper attempts to examine the ways in which ISA as an intergovernmental organization under Indian leadership can leverage the cause of clean energy (solar) diplomacy and effectively shape partnerships and collaborations with other developing countries in terms of sharing solar technology, capacity building, risk mitigation, mobilizing financial investment and providing an aggregate market. A more specific focus of ISA is on the developing countries, which in the absence of a collective, are constrained by technology and capital scarcity, despite being naturally endowed with solar resources. Solar rich but finance-constrained economies face political risk, foreign exchange risk, and off-taker risk. Scholars argue that aligning India’s climate change discourse and growth prospects in its engagements, collaborations, and partnerships at the bilateral, multilateral and regional level can help promote trade, attract investments, and promote resilient energy transition both in India and in partner countries. For developing countries, coming together in an action-oriented way on issues of climate and clean energy is particularly important since it is developing and underdeveloped countries that face multiple and coalescing challenges such as the adverse impact of climate change, uneven and low access to reliable energy, and pressing employment needs. Investing in green recovery is agreed to be an assured way to create resilient value chains, create sustainable livelihoods, and help mitigate climate threats. If India is able to ‘green its growth’ process, it holds the potential to emerge as a climate leader internationally. It can use its experience in the renewable sector to guide other developing countries in balancing multiple similar objectives of development, energy security, and sustainability. The challenges underlying solar expansion in India have lessons to offer other developing countries, giving India an opportunity to assume a leadership role in solar diplomacy and expand its geopolitical influence through inter-governmental organizations such as ISA. It is noted that India has limited capacity to directly provide financial funds and support and is not a leading manufacturer of cheap solar equipment, as does China; however, India can nonetheless leverage its large domestic market to scale up the commercialization of solar power and offer insights and learnings to similarly placed abundant solar countries. The paper examines the potential of and limits placed on India’s solar diplomacy.

Keywords: climate diplomacy, energy security, solar diplomacy, renewable energy

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Authors: Alfredo Fortunato, Carmelofrancesco Origlia, Sara Laurita, Rossella Nicoletti

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In the post-pandemic recovery phase of tourism, the role of a Destination Management Organization (DMO) as a coordinated management system of all the elements that make up a destination (attractions, access, marketing, human resources, brand, pricing, etc.) is also becoming relevant for local territories. The objective of a DMO is to maximize the visitor's perception of value and quality while ensuring the competitiveness and sustainability of the destination, as well as the long-term preservation of its natural and cultural assets, and to catalyze benefits for the local economy and residents. In carrying out the multiple functions to which it is called, the DMO can leverage a collective intelligence that comes from the ability to pool information, explicit and tacit knowledge, and relationships of the various stakeholders: policymakers, public managers and officials, entrepreneurs in the tourism supply chain, researchers, data journalists, schools, associations and committees, citizens, etc. The DMO potentially has at its disposal large volumes of data and many of them at low cost, that need to be properly processed to produce value. Based on these assumptions, the paper presents a conceptual framework for building an information system to support the DMO in the intelligent management of a tourist destination tested in an area of southern Italy. The approach adopted is data-informed and consists of four phases: (1) formulation of the knowledge problem (analysis of policy documents and industry reports; focus groups and co-design with stakeholders; definition of information needs and key questions); (2) research and metadatation of relevant sources (reconnaissance of official sources, administrative archives and internal DMO sources); (3) gap analysis and identification of unconventional information sources (evaluation of traditional sources with respect to the level of consistency with information needs, the freshness of information and granularity of data; enrichment of the information base by identifying and studying web sources such as Wikipedia, Google Trends, Booking.com, Tripadvisor, websites of accommodation facilities and online newspapers); (4) definition of the set of indicators and construction of the information base (specific definition of indicators and procedures for data acquisition, transformation, and analysis). The framework derived consists of 6 thematic areas (accommodation supply, cultural heritage, flows, value, sustainability, and enabling factors), each of which is divided into three domains that gather a specific information need to be represented by a scheme of questions to be answered through the analysis of available indicators. The framework is characterized by a high degree of flexibility in the European context, given that it can be customized for each destination by adapting the part related to internal sources. Application to the case study led to the creation of a decision support system that allows: •integration of data from heterogeneous sources, including through the execution of automated web crawling procedures for data ingestion of social and web information; •reading and interpretation of data and metadata through guided navigation paths in the key of digital story-telling; •implementation of complex analysis capabilities through the use of data mining algorithms such as for the prediction of tourist flows.

Keywords: collective intelligence, data framework, destination management, smart tourism

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Authors: Jacqueline Eleonora Ek, Michael Spiteri, Chris Giordimaina, Pierre Agius

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Background: Malta is known for being a key player as a frontline country with regard to irregular immigration from Africa to Europe. Every year the island experiences an influx of migrants as boat movement across the Mediterranean continues to be a humanitarian challenge. Irregular immigration and applying for asylum is both a lengthy and mentally demanding process. Those doing so are often faced with multiple challenges, which can adversely affect their mental health. Between January and August 2020, Malta disembarked 2 162 people rescued at sea, 463 of them between July & August. Given the small size of the Maltese islands, this regulation places a disproportionately large burden on the country, creating a backlog in the processing of asylum applications resulting in increased time periods of detention. These delays reverberate throughout multiple management pathways resulting in prolonged periods of detention and challenging access to health services. Objectives: To better understand the spatial dimensions of this humanitarian crisis, this study aims to assess disparities in the acute medical management of migrants presenting to the emergency department (ED) with acute mental health presentations as compared to that of local and non-local residents. Method: In this retrospective study, 17795 consecutive ED attendances were reviewed to look for acute mental health presentations. These were further evaluated to assess discrepancies in transportation routes to hospital, nature of presenting complaint, effects of language barriers, use of CT brain, treatment given at ED, availability of psychiatric reviews, and final admission/discharge plans. Results: Of the ED attendances, 92.3% were local residents, and 7.7% were non-locals. Of the non-locals, 13.8% were migrants, and 86.2% were other-non-locals. Acute mental health presentations were seen in 1% of local residents; this increased to 20.6% in migrants. 56.4% of migrants attended with deliberate self-harm; this was lower in local residents, 28.9%. Contrastingly, in local residents, the most common presenting complaint was suicidal thought/ low mood 37.3%, the incidence was similar in migrants at 33.3%. The main differences included 12.8% of migrants presenting with refused oral intake while only 0.6% of local residents presented with the same complaints. 7.7% of migrants presented with a reduced level of consciousness, no local residents presented with this same issue. Physicians documented a language barrier in 74.4% of migrants. 25.6% were noted to be completely uncommunicative. Further investigations included the use of a CT scan in 12% of local residents and in 35.9% of migrants. The most common treatment administered to migrants was supportive fluids 15.4%, the most common in local residents was benzodiazepines 15.1%. Voluntary psychiatric admissions were seen in 33.3% of migrants and 24.7% of locals. Involuntary admissions were seen in 23% of migrants and 13.3% of locals. Conclusion: Results showed multiple disparities in health management. A meeting was held between entities responsible for migrant health in Malta, including the emergency department, primary health care, migrant detention services, and Malta Red Cross. Currently, national quality-improvement initiatives are underway to form new pathways to improve patient-centered care. These include an interpreter unit, centralized handover sheets, and a dedicated migrant health service.

