Search results for: Pardis Simon

Authors: Simon Mensah Ofosu

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Illicit surface mining activities pollutes agricultural lands and water bodies and results in accumulation of heavy metals in vegetables cultivated in such areas. Heavy metal (HM) accumulation in vegetables is a serious food safety issues due to the adverse effects of metal toxicities, hence the need to investigate the levels of these metals in cultivated vegetables in the eastern region. Cocoyam leaves, cabbage and cucumber were sampled from selected farms in mining areas (Atiwa District) and non -mining areas (Yilo Krobo and East Akim District) of the region for the study. Levels of Cadmium, Lead, Mercury and Arsenic were investigated in the vegetables with Atomic Absorption Spectrometer, and the results statistically analyzed with Microsoft Office Excel (2013) Spread Sheet and ANOVA. Cadmium (Cd) and arsenic (As) were the highest and least concentrated HM in the vegetables sampled, respectively. The mean concentrations of Cd and Pb in cabbage (0.564 mg/kg, 0.470 mg/kg), cucumber (0.389 mg/kg, 0.190 mg/kg), cocoyam leaves (0.410 mg/kg, 0.256 mg/kg) respectively from the mining areas exceeded the permissible limits set by Joint FAO/WHO. The mean concentrations of the metals in vegetables from the mining and non-mining areas varied significantly (P<0.05). The Target Hazard Quotient (THQ) was used to assess the health risk posed to the human population via vegetable consumption. The THQ values of cadmium, mercury, and lead in adults and children through vegetable consumption in the mining areas were greater than 1 (THQ >1). This indicates the potential health risk that the children and adults may be facing. The THQ values of adults and children in the non-mining areas were less than the safe limit of 1 (THQ<1), hence no significant health risk posed to the population from such areas.

Keywords: food safety, risk assessment, illicit mining, public health, contaminated vegetables

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Authors: Simon Mauma Efange

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The main aims of this research were to describe, in co-relational terms, the relationship, if any, between reading comprehension and academic achievement in science studied at the secondary level and, secondly, to find out possible trends in gender differences, such as whether boys would perform better than girls or vice versa. This research employed a quantitative design. Two kinds of instruments were employed: the Oxford Online Placement Test and the Local Assessment System Test. The Oxford Online Placement Test assesses students' English level quickly and easily. The results of these tests were subjected to statistical analysis using a special statistical software called SPSS. Statistical tools such as mean, standard deviation, percentages, frequencies, t-tests, and Pearson’s coefficient of correlation were used for the analysis of the results. Results of the t-test showed that the means are significantly different. Calculating the p-value revealed that the results were extremely statistically significant at p <.05. The value of r (Pearson correlation coefficient) was 0.2868. Although technically there is a positive correlation, the relationship between the variables is only weak (the closer the value is to zero, the weaker the relationship). However, in conclusion, calculations from the t-test using SPSS revealed that the results were statistically significant at p <.05, confirming a relationship between the two variables, and high scores in reading will give rise to slightly high scores in science. The research also revealed that having a high score in reading comprehension doesn’t necessarily mean having a high score in science or vice versa. Female subjects performed much better than male subjects in both tests, which is in line with the literature reviewed for this research.

Keywords: achievement in science, achievement in English, and bilingual students, relationship

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Authors: Mara F. Müller, Simon C. Griffith, Tara L. Crewe, Mirjam Kaestli, Sydney J. Collett, Ian J. Radford, Hamish A. Campbell

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The intensity and frequency of heat waves have been progressively increasing because of climate change. Passerines that inhabit very hot regions are already close to their physiological thermal limit and are thus considered highly susceptible to increased ambient temperatures. However, the extent by which passerines behaviorally compensate for extreme heat in their natural habitat has rarely been assessed due to monitoring challenges. To address this knowledge gap, coded VHF-nano transmitters were attached to a tropical passerine (Gouldian finch, Chloebia gouldiae). Fine-scale activity and movement were monitored throughout the hottest and driest period of the year using an array of static VHF-receivers. The finches were found to typically show a peak activity for a few hours at sunrise and remained relatively quiescent for the rest of the day. However, on extremely hot days (max temperature >38ºC), finches showed higher activity levels earlier in the morning and presented a second peak in the afternoon. Gouldian finches are physiologically challenged when ambient temperatures exceed 38ºC, suggesting the shift in movement activity reflects a behavioral mitigation strategy to extreme heat. These tropical finches already exist on an energetic knife-edge during this time of the year due to resource scarcity. Hence, the increased energetic expenditure to mitigate thermal stress may be detrimental. The study demonstrates the value of VHF-telemetry technology in monitoring the impact of global change on the biology of small-bodied mobile species.

Keywords: animal tracking, biotelemetry, climate change, extreme heat, movement activity, radiotelemetry, VHF-telemetry

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Authors: A. Hayrapetyan, A. Simon, P. Marques, G. Renart

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Business survival is a question of greatest interest for any economy. Firm characteristics that can explain or predict performance and, ultimately, business survival become of the greatest significance, as the sustainable longevity of any business can mean health for the future of the country. Family Firms (FFs) are one of the most ubiquitous forms of business worldwide, as more than half of European firms (60%) are considered as family firms. Therefore, the inherent characteristics of FFs are one of the possible explanatory variables for firm survival because FFs have strategic goals that differentiate them from other types of businesses. Although there is literature on the performance of FFs across generations, there are fewer studies on the factors that impact the survival of family and non-family FFs, as there is a lack of data on failed firms. To address this gap, this paper explores the differential survival of family firms versus non-family firms with a representative sample of companies of the region of Catalonia (Northeast of Spain) that were adhoc classified as family or nonfamily firms, as well as classified as failed or surviving, since no census data for family firms or for failed firms is available in Spain. By using the COX regression model on a representative sample of 629 family and non-family firms, this study investigates to what extent financial ratios, such as Liquidity, Solvency Rate can impact business survival, taking into consideration the socioemotional side of family firms, as well as revealing the differences between family and non-family firms. The findings show that the liquidity rate is significant for non-family firm survival, whereas not for family firms. On the other hand, FFs can benefit while having a higher solvency rate. Ultimately, this paper discovers that FFs increase their chances of survival when they are small, as the growth in size starts negatively impacting the socioemotional objectives of the firm. This study proves the existence of significant differences between family and non-family firms’ survival during economic crises, suggesting that the prioritization of emotional wealth creates distinct conditions for both types of firms.

