Search results for: fibroblast growth factor 21

Authors: Loyd R. Hook, Maryam Moharek

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With the envisioned future growth of low altitude urban aircraft operations for airborne delivery service and advanced air mobility, strategies to coordinate and deconflict aircraft flight paths must be prioritized. Autonomous coordination and planning of flight trajectories is the preferred approach to the future vision in order to increase safety, density, and efficiency over manual methods employed today. Difficulties arise because any conflict resolution must be constrained by all other aircraft, all airspace restrictions, and all ground-based obstacles in the vicinity. These considerations make pair-wise tactical deconfliction difficult at best and unlikely to find a suitable solution for the entire system of vehicles. In addition, more traditional methods which rely on long time scales and large protected zones will artificially limit vehicle density and drastically decrease efficiency. Instead, strategic planning, which is able to respond to highly dynamic conditions and still account for high density operations, will be required to coordinate multiple vehicles in the highly constrained low altitude urban environment. This paper develops and evaluates such a planning algorithm which can be implemented autonomously across multiple aircraft and situations. Data from this evaluation provide promising results with simulations showing up to 10 aircraft deconflicted through a relatively narrow low-altitude urban canyon without any vehicle to vehicle or obstacle conflict. The algorithm achieves this level of coordination beginning with the assumption that each vehicle is controlled to follow an independently constructed flight path, which is itself free of obstacle conflict and restricted airspace. Then, by preferencing speed change deconfliction maneuvers constrained by the vehicles flight envelope, vehicles can remain as close to the original planned path and prevent cascading vehicle to vehicle conflicts. Performing the search for a set of commands which can simultaneously ensure separation for each pair-wise aircraft interaction and optimize the total velocities of all the aircraft is further complicated by the fact that each aircraft's flight plan could contain multiple segments. This means that relative velocities will change when any aircraft achieves a waypoint and changes course. Additionally, the timing of when that aircraft will achieve a waypoint (or, more directly, the order upon which all of the aircraft will achieve their respective waypoints) will change with the commanded speed. Put all together, the continuous relative velocity of each vehicle pair and the discretized change in relative velocity at waypoints resembles a hybrid reachability problem - a form of control reachability. This paper proposes two methods for finding solutions to these multi-body problems. First, an analytical formulation of the continuous problem is developed with an exhaustive search of the combined state space. However, because of computational complexity, this technique is only computable for pairwise interactions. For more complicated scenarios, including the proposed 10 vehicle example, a discretized search space is used, and a depth-first search with early stopping is employed to find the first solution that solves the constraints.

Keywords: strategic planning, autonomous, aircraft, deconfliction

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Authors: Mala Mukherjee

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Background: India is urbanizing very fast and urbanisation in India is treated as one of the most crucial components of economic growth. Though the pace of urbanisation (31.6 per cent in 2011) is however slower and lower than the average for Asia but the absolute number of people residing in cities and towns has increased substantially. Rapid urbanization leads to urban poverty and it is well represented in slums. Currently India has four metropolises and 53 million plus cities. All of them have significant slum population but the standard of living and success of slum development programmes varies across regions. Objectives: Objectives of the paper are to show how urbanisation and slum development varies across space; to show spatial variation in the standard of living in Indian slums; to analyse how the implementation of slum development policies like JNNURM, Rajiv Awas Yojana varies across cities and bring different results in different regions and what are the factors responsible for such variation. Data Sources and Methodology: Census 2011 data on urban population and slum households and amenities have been used for analysing the regional variation of urbanisation in 53 million plus cities of India. Special focus has been put on Kolkata Metropolitan Area. Statistical techniques like z-score and PCA have been employed to work out Standard of Living Deprivation score for all the slums of 53 metropolises. ARC-GIS software is used for making maps. Standard of living has been measured in terms of access to basic amenities, infrastructure and assets like drinking water, sanitation, housing condition, bank account, and so on. Findings: 1. The first finding reveals that migration and urbanization is very high in Greater Mumbai, Delhi, Bangaluru, Chennai, Hyderabad and Kolkata; but slum population is high in Greater Mumbai (50% population live in slums), Meerut, Faridabad, Ludhiana, Nagpur, Kolkata etc. Though the rate of urbanization is high in southern and western states but the percentage of slum population is high in northern states (except Greater Mumbai). 2. Standard of Living also varies widely. Slums of Greater Mumbai and North Indian Cities score fairly high in the index indicating the fact that standard of living is high in those slums compare to the slums in eastern India (Dhanbad, Jamshedpur, Kolkata). Therefore, though Kolkata have relatively lesser percentage of slum population compare to north and south Indian cities but the standard of living in Kolkata’s slums is deplorable. 3. It is interesting to note that even within Kolkata Metropolitan Area slums located in the southern and eastern municipal towns like Rajpur-Sonarpur, Pujali, Diamond Harbour, Baduria and Dankuni have lower standard of living compare to the slums located in the Hooghly Industrial belt like Titagarh, Rishrah, Srerampore etc. Slums of the Hooghly Industrial Belt are older than the slums located in eastern and southern part of the urban agglomeration. 4. Therefore, urban development and emergence of slums should not be the only issue of urban governance but standard of living should be the main focus. Slums located in the main cities like Delhi, Mumbai, Kolkata get more attention from the urban planners and similarly, older slums in a city receives greater political attention compare to the slums of smaller cities and newly emerged slums of the peripheral parts.

Keywords: urbanisation, slum, spatial variation, India

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Authors: Ekaterina Zvorykina

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Nowadays, Arctic and Antarctic regions are distinguished to be one of the most important strategic resources for global development. Nonetheless, living conditions in Arctic regions still demand certain improvements. As soon as the region is rarely populated, one of the main points of interest is health accommodation of the people, who migrate to Arctic region for permanent and shift work. At Arctic and Antarctic latitudes, personnel face polar day and polar night conditions during the time of the year. It means that they are deprived of natural sunlight in winter season and have continuous daylight in summer. Firstly, the change in light intensity during 24-hours period due to migration affects circadian rhythms. Moreover, the controlled artificial light in winter is also an issue. The results of the recent studies on night shift medical professionals, who were exposed to permanent artificial light, have already demonstrated higher risks in cancer, depression, Alzheimer disease. Moreover, people exposed to frequent time zones change are also subjected to higher risks of heart attack and cancer. Thus, our main goals are to understand how high latitude work and living conditions can affect human health and how it can be prevented. In our study, we analyze molecular and cellular factors, which play important role in circadian rhythm change and distinguish main risk groups in people, migrating to high latitudes. The main well-studied index of circadian timing is melatonin or its metabolite 6-sulfatoxymelatonin. In low light intensity melatonin synthesis is disturbed and as a result human organism requires more time for sleep, which is still disregarded when it comes to working time organization. Lack of melatonin also causes shortage in serotonin production, which leads to higher depression risk. Melatonin is also known to inhibit oncogenes and increase apoptosis level in cells, the main factors for tumor growth, as well as circadian clock genes (for example Per2). Thus, people who work in high latitudes can be distinguished as a risk group for cancer diseases and demand more attention. Clock/Clock genes, known to be one of the main circadian clock regulators, decrease sensitivity of hypothalamus to estrogen and decrease glucose sensibility, which leads to premature aging and oestrous cycle disruption. Permanent light exposure also leads to accumulation superoxide dismutase and oxidative stress, which is one of the main factors for early dementia and Alzheimer disease. We propose a new screening system adjusted for people, migrating from middle to high latitudes and accommodation therapy. Screening is focused on melatonin and estrogen levels, sleep deprivation and neural disorders, depression level, cancer risks and heart and vascular disorders. Accommodation therapy includes different types artificial light exposure, additional melatonin and neuroprotectors. Preventive procedures can lead to increase of migration intensity to high latitudes and, as a result, the prosperity of Arctic region.

Keywords: circadian rhythm, high latitudes, melatonin, neuroprotectors

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Authors: Briohny H. Spencer, Russ Chess-Williams, Catherine McDermott, Shailendra Anoopkumar-Dukie, David Christie

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Background: Prostate cancer is the second most common cancer diagnosed in men worldwide and the most prevalent in Australian men. In 2015, it was estimated that approximately 18,000 new cases of prostate cancer were diagnosed in Australia. Currently, for localised disease, androgen depravation therapy (ADT) and radiotherapy are a major part of the curative management of prostate cancer. ADT acts to reduce the levels of circulating androgens, primarily testosterone and the locally produced androgen, dihydrotestosterone (DHT), or by preventing the subsequent activation of the androgen receptor. Thus, the growth of the cancerous cells can be reduced or ceased. Radiation techniques such as brachytherapy (radiation delivered directly to the prostate by transperineal implant) or external beam radiation therapy (exposure to a sufficient dose of radiation aimed at eradicating malignant cells) are also common techniques used in the treatment of this condition. Radiotherapy (RT) has significant limitations, including reduced effectiveness in treating malignant cells present in hypoxic microenvironments leading to radio-resistance and poor clinical outcomes and also the significant side effects for the patients. Alpha1-adrenoceptor antagonists are used for many prostate cancer patients to control lower urinary tract symptoms, due to the progression of the disease itself or may arise as an adverse effect of the radiotherapy treatment. In Australia, a significant number (not a majority) of patients receive a α1-ADR antagonist and four drugs are available including prazosin, terazosin, alfuzosin and tamsulosin. There is currently limited published data on the effects of α1-ADR antagonists during radiotherapy, but it suggests these medications may improve patient outcomes by enhancing the effect of radiotherapy. Aim: To determine the impact of α1-ADR antagonists treatments on time to biochemical relapse following radiotherapy. Methods: A retrospective study of male patients receiving radiotherapy for biopsy-proven localised prostate cancer was undertaken to compare cancer outcomes for drug-naïve patients and those receiving α1-ADR antagonist treatments. Ethical approval for the collection of data at Genesis CancerCare QLD was obtained and biochemical relapse (defined by a PSA rise of >2ng/mL above the nadir) was recorded in months. Rates of biochemical relapse, prostate specific antigen doubling time (PSADT) and Kaplan-Meier survival curves were also compared. Treatment groups were those receiving α1-ADR antagonists treatment before or concurrent with their radiotherapy. Data was statistically analysed using One-way ANOVA and results expressed as mean ± standard deviation. Major findings: The mean time to biochemical relapse for tamsulosin, prazosin, alfuzosin and controls were 45.3±17.4 (n=36), 41.5±19.6 (n=11), 29.3±6.02 (n=6) and 36.5±17.6 (n=16) months respectively. Tamsulosin, prazosin but not alfuzosin delayed time to biochemical relapse although the differences were not statistically significant. Conclusion: Preliminary data for the prior and/or concurrent use of tamsulosin and prazosin showed a positive trend in delaying time to biochemical relapse although no statistical significance was shown. Larger clinical studies are indicated and with thousands of patient records yet to be analysed, it may determine if there is a significant effect of these drugs on control of prostate cancer.

