Search results for: targeting antibodies

Authors: Mulugeta Shegaze, Mekitie Wondafrash, Alemayehu A. Alemayehu, Shikur Mohammed, Zewdu Shewangezaw, Mukerem Abdo, Gebresilasea Gendisha

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Background: The 2004 World Health Assembly called for specific actions to halt the overweight and obesity epidemic that is currently penetrating urban populations in the developing world. Adolescents require particular attention due to their vulnerability to develop obesity and the fact that adolescent weight tracks strongly into adulthood. However, there is scarcity of information on the modifiable risk factors to be targeted for primary intervention among urban adolescents in Ethiopia. This study was aimed at determining the magnitude and risk factors of overweight and obesity among high school adolescents in Addis Ababa. Methods: An institution-based cross-sectional study was conducted in February and March 2014 on 456 randomly selected adolescents from 20 high schools in Addis Ababa city.  Demographic data and other risk factors of overweight and obesity were collected using self-administered structured questionnaire, whereas anthropometric measurements of weight and height were taken using calibrated equipment and standardized techniques. The WHO STEPS instrument for chronic disease risk was applied to assess dietary habit and physical activity. Overweight and obesity status was determined based on BMI-for-age percentiles of WHO 2007 reference population. Results: The prevalence rates of overweight, obesity, and overall overweight/ obesity among high school adolescents in Addis Ababa were 9.7% (95%CI = 6.9-12.4%), 4.2% (95%CI = 2.3-6.0%), and 13.9% (95%CI = 10.6-17.1%), respectively. Overweight/obesity prevalence was highest among female adolescents, in private schools, and in the higher wealth category. In multivariable regression model, being female [AOR(95%CI) = 5.4(2.5,12.1)], being from private school [AOR(95%CI) = 3.0(1.4,6.2)], having >3 regular meals [AOR(95%CI) = 4.0(1.3,13.0)], consumption of sweet foods [AOR(95%CI) = 5.0(2.4,10.3)] and spending >3 hours/day sitting [AOR(95%CI) = 3.5(1.7,7.2)] were found to increase overweight/ obesity risk, whereas high Total Physical Activity level [AOR(95%CI) = 0.21(0.08,0.57)] and better nutrition knowledge [AOR(95%CI) = 0.160.07,0.37)] were found protective. Conclusions: More than one in ten of the high school adolescents were affected by overweight/obesity with dietary habit and physical activity are important modifiable risk factors. Well-tailored nutrition education program targeting lifestyle change should be initiated with more emphasis to female adolescents and students in private schools.

Keywords: adolescents, NCDs, overweight, obesity

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Authors: Shujun Xie, Shirong Zhang, Shenglin Ma

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Background: Chronic inflammation might lead to many malignancies, and inadequate resolution could play a crucial role in tumor invasion, progression, and metastases. A randomised, double-blind, placebo-controlled trial shows that IL-1β inhibition with canakinumab could reduce incident lung cancer and lung cancer mortality in patients with atherosclerosis. The process and secretion of proinflammatory cytokine IL-1β are controlled by the inflammasome. Here we showed the correlation of the innate immune system and afatinib, a tyrosine kinase inhibitor targeting epidermal growth factor receptor (EGFR) in non-small cell lung cancer. Methods: Murine Bone marrow derived macrophages (BMDMs), peritoneal macrophages (PMs) and THP-1 were used to check the effect of afatinib on the activation of NLRP3 inflammasome. The assembly of NLRP3 inflammasome was check by co-immunoprecipitation of NLRP3 and apoptosis-associated speck-like protein containing CARD (ASC), disuccinimidyl suberate (DSS)-cross link of ASC. Lipopolysaccharide (LPS)-induced sepsis and Alum-induced peritonitis were conducted to confirm that afatinib could inhibit the activation of NLRP3 in vivo. Peripheral blood mononuclear cells (PBMCs) from non-small cell lung cancer (NSCLC) patients before or after taking afatinib were used to check that afatinib inhibits inflammation in NSCLC therapy. Results: Our data showed that afatinib could inhibit the secretion of IL-1β in a dose-dependent manner in macrophage. Moreover, afatinib could inhibit the maturation of IL-1β and caspase-1 without affecting the precursors of IL-1β and caspase-1. Next, we found that afatinib could block the assembly of NLRP3 inflammasome and the ASC speck by blocking the interaction of the sensor protein NLRP3 and the adaptor protein ASC. We also found that afatinib was able to alleviate the LPS-induced sepsis in vivo. Conclusion: Our study found that afatinib could inhibit the activation of NLRP3 inflammasome in macrophage, providing new evidence that afatinib could target the innate immune system to control chronic inflammation. These investigations will provide significant experimental evidence in afatinib as therapeutic drug for non-small cell lung cancer or other tumors and NLRP3-related diseases and will explore new targets for afatinib.