Keywords: COX regression, economy crises, family firm, non-family firm, survival

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Authors: Simon Strande Henriksen

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When a city and country decide to undertake an Olympic Games, they do so with the notion that hosting the Olympics will provide direct financial benefits to the city, country, and national companies. Like many activities, the Olympic Games tend to be more popular when it is warm, and the athletes are known, and therefore this paper will only focus on the two latest Olympic Summer Games. Cities and countries continue to invest billions of dollars in infrastructure to secure the role of being Olympic hosts. The multiple investments expect to provide both economic growth and a lasting legacy for the citizens. This study aims to determine whether host country companies experience superior economic impact from the Olympics. Building on existing work within the Olympic field of research, it asks: Do companies in host countries of the Olympic Summer Games experience a superior increase in operating revenue and return on assets compared to other comparable countries? In this context, comparable countries are the two candidates following the host city in the bidding procedure. Based on methods used by scholars, a panel data regression was conducted on revenue growth rate and return on assets, to determine if host country companies see a positive relation with hosting the Olympic Games. Combined with an analysis of motivation behind hosting the Olympics, the regression showed no significant positive relations across all analyses, besides in one instance. Indications of a relationship between company performance and economic motivation were found to be present. With the results indicating a limited effect on company growth, it is recommended that prospective host cities and countries carefully consider possible implications the role of being an Olympic host might have on national companies.

Keywords: cross-country analysis, mega-event, multiple regression, quantitative analysis

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Authors: Simon Elias Bibri, Vera Minavere Bardici

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In this article, we investigate framing, discursive and material selectivity as important issues that need to be addressed in the planning of eco–city as a model of sustainable urban form. Focusing on the Stockholm region in Sweden, we discuss issues of the contribution of eco–city model to sustainability and examine key themes associated with the construction of the discourse on eco–city projects, namely the integration of environmental, economic, and social sustainability as well as design and technology as solutions in urban projects documents pertaining specifically to Hammarby Sjöstad and Stockholm Royal Seaport. The article is divided into four sections. First, we elucidate the concept and problem of framing and discursive and material selectivity. Second, we briefly discuss the discourse of sustainability, sustainable urban forms, and eco–city, pointing out some key issues that need to be addressed in sustainable urban planning. In the third and main section of the article, we investigate plans and projects for sustainable urban development, focusing on framing and discursive and material selectivity issues in the construction of the discourse on eco–city projects in Stockholm and discussing the findings in terms of the integration of sustainability dimensions, the economic benefits of and the negative environmental effects of energy efficiency and green technology, the shaping influence of cultural frames, the links of eco–city to macro–processes of regulation, the technological orientation of eco–city projects and the associated selectivity aspects. The article concludes with a call for further research for the possibilities for a more environmentally sound and holistic approach to sustainable urban forms.

Keywords: framing, selectivity, sustainability, eco–city, sustainable urban form, design, energy efficiency, green technology, Hammarby Sjöstad, Stockholm Royal Seaport

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Authors: Felix Eyben, Simon Schaffrath, Markus Feldmann

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A building should maximize the potential for use through its design. Therefore, flexible use is always important when designing a steel structure. To create flexibility, steel beams with web openings are increasingly used, because these offer the advantage that cables, pipes and other technical equipment can easily be routed through without detours, allowing for more space-saving and aesthetically pleasing construction. This can also significantly reduce the height of ceiling systems. Until now, beams with web openings were not explicitly considered in the European standard. However, this is to be done with the new EN 1993-1-13, in which design rules for different opening forms are defined. In order to further develop the design concepts, beams with web openings under bending are therefore to be investigated in terms of damage mechanics as part of a German national research project aiming to optimize the verifications for steel structures based on a wider database and a validated damage prediction. For this purpose, first, fundamental factors influencing the load-bearing behavior of girders with web openings under bending load were investigated numerically without taking material damage into account. Various parameter studies were carried out for this purpose. For example, the factors under study were the opening shape, size and position as well as structural aspects as the span length, arrangement of stiffeners and loading situation. The load-bearing behavior is evaluated using resulting load-deformation curves. These results are compared with the design rules and critically analyzed. Experimental tests are also planned based on these results. Moreover, the implementation of damage mechanics in the form of the modified Bai-Wierzbicki model was examined. After the experimental tests will have been carried out, the numerical models are validated and further influencing factors will be investigated on the basis of parametric studies.

Keywords: damage mechanics, finite element, steel structures, web openings

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Authors: Kristina Jansen, Maximilian Lennartz, Patrick Lebok, Guido Sauter, Ronald Simon, David Dum, Stefan Steurer

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DOG1 (Discovered on GIST1) is a voltage-gated calcium-activated chloride and bicarbonate channel that is highly expressed in interstitial cells of Cajal and in gastrointestinal stromal tumors (GIST) derived from Cajal cells. To systematically determine in what tumor entities and normal tissue types DOG1 may be further expressed, a tissue microarray (TMA) containing 15,965 samples from 121 different tumor types and subtypes as well as 608 samples of 76 different normal tissue types were analyzed by immunohistochemistry. DOG1 immunostaining was found in 67 tumor types, including GIST (95.7%), esophageal squamous cell carcinoma (31.9%), pancreatic ductal adenocarcinoma (33.6%), adenocarcinoma of the Papilla Vateri (20%), squamous cell carcinoma of the vulva (15.8%) and the oral cavity (15.3%), mucinous ovarian cancer (15.3%), esophageal adenocarcinoma (12.5%), endometrioid endometrial cancer (12.1%), neuroendocrine carcinoma of the colon (11.1%) and diffuse gastric adenocarcinoma (11%). Low level-DOG1 immunostaining was seen in 17 additional tumor entities. DOG1 expression was unrelated to histopathological parameters of tumor aggressiveness and/or patient prognosis in cancers of the breast (n=1,002), urinary bladder (975), ovary (469), endometrium (173), stomach (233), and thyroid gland (512). High DOG1 expression was linked to estrogen receptor expression in breast cancer (p<0.0001) and the absence of HPV infection in squamous cell carcinomas (p=0.0008). In conclusion, our data identify several tumor entities that can show DOG1 expression levels at similar levels as in GIST. Although DOG1 is tightly linked to a diagnosis of GIST in spindle cell tumors, the differential diagnosis is much broader in DOG1 positive epithelioid neoplasms.