Keywords: alpha1-adrenoceptor antagonists, biochemical relapse, prostate cancer, radiotherapy

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Authors: Vipin Bhandari, Anupama Singh, Kopal Gupta

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Solid state fermentation, an eminent bioconversion technique for converting many biological substrates into a value-added product, has proven its role in the biotransformation of crops by nutritionally enriching them. Hence, an effort was made for nutritional enhancement of underutilized crops viz. barnyard millet, amaranthus and horse gram based composite flour using SSF. The grains were given pre-treatments before fermentation and these pre-treatments proved quite effective in diminishing the level of antinutrients in grains and in improving their nutritional characteristics. The present study deals with the enhancement of nutritional characteristics of underutilized crops viz. barnyard millet, amaranthus and horsegram based composite flour using solid state fermentation (SSF) as the principle bioconversion technique to convert the composite flour substrate into a nutritionally enriched value added product. Response surface methodology was used to design the experiments. The variables selected for the fermentation experiments were substrate particle size, substrate blend ratio, fermentation time, fermentation temperature and moisture content having three levels of each. Seventeen designed experiments were conducted randomly to find the effect of these variables on microbial count, reducing sugar, pH, total sugar, phytic acid and water absorption index. The data from all experiments were analyzed using Design Expert 8.0.6 and the response functions were developed using multiple regression analysis and second order models were fitted for each response. Results revealed that pretreatments proved quite handful in diminishing the level of antinutrients and thus enhancing the nutritional value of the grains appreciably, for instance, there was about 23% reduction in phytic acid levels after decortication of barnyard millet. The carbohydrate content of the decorticated barnyard millet increased to 81.5% from initial value of 65.2%. Similarly popping and puffing of horsegram and amaranthus respectively greatly reduced the trypsin inhibitor activity. Puffing of amaranthus also reduced the tannin content appreciably. Bacillus subtilis was used as the inoculating specie since it is known to produce phytases in solid state fermentation systems. These phytases remarkably reduce the phytic acid content which acts as a major antinutritional factor in food grains. Results of solid state fermentation experiments revealed that phytic acid levels reduced appreciably when fermentation was allowed to continue for 72 hours at a temperature of 35°C. Particle size and substrate blend ratio also affected the responses positively. All the parameters viz. substrate particle size, substrate blend ratio, fermentation time, fermentation temperature and moisture content affected the responses namely microbial count, reducing sugar, pH, total sugar, phytic acid and water absorption index but the effect of fermentation time was found to be most significant on all the responses. Statistical analysis resulted in the optimum conditions (particle size 355µ, substrate blend ratio 50:20:30 of barnyard millet, amaranthus and horsegram respectively, fermentation time 68 hrs, fermentation temperature 35°C and moisture content 47%) for maximum reduction in phytic acid. The model F- value was found to be highly significant at 1% level of significance in case of all the responses. Hence, second order model could be fitted to predict all the dependent parameters. The effect of fermentation time was found to be most significant as compared to other variables.

Keywords: composite flour, solid state fermentation, underutilized crops, cereals, fermentation technology, food processing

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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 the 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 the 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, 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 an attention mechanism. In previous works 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 the presence of large amounts of training examples, which may be difficult to compile in many real-world gene circuit designs.

Keywords: machine learning, classification and regression, gene circuit design, bidirectional transformers

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Authors: Rasha Elsawy

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Aside from the rapid growth of global information technology and the Internet, another key trend is the swift proliferation of wearable technologies. The future of wearable technologies is very bright as an emerging revolution in this technological world. Beyond this, individual continuance intention toward IT is an important area that drew academics' and practitioners' attention. The literature review exhibits that continuance usage is an important concern that needs to be addressed for any technology to be advantageous and for consumers to succeed. However, consumers noticeably abandon their wearable devices soon after purchase, losing all subsequent benefits that can only be achieved through continued usage. Purpose-This thesis aims to develop an integrated model designed to explain and predict consumers' behavioural intention(BI) and continued use (CU) of wearable fitness technology (WFT) to identify the determinants of the CU of technology. Because of this, the question arises as to whether there are differences between technology adoption and post-adoption (CU) factors. Design/methodology/approach- The study employs the unified theory of acceptance and use of technology2 (UTAUT2), which has the best explanatory power, as an underpinning framework—extending it with further factors, along with user-specific personal characteristics as moderators. All items will be adapted from previous literature and slightly modified according to the WFT/SW context. A longitudinal investigation will be carried out to examine the research model, wherein a survey will include these constructs involved in the conceptual model. A quantitative approach based on a questionnaire survey will collect data from existing wearable technology users. Data will be analysed using the structural equation modelling (SEM) method based on IBM SPSS statistics and AMOS 28.0. Findings- The research findings will provide unique perspectives on user behaviour, intention, and actual continuance usage when accepting WFT. Originality/value- Unlike previous works, the current thesis comprehensively explores factors that affect consumers' decisions to continue using wearable technology. That is influenced by technological/utilitarian, affective, emotional, psychological, and social factors, along with the role of proposed moderators. That novel research framework is proposed by extending the UTAUT2 model with additional contextual variables classified into Performance Expectancy, Effort Expectancy, Social Influence (societal pressure regarding body image), Facilitating Conditions, Hedonic Motivation (to be split up into two concepts: perceived enjoyment and perceived device annoyance), Price value, and Habit-forming techniques; adding technology upgradability as determinants of consumers' behavioural intention and continuance usage of Information Technology (IT). Further, using personality traits theory and proposing relevant user-specific personal characteristics (openness to technological innovativeness, conscientiousness in health, extraversion, neuroticism, and agreeableness) to moderate the research model. Thus, the present thesis obtains a more convincing explanation expected to provide theoretical foundations for future emerging IT (such as wearable fitness devices) research from a behavioural perspective.

Keywords: wearable technology, wearable fitness devices/smartwatches, continuance use, behavioural intention, upgradability, longitudinal study

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Authors: Muna Shafiq

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Growth in international immigration is a reflection of increased migration patterns in Canada and in other parts of the world. Canada continues to promote itself as a bilingual country, yet the bilingual French and English population numbers do not reflect this platform. Each province’s integration policies focus only on second language learning of either English or French. Moreover, since English Canadians outnumber French Canadians, maintaining, much less increasing, English-French bilingualism appears unrealistic. One solution to increasing Canadian bilingualism requires creating intercultural communication initiatives between youth in Quebec and the rest of Canada. Specifically, the focus is on active, experiential learning, where intercultural competencies develop outside traditional classroom settings. The target groups are Generation Y Millennials and Generation Z Linksters, the next generations in the career and parenthood lines. Today, Canada’s education system, like many others, must continually renegotiate lines between programs it offers its immigrant and native communities. While some purists or right-wing nationalists would disagree, the survival of bilingualism in Canada has little to do with reducing immigration. Children and youth immigrants play a valuable role in increasing Canada’s French and English speaking communities. For instance, a focus on more immersion, over core French education programs for immigrant children and youth would not only increase bilingual rates; it would develop meaningful intercultural attachments between Canadians. Moreover, a vigilant increase of funding in French immersion programs is critical, as are new initiatives that focus on experiential language learning for students in French and English language programs. A favorable argument supports the premise that other than French-speaking students in Québec and elsewhere in Canada, second and third generation immigrant students are excellent ambassadors to promote bilingualism in Canada. Most already speak another language at home and understand the value of speaking more than one language in their adopted communities. Their dialogue and participation in experiential language exchange workshops are necessary. If the proposed exchanges take place inter-provincially, the momentum to increase collective regional voices increases. This regional collectivity can unite Canadians differently than nation-targeted initiatives. The results from an experiential youth exchange organized in 2017 between students at the crossroads of Generation Y and Generation Z in Vancouver and Quebec City respectively offer a promising starting point in assessing the strength of bringing together different regional voices to promote bilingualism. Code-switching between standard, international French Vancouver students, learn in the classroom versus more regional forms of Quebec French spoken locally created regional connectivity between students. The exchange was equally rewarding for both groups. Increasing their appreciation for each other’s regional differences allowed them to contribute actively to their social and emotional development. Within a sociolinguistic frame, this proposed model of experiential learning does not focus on hands-on work experience. However, the benefits of such exchanges are as valuable as work experience initiatives developed in experiential education. Students who actively code switch between French and English in real, not simulated contexts appreciate bilingualism more meaningfully and experience its value in concrete terms.