Keywords: emergency department, communication, health, migration

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Authors: F. Iberraken, R. Medjoudj, D. Aissani

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The development of the smart grids concept is built around two separate definitions, namely: The European one oriented towards sustainable development and the American one oriented towards reliability and security of supply. In this paper, we have investigated reliability merits enabling decision-makers to provide a high quality of service. It is based on system behavior using interruptions and failures modeling and forecasting from one hand and on the contribution of information and communication technologies (ICT) to mitigate catastrophic ones such as blackouts from the other hand. It was found that this concept has been adopted by developing and emerging countries in short and medium terms followed by sustainability concept at long term planning. This work has highlighted the reliability merits such as: Benefits, opportunities, costs and risks considered as consistent units of measuring power customer satisfaction. From the decision making point of view, we have used the analytic hierarchy process (AHP) to achieve customer satisfaction, based on the reliability merits and the contribution of such energy resources. Certainly nowadays, fossil and nuclear ones are dominating energy production but great advances are already made to jump into cleaner ones. It was demonstrated that theses resources are not only environmentally but also economically and socially sustainable. The paper is organized as follows: Section one is devoted to the introduction, where an implicit review of smart grids development is given for the two main concepts (for USA and Europeans countries). The AHP method and the BOCR developments of reliability merits against power customer satisfaction are developed in section two. The benefits where expressed by the high level of availability, maintenance actions applicability and power quality. Opportunities were highlighted by the implementation of ICT in data transfer and processing, the mastering of peak demand control, the decentralization of the production and the power system management in default conditions. Costs were evaluated using cost-benefit analysis, including the investment expenditures in network security, becoming a target to hackers and terrorists, and the profits of operating as decentralized systems, with a reduced energy not supplied, thanks to the availability of storage units issued from renewable resources and to the current power lines (CPL) enabling the power dispatcher to manage optimally the load shedding. For risks, we have razed the adhesion of citizens to contribute financially to the system and to the utility restructuring. What is the degree of their agreement compared to the guarantees proposed by the managers about the information integrity? From technical point of view, have they sufficient information and knowledge to meet a smart home and a smart system? In section three, an application of AHP method is made to achieve power customer satisfaction based on the main energy resources as alternatives, using knowledge issued from a country that has a great advance in energy mutation. Results and discussions are given in section four. It was given us to conclude that the option to a given resource depends on the attitude of the decision maker (prudent, optimistic or pessimistic), and that status quo is neither sustainable nor satisfactory.

Keywords: reliability, AHP, renewable energy resources, smart grids

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Authors: Andrew Laming, John Hattie, Mark Wilson

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Nine Queensland Independent high schools provided deidentified student-matched ATAR and NAPLAN data for all 1217 ATAR graduates since 2020 who also sat NAPLAN at the school. Graduating cohorts from the nine schools contained a mean 100 ATAR graduates with previous NAPLAN data from their school. Excluded were vocational students (mean=27) and any ATAR graduates without NAPLAN data (mean=20). Based on Index of Community Socio-Educational Access (ICSEA) prediction, all schools had larger that predicted proportions of their students graduating with ATARs. There were an additional 173 students not releasing their ATARs to their school (14%), requiring this data to be inferred by schools. Gain was established by first converting each student’s strongest NAPLAN domain to a statewide percentile, then subtracting this result from final ATAR. The resulting ‘percentile shift’ was corrected for plausible ATAR participation at each NAPLAN level. Strongest NAPLAN domain had the highest correlation with ATAR (R2=0.58). RESULTS School mean NAPLAN scores fitted ICSEA closely (R2=0.97). Schools achieved a mean cohort gain of two ATAR rankings, but only 66% of students gained. This ranged from 46% of top-NAPLAN decile students gaining, rising to 75% achieving gains outside the top decile. The 54% of top-decile students whose ATAR fell short of prediction lost a mean 4.0 percentiles (or 6.2 percentiles prior to correction for regression to the mean). 71% of students in smaller schools gained, compared to 63% in larger schools. NAPLAN variability in each of the 13 ICSEA1100 cohorts was 17%, with both intra-school and inter-school variation of these values extremely low (0.3% to 1.8%). Mean ATAR change between years in each school was just 1.1 ATAR ranks. This suggests consecutive school cohorts and ICSEA-similar schools share very similar distributions and outcomes over time. Quantile analysis of the NAPLAN/ATAR revealed heteroscedasticity, but splines offered little additional benefit over simple linear regression. The NAPLAN/ATAR R2 was 0.33. DISCUSSION Standardised data like NAPLAN and ATAR offer educators a simple no-cost progression metric to analyse performance in conjunction with their internal test results. Change is expressed in percentiles, or ATAR shift per student, which is layperson intuitive. Findings may also reduce ATAR/vocational stream mismatch, reveal proportions of cohorts meeting or falling short of expectation and demonstrate by how much. Finally, ‘crashed’ ATARs well below expectation are revealed, which schools can reasonably work to minimise. The percentile shift method is neither value-add nor a growth percentile. In the absence of exit NAPLAN testing, this metric is unable to discriminate academic gain from legitimate ATAR-maximizing strategies. But by controlling for ICSEA, ATAR proportion variation and student mobility, it uncovers progression to ATAR metrics which are not currently publicly available. However achieved, ATAR maximisation is a sought-after private good. So long as standardised nationwide data is available, this analysis offers useful analytics for educators and reasonable predictivity when counselling subsequent cohorts about their ATAR prospects.  