Keywords: inflammasome, afatinib, inflammation, tyrosine kinase inhibitor

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Authors: Anoush Saadatmehr

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Design and build of large clear span structures have always been demanding in the construction industry targeting industrial and commercial buildings around the world. The function of these spectacular structures encompasses distinguished types of building such as aircraft and airship hangars, warehouses, bulk storage buildings, sports and recreation facilities. From an engineering point of view, there are various types of steel structure systems that are often adopted in large-span buildings like conventional trusses, space frames and cable-supported roofs. However, this paper intends to investigate and review an innovative light, economic and quickly erected large span steel structure renowned as “Stressed-Arch,” which has several advantages over the other common types of structures. This patented system integrates the use of cold-formed hollow section steel material with high-strength pre-stressing strands and concrete grout to establish an arch shape truss frame anywhere there is a requirement to construct a cost-effective column-free space for spans within the range of 60m to 180m. In this study and firstly, the main structural properties of the stressed-arch system and its components are discussed technically. These features include nonlinear behavior of truss chords during stress-erection, the effect of erection method on member’s compressive strength, the rigidity of pre-stressed trusses to overcome strict deflection criteria for cases with roof suspended cranes or specialized front doors and more importantly, the prominent lightness of steel structure. Then, the effects of utilizing pre-stressing strands to safeguard a smooth process of installation of main steel members and roof components and cladding are investigated. In conclusion, it is shown that the Stressed-Arch system not only provides an optimized light steel structure up to 30% lighter than its conventional competitors but also streamlines the process of building erection and minimizes the construction time while preventing the risks of working at height.

Keywords: large span structure, pre-stressed steel truss, stressed-arch building, stress-erection, steel structure

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Authors: Memory Ranga, Phillip Pretorious

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The South African Government has invested a lot of money in Information Technology Governance (ITG) within the Government departments. The ITG framework was spearheaded by the Department of Public Service and Administration (DPSA). This led to the development of a governing ITG DPSA framework and later the Government Wide Enterprise Architecture (GWEA) Framework for assisting the departments to implement ITG. In addition to this, the government departments have adopted the Information Systems Audit and Control Association (ISACA) Control Objectives for Information and Related Technology (COBIT) for ITG processes. Despite all these available frameworks, departments fail to fully capitalise and improve the ITG processes mainly as these are too generic and difficult to apply for specific governance needs. There has been less research done to evaluate the progress on ITG initiatives within the government departments. This paper aims to evaluate the existing ITG frameworks within selected government departments in South Africa. A quantitative research approach was used in this study. Data was collected through an online questionnaire targeting ICT Managers and Directors from government departments. The study is undertaken within a case study and only the Eastern Cape Province was selected for the research. Document review mainly on ITG framework and best practices was also used. Data was analysed using the Google Analytic tools and SPSS. A one–sample Chi-Squared Test was used to verity the evaluation findings. Findings show that there is evidence that the current guiding National governance framework (DPSA) is out dated and does not accommodate the new changes in other governance frameworks. The Eastern Cape Government Departments have spent huge amount of money on ITG but not yet able to identify the benefits of the ITG initiatives. The guiding framework is rigid and does to address some of the departmental needs making it difficult to be flexible and apply the DPSA framework. Furthermore, despite the large budget on ITG, the departments still find themselves with many challenges and unable to improve some of the processes and services. All the engaged Eastern Cape departments have adopted the COBIT framework, but none has been conducting COBIT maturity Assessment which is a functionality of COBIT. There is evidence of too many the ITG frameworks and underutilisation of these frameworks. The study provides a comprehensive evaluation of the ITG frameworks that have been adopted by the South African Government Departments in the Eastern Cape Province. The evaluation guides and recommends the government departments to rethink and adopt ITG frameworks that could be customised to accommodate their needs. The adoption and application of ITG by government departments should assist in better governance and service delivery to the citizens.