Keywords: experiential learning, intercultural communication, social and emotional learning, sociolinguistic code-switching

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Authors: Dilnee D. Suraweera, Tim Groom, Brian Chung, Brendan Bond, Andrew Schipp, Marc E. Nicolas

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Pyrethrum (Tanacetum cinerariifolium) is a perennial plant belongs to family Asteraceae. This is cultivated commercially for extraction of natural insecticide pyrethrins, which accumulates in their flower head achenes. Approximately 94% of the pyrethrins are produced within secretory ducts and trichomes of achenes of the mature pyrethrum flower. This is the most widely used botanical insecticide in the world and Australia is the current largest pyrethrum producer in the world. Rainfall in pyrethrum growing regions in Australia during pyrethrum flowering period, in late spring and early summer is significantly less. Due to lack of adequate soil moisture and under elevated temperature conditions during post-anthesis period, resulting in yield reductions. Therefore, understanding of yield responses of pyrethrum to irrigation is important for Pyrethrum as a commercial crop. Irrigation management has been identified as a key area of pyrethrum crop management strategies that could be manipulated to increase yield. Pyrethrum is a comparatively drought tolerant plant and it has some ability to survive in dry conditions due to deep rooting. But in dry areas and in dry seasons, the crop cannot reach to its full yield potential without adequate soil moisture. Therefore, irrigation is essential during the flowering period prevent crop water stress and maximise yield. Irrigation during the water deficit period results in an overall increased rate of water uptake and growth by the plant which is essential to achieve the maximum yield benefits from commercial crops. The effects of irrigation treatments applied at post-anthesis period on pyrethrum yield responses were studied in two irrigation methods. This was conducted in a first harvest commercial pyrethrum field in Waubra, Victoria, during 2012/2013 season. Drip irrigation and overhead sprinkler irrigation treatments applied during whole flowering period were compared with ‘rainfed’ treatment in relation to flower yield and pyrethrin yield responses. The results of this experiment showed that the application of 180mm of irrigation throughout the post-anthesis period, from early flowering stages to physiological maturity under drip irrigation treatment increased pyrethrin concentration by 32%, which combined with the 95 % increase in the flower yield to give a total pyrethrin yield increase of 157%, compared to the ‘rainfed’ treatment. In contrast to that overhead sprinkler irrigation treatment increased pyrethrin concentration by 19%, which combined with the 60 % increase in the flower yield to give a total pyrethrin yield increase of 91%, compared to the ‘rainfed’ treatment. Irrigation treatments applied throughout the post-anthesis period significantly increased flower yield as a result of enhancement of number of flowers and flower size. Irrigation provides adequate soil moisture for flower development in pyrethrum which slows the rate of flower development and increases the length of the flowering period, resulting in a delayed crop harvest (11 days) compared to the ‘rainfed’ treatment. Overall, irrigation has a major impact on pyrethrin accumulation which increases the rate and duration of pyrethrin accumulation resulting in higher pyrethrin yield per flower at physiological maturity. The findings of this study will be important for future yield predictions and to develop advanced agronomic strategies to maximise pyrethrin yield in pyrethrum.

Keywords: achene, drip irrigation, overhead irrigation, pyrethrin

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Authors: Rui Pedro de Sousa Guimarães Ferreira, Carlos Alberto Maia Domínguez

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Despite the ambitions to achieve climate neutrality by 2050, to fulfill the Paris Agreement's goals, the building and construction sector remains one of the most resource-intensive and greenhouse gas-emitting industries in the world, accounting for 40% of worldwide CO ₂ emissions. Over the past few decades, globalization and population growth have led to an exponential rise in demand in the housing market and, by extension, in the building industry. Considering this housing crisis, it is obvious that we will not stop building in the near future. However, the transition, which has already started, is challenging and complex because it calls for the worldwide participation of numerous organizations in altering how building systems, which have been a part of our everyday existence for over a century, are used. Wood is one of the alternatives that is most frequently used nowadays (under responsible forestry conditions) because of its physical qualities and, most importantly, because it produces fewer carbon emissions during manufacturing than steel or concrete. Furthermore, as wood retains its capacity to store CO ₂ after application and throughout the life of the building, working as a natural carbon filter, it helps to reduce greenhouse gas emissions. After a century-long focus on other materials, in the last few decades, technological advancements have made it possible to innovate systems centered around the use of wood. However, there are still some questions that require further exploration. It is necessary to standardize production and manufacturing processes based on prefabrication and modularization principles to achieve greater precision and optimization of the solutions, decreasing building time, prices, and waste from raw materials. In addition, this approach will make it possible to develop new architectural solutions to solve the rigidity and irreversibility of buildings, two of the most important issues facing housing today. Most current models are still created as inflexible, fixed, monofunctional structures that discourage any kind of regeneration, based on matrices that sustain the conventional family's traditional model and are founded on rigid, impenetrable compartmentalization. Adaptability and flexibility in housing are, and always have been, necessities and key components of architecture. People today need to constantly adapt to their surroundings and themselves because of the fast-paced, disposable, and quickly obsolescent nature of modern items. Migrations on a global scale, different kinds of co-housing, or even personal changes are some of the new questions that buildings have to answer. Designing with the reversibility of construction systems and materials in mind not only allows for the concept of "looping" in construction, with environmental advantages that enable the development of a circular economy in the sector but also unleashes multiple social benefits. In this sense, it is imperative to develop prefabricated and modular construction systems able to address the formalization of a reversible proposition that adjusts to the scale of time and its multiple reformulations, many of which are unpredictable. We must allow buildings to change, grow, or shrink over their lifetime, respecting their nature and, finally, the nature of the people living in them. It´s the ability to anticipate the unexpected, adapt to social factors, and take account of demographic shifts in society to stabilize communities, the foundation of real innovative sustainability.

Keywords: modular, timber, flexibility, housing

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Authors: Chales Mumbere Musavandalo, Lucie B. Mugherwa, Gloire Kayitoghera Mulondi, Naanson Bweya, Muyisa Musongora, Francis Lelo Nzuzi

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The landscape of the Okapi Wildlife Reserve in the Democratic Republic of Congo harbors a large community of Mbuti indigenous peoples, often described as the guardians of nature. Living in and off the forest has long been a sustainable strategy for preserving natural resources. This strategy, seen as a form of eco-responsible citizenship, draws upon ethnobotanical knowledge passed down through generations. However, these indigenous communities are facing socio-cultural upheaval, which impacts their traditional way of life. This study aims to assess the relationship between the Mbuti indigenous people’s way of life and the preservation of the Okapi Wildlife Reserve. The study was conducted under the assumption that, despite socio-cultural upheavals, the forest and its resources remain central to the Mbuti way of life. The study was conducted in six encampments, three of which were located inside the forest and two in the anthropized zone. The methodological approach initially involved group interviews in six Mbuti encampments. The objective of these interviews was to determine how these people perceive the various services provided by the forest and the resources obtained from this habitat. The technique of using pebbles was adopted to adapt the exercise of weighting services and resources to the understanding of these people. Subsequently, the study carried out ethnobotanical surveys to identify the wood resources frequently used by these communities. This survey was completed in third position by a transect inventory of 1000 m length and 25 m width in order to enhance the understanding of the abundance of these resources around the camps. Two transects were installed in each camp to carry out this inventory. Traditionally, the Mbuti communities sustain their livelihood through hunting, fishing, gathering for self-consumption, and basketry. The Manniophyton fulvum-based net remains the main hunting tool. The primary forest and the swamp are two habitats from which these peoples derive the majority of their resources. However, with the arrival of the Bantu people, who introduced agriculture based on cocoa production, the Mbuti communities started providing services to the Bantu in the form of labor and field guarding. This cultural symbiosis between Mbute and Bantu has also led to non-traditional practices, such as the use of hunting rifles instead of nets and fishing nets instead of creels. The socio-economic and ecological environment in which Mbuti communities live is changing rapidly, including the resources they depend on. By incorporating the time factor into their perception of ecosystem services, only their future (p-value = 0, 0,121), the provision of wood for energy (p-value = 0,1976), and construction (p-value = 0,2548) would be closely associated with the forest in their future. For other services, such as food supply, medicine, and hunting, adaptation to Bantu customs is conceivable. Additionally, the abundance of wood used by the Mbuti people has been high around encampments located in intact forests and low in those in anthropized areas. The traditional way of life of the Mbuti communities is influenced by the cultural symbiosis, reflected in their habits and the availability of resources. The land tenure security of Mbuti areas is crucial to preserve their tradition and forest biodiversity. Conservation efforts in the Okapi Wildlife Reserve must consider this cultural dynamism and promote positive values for the flagship species. The oversight of subsistence hunting is imperative to curtail the transition of these communities to poaching.

Keywords: traditional life, conservation, Indigenous people, cultural symbiosis, forest

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Authors: Rewati Raman, Uttam K. Roy

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One of the main adversaries of city planning in present times is the ever-expanding problem of urbanization and the antagonistic issues accompanying it. The prevalent challenges in urbanization such as population growth, urban sprawl, poverty, inequality, pollution, congestion, etc. call for reforms in the urban fabric as well as in planning theory and practice. One of the various paradigms of city planning, land use planning, has been the major instruments for spatial planning of cities and regions in India. Zoning regulation based land use planning in the form of land use and development control plans (LUDCP) and development control regulations (DCR) have been considered mainstream guiding principles in land use planning for decades. In spite of many advantages of such zoning based regulations, over a period of time, it has been critiqued by scholars for its own limitations of isolation and lack of vitality, inconvenience in business in terms of proximity to residence and low operating cost, unsuitable environment for small investments, higher travel distance for facilities, amenities and thereby higher expenditure, safety issues etc. Mixed land use has been advocated as a tool to avoid such limitations in city planning by researchers. In addition, mixed land use can offer many advantages like housing variety and density, the creation of an economic blend of compatible land use, compact development, stronger neighborhood character, walkability, and generation of jobs, etc. Alternatively, the mixed land use beyond a suitable balance of use can also bring disadvantages like traffic congestion, encroachments, very high-density housing leading to a slum like condition, parking spill out, non-residential uses operating on residential premises paying less tax, chaos hampering residential privacy, pressure on existing infrastructure facilities, etc. This research aims at studying and outlining the various challenges and potentials of mixed land use zoning, through modeling tools, as a competent instrument for city planning in lieu of the present urban scenario. The methodology of research adopted in this paper involves the study of a mixed land use neighborhood in India, identification of indicators and parameters related to its extent and spatial pattern and the subsequent use of system dynamics as a modeling tool for simulation. The findings from this analysis helped in identifying the various advantages and challenges associated with the dynamic nature of a mixed use urban settlement. The results also confirmed the hypothesis that mixed use neighborhoods are catalysts for employment generation, socioeconomic gains while improving vibrancy, health, safety, and security. It is also seen that certain challenges related to chaos, lack of privacy and pollution prevail in mixed use neighborhoods, which can be mitigated by varying the percentage of mixing as per need, ensuring compatibility of adjoining use, institutional interventions in the form of policies, neighborhood micro-climatic interventions, etc. Therefore this paper gives a consolidated and holistic framework and quantified outcome pertaining to the extent and spatial pattern of mixed land use that should be adopted to ensure sustainable urban planning.