Keywords: biomarker, DOG1, immunohistochemistry, tissue microarray

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Authors: Rabih Joseph Nabhan

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This case study explores the impact of two major computer software programs Learn to Speak English and Learn English Spelling and Pronunciation, and some Internet search engines such as Google on mending the decoding and spelling deficiency of Simon X, a dyslexic student. The improvement in decoding and spelling may result in better reading comprehension and composition writing. Some computer programs and Internet materials can help regain the missing awareness and consequently restore his self-confidence and self-esteem. In addition, this study provides a systematic plan comprising a set of activities (four computer programs and Internet materials) which address the problem from the lowest to the highest levels of phoneme and phonological awareness. Four methods of data collection (accounts, observations, published tests, and interviews) create the triangulation to validly and reliably collect data before the plan, during the plan, and after the plan. The data collected are analyzed quantitatively and qualitatively. Sometimes the analysis is either quantitative or qualitative, and some other times a combination of both. Tables and figures are utilized to provide a clear and uncomplicated illustration of some data. The improvement in the decoding, spelling, reading comprehension, and composition writing skills that occurred is proved through the use of authentic materials performed by the student under study. Such materials are a comparison between two sample passages written by the learner before and after the plan, a genuine computer chat conversation, and the scores of the academic year that followed the execution of the plan. Based on these results, the researcher recommends further studies on other Lebanese dyslexic learners using the computer to mend their language problem in order to design and make a most reliable software program that can address this disability more efficiently and successfully.

Keywords: analysis, awareness, dyslexic, software

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Authors: Van Huong Do, Simon Walton, German Amaya, Madeline Batsiokis, Sally Catt, Andrew Taylor-Robinson

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Identification of the most suitable stages of bovine in vitro-derived blastocysts (early, expanded and hatching) prior to vitrification is a straightforward process that facilitates the decision as to which blastocyst stage to use for transfer of fresh and vitrified embryos. Research on in vitro evaluation of suitable stages has shown that the more advanced developmental stage of blastocysts is recommended for fresh embryo transfer while the earlier stage is proposed for embryo transfer following vitrification. There is, however, limited information on blastocyst stages using in vivo assessment. Hence, the aim of the present study was to determine the optimal stage of a blastocyst for vitrification and embryo transfer through a two-step procedure of embryo transfer followed by pregnancy testing at 35, 60 and 90 days of pregnancy. 410 good quality oocytes aspirated by the ovum pick-up technique from 8 donor cows were subjected to in vitro embryo production, vitrification and embryo transfer. Good quality embryos were selected, subjected to vitrification and embryo transfer. Subsequently, 77 vitrified embryos at different blastocyst stages were transferred to synchronised recipient cows. The overall cleavage and blastocyst rates of oocytes were 68.8% and 41.7%, respectively. In addition, the fertility and blastocyst production of 6 bulls used for in vitro fertilization was examined and shown to be statistically different (P<0.05). Results of ongoing pregnancy trials conducted at 35 days, 60 days and 90 days will be discussed. However, preliminary data indicate that individual bulls demonstrate distinctly different fertility performance in vitro. Findings from conception rates would provide a useful tool to aid selection of bovine in vitro-derived embryos for vitrification and embryo transfer in commercial settings.

Keywords: blastocyst, embryo transfer, in vitro-derived embryos, ovum pick-up, vitrification

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Authors: Wafula Simon Peter, Kimuli Nabayego Ibtihal, Nabaggala Kimuli Nashua

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The worldwide use of information and communications technology (ICT) equipment and other electronic equipment is growing and consequently, there is a growing amount of equipment that becomes waste after its time in use. This growth is expected to accelerate since equipment lifetime decreases with time and growing consumption. As a result, e-waste is one of the fastest-growing waste streams globally. The United Nations University (UNU) calculates in its second Global E-waste Monitor 44.7 million metric tonnes (Mt) of e-waste were generated globally in 2016. The study population was 80 respondents, from which a sample of 69 respondents was selected using simple and purposive sampling techniques. This research was carried out to investigate the problem of e-waste and come up with a framework to improve e-waste management. The objective of the study was to develop a framework for improving e-waste management at the College of Engineering, Design, Art and Technology (CEDAT). This was achieved by breaking it down into specific objectives, and these included the establishment of the policy and other Regulatory frameworks being used in e-waste management at CEDAT, the determination of the effectiveness of the e-waste management practices at CEDAT, the establishment of the critical challenges constraining e-waste management at the College, development of a framework for e-waste management. The study reviewed the e-waste regulatory framework used at the college and then collected data which was used to come up with a framework. The study also established that weak policy and regulatory framework, lack of proper infrastructure, improper disposal of e-waste and a general lack of awareness of the e-waste and the magnitude of the problem are the critical challenges of e-waste management. In conclusion, the policy and regulatory framework should be revised, localized and strengthened to contextually address the problem. Awareness campaigns, the development of proper infrastructure and extensive research to establish the volumes and magnitude of the problems will come in handy. The study recommends a framework for the improvement of e-waste.

Keywords: e-waste, treatment, disposal, computers, model, management policy and guidelines

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Authors: Mukisa Simon Peter Turker, Etomaru Irene

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This study examined factors determining the success of University-Industry Collaboration (UIC) in the science academic units (SAUs) at Makerere University. This was prompted by concerns about weak linkages between industry and the academic units at Makerere University. The study examined institutional, relational, output, and framework factors determining the success of UIC in the science academic units at Makerere University. The study adopted a predictive cross-sectional survey design. Data was collected using a questionnaire survey from 172 academic staff from the six SAUs at Makerere University. Stratified, proportionate, and simple random sampling techniques were used to select the samples. The study used descriptive statistics and linear multiple regression analysis to analyze data. The study findings reveal a coefficient of determination (R-square) of 0.403 at a significance level of 0.000, suggesting that UIC success was 40.3% at a standardized error of estimate of 0.60188. The strength of association between Institutional factors, Relational factors, Output factors, and Framework factors, taking into consideration all interactions among the study variables, was at 64% (R= 0.635). Institutional, Relational, Output and Framework factors accounted for 34% of the variance in the level of UIC success (adjusted R2 = 0.338). The remaining variance of 66% is explained by factors other than Institutional, Relational, Output, and Framework factors. The standardized coefficient statistics revealed that Relational factors (β = 0.454, t = 5.247, p = 0.000) and Framework factors (β = 0.311, t = 3.770, p = 0.000) are the only statistically significant determinants of the success of UIC in the SAU in Makerere University. Output factors (β = 0.082, t =1.096, p = 0.275) and Institutional factors β = 0.023, t = 0.292, p = 0.771) turned out to be statistically insignificant determinants of the success of UIC in the science academic units at Makerere University. The study concludes that Relational Factors and Framework Factors positively and significantly determine the success of UIC, but output factors and institutional factors are not statistically significant determinants of UIC in the SAUs at Makerere University. The study recommends strategies to consolidate Relational and Framework Factors to enhance UIC at Makerere University and further research on the effects of Institutional and Output factors on the success of UIC in universities.