Keywords: information technology governance, COBIT, evaluate, framework, governance, DPSA framework

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Authors: Isabella B. Davidman

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Violence used against Jewish women in both the Eastern European pogroms and during the Nazi era was specifically gendered, targeting their female identity and dignity of womanhood. Not only did these acts of gendered violence dehumanize Jewish women, but they also hurt the Jewish community as a whole. The devastating sexual violence that women endured during the pogroms and the Nazi era caused profound trauma. Out of shame and fear, silence about women’s experiences of sexual abuse manifests in forms that words cannot translate. Women have turned to art and other means of storytelling to convey their female experiences in visual and non-verbal ways. Therefore, this paper aims to address the historical accounts of gendered violence against Jewish women during the pogroms and Nazi era, as well as art that reflects upon the female experience, in order to understand the emotional impact resulting from these events. To analyze the artwork, a feminist analysis was used to understand the intersection of gender with the other systems of inequality, such as systemic anti-semitism, in women’s lives; this ultimately explained the ways in which cultural productions undermine and reinforce the political and social oppression of women by exploring how art confronts the exploitation of women's bodies. By analyzing the art in the context of specific acts of violence, such as public rape, as a strategic weapon, we are able to understand women’s experiences and how these experiences, in turn, challenged their womanhood. Additionally, these atrocities, which often occurred in the public space, were dismissed and forgotten due to the social stigma of rape. In this sense, the experiences of women in pogroms and the Nazi era were both highly unacknowledged and forgotten. Therefore, the art that was produced during those time periods, as well as those after those events, gives voice to the profound silence on the narratives of Jewish women. Sexual violence is a weapon of war used to cause physical and psychological destruction, not only as a product of war. In both the early twentieth-century pogroms and the Holocaust, the sexual violence that Jewish women endured was fundamentally the same: the rape of Jewish women became a focal target in the theater of violence– women were not raped because they were women, but specifically, because they were Jewish women. Although the events of the pogroms and the Holocaust are in the past, the art that serves as testimony to the experience of Jewish women remains an everlasting reminder of the gendered violence that occurred. Even though covert expressions, such as an embroidered image of a bird eating an apple, the artwork gives voice to the many silenced victims of sexualized and gendered violence.

Keywords: gendered violence, holocaust, Nazi era, pogroms

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Authors: Masome Moeni, Roya Abedizadeh, Elham Aram, Hamid Sadeghi-Abandansari, Davood Sabour, Robert Menzel, Ali Hassanpour

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Significant number of studies and preclinical research in formulation of cancer nano-pharmaceutics have led to an improvement in cancer care. Nonetheless, the antineoplastic agents have ‘failed to live up to its promise’ since their clinical performance is moderately low. For almost ninety years, iron oxide nanoparticles (IONPS) have managed to keep its reputation in clinical application due to their low toxicity, versatility and multi-modal capabilities. Drug Administration approved utilization of IONPs for diagnosis of cancer as contrast media in magnetic resonance imaging, as heat mediator in magnetic hyperthermia and for the treatment of iron deficiency. Furthermore, IONPs have high drug-loading capacity, which makes them good candidates as therapeutic agent transporters. There are yet challenges to overcome for successful clinical application of IONPs, including stability of drug and poor delivery, which might lead to (i) drug resistance, (ii) shorter blood circulation time, and (iii) rapid elimination and adverse side effects from the system. In this study, highly stable and super paramagnetic IONPs were prepared for efficient and targeted drug delivery in cancer treatment. The synthesis procedure was briefly involved the production of IONPs via co-precipitation followed by coating with tetraethyl orthosilicate and 3-aminopropylethoxysilane and grafting with folic acid for stability targeted purposes and controlled drug release. Physiochemical and morphological properties of modified IONPs were characterised using different analytical techniques. The resultant IONPs exhibited clusters of 10 nm spherical shape crystals with less than 100 nm size suitable for drug delivery. The functionalized IONP showed mesoporous features, high stability, dispersibility and crystallinity. Subsequently, the functionalized IONPs were successfully loaded with oxaliplatin, a chemotherapeutic agent, for a controlled drug release in an actively targeting cancer cells. FT-IR observations confirmed presence of oxaliplatin functional groups, while ICP-MS results verified the drug loading was ~ 1.3%.