Keywords: NAPLAN, ATAR, analytics, measurement, gain, performance, data, percentile, value-added, high school, numeracy, reading comprehension, variability, regression to the mean

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Authors: Sara Mosteller, Larissa K. Samuelson, Sobanawartiny Wijeakumar, John P. Spencer

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This study was designed to examine how humans are able to teach and learn semantic information as well as cooperate in order to jointly achieve sophisticated goals. Specifically, we are measuring individual differences in how these abilities develop from foundational building blocks in early childhood. The current study adopts a paradigm for novel noun learning developed by Samuelson, Smith, Perry, and Spencer (2011) to a hyperscanning paradigm [Cui, Bryant and Reiss, 2012]. This project measures coordinated brain activity between a parent and child using simultaneous functional near infrared spectroscopy (fNIRS) in pairs of 2.5, 3.5 and 4.5-year-old children and their parents. We are also separately testing pairs of adult friends. Children and parents, or adult friends, are seated across from one another at a table. The parent (in the developmental study) then teaches their child the names of novel toys. An experimenter then tests the child by presenting the objects in pairs and asking the child to retrieve one object by name. Children are asked to choose from both pairs of familiar objects and pairs of novel objects. In order to explore individual differences in cooperation with the same participants, each dyad plays a cooperative game of Jenga, in which their joint score is based on how many blocks they can remove from the tower as a team. A preliminary analysis of the noun-learning task showed that, when presented with 6 word-object mappings, children learned an average of 3 new words (50%) and that the number of objects learned by each child ranged from 2-4. Adults initially learned all of the new words but were variable in their later retention of the mappings, which ranged from 50-100%. We are currently examining differences in cooperative behavior during the Jenga playing game, including time spent discussing each move before it is made. Ongoing analyses are examining the social dynamics that might underlie the differences between words that were successfully learned and unlearned words for each dyad, as well as the developmental differences observed in the study. Additionally, the Jenga game is being used to better understand individual and developmental differences in social coordination during a cooperative task. At a behavioral level, the analysis maps periods of joint visual attention between participants during the word learning and the Jenga game, using head-mounted eye trackers to assess each participant’s first-person viewpoint during the session. We are also analyzing the coherence in brain activity between participants during novel word-learning and Jenga playing. The first hypothesis is that visual joint attention during the session will be positively correlated with both the number of words learned and with the number of blocks moved during Jenga before the tower falls. The next hypothesis is that successful communication of new words and success in the game will each be positively correlated with synchronized brain activity between the parent and child/the adult friends in cortical regions underlying social cognition, semantic processing, and visual processing. This study probes both the neural and behavioral mechanisms of learning and cooperation in a naturalistic, interactive and developmental context.

Keywords: communication, cooperation, development, interaction, neuroscience

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Authors: Tzipi Eshet

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The primary objectives of this work are the examination of public preferences and attributed importance to different characteristics of coastal cliff protection alternatives, and drawing conclusions about the applicable alternative in Beit-Yanai beach. Erosion of coastal cliffs is a natural phenomenon that occurs in many places in the world. This creates problems along the coastlines, which are densely populated areas with highly developed economic activity. In recent years, various aspects of the aeolianite cliffs along the Israeli coast have been studied extensively. There is a consensus among researchers regarding a general trend of cliff retreat. This affects civilian infrastructure, wildlife habitats and heritage values, as well as Increases the risk to human life. The Israeli government, committed to the integrated coastal zones management approach, decided on a policy and guidelines to deal with cliff erosion, which includes establishing physical protection on land and in the sea, sand nourishment and runoff drainage. Physical protection solutions to reduce the rate of retreat of the cliffs are considerably important both for planning authorities and visitors to the beach. Direct costs of different protection alternatives, as well as external costs and benefits, may vary, thus affecting consumer preferences. Planning and execution of sustainable coastal cliff protection alternatives must take into account the different characteristics and their impact on aspects of economics, environment and leisure. The rocky shore of Beit-Yanai Beach was chosen as a case study to examine the nature of the influence of various protective solutions on consumer preferences. This beach is located in the center of Israel's coastline, and acts as a focus of attraction for recreation, land and sea sports, and educational activities as well. If no action will be taken, cliff retreat will continue. A survey was conducted to reveal the importance of coastal protection alternatives characteristics and the visual preferences to visitors at beach Beit-Yanai and residents living on the cliff (N=287). Preferences and willingness-to-pay were explored using Contingent-Ranking and Choice-Experiments techniques. Results show that visitors’ and residents’ willingness-to-pay for coastal cliff protection alternatives is affected both by financial and environmental aspects, as well as leisure. They prefer coastal cliff protection alternatives that are not visible and do not need constant maintenance, do not affect the quality of seawater or the habitats of wildlife and do not lower the security level of the swimmers. No significant difference was found comparing willingness-to-pay among local and non-local users. Additionally, they mostly prefer a protection solution which is integrated in the coastal landscape and maintains the natural appearance of the beach. Of the possible protection alternatives proposed for the protection of the cliff in Beit Yanai beach are two techniques that meet public preferences: rock revetments and submerged detached breakwaters. Results indicate that the visiting public prefer the implementation of these protection alternatives and will be willing to pay for them. Future actions to reduce retreat rate in Beit-Yanai have to consider implications on the economic, environmental and social conditions, along with weighting public interest against the interest of the individual.

Keywords: contingent-ranking, choice-experiments, coastal cliff protection, erosion of coastal cliffs, environment

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Authors: Mei Chen, Yingping Hou, Michelle Hao, Soheil Aghamohammadzadeh, Esteban Terzo, Roger Clark, Vijay Modur