Keywords: university-industry collaboration, output factors, relational factors, framework factors, institutional factors

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Authors: Norbert Simon, Rodeano Roslee, Abdul Ghani Rafek, Goh Thian Lai, Azimah Hussein, Lee Khai Ern

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The 54 km stretch of Ranau-Tambunan (RTM) road in Sabah is subjected to slope failures almost every year. This study is focusing on identifying section of roads that are susceptible to failure based on temporal landslide density and lineament density analyses. In addition to the analyses, the rock slopes in several sections of the road were assessed using the geological strength index (GSI) technique. The analysis involved 148 landslides that were obtained in 1978, 1994, 2009 and 2011. The landslides were digitized as points and the point density was calculated based on every 1km2 of the road. The lineaments of the area was interpreted from Landsat 7 15m panchromatic band. The lineament density was later calculated based on every 1km2 of the area using similar technique with the slope failure density calculation. The landslide and lineament densities were classified into three different classes that indicate the level of susceptibility (low, moderate, high). Subsequently, the two density maps were overlap to produce the final susceptibility map. The combination of both high susceptibility classes from these maps signifies the high potential of slope failure in those locations in the future. The final susceptibility map indicates that there are 22 sections of the road that are highly susceptible. Seven rock slopes were assessed along the RTM road using the GSI technique. It was found from the assessment that rock slopes along this road are highly fractured, weathered and can be classified into fair to poor categories. The poor condition of the rock slope can be attributed to the high lineament density that presence in the study area. Six of the rock slopes are located in the high susceptibility zones. A detailed investigation on the 22 high susceptibility sections of the RTM road should be conducted due to their higher susceptibility to failure, in order to prevent untoward incident to road users in the future.

Keywords: GSI, landslide, landslide density, landslide susceptibility, lineament density

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Authors: Tuaumelsan Shumye Gebre, Shimelis Admassu Emire, Simon Okomo Aloo, Ramachandran Chelliah, Deog-Hwan Oh

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This study investigates the fermentation of cereal substrates, based on the Ethiopian traditional beverage borde, using probiotic strains of Pediococcus acidilactici WS07 and Saccharomyces cerevisiae AM18 used singly and in co-culture. The pH and titratable acidity, microbial growth dynamics, fermentable sugars profile, volatile organic compounds, total flavonoid content, total phenolic content, antioxidant activity, pancreatic lipase, and α-glucosidase inhibition were analyzed. The viability of every tested strain remained higher than 7 log CFU/mL, satisfying the requirements suggested for probiotic food items. The formation of organic acids is what caused the pH to decrease from roughly 6.6 to 3.8, yet this had no effect on the viability of the microorganisms. The fermentation process, involving P. acidilactici WS07 and S. cerevisiae AM18, led to the utilization of initial carbohydrates, production of organic acids, and generation of volatile compounds that enhance flavor and aroma. Ethanol and glycerol concentrations increased during fermentation, particularly in co-culture assays, contributing to the sensory qualities and stability of the beverages. The primary organic acids generated during fermentation were lactic and acetic acids. A total of 22 volatile substances, such as acids, alcohols, aldehydes, esters, ketones, and other substances, were found. Furthermore, the study demonstrates that fermentation of maize and sorghum with P. acidilactici WS07 and S. cerevisiae AM18 enhances the antioxidant activity and inhibition of pancreatic lipase and α-glucosidase, suggesting potential benefits in managing obesity and diabetes. Therefore, co-cultivating S. cerevisiae AM18 and P. acidilactici WS07 in cereal fermentation led to the successful production of probiotic drinks.

Keywords: probiotic beverage, Pediococcus acidilactici, Saccharomyces cerevisiae, volatile compounds

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Authors: Kelly E. Tow, Peter Caputi, Claudia Rogge, Thomas Lee, Simon R. Knowles

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Inflammatory Bowel Disease (IBD) is a serious chronic health condition, characterised by inflammation of the gastrointestinal tract. Individuals with active IBD experience severe abdominal symptoms, which can adversely impact their physical and mental health, as well as their quality of life (QoL). Given that stress may exacerbate IBD symptoms and is frequently highlighted as a contributing factor for the development of psychological difficulties and poorer QoL, it is vital to investigate stress-management strategies aimed at improving the lives of those with IBD. The present study extends on the limited research in IBD cohorts by exploring the role of dispositional mindfulness and its impact on psychological well-being and QoL. The study examined how disease activity and dispositional mindfulness were related to psychological distress and QoL in a cohort of IBD patients. The potential role of dispositional mindfulness as a moderator between stress and anxiety, depression and QoL in these individuals was also examined. Participants included 47 patients with a clinical diagnosis of IBD. Each patient completed a series of psychological questionnaires and was assessed by a gastroenterologist to determine their disease activity levels. Correlation analyses indicated that disease activity was not significantly related to psychological distress or QoL in the sample of IBD patients. However, dispositional mindfulness was inversely related to psychological distress and positively related to QoL. Furthermore, moderation analyses demonstrated a significant interaction between stress and dispositional mindfulness on anxiety. These findings demonstrate that increased levels of dispositional mindfulness may be beneficial for individuals with IBD. Specifically, the results indicate positive links between dispositional mindfulness, general psychological well-being and QoL, and suggest that dispositional mindfulness may attenuate the negative impacts of stress on levels of anxiety in IBD patients. While further research is required to validate and expand on these findings, the current study highlights the importance of addressing psychological factors in IBD and indicates support for the use of mindfulness-based interventions for patients with the disease.

Keywords: anxiety, depression, dispositional mindfulness, inflammatory bowel disease, quality of life, stress

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Authors: Nduduzo Andrias Ngxongo, Nsizwazikhona Simon Chili

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This analytical exploration illustrates how the non-existence of a proper marketing strategy for a tourism destination may have resulted in a radical decline in both financial outputs and visitor arrivals. The marketing strategy is considered as the foundation for any tourism destination’s marketing tactics. Tourism destinations are ought to have dynamic and adaptive marketing strategies that will develop a promotional approach to help the destination to gain market share, identify its target markets, stay relevant to its existing clients, attract new visitors, and increase profits-earned. Accordingly, the Moses Mabhida Stadium (MMS), one of the prominent tourist attractions in KwaZulu-Natal; boasting a world-class architectural design, several international prestigious awards, and vibrant, adventurous activities, has in recent years suffered a gradual slump in both visitors and profits. Therefore, the basis of this paper was to thoroughly establish precisely how the existing MMS marketing strategy may be a basis for a decline in the number of visitors and profits-earned in recent years. The study adopted mixed method research strategy, with 380 participants. The outcome of the study suggests some costly disparities in the marketing strategy of MMS which has led to poor performance and a loss in tourism market share. In consequence, the outcome further suggests that the non-existence of market research analysis and destination marketing tools contributed vastly to the in-progress dilemma. This fact-finding exploration provides a birds-eye outlook of MMS marketing strategy, and based on the results, the study recommends for the introduction of a more far-reaching and revitalising marketing strategy through; constant and persistent market research initiatives, minimal political interference in the administration of state-funded organisations, reassessment of the feasibility study, vigorous, and sourcing of proficient personnel.