Keywords: mixed land use, sustainable development, system dynamics analysis, urban dynamics modelling

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Authors: Ellana Boada, Eric Santos-Clotas, Alba Cabrera-Codony, Maria Martin, Lluis Baneras, Frederic Gich

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Volatile methylsiloxanes (VMS) are a group of manmade silicone compounds widely used in household and industrial applications that end up on the biogas produced through the anaerobic digestion of organic matter in landfills and wastewater treatment plants. The presence of VMS during the biogas energy conversion can cause damage on the engines, reducing the efficiency of this renewable energy source. Non regenerative adsorption onto activated carbon is the most widely used technology to remove siloxanes from biogas, while new trends point out that biotechnology offers a low-cost and environmentally friendly alternative to conventional technologies. The first objective of this research was to enrich, isolate and identify bacterial species able to grow using siloxane molecules as a sole carbon source: anoxic wastewater sludge was used as initial inoculum in liquid anoxic enrichments, adding D4 (as representative siloxane compound) previously adsorbed on activated carbon. After several months of acclimatization, liquid enrichments were plated onto solid media containing D4 and thirty-four bacterial isolates were obtained. 16S rRNA gene sequencing allowed the identification of strains belonging to the following species: Ciceribacter lividus, Alicycliphilus denitrificans, Pseudomonas aeruginosa and Pseudomonas citronellolis which are described to be capable to degrade toxic volatile organic compounds. Kinetic assays with 8 representative strains revealed higher cell growth in the presence of D4 compared to the control. Our second objective was to characterize the community composition and diversity of the microbial community present in the enrichments and to elucidate whether the isolated strains were representative members of the community or not. DNA samples were extracted, the 16S rRNA gene was amplified (515F & 806R primer pair), and the microbiome analyzed from sequences obtained with a MiSeq PE250 platform. Results showed that the retrieved isolates only represented a minor fraction of the microorganisms present in the enrichment samples, which were represented by Alpha, Beta, and Gamma proteobacteria as dominant groups in the category class thus suggesting that other microbial species and/or consortia may be important for D4 biodegradation. These results highlight the need of additional protocols for the isolation of relevant D4 degraders. Currently, we are developing molecular tools targeting key genes involved in siloxane biodegradation to identify and quantify the capacity of the isolates to metabolize D4 in batch cultures supplied with a synthetic gas stream of air containing 60 mg m⁻³ of D4 together with other volatile organic compounds found in the biogas mixture (i.e. toluene, hexane and limonene). The isolates were used as inoculum in a biotrickling filter containing lava rocks and activated carbon to assess their capacity for siloxane removal. Preliminary results of biotrickling filter performance showed 35% of siloxane biodegradation in a contact time of 14 minutes, denoting that biological siloxane removal is a promising technology for biogas upgrading.

Keywords: bacterial cultivation, biogas upgrading, microbiome, siloxanes

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Authors: Jonathan Nii Laryea Ashong, Samuel Opare

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Current sustainable cities debate focuses on the formidable problems for the Ghana’s largest urban and rural agglomerations, the majority of all urban dwellers continue to reside in far smaller urban settlements. It is estimated that by year 2030, almost all the Ghana’s population growth will likely be intense in urban areas including Nkawkaw in the Kwahu West Municipality of Ghana. Nkawkaw is situated on the road and former railway between Accra and Kumasi, and lies about halfway between these cities. It is also connected by road to Koforidua and Konongo. According to the 2013 census, Nkawkaw has a settlement population of 61,785. Many international agencies, government and private architectures’ are been asked to adequately recognize the naming of streets and property addressing system among the 170 districts across Ghana. The naming of streets and numbering of properties is to assist Metropolitan, Municipal and District Assemblies to manage the processes for establishing coherent address system nationally. Street addressing in the Nkawkaw in the Kwahu West Municipality which makes it possible to identify the location of a parcel of land, public places or dwellings on the ground based on system of names and numbers, yet agreement on how to progress towards it remains elusive. Therefore, reliable and effective development control for proper street naming and property addressing systems are required. The Intelligent Addressing (IA) technology from the UK is being used to name streets and properties in Ghana. The intelligent addressing employs the technique of unique property Reference Number and the unique street reference number which would transform national security and other service providers’ ability to respond rapidly to distress calls. Where name change is warranted following the review of existing streets names, the Physical Planning Department (PPDs) shall, in consultation with the relevant traditional authorities and community leadership (or relevant major stakeholders), select a street name in accordance with the provisions of the policy and the processes outlined for street name change for new development. In the case of existing streets with no names, the respective PPDs shall, in consultation with the relevant traditional authorities and community leadership (or relevant major stakeholders), select a street name in accordance with the requirements set out in municipality. Naming of access ways proposed for new developments shall be done at the time of developing sector layouts (subdivision maps) for the designated areas. In the case of private gated developments, the developer shall submit the names of the access ways as part of the plan and other documentation forwarded to the Municipal District Assembly for approval. The names shall be reviewed first by the PPD to avoid duplication and to ensure conformity to the required standards before submission to the Assembly’s Statutory Planning Committee for approval. The Kwahu West Municipality is supposed to be self-sustaining, providing basic services to inhabitants as a result of proper planning layouts, street naming and property addressing system that prevail in the area. The implications of these future projections are discussed.

Keywords: Nkawkaw, Kwahu west municipality, street naming, property, addressing system

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Authors: Muhammad Hanif Amiri, Edris Sadeqy, Ahmad Freed Osman

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International Conference on Architectural Engineering and Skyscraper (ICAES 2016) on January 18 - 19, 2016 is aimed to exchange new ideas and application experiences face to face, to establish business or research relations and to find global partners for future collaboration. Therefore, we are very keen to participate and share our issues in order to get valuable feedbacks of the conference participants. Urbanization is a controversial issue all around the world. Substandard and unplanned urbanization has many implications on a social, cultural and economic situation of population life. Unplanned and illegal construction has become a critical issue in Afghanistan particularly Kabul city. In addition, lack of municipal bylaws, poor municipal governance, lack of development policies and strategies, budget limitation, low professional capacity of ainvolved private sector in development and poor coordination among stakeholders are the other factors which made the problem more complicated. The main purpose of this research paper is to review urbanization pattern of Kabul city and find out the improvement solutions and to evaluate the increasing of population density which caused vast illegal and unplanned development which finally converts the Kabul city to a slam area as the whole. The Kabul city Master Plan was reviewed in the year 1978 and revised for the planned 2million population. In 2001, the interim administration took place and the city became influx of returnees from neighbor countries and other provinces of Afghanistan mostly for the purpose of employment opportunities, security and better quality of life, therefore, Kabul faced with strange population growth. According to Central Statistics Organization of Afghanistan population of Kabul has been estimated approx. 5 million (2015), however a new Master Plan has been prepared in 2009, but the existing challenges have not been dissolved yet. On the other hand, 70% of Kabul population is living in unplanned (slam) area and facing the shortage of drinking water, inexistence of sewerage and drainage network, inexistence of proper management system for solid waste collection, lack of public transportation and traffic management, environmental degradation and the shortage of social infrastructure. Although there are many problems in Kabul city, but still the development of 22 townships are in progress which caused the great attraction of population. The research is completed with a detailed analysis on four main issues such as elimination of duplicated administrations, Development of regions, Rehabilitation and improvement of infrastructure, and prevention of new townships establishment in Kabul Central Core in order to mitigate the problems and constraints which are the foundation and principal to find the point of departure for an objective based future development of Kabul city. The closure has been defined to reflect the stage-wise development in light of prepared policy and strategies, development of a procedure for the improvement of infrastructure, conducting a preliminary EIA, defining scope of stakeholder’s contribution and preparation of project list for initial development. In conclusion this paper will help the transformation of Kabul city.

Keywords: development of regions, illegal construction, population density, urbanization pattern

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Authors: Adedayo B. Adegbaju, Carel B. Schoeman, Ilse M. Schoeman

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The unique urban contexts that emanated from the apartheid history of South Africa informed the transport landscape of the City of Johannesburg. Apartheid‘s divisive spatial planning and land use management policies promoted sprawling and separated workers from job opportunities. This was further exacerbated by poor funding of public transport and road designs that encouraged the use of private cars. However, the democratization of the country in 1994 and the hosting of the 2010 FIFA World Cup provided a new impetus to the city’s public transport-oriented urban planning inputs. At the same time, the state’s new approach to policy formulations that entails the provision of public transport as one of the tools to end years of marginalization and inequalities soon began to largely reflect in planning decisions of other spheres of government. The Rea Vaya BRT and the Gautrain were respectively implemented by the municipal and provincial governments to demonstrate strong political will and commitment to the new policy direction. While the Gautrain was implemented to facilitate elite movement within Gauteng and to crowd investments and economic growths around station nodes, the BRT was provided for previously marginalized public transport users to provide a sustainable alternative to the dominant minibus taxi. The aim of this research is to evaluate the spatial impacts of the Gautrain and Rea Vaya BRT on the City of Johannesburg and to inform future outcomes by determining the existing potentials. By using the case study approach with a focus on the BRT and fast rail in a metropolitan context, the triangulation research method, which combines various data collection methods, was used to determine the research outcomes. The use of interviews, questionnaires, field observation, and databases such as REX, Quantec, StatsSA, GCRO observatory, national and provincial household travel surveys, and the quality of life surveys provided the basis for data collection. The research concludes that the Gautrain has demonstrated that viable alternatives to the private car can be provided, with its satisfactory feedbacks from users; while some of its station nodes (Sandton, Rosebank) have shown promises of transit-oriented development, one of the project‘s key objectives. The other stations have been unable to stimulate growth due to reasons like non-implementation of their urban design frameworks and lack of public sector investment required to attract private investors. The Rea Vaya BRT continues to be expanded in spite of both its inability to induce modal change and its low ridership figures. The research identifies factors like the low peak to base ratio, pricing, and the city‘s disjointed urban fabric as some of the reasons for its below-average performance. By drawing from the highlights and limitations, the study recommends that public transport provision should be institutionally integrated across and within spheres of government. Similarly, harmonization of the funding structure, better understanding of users’ needs, and travel patterns, underlined with continuity of policy direction and objectives, will equally promote optimal outcomes.