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Background: Recessive Dystrophic Epidermolysis Bullosa (RDEB) is a genetic skin condition characterized by skin tearing and unremitting blistering upon minimal trauma. Repeated blistering, fibrosis, and scarring lead to aggressive squamous cell carcinoma later in life. RDEB is caused by mutations in the COL7A1 gene encoding collagen type VII (C7), the major component of anchoring fibrils mediating epidermis-dermis adherence. Nonsense mutations in the COL7A1 gene of a subset of RDEB patients leads to premature termination codons (PTC). Similarly, most Junctional Epidermolysis Bullosa (JEB) cases are caused by nonsense mutations in the LAMB3 gene encoding the β3 subunit of laminin 332. Currently, there is an unmet need for the treatment of RDEB and JEB. Zikani Therapeutics has discovered an array of macrocyclic compounds with ring structures similar to macrolide antibiotics that can facilitate readthrough activity of nonsense mutations in the COL7A1 and LAMB3 genes by acting as Ribosome Modulating Agents (RMAs). The medicinal chemistry synthetic advancements of these macrocyclic compounds have allowed targeting the human ribosome while preserving the structural elements responsible for the safety and pharmacokinetic profile of clinically used macrolide antibiotics. Methods: C7 expression was used as a measure of readthrough activity by immunoblot assays in two primary human fibroblasts from RDEB patients (R578X/R578X and R163X/R1683X-COL7A1). Similarly, immunoblot assays in C325X/c.629-12T > A-LAMB3 keratinocytes were used to measure readthrough activity for JEB. The relative readthrough activity of each compound was measured relative to Gentamicin. An imaging-based fibroblast migration assay was used as an assessment of C7 functionality in RDEB-fibroblasts over 16-20 hrs. The incubation period for the above experiments was 48 hrs for RDEB fibroblasts and 72 hours for JEB keratinocytes. Results: 9 RMAs demonstrated increased protein expression in both patient RDEB fibroblasts. The highest readthrough activity at tested concentrations without cytotoxicities increased protein expression up to 179% of Gentamicin (400 µg/ml), with favored readthrough activity in R163X/R1683X-COL7A1 fibroblasts. Concurrent with protein expression, fibroblast hypermotility phenotype observed in RDEB was rescued by reducing motility by ~35% to WT levels (the same level as 690 µM Gentamicin treated cells). Laminin β3 expression was also shown to be increased by 6 RMAs in keratinocytes to 33-83% of (400 µg/ml) Gentamicin. Conclusions: To date, 9 RMAs have been identified that enhance the expression of functional C7 in a mutation-dependent manner in two different RDEB patient fibroblast backgrounds (R578X/R578X and R163X/R1683X-COL7A1). A further 6 RMAs have been identified that enhance the readthrough of C325X-LAMB3 in JEB patient keratinocytes. Based on the clinical trial conducted by us with topical gentamycin in 2017, Zikani’s RMAs achieve clinically significant levels of read-through for the treatment of recessive dystrophic and Junctional Epidermolysis Bullosa.

Keywords: epidermolysis bullosa, nonsense mutation, readthrough, ribosome modulation

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Authors: Lynn Sheridan, Dennis Alonzo, Hoa Nguyen, Andy Gao, Tracy Durksen

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Disruptions to teaching (e.g., COVID-related) have increased work demands for teachers. There is an opportunity for research to explore evidence-informed steps to support teachers. Collective evidence informs data on teachers’ personal attributes (e.g., self-efficacy beliefs) in the workplace are seen to promote success in teaching and support teacher engagement. Teacher engagement plays a role in students’ learning and teachers’ effectiveness. Engaged teachers are better at overcoming work-related stress, burnout and are more likely to take on active roles. Teachers’ commitment is influenced by a host of personal (e.g., teacher well-being) and environmental factors (e.g., job stresses). The job demands-resources model provided a conceptual basis for examining how teachers’ well-being, and is influenced by job demands and job resources. Job demands potentially evoke strain and exceed the employee’s capability to adapt. Job resources entail what the job offers to individual teachers (e.g., organisational support), helping to reduce job demands. The application of the job demands-resources model involves gathering an evidence-base of and connection to personal attributes (job resources). The study explored the association between constructs (resilience, adaptability, commitment, self/collective efficacy) and a teacher’s engagement with the job. The paper sought to elaborate on the model and determine the associations between key constructs of well-being (resilience, adaptability), commitment, and motivation (self and collective-efficacy beliefs) to teachers’ engagement in teaching. Data collection involved online a multi-dimensional instrument using validated items distributed from 2020-2022. The instrument was designed to identify construct relationships. The participant number was 170. Data Analysis: The reliability coefficients, means, standard deviations, skewness, and kurtosis statistics for the six variables were completed. All scales have good reliability coefficients (.72-.96). A confirmatory factor analysis (CFA) and structural equation model (SEM) were performed to provide measurement support and to obtain latent correlations among factors. The final analysis was performed using structural equation modelling. Several fit indices were used to evaluate the model fit, including chi-square statistics and root mean square error of approximation. The CFA and SEM analysis was performed. The correlations of constructs indicated positive correlations exist, with the highest found between teacher engagement and resilience (r=.80) and the lowest between teacher adaptability and collective teacher efficacy (r=.22). Given the associations; we proceeded with CFA. The CFA yielded adequate fit: CFA fit: X (270, 1019) = 1836.79, p < .001, RMSEA = .04, and CFI = .94, TLI = .93 and SRMR = .04. All values were within the threshold values, indicating a good model fit. Results indicate that increasing teacher self-efficacy beliefs will increase a teacher’s level of engagement; that teacher ‘adaptability and resilience are positively associated with self-efficacy beliefs, as are collective teacher efficacy beliefs. Implications for school leaders and school systems: 1. investing in increasing teachers’ sense of efficacy beliefs to manage work demands; 2. leadership approaches can enhance teachers' adaptability and resilience; and 3. a culture of collective efficacy support. Preparing teachers for now and in the future offers an important reminder to policymakers and school leaders on the importance of supporting teachers’ personal attributes when faced with the challenging demands of the job.

Keywords: collective teacher efficacy, teacher self-efficacy, job demands, teacher engagement

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Authors: Md. Abu Sufian, Robiqul Islam, Imam Hossain Shajid, Mahesh Hanumanthu, Jarasree Varadarajan, Md. Sipon Miah, Mingbo Niu