Keywords: tourism, destination, marketing , marketing strategy

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Authors: Bauta J., Raynaud C., Vaca-Medina G., Simon V., Roully A., Vandenbossche V.

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Sargassum is a brown algae, originally found in the Sargasso Sea, located in the Caribbean region and the Gulf of Mexico. The flow of Sargassum is becoming a critical environmental problem all over the Caribbean islands particularly. In Guadeloupe alone, around 80,000 tons of seaweed are stranded during the season. Since the appearance of the first waves of Sargassum algae, several measures have been taken to collect them to keep the beaches clean. Nevertheless, 90% of the collected algae are currently stored without recovery. The lack of research initiative demands a more in-depth exploration of Sargassum algae chemistry, targeted towards added value applications and their development. In this context, the aim of the study was to develop a biorefinery process to valorize Sargassum as a source of bioactive natural substances and as raw material to produce biomaterials simultaneously. The technology used was the twin-screw extrusion, which allows to achieve continuously in the same machine different unit fractionation operations. After the identification of the molecules of interest in Sargassum algae, different operating conditions of thermo-mechanical treatment were applied in a twin-screw extruder. The nature of the solvent, the configuration of the extruder, the screw profile, and the temperature profile were studied in order to fractionate the algal biomass and to allow the recovery of a bioactive liquid fraction of interest and a solid residue suitable for the production of biomaterials. Each bioactive liquid fraction was characterized and strategic ways of adding value were proposed. In parallel, the possibility of using the solid residue to produce biomaterials was studied by setting up Dynamic Vapour Sorption (DVS) and basic Pressure-Volume-Temperature (PVT) analyses. The solid residue was molded by compression cooking. The obtained materials were finally characterized mechanically. The results obtained were very comforting and gave some perspectives to find an interesting valorization for the Sargassum algae.

Keywords: seaweeds, twin-screw extrusion, fractionation, bioactive compounds, biomaterials, biomass

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Authors: Manon Giraud, Francois-Damien Delapierre, Guenaelle Jasmin-Lebras, Cecile Feraudet-Tarisse, Stephanie Simon, Claude Fermon

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Early diagnosis or detection of harmful substances at low level is a growing field of high interest. The ideal test should be cheap, easy to use, quick, reliable, specific, and with very low detection limit. Combining the high specificity of antibodies-functionalized magnetic beads used to immune-capture biologic objects and the high sensitivity of a GMR-based sensors, it is possible to even detect these biologic objects one by one, such as a cancerous cell, a bacteria or a disease biomarker. The simplicity of the detection process makes its use possible even for untrained staff. Giant Magneto Resistance (GMR) is a recently discovered effect consisting in the electrical resistance modification of some conductive layers when exposed to a magnetic field. This effect allows the detection of very low variations of magnetic field (typically a few tens of nanoTesla). Magnetic nanobeads coated with antibodies targeting the analytes are mixed with a biological sample (blood, saliva) and incubated for 45 min. Then the mixture is injected in a very simple microfluidic chip and circulates above a GMR sensor that detects changes in the surrounding magnetic field. Magnetic particles do not create a field sufficient to be detected. Therefore, only the biological objects surrounded by several antibodies-functionalized magnetic beads (that have been captured by the complementary antigens) are detected when they move above the sensor. Proof of concept has been carried out on NS1 mouse cancerous cells diluted in PBS which have been bonded to magnetic 200nm particles. Signals were detected in cells-containing samples while none were recorded for negative controls. Binary response was hence assessed for this first biological model. The precise quantification of the analytes and its detection in highly diluted solution is the step now in progress.

Keywords: early diagnosis, giant magnetoresistance, lab-on-a-chip, submicron particle

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Authors: Shima Taheri, Simon Clark

Abstract:

Concrete is an essential building material used in the majority of structures. Degradation of concrete over time increases the life-cycle cost of an asset with an estimated annual cost of billions of dollars to national economies. Most of the concrete failure occurs due to cracks, which propagate through a structure and cause weakening leading to failure. Stopping crack propagation is thus the key to protecting concrete structures from failure and is the best way to prevent inconveniences and catastrophes. Furthermore, the majority of cracks occur deep within the concrete in inaccessible areas and are invisible to normal inspection. Few materials intrinsically possess self-healing ability, but one that does is concrete. However, self-healing in concrete is limited to small dormant cracks in a moist environment and is difficult to control. In this project, we developed a method for self-healing of nascent fractures in concrete components through the automatic release of self-curing healing agents encapsulated in breakable nano- and micro-structures. The Poly(methyl methacrylate) (PMMA) based two-part adhesive is encapsulated in core-shell structures with brittle/weak inert shell, synthesized via miniemulsion/solvent evaporation polymerization. Stress fields associated with propagating cracks can break these capsules releasing the healing agents at the point where they are needed. The shell thickness is playing an important role in preserving the content until the final setting of concrete. The capsules can also be surface functionalized with carboxyl groups to overcome the homogenous mixing issues. Currently, this formulated self-healing system can replace up to 1% of cement in a concrete formulation. Increasing this amount to 5-7% in the concrete formulation without compromising compression strength and shrinkage properties, is still under investigation. This self-healing system will not only increase the durability of structures by stopping crack propagation but also allow the use of less cement in concrete construction, thereby adding to the global effort for CO2 emission reduction.

Keywords: self-healing concrete, concrete crack, concrete deterioration, durability

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Authors: Christian Fercher, Jiaul Islam, Simon R. Corrie

Abstract:

Fluorescence-based immunodiagnostics are an emerging field in biosensor development and exhibit several advantages over traditional detection methods. While various affinity biosensors have been developed to generate a fluorescence signal upon sensing varying concentrations of analytes, reagentless, reversible, and continuous monitoring of complex biological samples remains challenging. Here, we aimed to genetically engineer biosensors based on single-chain antibody fragments (scFv) that are site-specifically labeled with environmentally sensitive fluorescent unnatural amino acids (UAA). A rational design approach resulted in quantifiable analyte-dependent changes in peak fluorescence emission wavelength and enabled antigen detection in vitro. Incorporation of a polarity indicator within the topological neighborhood of the antigen-binding interface generated a titratable wavelength blueshift with nanomolar detection limits. In order to ensure continuous analyte monitoring, scFv candidates with fast binding and dissociation kinetics were selected from a genetic library employing a high-throughput phage display and affinity screening approach. Initial rankings were further refined towards rapid dissociation kinetics using bio-layer interferometry (BLI) and surface plasmon resonance (SPR). The most promising candidates were expressed, purified to homogeneity, and tested for their potential to detect biomarkers in a continuous microfluidic-based assay. Variations of dissociation kinetics within an order of magnitude were achieved without compromising the specificity of the antibody fragments. This approach is generally applicable to numerous antibody/antigen combinations and currently awaits integration in a wide range of assay platforms for one-step protein quantification.