Keywords: bus rapid transit, Gautrain, Rea Vaya, sustainable transport, spatial and transport planning, transit oriented development

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Authors: Tamar Lin, Nufar Buchshtab, Yifat Elharar, Julian Nicenboim, Rotem Edgar, Iddo Weiner, Lior Zelcbuch, Ariel Cohen, Sharon Kredo-Russo, Inbar Gahali-Sass, Naomi Zak, Sailaja Puttagunta, Merav Bassan

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Background: Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disorder that is characterized by dry skin and flares of eczematous lesions and intense pruritus. Multiple lines of evidence suggest that AD is associated with increased colonization by Staphylococcus aureus, which contributes to disease pathogenesis through the release of virulence factors that affect both keratinocytes and immune cells, leading to disruption of the skin barrier and immune cell dysfunction. The aim of the current study is to develop a bacteriophage-based product that specifically targets S. aureus. Methods: For the discovery of phage, environmental samples were screened on 118 S. aureus strains isolated from skin samples, followed by multiple enrichment steps. Natural phages were isolated, subjected to Next-generation Sequencing (NGS), and analyzed using proprietary bioinformatics tools for undesirable genes (toxins, antibiotic resistance genes, lysogeny potential), taxonomic classification, and purity. Phage host range was determined by an efficiency of plating (EOP) value above 0.1 and the ability of the cocktail to completely lyse liquid bacterial culture under different growth conditions (e.g., temperature, bacterial stage). Results: Sequencing analysis demonstrated that the 118 S. aureus clinical strains were distributed across the phylogenetic tree of all available Refseq S. aureus (~10,750 strains). Screening environmental samples on the S. aureus isolates resulted in the isolation of 50 lytic phages from different genera, including Silviavirus, Kayvirus, Podoviridae, and a novel unidentified phage. NGS sequencing confirmed the absence of toxic elements in the phages’ genomes. The host range of the individual phages, as measured by the efficiency of plating (EOP), ranged between 41% (48/118) to 79% (93/118). Host range studies in liquid culture revealed that a subset of the phages can infect a broad range of S. aureus strains in different metabolic states, including stationary state. Combining the single-phage EOP results of selected phages resulted in a broad host range cocktail which infected 92% (109/118) of the strains. When tested in vitro in a liquid infection assay, clearance was achieved in 87% (103/118) of the strains, with no evidence of phage resistance throughout the study (24 hours). A S. aureus host was identified that can be used for the production of all the phages in the cocktail at high titers suitable for large-scale manufacturing. This host was validated for the absence of contaminating prophages using advanced NGS methods combined with multiple production cycles. The phages are produced under optimized scale-up conditions and are being used for the development of a topical formulation (BX005) that may be administered to subjects with atopic dermatitis. Conclusions: A cocktail of natural phages targeting S. aureus was effective in reducing bacterial burden across multiple assays. Phage products may offer safe and effective steroid-sparing options for atopic dermatitis.

Keywords: atopic dermatitis, bacteriophage cocktail, host range, Staphylococcus aureus

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Authors: V. Howard, R. Maguire, S. Corrigan

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Background: Type 1 Diabetes (T1D) is a chronic autoimmune disease, typically diagnosed in childhood. T1D puts an enormous strain on families; controlling blood-glucose in children is difficult and the consequences of poor control for patient health are significant. Successful illness management and better health outcomes can be dependent on quality of caregiving. On diagnosis, parent-caregivers face a steep learning curve as T1D care requires a significant level of knowledge to inform complex decision making throughout the day. The majority of illness management is carried out in the home setting, independent of clinical health providers. Parent-caregivers vary in their level of knowledge and their level of engagement in applying this knowledge in the practice of illness management. Enabling researchers to quantify these aspects of the caregiver experience is key to identifying targets for psychosocial support interventions, which are desirable for reducing stress and anxiety in this highly burdened cohort, and supporting better health outcomes in children. Currently, there are limited tools available that are designed to capture this information. Where tools do exist, they are not comprehensive and do not adequately capture the lived experience. Objectives: Development of quantitative tools, informed by lived experience, to enable researchers gather data on parent-caregiver knowledge and engagement, which accurately represents the experience/cohort and enables exploration of questions that are of real-world value to the cohort themselves. Methods: This research employed an engaged approach to address the problem of quantifying two key aspects of caregiver diabetes management: Knowledge and engagement. The research process was multi-staged and iterative. Stage 1: Working from a constructivist standpoint, literature was reviewed to identify relevant questionnaires, scales and single-item measures of T1D caregiver knowledge and engagement, and harvest candidate questionnaire items. Stage 2: Aggregated findings from the review were circulated among a PPI (patient and public involvement) expert panel of caregivers (n=6), for discussion and feedback. Stage 3: In collaboration with the expert panel, data were interpreted through the lens of lived experience to create a long-list of candidate items for novel questionnaires. Items were categorized as either ‘knowledge’ or ‘engagement’. Stage 4: A Delphi-method process (iterative surveys) was used to prioritize question items and generate novel questions that further captured the lived experience. Stage 5: Both questionnaires were piloted to refine wording of text to increase accessibility and limit socially desirable responding. Stage 6: Tools were piloted using an online survey that was deployed using an online peer-support group for caregivers for Juveniles with T1D. Ongoing Research: 123 parent-caregivers completed the survey. Data analysis is ongoing to establish face and content validity qualitatively and through exploratory factor analysis. Reliability will be established using an alternative-form method and Cronbach’s alpha will assess internal consistency. Work will be completed by early 2024. Conclusion: These tools will enable researchers to gain deeper insights into caregiving practices among parents of juveniles with T1D. Development was driven by lived experience, illustrating the value of engaged research at all levels of the research process.

Keywords: caregiving, engaged research, juvenile type 1 diabetes, quantified engagement and knowledge

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Authors: Lizinis Cassendra Frederick Dony, Jirom Jeremy Frederick Dony, Andrew Nicholas, Dewi Binti Tajuddin

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Starting and surviving a business is influenced by various entrepreneurship socio-economics activities. The study revealed that some of the entrepreneurs are not registered under SME but running own business as an intermediary with the private organization entrusted as “Self-Employed.” SME is known as “Small Medium Enterprise” contributes growth in Malaysia. Therefore, the entrepreneurialism business interest and entrepreneurial intention enhancing new spurring production, expanding employment opportunities, increasing productivity, promoting exports, stimulating innovation and providing new avenue in the business market place. This study has identified the unique contribution to the full understanding of complex mechanisms through entrepreneurship obstacles and education impacts on happiness and well-being to society. Moreover, “Ethnic” term has defined as a curious meaning refers to a classification of a large group of people customs implies to ancestral, racial, national, tribal, religious, linguistic and cultural origins. It is a social phenomenon.1 According to Sabah data population is amounting to 2,389,494 showed the predominant ethnic group being the Kadazan Dusun (18.4%) followed by Bajau (17.3%) and Malays (15.3%). For the year 2010, data statistic immigrants population report showed the amount to 239,765 people which cover 4% of the Sabahan’s population.2 Sabah has numerous group of talented entrepreneurs. The business environment among the minority ethnics are influenced with the business sentiment competition. The literature on ethnic entrepreneurship recognizes two main type entrepreneurships: the middleman and enclave entrepreneurs. According to Adam Smith,3 there are evidently some principles disposition to admire and maintain the distinction business rank status and cause most universal business sentiments. Due to credit barriers competition, the minority ethnics are losing the business market and since 2014, many illegal immigrants have been found to be using permits of the locals to operate businesses in Malaysia.4 The development of small business entrepreneurship among the minority ethnics in Sabah evidenced based variety of complex perception and differences concepts. The studies also confirmed the effects of heterogeneity on group decision and thinking caused partly by excessive pre-occupation with maintaining cohesiveness and the presence of cultural diversity in groups should reduce its probability.5 The researchers proposed that there are seven success determinants particularly to determine the involvement of minority ethnics comparing to the involvement of the immigrants in Sabah. Although, (SMEs) have always been considered the backbone of the economy development, the minority ethnics are often categorized it as the “second-choice.’ The study showed that illegal immigrants entrepreneur imposed a burden on Sabahan social programs as well as the prison, court and health care systems. The tension between the need for cheap labor and the impulse to protect Malaysian in Sabah workers, entrepreneurs and taxpayers, among the subjects discussed in this study. This is clearly can be advantages and disadvantages to the Sabah economic development.