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Coronary Heart Disease (CHD) remains a principal cause of global morbidity and mortality, characterized by atherosclerosis—the build-up of fatty deposits inside the arteries. The study introduces an innovative methodology that leverages cloud-based platforms like AWS Live Streaming and Artificial Intelligence (AI) to early detect and prevent CHD symptoms in web applications. By employing novel simulation processes and AI algorithms, this research aims to significantly mitigate the health and societal impacts of CHD. Methodology: This study introduces a novel simulation process alongside a multi-phased model development strategy. Initially, health-related data, including heart rate variability, blood pressure, lipid profiles, and ECG readings, were collected through user interactions with web-based applications as well as API Integration. The novel simulation process involved creating synthetic datasets that mimic early-stage CHD symptoms, allowing for the refinement and training of AI algorithms under controlled conditions without compromising patient privacy. AWS Live Streaming was utilized to capture real-time health data, which was then processed and analysed using advanced AI techniques. The novel aspect of our methodology lies in the simulation of CHD symptom progression, which provides a dynamic training environment for our AI models enhancing their predictive accuracy and robustness. Model Development: it developed a machine learning model trained on both real and simulated datasets. Incorporating a variety of algorithms including neural networks and ensemble learning model to identify early signs of CHD. The model's continuous learning mechanism allows it to evolve adapting to new data inputs and improving its predictive performance over time. Results and Findings: The deployment of our model yielded promising results. In the validation phase, it achieved an accuracy of 92% in predicting early CHD symptoms surpassing existing models. The precision and recall metrics stood at 89% and 91% respectively, indicating a high level of reliability in identifying at-risk individuals. These results underscore the effectiveness of combining live data streaming with AI in the early detection of CHD. Societal Implications: The implementation of cloud-based AI for CHD symptom detection represents a significant step forward in preventive healthcare. By facilitating early intervention, this approach has the potential to reduce the incidence of CHD-related complications, decrease healthcare costs, and improve patient outcomes. Moreover, the accessibility and scalability of cloud-based solutions democratize advanced health monitoring, making it available to a broader population. This study illustrates the transformative potential of integrating technology and healthcare, setting a new standard for the early detection and management of chronic diseases.

Keywords: coronary heart disease, cloud-based ai, machine learning, novel simulation techniques, early detection, preventive healthcare

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Authors: Diana Reckien

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Vulnerability assessments are increasingly used to support policy-making in complex environments, like urban areas. Usually, vulnerability studies include the construction of aggregate (sub-) indices and the subsequent mapping of indices across an area of interest. Vulnerability studies show a couple of advantages: they are great communication tools, can inform a wider general debate about environmental issues, and can help allocating and efficiently targeting scarce resources for adaptation policy and planning. However, they also have a number of challenges: Vulnerability assessments are constructed on the basis of a wide range of methodologies and there is no single framework or methodology that has proven to serve best in certain environments, indicators vary highly according to the spatial scale used, different variables and metrics produce different results, and aggregate or composite vulnerability indicators that are mapped easily distort or bias the picture of vulnerability as they hide the underlying causes of vulnerability and level out conflicting reasons of vulnerability in space. So, there is urgent need to further develop the methodology of vulnerability studies towards a common framework, which is one reason of the paper. We introduce a social vulnerability approach, which is compared with other approaches of bio-physical or sectoral vulnerability studies relatively developed in terms of a common methodology for index construction, guidelines for mapping, assessment of sensitivity, and verification of variables. Two approaches are commonly pursued in the literature. The first one is an additive approach, in which all potentially influential variables are weighted according to their importance for the vulnerability aspect, and then added to form a composite vulnerability index per unit area. The second approach includes variable reduction, mostly Principal Component Analysis (PCA) that reduces the number of variables that are interrelated into a smaller number of less correlating components, which are also added to form a composite index. We test these two approaches of constructing indices on the area of New York City as well as two different metrics of variables used as input and compare the outcome for the 5 boroughs of NY. Our analysis yields that the mapping exercise yields particularly different results in the outer regions and parts of the boroughs, such as Outer Queens and Staten Island. However, some of these parts, particularly the coastal areas receive the highest attention in the current adaptation policy. We imply from this that the current adaptation policy and practice in NY might need to be discussed, as these outer urban areas show relatively low social vulnerability as compared with the more central parts, i.e. the high dense areas of Manhattan, Central Brooklyn, Central Queens and the Southern Bronx. The inner urban parts receive lesser adaptation attention, but bear a higher risk of damage in case of hazards in those areas. This is conceivable, e.g., during large heatwaves, which would more affect more the inner and poorer parts of the city as compared with the outer urban areas. In light of the recent planning practice of NY one needs to question and discuss who in NY makes adaptation policy for whom, but the presented analyses points towards an under representation of the needs of the socially vulnerable population, such as the poor, the elderly, and ethnic minorities, in the current adaptation practice in New York City.

Keywords: vulnerability mapping, social vulnerability, additive approach, Principal Component Analysis (PCA), New York City, United States, adaptation, social sensitivity

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Authors: Vijaya Dixit Aasheesh Dixit

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Shipbuilding industry operates in Engineer Procure Construct (EPC) context. Product mix of a shipyard comprises of various types of ships like bulk carriers, tankers, barges, coast guard vessels, sub-marines etc. Each order is unique based on the type of ship and customized requirements, which are engineered into the product right from design stage. Thus, to execute every new project, a shipyard needs to upgrade its production expertise. As a result, over the long run, holistic learning occurs across different types of projects which contributes to the knowledge base of the shipyard. Simultaneously, in the short term, during execution of a project comprising of multiple sister ships, repetition of similar tasks leads to learning at activity level. This research aims to capture above learnings of a shipyard and incorporate learning curve effect in project scheduling and materials procurement to improve project performance. Extant literature provides support for the existence of such learnings in an organization. In shipbuilding, there are sequences of similar activities which are expected to exhibit learning curve behavior. For example, the nearly identical structural sub-blocks which are successively fabricated, erected, and outfitted with piping and electrical systems. Learning curve representation can model not only a decrease in mean completion time of an activity, but also a decrease in uncertainty of activity duration. Sister ships have similar material requirements. The same supplier base supplies materials for all the sister ships within a project. On one hand, this provides an opportunity to reduce transportation cost by batching the order quantities of multiple ships. On the other hand, it increases the inventory holding cost at shipyard and the risk of obsolescence. Further, due to learning curve effect the production scheduled of each consequent ship gets compressed. Thus, the material requirement schedule of every next ship differs from its previous ship. As more and more ships get constructed, compressed production schedules increase the possibility of batching the orders of sister ships. This work aims at integrating materials management with project scheduling of long duration projects for manufacturing of multiple sister ships. It incorporates the learning curve effect on progressively compressing material requirement schedules and addresses the above trade-off of transportation cost and inventory holding and shortage costs while satisfying budget constraints of various stages of the project. The activity durations and lead time of items are not crisp and are available in the form of probabilistic distribution. A Stochastic Mixed Integer Programming (SMIP) model is formulated which is solved using evolutionary algorithm. Its output provides ordering dates of items and degree of order batching for all types of items. Sensitivity analysis determines the threshold number of sister ships required in a project to leverage the advantage of learning curve effect in materials management decisions. This analysis will help materials managers to gain insights about the scenarios: when and to what degree is it beneficial to treat a multiple ship project as an integrated one by batching the order quantities and when and to what degree to practice distinctive procurement for individual ship.