Keywords: antibody engineering, biosensor, phage display, unnatural amino acids

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Authors: Ningfei Xiao, Simon Twose, Hannah Hopewell

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In urban settings worldwide, artists and researchers have drawn from shamanic healing, providing insightful responses to the environment. This project is a transdisciplinary creative research project where architecture and art practice draw from shamanic healing and provide the potential to expand knowledge of public space and inspire more aesthetic explorations of public spatial visions. The research started from the encounters with the Ewengki/Evenki shaman tribe in settlement areas of northern China in 2019 and extended through the partnerships with Maori artists in Poneke Aotearoa, New Zealand, in 2023. Based on the learnings and collaborations with female indigenous tradition practitioners and the healing that the researcher received from the land, a spatial installation exhibition was developed in this project. Indigenous practices are intricately woven with contemporary technology, merging visuals, soundscapes, and other non-visual aesthetics influenced by the researcher's personal experiences of embodied shamanic healing with brainwave generative technology. This synthesis seeks to ritualize and reimagine future public spaces, encompassing streetscapes and greenscapes from China to Aotearoa, and fostering connections between urbanized human body, mind, spirit, and land. In doing so, the project presents a feminist posthuman inquiry into how individuals perceive materiality within the context of a future city. Grounded in creative research and embodied methodologies, this paper focuses on the conceptual and autoethnographic aspects of visual-non-visual aesthetics and their creative representation. Through the exploration of aesthetics beyond the visual realm within urban and spatial contexts, this project showcases the spatial installation exhibition as an example of shamanic influence and related response to public space through embodied artistry and transdisciplinary creative inquiry.

Keywords: aesthetic, embodiment, visual and/or non-visual, spatial installation, shamanic healing, public space

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Authors: M. Schapira, S. Françoise, F. Maheux, O. Pierre-Duplessix, E. Rabiller, B. Simon, R. Le Gendre

Abstract:

Pico- and nano-phytoplankton are abundant and ecologically critical components of the autotrophic communities in the pelagic realm. While the role of physical forcing related to tidal cycle, water mass intrusion, nutrient availability, mixing and stratification on microphytoplankton blooms have been widely investigated, these are often overlooked for pico- and nano-phytoplankton especially in estuarine waters. This study investigates changes in abundances and community composition of pico- and nano-phytoplankton under different estuarine tidal conditions in the mouth of the Seine River in relation to nutrient availability, water column stratification and spatially localized currents. Samples were collected each day at high tide, over spring tide to neap tide cycle, from 21 stations homogeneously distributed in the Seine river month in May 2011. Vertical profiles of temperature, salinity and fluorescence were realized at each sampling station. Sub-surface water samples (i.e. 1 m depth) were collected for nutrients (i.e. N, P and Si), phytoplankton biomass (i.e. Chl a) and pico- and nano-phytoplankton enumeration and identification. Pico- and nano-phytoplankton populations were identified and quantified using flow cytometry. Total abundances tend to decrease from spring tide to neap tide. Samples were characterized by high abundances of Synechococcus and Cryptophyceae. The composition of the pico- and nano-phytoplankton varied greatly under the different estuarine tidal conditions. Moreover, at the scale of the river mouth, the pico- and nano-phytoplankton population exhibited patchy distribution patterns that were closely controlled by water mass intrusion from the Sea, freshwater inputs from the Seine River and the geomorphology of the river mouth. This study highlights the importance of physical forcing to the community composition of pico- and nano-phytoplankton that may be critical for the structure of the pelagic food webs in estuarine and adjacent coastal seas.

Keywords: nanophytoplancton, picophytoplankton, physical forcing, river mouth, tidal cycle

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Authors: Hong-Yan Wang, Jian-Bo Zhou, Simon A. Wilde

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Since the Paleozoic, the tectonic evolution of northeastern Eurasia has been dominated by the Paleo-Asian Ocean and the Paleo-Pacific Ocean tectonic domains. However, the spatiotemporal framework and the timing of the tectonic transition between these two oceanic domains remain enigmatic. To address this issue, this study investigated the petrological, geochronological, and geochemical characters of chlorite schist, andesite and sandstone along the convergent margin (Jilin-Yanji Suture) between the Northeast China terranes and the North China craton in central Jilin Province, China. The results show that the protoliths of chlorite schists and the andesite samples are high-Mg andesites formed in the Early Triassic (249 ± 3 Ma - 246 ± 4 Ma), and their magma source was produced by the metasomatized mantle wedge by subducted slab-derived fluids in a continental island arc setting. The sandstones are immature graywackes with a maximum depositional age of Early Triassic (248 ± 1 Ma), they were formed in a sedimentary basin (most likely an intra-arc basin) intimately associated with one or more continental arcs along the northeastern edge of the North China craton and their sediments were largely derived from coeval magmatic rocks in a juvenile continental arc. Based on the new results and the field investigation, this study suggests that the continental arcs along the northeastern edge of the North China Craton were caused by the southwestward subduction of the Jilin-Heilongjiang Ocean during the early Mesozoic. There is a distinct temporal gap between the closure of the Paleo-Asian Ocean (ca. 260 Ma) and the onset of Paleo-Pacific plate subduction (234–220 Ma), which is essentially coeval with the southwestward subduction of the Jilin-Heilongjiang Ocean between 256 Ma and 239 Ma, meaning the latter is a key link that marks the transition between these two tectonic domains.

Keywords: intra-arc basin, high-Mg andesites, early Mesozoic, Jilin-Heilongjiang Ocean, tectonic transition in northeastern Eurasia

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Authors: Myriam Rousseau, Suzie McKinnon, Mathieu Mireault, Anaïs V. Berthiaume, Marie-Hélène Poulin, Jacinthe Bourassa, Louis-Simon Maltais

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The increasing presence of young people with autism is forcing schools to adapt to this new situation and to offer services that meet the needs of this clientele. However, school staff often feels unqualified to support these students, lacking the preparation, skills and training to meet their needs. Continuing education for these staff is therefore essential to ensure that they can meet the needs of these students. As a result, the Government of Quebec has developed a bilingual (French and English) online training on autism specific to the needs of school staff. Therefore, adequate training for all school staff is likely to provide quality learning opportunities for these students. The research project focuses on the participants' appreciation, contributions, and social validity of the training. More specifically, it aims to: 1) evaluate the knowledge and self-efficacy of the participants, 2) evaluate the social validity and 3) document the evaluation of the ergonomics of the platform hosting the training. The evaluation carried out as part of this descriptive study uses a quantitative method. Data are collected using questionnaires completed online. The analysis of preliminary data reveals that participants' knowledge of autism and their sense of self-efficacy increased significantly. They value the training positively and consider it to be acceptable, appropriate, and suitable. The participants find it important for school staff to take this training. Almost all the items measuring the ergonomics of the platform have averages above 4.57/5. In general, the study shows that the training allows participating of the trainee school staff to improve their knowledge of autism and their sense of self-efficacy with young people with autism. In addition, participants recognize that the training has good social validity and appreciate the online modality. However, these results should be interpreted with caution given the limited number of participants who completed the research project. It is therefore important to continue the research with a larger number of participants to allow an adequate and general representativeness of the social validity, the feeling of competence and the appreciation of the platform.