Keywords: entrepreneurial firms, self-employed, immigrants, minority ethnic, economic impacts

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Authors: Sergey Kozlov, Juliya Kozlova

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Introduction: The increased attention of researchers to an explosive trauma around the world is associated with a constant renewal of military weapons and a significant increase in terrorist activities using explosive devices. Explosive wave is a well known damaging factor of explosion. The most sensitive to the action of explosive wave in the human body are the head brain, lungs, intestines, urine bladder. The severity of damage to these organs depends on the distance from the explosion epicenter to the object, the power of the explosion, presence of barriers, parameters of the body position, and the presence of protective clothing. One of the places where a shock wave acts, in human tissues and organs, is the vascular endothelial barrier, which suffers the greatest damage in the head brain and lungs. The objective of the study was to determine the pathomorphological changes of the head brain followed the action of explosive wave. Materials and methods of research: To achieve the purpose of the study, there have been studied 6 male corpses delivered to the morgue of Municipal Institution "Dnipropetrovsk regional forensic bureau" during 2014-2016 years. The cause of death of those killed was a military explosive injury. After a visual external assessment of the head brain, for histological study there was conducted the 1 x 1 x 1 cm/piece sampling from different parts of the head brain, i.e. the frontal, parietal, temporal, occipital sites, and also from the cerebellum, pons, medulla oblongata, thalamus, walls of the lateral ventricles, the bottom of the 4th ventricle. Pieces of the head brain were immersed in 10% formalin solution for 24 hours. After fixing, the paraffin blocks were made from the material using the standard method. Then, using a microtome, there were made sections of 4-6 micron thickness from paraffin blocks which then were stained with hematoxylin and eosin. Microscopic analysis was performed using a light microscope with x4, x10, x40 lenses. Results of the study: According to the results of our study, injuries of the head brain were divided into macroscopic and microscopic. Macroscopic injuries were marked according to the results of visual assessment of haemorrhages under the membranes and into the substance, their nature, and localisation, areas of softening. In the microscopic study, our attention was drawn to both vascular changes and those of neurons and glial cells. Microscopic qualitative analysis of histological sections of different parts of the head brain revealed a number of structural changes both at the cellular and tissue levels. Typical changes in most of the studied areas of the head brain included damages of the vascular system. The most characteristic microscopic sign was the separation of vascular walls from neuroglia with the formation of perivascular space. Along with this sign, wall fragmentation of these vessels, haemolysis of erythrocytes, formation of haemorrhages in the newly formed perivascular spaces were found. In addition to damages of the cerebrovascular system, destruction of the neurons, presence of oedema of the brain tissue were observed in the histological sections of the brain. On some sections, the head brain had a heterogeneous step-like or wave-like nature. Conclusions: The pathomorphological microscopic changes in the brain, identified in the study on the died of explosive traumas, can be used for diagnostic purposes in conjunction with other characteristic signs of explosive trauma in forensic and pathological studies. The complex of microscopic signs in the head brain, i.e. separation of blood vessel walls from neuroglia with the perivascular space formation, fragmentation of walls of these blood vessels, erythrocyte haemolysis, formation of haemorrhages in the newly formed perivascular spaces is the direct indication of explosive wave action.

Keywords: blast wave, neurotrauma, human, brain

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Authors: Priyanka Yadav, Umesh Bnasal, Yashvinder Kumar

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The placenta is an important structure that provides oxygen and nutrients to the growing fetus in utero. It is usually thrown away after birth, but it has a therapeutic role in the regeneration of tissue. It is covered by the amniotic membrane, which can be easily separated into the amnion layer and the chorion layer—the amnion layer act as a biofilm for the healing of burn wound and non-healing ulcers. The freshly collected membrane has stem cells, cytokines, growth factors, and anti-inflammatory properties, which act as a biofilm for the healing of wounds. It functions as a barrier and prevents heat and water loss and also protects from bacterial contamination, thus supporting the healing process. The application of Amnion membranes has been successfully used for wound and reconstructive purposes for decades. It is a very cheap and easy process and has shown superior results to allograft and xenograft. However, there are very few case reports of amnion membrane grafting in newborns; we intend to highlight its therapeutic importance in burn injuries in newborns. We present a case of 9 days old male neonate who presented to the neonatal unit of Maulana Azad Medical College with a complaint of fluid-filled blisters and burns wound on the body for six days. He was born outside the hospital at 38 weeks of gestation to a 24-year-old primigravida mother by vaginal delivery. The presentation was cephalic and the amniotic fluid was clear. His birth weight was 2800 gm and APGAR scores were 7 and 8 at 1 and 5 minutes, respectively. His anthropometry was appropriate for gestational age. He developed respiratory distress after birth requiring oxygen support by nasal prongs for three days. On the day of life three, he developed blisters on his body, starting from than face then over the back and perineal region. At a presentation on the day of life nine, he had blisters and necrotic wound on the right side of the face, back, right shoulder and genitalia, affecting 60% of body surface area with full-thickness loss of skin. He was started on intravenous antibiotics and fluid therapy. Pus culture grew Pseudomonas aeuroginosa, for which culture-specific antibiotics were started. Plastic surgery reference was taken and regular wound dressing was done with antiseptics. He had a storming course during the hospital stay. On the day of life 35 when the baby was hemodynamically stable, amnion membrane grafting was done on the wound site; for the grafting, fresh amnion membrane was removed under sterile conditions from the placenta obtained by caesarean section. It was then transported to the plastic surgery unit in half an hour in a sterile fluid where the graft was applied over the infant’s wound. The amnion membrane grafting was done twice in two weeks for covering the whole wound area. After successful uptake of amnion membrane, skin from the thigh region was autografted over the whole wound area by Meek technique in a single setting. The uptake of autograft was excellent and most of the areas were healed. In some areas, there was patchy regeneration of skin so dressing was continued. The infant was discharged after three months of hospital stay and was later followed up in the plastic surgery unit of the hospital.

Keywords: amnion membrane grafting, autograft, meek technique, newborn, regeneration of skin

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Authors: Kyriaki Hatziagapiou, Konstantinos Bethanis, Olti Nikola, Elias Christoforides, Eleni Koniari, Eleni Kakouri, George Lambrou, Christina Kanaka-Gantenbein

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Glioblastoma multiforme (GBM) remains a serious health challenge, as current therapeutic modalities continue to yield unsatisfactory results, with the average survival rarely exceeding 1-2 years. Natural compounds still provide some of the most promising approaches for discovering new drugs. The non-psychotropic cannabidiol (CBD) deriving from Cannabis sativa L. provides such promise. CBD is endowed with anticancer, antioxidant, and genoprotective properties as established in vitro and in in vivo experiments. CBD’s selectivity towards cancer cells and its safe profile suggest its usage in cancer therapies. However, the bioavailability of oral CBD is low due to poor aqueous solubility, erratic gastrointestinal absorption, and significant first-pass metabolism, hampering its therapeutic potential and resulting in a variable pharmacokinetic profile. In this context, CBD can take great advantage of nanomedicine-based formulation strategies. Cyclodextrins (CDs) are cyclic oligosaccharides used in the pharmaceutical industry to incorporate apolar molecules inside their hydrophobic cavity, increasing their stability, water solubility, and bioavailability or decreasing their side effects. CBD-inclusion complexes with CDs could be a good strategy to improve its properties, like solubility and stability to harness its full therapeutic potential. The current research aims to study the potential cytotoxic effect of CBD and CBD-CDs complexes CBD-RMβCD (randomly methylated β-cyclodextrin) and CBD-HPβCD (hydroxypropyl-b-CD) on the A172 glioblastoma cell line. CBD is diluted in 10% DMSO, and CBD/CDs solutions are prepared by mixing solid CBD, solid CDs, and dH2O. For the biological assays, A172 cells are incubated at a range of concentrations of CBD, CBD-RMβCD and CBD-HPβCD, RMβCD, and HPβCD (0,03125-4 mg/ml) at 24, 48, and 72 hours. Analysis of cell viability after incubation with the compounds is performed with Alamar Blue viability assay. CBD’s dilution to DMSO 10% was inadequate, as crystals are observed; thus cytotoxicity experiments are not assessed. CBD’s solubility is enhanced in the presence of both CDs. CBD/CDs exert significant cytotoxicity in a dose and time-dependent manner (p < 0.005 for exposed cells to any concentration at 48, 72, and 96 hours versus cells not exposed); as their concentration and time of exposure increases, the reduction of resazurin to resofurin decreases, indicating a reduction in cell viability. The cytotoxic effect is more pronounced in cells exposed to CBD-HPβCD for all concentrations and time-points. RMβCD and HPβCD at the highest concentration of 4 mg/ml also exerted antitumor action per se since manifesting cell growth inhibition. The results of our study could afford the basis of research regarding the use of natural products and their inclusion complexes as anticancer agents and the shift to targeted therapy with higher efficacy and limited toxicity. Acknowledgments: The research is partly funded by ΙΚΥ (State Scholarships Foundation) – Post-doc Scholarships-Partnership Agreement 2014-2020.

Keywords: cannabidiol, cyclodextrins, glioblastoma, hydroxypropyl-b-Cyclodextrin, randomly-methylated-β-cyclodextrin

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Authors: Suman Chaudhary, Rupinder K. Kanwar, Jagat R. Kanwar

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Azadirachta indica, also known as Neem belonging to the mahogany family is actively gaining interest in the era of modern day medicine due to its extensive applications in homeopathic medicine such as Ayurveda and Unani. More than 140 phytochemicals have been extracted from neem leaves, seed, bark and flowers for agro-medicinal applications. Among the various components, neem leaf protein (NLP) is currently the most investigated active ingredient, due to its immunomodulatory activities against tumor growth. However, these therapeutic ingredients of neem are susceptible to degradation and cannot withstand the drastic pH changes under physiological environment, and therefore, there is an urgent need of an alternative strategy such as a nano-delivery system to exploit its medicinal benefits. This study hypothesizes that guar gum (GG) derived biodegradable nano-carrier based encapsulation of NLP will improve its stability, specificity and sensitivity, thus facilitating targeted anti-cancer therapeutics. GG is a galactomannan derived from the endosperm of the guar beans seeds. Synthesis of guar nanocapsules (NCs) was performed using nanoprecipitation technique where the GG was encapsulated with NLP. Preliminary experiments conducted to characterize the NCs confirmed spherical morphology with a narrow size distribution of 30-40 nm. Differential scanning colorimetric analysis (DSC) validated the stability of these NCs even at a temperature range of 50-60°C which was well within the physiological and storage conditions. Thermogravimetric (TGA) analysis indicated high decomposition temperature of these NCs ranging upto 350°C. Additionally, Fourier Transform Infrared spectroscopy (FTIR) and the SDS-PAGE data acquired confirmed the successful encapsulation of NLP in the NCs. The anti-cancerous therapeutic property of this NC was tested on colon cancer cells (caco-2) as they are one of the most prevalent form of cancer. These NCs (both NLP loaded and void) were also tested on human intestinal epithelial cells (FHs 74) cells to evaluate their effect on normal cells. Cytotoxicity evaluation of the NCs in the cell lines confirmed that the IC50 for NLP in FHs 74 cells was ~2 fold higher than in caco-2 cells, indicating that this nanoformulation system possessed biocompatible anti-cancerous properties Immunoconfocal microscopy analysis confirmed the time dependent internalization of the NCs within 6h. Recent findings performed using Annexin V and PI staining indicated a significant increase (p ≤ 0.001) in the early and late apoptotic cell population when treated with the NCs signifying the role of NLP in inducing apoptosis in caco-2 cells. This was further validated using Western blot, Polymerase chain reaction (PCR) and Fluorescence activated cell sorter (FACS) aided protein expressional analysis which presented a downregulation of survivin, an anti-apoptotic cell marker and upregulation of Bax/Bcl-2 ratio (pro-apoptotic indicator). Further, both the NLP NC and unencapsulated NLP treatment destabilized the mitochondrial membrane potential subsequently facilitating the release of the pro-apoptotic caspase cascade initiator, cytochrome-c. Future studies will be focused towards granting specificity to these NCs towards cancer cells, along with a comprehensive analysis of the anti-cancer potential of this naturally occurring compound in different cancer and in vivo animal models, will validate the clinical application of this unprecedented protein therapeutic.