Keywords: learning curve, materials management, shipbuilding, sister ships

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Authors: Sara Saboonian, Pierre Filion

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The dispersed-suburban model has been the dominant one across North America for the past seventy years, characterized by automobile reliance, low density, and land-use specialization. Two planning models have emerged as possible alternatives to address the ills inflicted by this development pattern. First, there is intensification, which promotes efficient infrastructure by connecting high-density, multi-functional, and walkable nodes with public transit services within the suburban landscape. Second is green infrastructure, which provides environmental health and human well-being by preserving and restoring ecosystem services. This research studies incompatibilities and the possibility of amalgamating the two alternatives in an attempt to develop a comprehensive alternative to suburban model that advocates density, multi-functionality and transit- and pedestrian-conduciveness, with measures capable of mitigating the adverse environmental impacts of compactness. The research investigates three Canadian urban growth centers, where intensification is the current planning practice, and the awareness of green infrastructure benefits is on the rise. However, these three centers are contrasted by their development stage, the presence or absence of protected natural land, their environmental approach, and their adverse environmental consequences according to the planning cannons of different periods. The methods include reviewing the literature on green infrastructure planning, criticizing the Ontario provincial plans for intensification, surveying residents’ preferences for alternative models, and interviewing officials who deal with the local planning for the centers. Moreover, the research draws on recalling debates between New Urbanism and Landscape/Ecological Urbanism. The case studies expose the difficulties in creating urban growth centres that accommodate green infrastructure while adhering to intensification principles. First, the dominant status of intensification and the obstacles confronting intensification have monopolized the planners’ concerns. Second, the tension between green infrastructure and intensification explains the absence of the green infrastructure typologies that correspond to intensification-compatible forms and dynamics. Finally, the lack of highlighted social-economic benefits of green infrastructure reduces residents’ participation. Moreover, the results from the research provide insight into predominating urbanization theories, New Urbanism and Landscape/Ecological Urbanism. In order to understand political, planning, and ecological dynamics of such blending, dexterous context-specific planning is required. Findings suggest the influence of the following factors on amalgamating intensification and green infrastructure. Initially, producing ecosystem services-based justifications for green infrastructure development in the intensification context provides an expert-driven backbone for the implementation programs. This knowledge-base should be translated to effectively imbue different urban stakeholders. Moreover, due to the limited greenfields in intensified areas, spatial distribution and development of multi-level corridors such as pedestrian-hospitable settings and transportation networks along green infrastructure measures are required. Finally, to ensure the long-term integrity of implemented green infrastructure measures, significant investment in public engagement and education, as well as clarification of management responsibilities is essential.

Keywords: ecosystem services, green infrastructure, intensification, planning

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Authors: Juliane Toce, Steven Holochwost

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A substantial and growing literature has demonstrated that arts education benefits young children’s socioemotional and cognitive development. Less is known about the capacity of arts-integrated instruction to yield benefits to similar domains, particularly among demographically and socioeconomically diverse groups of young children. However, the small literature on this topic suggests that arts-integrated instruction may foster young children’s socioemotional and cognitive development by presenting opportunities to 1) engage in instructional content in diverse ways, 2) experience and regulate strong emotions, 3) experience growth-oriented feedback, and 4) engage in collaborative work with peers. Start with the Art is a new program of arts-integrated instruction currently being implemented in four schools in a school district that serves students from a diverse range of backgrounds. The program employs a co-teaching model in which teaching artists and classroom teachers engage in collaborative lesson planning and instruction over the course of the academic year and is currently the focus of an impact study featuring a randomized-control design, as well as an implementation study, both of which are funded through an Educational Innovation and Research grant from the United States Department of Education. The paper will present the early results from the Start with the Art implementation study. These results will provide an overview of the extent to which the program was implemented in accordance with design, with a particular emphasis on the degree to which the four opportunities enumerated above (e.g., opportunities to engage in instructional content in diverse ways) were presented to students. There will be a review key factors that may influence the fidelity of implementation, including classroom teachers’ reception of the program and the extent to which extant conditions in the classroom (e.g., the overall level of classroom organization) may have impacted implementation fidelity. With the explicit purpose of creating a program that values and meets the needs of the teachers and students, Start with the Art incorporates the feedback from individuals participating in the intervention. Tracing its trajectory from inception to ongoing development and examining the adaptive changes made in response to teachers' transformative experiences in the post-pandemic classroom, Start with the Art continues to solicit input from experts in integrating artistic content into core curricula within educational settings catering to students from under-represented backgrounds in the arts. Leveraging the input from this rich consortium of experts has allowed for a comprehensive evaluation of the program’s implementation. The early findings derived from the implementation study emphasize the potential of arts-integrated instruction to incorporate restorative practices. Such practices serve as a crucial support system for both students and educators, providing avenues for children to express themselves, heal emotionally, and foster social development, while empowering teachers to create more empathetic, inclusive, and supportive learning environments. This all-encompassing analysis spotlights Start with the Art’s adaptability to any learning environment through the program’s effectiveness, resilience, and its capacity to transform - through art - the classroom experience within the ever-evolving landscape of education.

Keywords: arts-integration, social emotional learning, diverse learners, co-teaching, teaching artists, post-pandemic teaching

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Authors: Nada Poropat Jeletic, Gordana Hrzica