Keywords: autism, online training, school staff, social validity

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Authors: Paolo Ragazzi, Olivier Peillon, Paul Fauris, Mathias Simon, Raul Navarro, Juan Carlos Martin, Oriol Casasayas, Laura Pacheco, Albert Perez-Bellmunt

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Introduction: The use of stretching techniques in the sports world is frequent and widely used for its many effects. One of the main benefits is the gain in flexibility, range of motion and facilitation of the sporting performance. Recently the use of Roller-Foam (RF) has spread in sports practice both at elite and recreational level for its benefits being similar to those observed in stretching. The objective of the following study is to compare the results of the Roller-Foam with the proprioceptive neuromuscular facilitation stretching (PNF) (one of the stretchings with more evidence) on the hamstring muscles. Study design: The design of the study is a single-blind, randomized controlled trial and the participants are 40 healthy volunteers. Intervention: The subjects are distributed randomly in one of the following groups; stretching (PNF) intervention group: 4 repetitions of PNF stretching (5seconds of contraction, 5 second of relaxation, 20 second stretch), Roller-Foam intervention group: 2 minutes of Roller-Foam was realized on the hamstring muscles. Main outcome measures: hamstring muscles flexibility was assessed at the beginning, during (30’’ of intervention) and the end of the session by using the Modified Sit and Reach test (MSR). Results: The baseline results data given in both groups are comparable to each other. The PNF group obtained an increase in flexibility of 3,1 cm at 30 seconds (first series) and of 5,1 cm at 2 minutes (the last of all series). The RF group obtained a 0,6 cm difference at 30 seconds and 2,4 cm after 2 minutes of application of roller foam. The results were statistically significant when comparing intragroups but not intergroups. Conclusions: Despite the fact that the use of roller foam is spreading in the sports and rehabilitation field, the results of the present study suggest that the gain of flexibility on the hamstrings is greater if PNF type stretches are used instead of RF. These results may be due to the fact that the use of roller foam intervened more in the fascial tissue, while the stretches intervene more in the myotendinous unit. Future studies are needed, increasing the sample number and diversifying the types of stretching.

Keywords: hamstring muscle, stretching, neuromuscular facilitation stretching, roller foam

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Authors: Lazarus Joseph Goje, Asamau Yusuf, Simon Gabriel Mafulul, Nabiha Garba, Nura Abubakar

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The emergence of insecticide resistance in Anopheles gambiae sensu lato poses a significant challenge to malaria control efforts, particularly in endemic regions like Gombe, Nigeria. This study aimed to investigate the mechanisms underlying pyrethroid resistance and identify the prevalent Anopheles species in the area. Morphological identification was performed using keys from Gille and Coetzee, confirmed by molecular techniques employing SINE200 PCR for precise species characterization. The results revealed that the Anopheles gambiae complex comprised 75% of the mosquito population, indicating its dominance in the region. Knockdown rate bioassays demonstrated a time-dependent increase in resistance to insecticides, with notable exceptions observed with deltamethrin. Susceptibility testing conducted 24 hours post-exposure confirmed that the population exhibited resistance to all tested insecticides, with DDT showing the highest resistance level. Molecular analysis identified Anopheles coluzzii as the most prevalent species in Gombe, followed by Anopheles arabiensis. Additionally, the prevalence of kdr alleles was assessed, revealing a significant correlation between the L1014F mutation and resistance phenotypes. Specifically, the frequency of the L1014F allele was linked to increased resistance levels, while the homozygous susceptible allele was also prevalent, suggesting the potential influence of other resistance mechanisms. In conclusion, this study highlights the critical need for ongoing surveillance of insecticide resistance in Anopheles gambiae populations. It underscores the importance of understanding the genetic basis of resistance to inform effective vector control strategies. The findings emphasize that adaptive management of insecticide use, considering the dynamics of resistance and species composition, is essential for enhancing malaria control efforts in Gombe State, Nigeria and similar regions.

Keywords: pyrethroid insecticide, resistance, susceptible, PCR, malaria

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Authors: Simon Shibru, Karen Vancampenhout, Jozef Deckers, Herwig Leirs

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We investigated the population size of the endemic and endangered Swayne’s Hartebeest (Alcelaphus buselaphus swaynei) in Nech Sar National Park from 2012 to 2014 and document the major threats why the species is on the verge of local extinction. The park was once known for its abundant density of Swayne’s Hartebeest. We used direct total count methods for a census. We administered semi-structured interviews and open-ended questionnaires with senior scouts who are the member of the local communities. Historical records were obtained to evaluate the population trends of the animals since 1974. The density of the animal decreased from 65 in 1974 to 1 individual per 100 km2 in 2014 with a decline of 98.5% in the past 40 years. The respondents agreed that the conservation status of the park was in its worst condition ever now with only 2 Swayne’s Hartebeest left, with a rapid decline from 4 individuals in 2012 and 12 individuals in 2009. Mainly hunting and habitat loss, but also the unsuitable season of reproduction and shortage of forage as minor factors were identified as threats for a local extinction of the Swayne’s Hartebeests. On the other hand, predation, fire, disease, and ticks were not considered a cause for the declining trend. Hunting happens mostly out of some kind of revenge since the local community thought that they were pushed out from the land because of the presence of Swayne's Hartebeest in the area. Respondents agreed that the revenge action of the local communities was in response to their unwillingness to be displaced from the park in 1982/3. This conflict situation is resulting from the exclusionary wildlife management policy of the country. We conclude that the human interventions in general and illegal hunting, in particular, pushed the Swayne’s Hartebeest to a point of local extinction. Therefore, we recommend inclusive wildlife management approach for continuing existence of the park together with its natural resources so that sustainable use of the resources is in place.