Keywords: anti-tumor, guar gum, nanocapsules, neem leaf protein

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Authors: Sajeli A. Begum, Ameer Basha, Kirti Hira, Rukaiyya Khan

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Cyclic dipeptides are simple diketopiperazine derivatives being investigated by several scientists for their biological effects which include anticancer, antimicrobial, haematological, anticonvulsant, immunomodulatory effect, etc. They are potentially active microbial metabolites having been synthesized too, for developing into drug candidates. Cultures of Pseudomonas species have earlier been reported to produce cyclic dipeptides, helping in quorum sensing signals and bacterial–host colonization phenomena during infections, causing cell anti-proliferation and immunosuppression. Fluorescing Pseudomonas species have been identified to secrete lipid derivatives, peptides, pyrroles, phenazines, indoles, aminoacids, pterines, pseudomonic acids and some antibiotics. In the present work, results of investigation on the cyclic dipeptide metabolites secreted by the culture broth of Pseudomonas species as potent pro-inflammatory cytokine inhibitors are discussed. The bacterial strain was isolated from the rhizospheric soil of groundnut crop and identified as Pseudomonas aeruginosa by 16S rDNA sequence (GenBank Accession No. KT625586). Culture broth of this strain was prepared by inoculating into King’s B broth and incubating at 30 ºC for 7 days. The ethyl acetate extract of culture broth was prepared and lyophilized to get a dry residue (EEPA). Lipopolysaccharide (LPS)-induced ELISA assay proved the inhibition of tumor necrosis factor-alpha (TNF-α) secretion in culture supernatant of RAW 264.7 cells by EEPA (IC50 38.8 μg/mL). The effect of oral administration of EEPA on plasma TNF-α level in rats was tested by ELISA kit. The LPS mediated plasma TNF-α level was reduced to 45% with 125 mg/kg dose of EEPA. Isolation of the chemical constituents of EEPA through column chromatography yielded ten cyclic dipeptides, which were characterized using nuclear magnetic resonance and mass spectroscopic techniques. These cyclic dipeptides are biosynthesized in microorganisms by multifunctional assembly of non-ribosomal peptide synthases and cyclic dipeptide synthase. Cyclo (Gly-L-Pro) was found to be more potentially (IC50 value 4.5 μg/mL) inhibiting TNF-α production followed by cyclo (trans-4-hydroxy-L-Pro-L-Phe) (IC50 value 14.2 μg/mL) and the effect was equal to that of standard immunosuppressant drug, prednisolone. Further, the effect was analyzed by determining mRNA expression of TNF-α in LPS-stimulated RAW 264.7 macrophages using quantitative real-time reverse transcription polymerase chain reaction. EEPA and isolated cyclic dipeptides demonstrated diminution of TNF-α mRNA expression levels in a dose-dependent manner under the tested conditions. Also, they were found to control the expression of other pro-inflammatory cytokines like IL-1β and IL-6, when tested through their mRNA expression levels in LPS-stimulated RAW 264.7 macrophages under LPS-stimulated conditions. In addition, significant inhibition effect was found on Nitric oxide production. Further all the compounds exhibited weak toxicity to LPS-induced RAW 264.7 cells. Thus the outcome of the study disclosed the effectiveness of EEPA and the isolated cyclic dipeptides in down-regulating key cytokines involved in pathophysiology of autoimmune diseases.In another study led by the investigators, microbial cyclic dipeptides were found to exhibit excellent antimicrobial effect against Fusarium moniliforme which is an important causative agent of Sorghum grain mold disease. Thus, cyclic dipeptides are emerging small molecular drug candidates for various autoimmune diseases.

Keywords: cyclic dipeptides, cytokines, Fusarium moniliforme, Pseudomonas, TNF-alpha

Procedia PDF Downloads 185

Authors: Marco F. Benaglia, Mei H. Chen, Kune M. Tsai, Chia H. Hung

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As societal and family structures, consumer dietary habits, and awareness about food safety and quality continue to evolve in most developed countries, the demand for refrigerated and frozen foods has been growing, and the issues related to their preservation have gained increasing attention. A well-established cold chain logistics system is essential to avoid any temperature abuse; therefore, assessing potential disruptions in the operational processes of cold chain logistics centers becomes pivotal. This study preliminarily employs HACCP to find disruption factors in cold chain logistics centers that may cause temperature abuse. Then, concept mapping is applied: selected experts engage in brainstorming sessions to identify any further factors. The panel consists of ten experts, including four from logistics and home delivery, two from retail distribution, one from the food industry, two from low-temperature logistics centers, and one from the freight industry. Disruptions include equipment-related aspects, human factors, management aspects, and process-related considerations. The areas of observation encompass freezer rooms, refrigerated storage areas, loading docks, sorting areas, and vehicle parking zones. The experts also categorize the disruption factors based on perceived similarities and build a similarity matrix. Each factor is evaluated for its impact, frequency, and investment importance. Next, multiple scale analysis, cluster analysis, and other methods are used to analyze these factors. Simultaneously, key disruption factors are identified based on their impact and frequency, and, subsequently, the factors that companies prioritize and are willing to invest in are determined by assessing investors’ risk aversion behavior. Finally, Cumulative Prospect Theory (CPT) is applied to verify the risk patterns. 66 disruption factors are found and categorized into six clusters: (1) "Inappropriate Use and Maintenance of Hardware and Software Facilities", (2) "Inadequate Management and Operational Negligence", (3) "Product Characteristics Affecting Quality and Inappropriate Packaging", (4) "Poor Control of Operation Timing and Missing Distribution Processing", (5) "Inadequate Planning for Peak Periods and Poor Process Planning", and (6) "Insufficient Cold Chain Awareness and Inadequate Training of Personnel". This study also identifies five critical factors in the operational processes of cold chain logistics centers: "Lack of Personnel’s Awareness Regarding Cold Chain Quality", "Personnel Not Following Standard Operating Procedures", "Personnel’s Operational Negligence", "Management’s Inadequacy", and "Lack of Personnel’s Knowledge About Cold Chain". The findings show that cold chain operators prioritize prevention and improvement efforts in the "Inappropriate Use and Maintenance of Hardware and Software Facilities" cluster, particularly focusing on the factors of "Temperature Setting Errors" and "Management’s Inadequacy". However, through the application of CPT theory, this study reveals that companies are not usually willing to invest in the improvement of factors related to the "Inappropriate Use and Maintenance of Hardware and Software Facilities" cluster due to its low occurrence likelihood, but they acknowledge the severity of the consequences if it does occur. Hence, the main implication is that the key disruption factors in cold chain logistics centers’ processes are associated with personnel issues; therefore, comprehensive training, periodic audits, and the establishment of reasonable incentives and penalties for both new employees and managers may significantly reduce disruption issues.

Keywords: concept mapping, cold chain, HACCP, cumulative prospect theory

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

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

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

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Authors: Michelle C. S. Azevedo, Priscila M. Colavite, Carolina F. Francisconi, Ana P. Trombone, Gustavo P. Garlet

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VIP (vasoactive intestinal peptide) know as a potential protective factor in the view of its marked immunosuppressive properties. In this work, we investigated a possible association of VIP with the clinical status of experimental periapical granulomas and the association with expression markers in the lesions potentially associated with periapical lesions pathogenesis. C57BL/6WT mice were treated or not with recombinant VIP. Animals with active/progressive (N=40), inactive/stable (N=70) periapical granulomas and controls (N=50) were anesthetized and the right mandibular first molar was surgically opened, allowing exposure of dental pulp. Endodontic pathogenic bacterial strains were inoculated: Porphyromonas gingivalis, Prevotella nigrescens, Actinomyces viscosus, and Fusobacterium nucleatum subsp. polymorphum. The cavity was not sealed after bacterial inoculation. During lesion development, animals were treated or not with recombinant VIP 3 days post infection. Animals were killed after 3, 7, 14, and 21 days of infection and the jaws were dissected. The extraction of total RNA from periodontal tissues was performed and the integrity of samples was checked. qPCR reaction using TaqMan chemistry with inventoried primers were performed in ViiA7 equipment. The results, depicted as the relative levels of gene expression, were calculated in reference to GAPDH and β-actin expression. Periodontal tissues from upper molars were vested and incubated supplemented RPMI, followed by processing with 0.05% DNase. Cell viability and couting were determined by Neubauer chamber analysis. For flow cytometry analysis, after cell counting the cells were stained with the optimal dilution of each antibody; (PE)-conjugated and (FITC)-conjugated antibodies against CD4, CD25, FOXP3, IL-4, IL-17 and IFN-γ antibodies, as well their respective isotype controls. Cells were analyzed by FACScan and CellQuest software. Results are presented as the number of cells in the periodontal tissues or the number of positive cells for each marker in the CD4+FOXp3+, CD4+IL-4+, CD4+IFNg+ and CD4+IL-17+ subpopulations. The levels mRNA were measured by qPCR. The VIP expression was predominated in inactive lesions, as well part of the clusters of cytokine/Th markers identified as protective factors and a negative correlation between VIP expression and lesion evolution was observed. A quantitative analysis of IL1β, IL17, TNF, IFN, MMP2, RANKL, OPG, IL10, TGFβ, CTLA4, COL5A1, CTGF, CXCL11, FGF7, ITGA4, ITGA5, SERP1 and VTN expression was measured in experimental periapical lesions treated with VIP 7 and 14 days after lesion induction and healthy animals. After 7 days, all targets presented a significate increase in comparison to untreated animals. About migration kinetics, profile of chemokine receptors expression of TCD4+ subsets and phenotypic analysis of Tregs, Th1, Th2 and Th17 cells during the course of experimental periodontal disease evaluated by flow cytometry and depicted as the number of positive cells for each marker. CD4+IFNg+ and CD4+FOXp3+ cells migration were significate increased 7 days post VIP treatment. CD4+IL17+ cells migration were significate increased 7 and 14 days post VIP treatment, CD4+IL4+ cells migration were significate increased 14 and 21 days post VIP treatment compared to the control group. In conclusion, our experimental data support VIP involvement in determining the inactivity of periapical lesions. Financial support: FAPESP #2015/25618-2.