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Bilingual conversational corpora represent a meaningful and the most comprehensive data source for investigating the genuine contact phenomena in non-monitored bi-lingual speech productions. They can be particularly useful for bilingual research since some features of bilingual interaction can hardly be accessed with more traditional methodologies (e.g., elicitation tasks). The method of language sampling provides the resources for describing language interaction in a bilingual community and/or in bilingual situations (e.g. code-switching, amount of languages used, number of languages used, etc.). To capture these phenomena in genuine communication situations, such sampling should be as close as possible to spontaneous communication. Bilingual spoken corpus design is methodologically demanding. Therefore this paper aims at describing the methodological challenges that apply to the corpus design of the conversational corpus design of the Istrian Istrovenetian-Croatian Bilingual Corpus. Croatian is the first official language of the Croatian-Italian officially bilingual Istria County, while Istrovenetian is a diatopic subvariety of Venetian, a longlasting lingua franca in the Istrian peninsula, the mother tongue of the members of the Italian National Community in Istria and the primary code of informal everyday communication among the Istrian Italophone population. Within the CLARIN infrastructure, TalkBank is being used, as it provides relevant procedures for designing and analyzing bilingual corpora. Furthermore, it allows public availability allows for easy replication of studies and cumulative progress as a research community builds up around the corpus, while the tools developed within the field of corpus linguistics enable easy retrieval and analysis of information. The method of language sampling employed is kept at the level of spontaneous communication, in order to maximise the naturalness of the collected conversational data. All speakers have provided written informed consent in which they agree to be recorded at a random point within the period of one month after signing the consent. Participants are administered a background questionnaire providing information about the socioeconomic status and the exposure and language usage in the participants social networks. Recording data are being transcribed, phonologically adapted within a standard-sized orthographic form, coded and segmented (speech streams are being segmented into communication units based on syntactic criteria) and are being marked following the CHAT transcription system and its associated CLAN suite of programmes within the TalkBank toolkit. The corpus consists of transcribed sound recordings of 36 bilingual speakers, while the target is to publish the whole corpus by the end of 2020, by sampling spontaneous conversations among approximately 100 speakers from all the bilingual areas of Istria for ensuring representativeness (the participants are being recruited across three generations of native bilingual speakers in all the bilingual areas of the peninsula). Conversational corpora are still rare in TalkBank, so the Corpus will contribute to BilingBank as a highly relevant and scientifically reliable resource for an internationally established and active research community. The impact of the research of communities with societal bilingualism will contribute to the growing body of research on bilingualism and multilingualism, especially regarding topics of language dominance, language attrition and loss, interference and code-switching etc.

Keywords: conversational corpora, bilingual corpora, code-switching, language sampling, corpus design methodology

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Authors: Stanislav Babaev, Vladimir Cuk, Sjef Cobben, Jan Desmet

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The procedures for performing harmonic studies for medium-voltage distribution feeders have become relatively mature topics since the early 1980s. The efforts of various electric power engineers and researchers were mainly focused on handling large harmonic non-linear loads connected scarcely at several buses of medium-voltage feeders. In order to assess the impact of these loads on the voltage quality of the distribution system, specific modeling and simulation strategies were proposed. These methodologies could deliver a reasonable estimation accuracy given the requirements of least computational efforts and reduced complexity. To uphold these requirements, certain analysis assumptions have been made, which became de facto standards for establishing guidelines for harmonic analysis. Among others, typical assumptions include balanced conditions of the study and the negligible impact of impedance frequency characteristics of various power system components. In latter, skin and proximity effects are usually omitted, and resistance and reactance values are modeled based on the theoretical equations. Further, the simplifications of the modelling routine have led to the commonly accepted practice of neglecting phase angle diversity effects. This is mainly associated with developed load models, which only in a handful of cases are representing the complete harmonic behavior of a certain device as well as accounting on the harmonic interaction between grid harmonic voltages and harmonic currents. While these modelling practices were proven to be reasonably effective for medium-voltage levels, similar approaches have been adopted for low-voltage distribution systems. Given modern conditions and massive increase in usage of residential electronic devices, recent and ongoing boom of electric vehicles, and large-scale installing of distributed solar power, the harmonics in current low-voltage grids are characterized by high degree of variability and demonstrate sufficient diversity leading to a certain level of cancellation effects. It is obvious, that new modelling algorithms overcoming previously made assumptions have to be accepted. In this work, a simulation approach aimed to deal with some of the typical assumptions is proposed. A practical low-voltage feeder is modeled in PowerFactory. In order to demonstrate the importance of diversity effect and harmonic interaction, previously developed measurement-based models of photovoltaic inverter and battery charger are used as loads. The Python-based script aiming to supply varying voltage background distortion profile and the associated current harmonic response of loads is used as the core of unbalanced simulation. Furthermore, the impact of uncertainty of feeder frequency-impedance characteristics on total harmonic distortion levels is shown along with scenarios involving linear resistive loads, which further alter the impedance of the system. The comparative analysis demonstrates sufficient differences with cases when all the assumptions are in place, and results indicate that new modelling and simulation procedures need to be adopted for low-voltage distribution systems with high penetration of non-linear loads and renewable generation.

Keywords: electric power system, harmonic distortion, power quality, public low-voltage network, harmonic modelling

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Authors: Monica Arnaudo, Monika Topel, Bjorn Laumert

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Within the Swedish context, the current trend of relatively low electricity prices promotes the electrification of the energy infrastructure. The residential heating sector takes part in this transition by proposing a switch from a centralized district heating system towards a distributed heat pumps-based setting. When it comes to urban environments, two issues arise. The first, seen from an electricity-sector perspective, is related to the fact that existing networks are limited with regards to their installed capacities. Additional electric loads, such as heat pumps, can cause severe overloads on crucial network elements. The second, seen from a heating-sector perspective, has to do with the fact that the indoor comfort conditions can become difficult to handle when the operation of the heat pumps is limited by a risk of overloading on the distribution grid. Furthermore, the uncertainty of the electricity market prices in the future introduces an additional variable. This study aims at assessing the extent to which distributed heat pumps can penetrate an existing heat energy network while respecting the technical limitations of the electricity grid and the thermal comfort levels in the buildings. In order to account for the multi-disciplinary nature of this research question, a cosimulation modeling approach was adopted. In this way, each energy technology is modeled in its customized simulation environment. As part of the cosimulation methodology: a steady-state power flow analysis in pandapower was used for modeling the electrical distribution grid, a thermal balance model of a reference building was implemented in EnergyPlus to account for space heating and a fluid-cycle model of a heat pump was implemented in JModelica to account for the actual heating technology. With the models set in place, different scenarios based on forecasted electricity market prices were developed both for present and future conditions of Hammarby Sjöstad, a neighborhood located in the south-east of Stockholm (Sweden). For each scenario, the technical and the comfort conditions were assessed. Additionally, the average cost of heat generation was estimated in terms of levelized cost of heat. This indicator enables a techno-economic comparison study among the different scenarios. In order to evaluate the levelized cost of heat, a yearly performance simulation of the energy infrastructure was implemented. The scenarios related to the current electricity prices show that distributed heat pumps can replace the district heating system by covering up to 30% of the heating demand. By lowering of 2°C, the minimum accepted indoor temperature of the apartments, this level of penetration can increase up to 40%. Within the future scenarios, if the electricity prices will increase, as most likely expected within the next decade, the penetration of distributed heat pumps can be limited to 15%. In terms of levelized cost of heat, a residential heat pump technology becomes competitive only within a scenario of decreasing electricity prices. In this case, a district heating system is characterized by an average cost of heat generation 7% higher compared to a distributed heat pumps option.