Keywords: hunting, habitat destruction, local extinction, Nech Sar National Park, Swayne’s Hartebeest

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Authors: Jonathan Josephs-Spaulding, Hannah Rettig, Simon Graspeunter, Jan Rupp, Christoph Kaleta

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Background: Recurrent urinary tract infections (rUTIs) are a global cause of emergency room visits and represent a significant burden for public health systems. Therefore, metatranscriptomic approaches to investigate metabolic exchange and crosstalk between uropathogenic Escherichia coli (UPEC), which is responsible for 90% of UTIs, and collaborating pathogens of the urogenital microbiome is necessary to better understand the pathogenetic processes underlying rUTIs. Objectives: This study aims to determine the level in which uropathogens optimize the host urinary metabolic environment to succeed during invasion. By developing patient-specific metabolic models of infection, these observations can be taken advantage of for the precision treatment of human disease. Methods: To date, we have set up an rUTI patient cohort and observed various urine-associated pathogens. From this cohort, we developed patient-specific metabolic models to predict bladder microbiome metabolism during rUTIs. This was done by creating an in silico metabolomic urine environment, which is representative of human urine. Metabolic models of uptake and cross-feeding of rUTI pathogens were created from genomes in relation to the artificial urine environment. Finally, microbial interactions were constrained by metatranscriptomics to indicate patient-specific metabolic requirements of pathogenic communities. Results: Metabolite uptake and cross-feeding are essential for strain growth; therefore, we plan to design patient-specific treatments by adjusting urinary metabolites through nutritional regimens to counteract uropathogens by depleting essential growth metabolites. These methods will provide mechanistic insights into the metabolic components of rUTI pathogenesis to provide an evidence-based tool for infection treatment.

Keywords: recurrent urinary tract infections, human microbiome, uropathogenic Escherichia coli, UPEC, microbial ecology

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Authors: Simon Nyarko

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This study examined the microbial flora contamination of the Ghanaian paper currency notes and antibiotic resistance in Ejura Municipal, Ashanti Region, Ghana. This is a descriptive cross-sectional study designed to assess the profile of microflora contamination of the Ghanaian paper currency notes and antibiotic-resistant in the Ejura Municipality. The research was conducted in Ejura, a town in the Ejura Sekyeredumase Municipal of the Ashanti region of Ghana. 70 paper currency notes which were freshly collected from the bank, consisting of 15 pieces of GH ¢1, GH ¢2, and GH ¢5, 10 pieces of GH ¢10 and GH ¢20, and 5 pieces of GH ¢50, were randomly sampled from people by exchanging their money in usage with those freshly secured from the bank. The surfaces of each GH¢ note were gently swabbed and sent to the lab immediately in sterile Zip Bags and sealed, and tenfold serial dilution was inoculated on plate count agar (PCA), MacConkey agar (MCA), mannitol salt agar (MSA), and deoxycholate citrate agar (DCA). For bacterial identification, the study used appropriate laboratory and biochemical tests. The data was analyzed using SPSS-IBM version 20.0. It was found that 95.2 % of the 70 GH¢ notes tested positive for one or more bacterial isolates. On each GH¢ note, mean counts on PCA ranged from 3.0 cfu/ml ×105 to 4.8 cfu/ml ×105. Of 124 bacteria isolated. 36 (29.03 %), 32 (25.81%), 16 (12.90 %), 20 (16.13%), 13 (10.48 %), and 7 (5.66 %) were from GH¢1, GH¢2, GH¢10, GH¢5, GH¢20, and GH¢50, respectively. Bacterial isolates were Escherichia coli (25.81%), Staphylococcus aureus (18.55%), coagulase-negative Staphylococcus (15.32%), Klebsiella species (12.10%), Salmonella species (9.68%), Shigella species (8.06%), Pseudomonas aeruginosa (7.26%), and Proteus species (3.23%). Meat shops, commercial drivers, canteens, grocery stores, and vegetable shops contributed 25.81 %, 20.16 %, 19.35 %, 17.74 %, and 16.94 % of GH¢ notes, respectively. There was 100% resistance of the isolates to Erythromycin (ERY), and Cotrimoxazole (COT). Amikacin (AMK) was the most effective among the antibiotics as 75% of the isolates were susceptible to it. This study has demonstrated that the Ghanaian paper currency notes are heavily contaminated with potentially pathogenic bacteria that are highly resistant to the most widely used antibiotics and are a threat to public health.

Keywords: microflora, antibiotic resistance, staphylococcus aureus, culture media, multi-drug resistance

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Authors: Fadia Gafri, Kathryn Mckintosh, Louise Young, Alan Harvey, Simon Mackay, Andrew Paul, Robin Plevin

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Nuclear factor-kappa B (NF-κB) is a ubiquitous transcription factor found originally to play a key role in regulating inflammation. However considerable evidence links this pathway to the suppression of apoptosis, cellular transformation, proliferation and invasion (Aggarwal et al., 2006). Moreover, recent studies have also linked inflammation to cancer progression making NF-κB overall a promising therapeutic target for drug discovery (Dobrovolskaia & Kozlov, 2005). In this study we examined the effect of the natural product canthin-6-one (SU182) as part of a CRUK small molecule drug discovery programme for effects upon the NF-κB pathway. Initial studies demonstrated that SU182 was found to have good potency against the inhibitory kappa B kinases (IKKs) at 30M in vitro. However, at concentrations up to 30M, SU182 had no effect upon TNFα stimulated loss in cellular IκBα or p65 phosphorylation in the keratinocyte cell line NCTC2544. Nevertheless, 30M SU182 reduced TNF-α / PMA-induced NF-κB-linked luciferase reporter activity to (22.9 ± 5%) and (34.6± 3 %, P<0.001) respectively, suggesting an action downstream of IKK signalling. Indeed, SU182 neither decreased NF-κB-DNA binding as assayed by EMSA nor prevented the translocation of p65 (NF-κB) to the nucleus assessed by immunofluorescence and subcellular fractionation. In addition to the inhibition of transcriptional activity of TNFα-induced NF-κB reporter activity SU182 significantly reduced PMA-induced AP-1-linked luciferase reporter activity to about (48± 9% at 30M, P<0.001) . This mode of inhibition was not sufficient to prevent the activation of NF-κB dependent induction of other proteins such as COX-2 and iNOS, or activated MAP kinases (p38, JNK and ERK1/2) in LPS stimulated RAW 264.7 macrophages. Taken together these data indicate the potential for SU182 to interfere with the transcription factors NF-κB and AP-1 at transcriptional level. However, no potential anti-inflammatory effect was indicated, further investigation for other NF-κB dependent proteins linked to survival are also required to identify the exact mechanism of action.

Keywords: Canthin-6-one, NF-κB, AP-1, phosphorylation, Nuclear translocation, DNA-binding activity, inflammatory proteins.

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