Keywords: chronic inflammation, cytokines, osteolytic lesions, VIP (Vasoactive Intestinal Peptide)

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Authors: Abdulaziz Alakeel, Abdulrahman Alomair, Mohammed Fouda

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Introduction: Methotrexate (MTX) is an antimetabolite used to treat multiple conditions, including neoplastic diseases, severe psoriasis, and rheumatoid arthritis. Skin cancer is the out-of-control growth of abnormal cells in the epidermis, the outermost skin layer, caused by unrepaired DNA damage that triggers mutations. These mutations lead the skin cells to multiply rapidly and form malignant tumors. The aim of this review is to evaluate the risk of skin cancer associated with the use of methotrexate and to suggest regulatory recommendations if required. Methodology: Signal Detection team at Saudi Food and Drug Authority (SFDA) performed a safety review using National Pharmacovigilance Center (NPC) database as well as the World Health Organization (WHO) VigiBase, alongside with literature screening to retrieve related information for assessing the causality between skin cancer and methotrexate. The search conducted in July 2020. Results: Four published articles support the association seen while searching in literature, a recent randomized control trial published in 2020 revealed a statistically significant increase in skin cancer among MTX users. Another study mentioned methotrexate increases the risk of non-melanoma skin cancer when used in combination with immunosuppressant and biologic agents. In addition, the incidence of melanoma for methotrexate users was 3-fold more than the general population in a cohort study of rheumatoid arthritis patients. The last article estimated the risk of cutaneous malignant melanoma (CMM) in a cohort study shows a statistically significant risk increase for CMM was observed in MTX exposed patients. The WHO database (VigiBase) searched for individual case safety reports (ICSRs) reported for “Skin Cancer” and 'Methotrexate' use, which yielded 121 ICSRs. The initial review revealed that 106 cases are insufficiently documented for proper medical assessment. However, the remaining fifteen cases have extensively evaluated by applying the WHO criteria of causality assessment. As a result, 30 percent of the cases showed that MTX could possibly cause skin cancer; five cases provide unlikely association and five un-assessable cases due to lack of information. The Saudi NPC database searched to retrieve any reported cases for the combined terms methotrexate/skin cancer; however, no local cases reported up to date. The data mining of the observed and the expected reporting rate for drug/adverse drug reaction pair is estimated using information component (IC), a tool developed by the WHO Uppsala Monitoring Centre to measure the reporting ratio. Positive IC reflects higher statistical association, while negative values translated as a less statistical association, considering the null value equal to zero. Results showed that a combination of 'Methotrexate' and 'Skin cancer' observed more than expected when compared to other medications in the WHO database (IC value is 1.2). Conclusion: The weighted cumulative pieces of evidence identified from global cases, data mining, and published literature are sufficient to support a causal association between the risk of skin cancer and methotrexate. Therefore, health care professionals should be aware of this possible risk and may consider monitoring any signs or symptoms of skin cancer in patients treated with methotrexate.

Keywords: methotrexate, skin cancer, signal detection, pharmacovigilance

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Authors: Chuanxiang Cheng, Tiantian Min, Jin Yue

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Antimicrobial active packaging enables extensive biological effects to improve food safety. However, the efficacy of antimicrobial packaging hinges on factors including the diffusion rate of the active agent toward the food surface, the initial content in the antimicrobial agent, and the targeted food shelf life. Among the possibilities of antimicrobial packaging design, an interesting approach involves the incorporation of volatile antimicrobial agents into the packaging material. In this case, the necessity for direct contact between the active packaging material and the food surface is mitigated, as the antimicrobial agent exerts its action through the packaging headspace atmosphere towards the food surface. However, it still remains difficult to achieve controlled and precise release of bioactive compounds to the specific target location with required quantity in food packaging applications. Remarkably, the development of stimuli-responsive materials for electrospinning has introduced the possibility of achieving controlled release of active agents under specific conditions, thereby yielding enduring biological effects. Relative humidity (RH) for the storage of food categories such as meat and aquatic products typically exceeds 90%. Consequently, high RH can be used as an abiotic trigger for the release of active agents to prevent microbial growth. Hence, a novel RH - responsive polyvinyl alcohol/chitosan (PVA/CS) composite nanofibrous film incorporated with 4-terpineol/β-cyclodextrin inclusion complexes (4-TA@β-CD ICs) was engineered by electrospinning that can be deposited as a functional packaging materials. The characterization results showed the thermal stability of the films was enhanced after the incorporation due to the hydrogen bonds between ICs and polymers. Remarkably, the 4 wt% 4-TA@β-CD ICs/PVA/CS film exhibited enhanced crystallinity, moderate hydrophilic (Water contact angle of 81.53°), light barrier property (Transparency of 1.96%) and water resistance (Water vapor permeability of 3.17 g mm/m2 h kPa). Moreover, this film also showed optimized mechanical performance with a Young’s modulus of 11.33 MPa, a tensile strength of 19.99 MPa and an elongation at break of 4.44 %. Notably, the antioxidant and antibacterial properties of this packaging material were significantly improved. The film demonstrated the half-inhibitory concentrations (IC50) values of 87.74% and 85.11% for scavenging 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2, 2′-azinobis (3-ethylbenzothiazoline-6-sulfonic) (ABTS) free radicals, respectively, in addition to an inhibition efficiency of 65% against Shewanella putrefaciens, the characteristic bacteria in aquatic products. Most importantly, the film achieved controlled release of 4-TA under high 98% RH by inducing the plasticization of polymers caused by water molecules, swelling of polymer chains, and destruction of hydrogen bonds within the cyclodextrin inclusion complex. Consequently, low relative humidity is suitable for the preservation of nanofibrous film, while high humidity conditions typical in fresh food packaging environments effectively stimulated the release of active compounds in the film. This film with a long-term antimicrobial effect successfully extended the shelf life of Litopenaeus vannamei shrimp to 7 days at 4 °C. This attractive design could pave the way for the development of new food packaging materials.

Keywords: controlled release, electrospinning, nanofibrous film, relative humidity–responsive, shrimp preservation

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Authors: Desireina Delancy, Tannice Hall, Eric Garraway, Dwight Robinson

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Aphis gossypii, as a pest, directly damages its host plant by extracting phloem sap (sucking) and indirectly damages it by the transmission of viruses, ultimately affecting the yield of the host. Due to its polyphagous nature, this species affects a wide range of host plants, some of which may serve as a reservoir for colonisation of important crops. In Jamaica, there have been outbreaks of viral plant pathogens that were transmitted by Aphis gossypii. Three such examples are Citrus tristeza virus, the Watermelon mosaic virus, and Papaya ringspot virus. Aphis gossypii also heavily colonized economically significant host plants, including pepper, eggplant, watermelon, cucumber, and hibiscus. To facilitate integrated pest management, it is imperative to understand the biology of the aphid and its host preference. Preliminary work in Jamaica has indicated differences in biology and host preference, as well as host variety within the species. However, specific details of fecundity, colony growth, host preference, distribution, and insecticide resistance of Aphis gossypii were unknown to the best of our knowledge. The aim was to investigate the following in relation to Aphis gossypii: influence of the host plant on colonization, life span, fecundity, population size, and morphology; the impact of host transfer on fecundity and population size as a measure of host preference and host transfer success and susceptibility to four commonly used insecticides. Fecundity and colony size were documented daily from aphids acclimatized on Capsicum chinense Jacquin 1776, Cucumis sativus Linnaeus 1630, Gossypium hirsutum Linnaeus 1751 and Abelmoschus esculentus (L.) Moench 1794 for three generations. The same measures were used after third instar aphids were transferred among the hosts as a measure of suitability and success. Mortality, and fecundity of survivors, were determined after aphids were exposed to varying concentrations of Actara®, Diazinon™, Karate Zeon®, and Pegasus®. Host preference results indicated that, over a 24-day period, Aphis gossypii reached its largest colony size on G. hirsutum (x̄ 381.80), with January – February being the most fecund period. Host transfer experiments were all significantly different, with the most significant occurring between transfers from C. chinense to C. sativus (p < 0.05). Colony sizes were found to increase significantly every 5 days, which has implications for regimes implemented to monitor and evaluate plots. Insecticides ranked on lethality are Karate Zeon®> Actara®> Pegasus® > Diazinon™. The highest LC50 values were obtained for aphids on G. hirsutum and C. chinense was with Pegasus® and for those on C. sativus with Diazinon™. Survivors of insecticide treatments had colony sizes on average that were 98 % less than untreated aphids. Cotton was preferred both in the field and in the glasshouse. It is on cotton the aphids settled first, had the highest fecundity, and the lowest mortality. Cotton can serve as reservoir for (re)populating other cotton or different host species based on migration due to overcrowding, heavy showers, high wind, or ant attendance. Host transfer success between all three hosts is highly probable within an intercropping system. Survivors of insecticide treatments can successfully repopulate host plants.

Keywords: Aphis gossypii, host-plant preference, colonization sequence, host transfers, insecticide susceptibility

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