Keywords: cosimulation, distributed heat pumps, district heating, electrical distribution grid, integrated energy systems

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Authors: Majed Al Otaibi, Melissa Lessard-Beaudoin, Amel Loudghi, Raphael Chouinard-Watkins, Melanie Plourde, Frederic Calon, C. Alexandre Castellano, Stephen Cunnane, Helene Payette, Pierrette Gaudreau, Denis Gris, Rona K. Graham

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Introduction: Alzheimer disease (AD) is a chronic disorder that affects millions of individuals worldwide. Symptoms include memory dysfunction, and also alterations in attention, planning, language and overall cognitive function. Olfactory dysfunction is a common symptom of several neurological disorders including AD. Studying the mechanisms underlying the olfactory dysfunction may therefore lead to the discovery of potential biomarkers and/or treatments for neurodegenerative diseases. Objectives: To determine if olfactory dysfunction predicts future cognitive impairment in the aging population and to characterize the olfactory system in a murine model expressing a genetic factor of AD. Method: For the human study, quantitative olfactory tests (UPSIT and OMT) have been done on 93 subjects (aged 80 to 94 years) from the Quebec Longitudinal Study on Nutrition and Successful Aging (NuAge) cohort accepting to participate in the ORCA secondary study. The telephone Modified Mini Mental State examination (t-MMSE) was used to assess cognition levels, and an olfactory self-report was also collected. In a separate cohort, olfactory cortical volume was calculated using MRI results from healthy old adults (n=25) and patients with AD (n=18) using the AAL single-subject atlas and performed with the PNEURO tool (PMOD 3.7). For the murine study, we are using Western blotting, RT-PCR and immunohistochemistry. Result: Human Study: Based on the self-report, 81% of the participants claimed to not suffer from any problem with olfaction. However, based on the UPSIT, 94% of those subjects showed a poor olfactory performance and different forms of microsmia. Moreover, the results confirm that olfactory function declines with age. We also detected a significant decrease in olfactory cortical volume in AD individuals compared to controls. Murine study: Preliminary data demonstrate there is a significant decrease in expression levels of the proform of caspase-3 and the caspase substrate STK3, in the olfactory bulb of mice expressing human APOE4 compared with controls. In addition, there is a significant decrease in the expression level of the caspase-9 proform and caspase-8 active fragment. Analysis of the mature neuron marker, NeuN, shows decreased expression levels of both isoforms. The data also suggest that Iba-1 immunostaining is increased in the olfactory bulb of APOE4 mice compared to wild type mice. Conclusions: The activation of caspase-3 may be the cause of the decreased levels of STK3 through caspase cleavage and may play role in the inflammation observed. In the clinical study, our results suggest that seniors are unaware of their olfactory function status and therefore it is not sufficient to measure olfaction using the self-report in the elderly. Studying olfactory function and cognitive performance in the aging population will help to discover biomarkers in the early stage of the AD.

Keywords: Alzheimer's disease, APOE4, cognition, caspase, brain atrophy, neurodegenerative, olfactory dysfunction

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Authors: R. Pardo, P. Menendez, MA Gil-Olarte, S. Sanchez, E. García, R. Quintana, J. Martín

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Introduction : Within oncoplastic breast techniques there is increased interest in immediate partial breast reconstruction. The volume resected is greater than that of conventional conservative techniques. Central tumours of the breast have classically been treated with a mastectomy with regard to oncological safety and cosmetic secondary effects after wide central resection of the nipple and breast tissue beneath. Oncological results for central quadrantectomy have a recurrence level, disease- free period and survival identical to mastectomy. Grissoti flap is an oncoplastic surgical technique that allows the surgeon to perform a safe central quadrantectomy with excellent cosmetic results. Material and methods: The Grissoti flap is a glandular cutaneous advancement rotation flap that can fill the defect in the central portion of the excised breast. If the inferior border is affected by tumour and further surgery is decided upon at the Multidisciplinary Team Meeting, it will be necessary to perform a mastectomy. All patients with a Grisotti flap undergoing surgery since 2009 were reviewed obtaining the following data: age, hystopathological diagnosis, size, operating time, volume of tissue resected, postoperative admission time, re-excisions due to positive margins affected by tumour, wound dehiscence, complications and recurrence. Analysis and results of sentinel node biopsy were also obtained. Results: 12 patients underwent surgery between 2009-2015. The mean age was 54 years (34-67) . All had a preoperative diagnosis of ductal infiltrative carcinoma of less than 2 cm,. Diagnosis was made with Ultrasound, Mamography or both . Magnetic resonance was used in 5 cases. No patients had preoperative positive axilla after ultrasound exploration. Mean operating time was 104 minutes (84-130). Postoperative stay was 24 hours. Mean volume resected was 159 cc (70-286). In one patient the surgical border was affected by tumour and a further procedure with resection of the affected border was performed as ambulatory surgery. The sentinel node biopsy was positive for micrometastasis in only two cases. In one case lymphadenectomy was performed in 2009. In the other, treated in 2015, no lymphadenectomy was performed as the patient had a favourable histopathological prognosis and the multidisciplinary team meeting agreed that lymphadenectomy was not required. No recurrence has been diagnosed in any of the patients who underwent surgery and they are all disease free at present. Conclusions: Conservative surgery for retroareolar central tumours of the breast results in good local control of the disease with free surgical borders, including resection of the nipple areola complex and pectoral major muscle fascia. Reconstructive surgery with the inferior Grissoti flap adequately fills the defect after central quadrantectomy with creation of a new cutaneous disc where a new nipple areola complex is reconstructed with a local flap or micropigmentation. This avoids the need for contralateral symmetrization. Sentinel Node biopsy can be performed without added morbidity. When feasible, the Grissoti flap will avoid skin-sparing mastectomy for central breast tumours that will require the use of an expander, prosthesis or myocutaneous flap, with all the complications of a more complex operation.

Keywords: Grisotti flap, oncoplastic surgery, central tumours, breast

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