Keywords: cancer treatment, chemotherapeutic agent, drug delivery, iron oxide, multi-functional nanoparticle

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Authors: Awadh O. Al-Anazi

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As part of the organizational needs toward successful maintaining activities, a proper management system need to be put in place, ensuring the effectiveness of maintenance activities. The management system shall clearly describes the process of identifying, prioritizing, planning, scheduling, execution, and providing valuable feedback for all maintenance activities. Completion and accuracy of the system with proper implementation shall provide the organization with a strong platform for effective maintenance activities that are resulted in efficient outcomes toward business success. The purpose of this research was to introduce a practical tool for measuring the maintenance efficiency level within Saudi organizations. A comprehensive study was launched across many maintenance professionals throughout Saudi leading organizations. The study covered five main categories: work process, identification, planning and scheduling, execution, and performance monitoring. Each category was evaluated across many dimensions to determine its current effectiveness through a five-level scale from 'process is not there' to 'mature implementation'. Wide participation was received, responses were analyzed, and the study was concluded by highlighting major gaps and improvement opportunities within Saudi organizations. One effective implementation of the efficiency enhancement efforts was deployed in Saudi Kayan (one of Sabic affiliates). Below details describes the project outcomes: SK overall maintenance wrench time was measured at 20% (on average) from the total daily working time. The assessment indicates the appearance of several organizational gaps, such as a high amount of reactive work, poor coordination and teamwork, Unclear roles and responsibilities, as well as underutilization of resources. Multidiscipline team was assigned to design and implement an appropriate work process that is capable to govern the execution process, improve the maintenance workforce efficiency, and maximize wrench time (targeting > 50%). The enhanced work process was introduced through brainstorming and wide benchmarking, incorporated with a proper change management plan and leadership sponsorship. The project was completed in 2018. Achieved Results: SK WT was improved to 50%, which resulted in 1) reducing the Average Notification completion time. 2) reducing maintenance expenses on OT and manpower support (3.6 MSAR Actual Saving from Budget within 6 months).

Keywords: efficiency, enhancement, maintenance, work force, wrench time

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Authors: Dolores Sucozhañay, Gustavo Pacheco, Paul Vanegas

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In the context of sustainable development and the transition towards a sustainable circular economy (CE), evaluating the social dimension remains a challenge. Therefore, developing a respective methodology is highly important. First, the change of the economic model may cause significant social effects, which today remain unaddressed. Second, following the current level of globalization, CE implementation requires targeting global material cycles and causes social impacts on potentially vulnerable social groups. A promising methodology is the Social Life Cycle Assessment (SLCA), which embraces the philosophy of life cycle thinking and provides complementary information to environmental and economic assessments. In this context, the present work uses the updated Social Life Cycle Assessment (SLCA) Guidelines 2020 to assess the social performance of the recycling system of Cuenca, Ecuador, to exemplify a social assessment method. Like many other developing countries, Ecuador heavily depends on the work of informal waste pickers (recyclers), who, even contributing to a CE, face harsh socio-economic circumstances, including inappropriate working conditions, social exclusion, exploitation, etc. Under a Reference Scale approach (Type 1), 12 impact subcategories were assessed through 73 site-specific inventory indicators, using an ascending reference scale ranging from -2 to +2. Findings reveal a social performance below compliance levels with local and international laws, basic societal expectations, and practices in the recycling sector; only eight and five indicators present a positive score. In addition, a social hotspot analysis depicts collection as the most time-consuming lifecycle stage and the one with the most hotspots, mainly related to working hours and health and safety aspects. This study provides an integrated view of the recyclers’ contributions, challenges, and opportunities within the recycling system while highlighting the relevance of assessing the social dimension of CE practices. It also fosters an understanding of the social impact of CE operations in developing countries, highlights the need for a close north-south relationship in CE, and enables the connection among the environmental, economic, and social dimensions.

Keywords: SLCA, circular economy, recycling, social impact assessment

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Authors: Faizan Sultan

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Non-government organizations (NGOs) in Pakistan have the potential to deliver services such as health, education, and rural development through targeting the most vulnerable communities of society. Having this significant importance, NGOs are facing numerous challenges in service delivery. So, there is a need to identify the challenges NGOs face in community development, particularly post-conflict development. The current study has analyzed the social and political constraints in development projects in the post-conflict region of the Swat district of Khyber Pakhtunkhwa. The objectives of this study are “What are the social and political constraints faced by the nongovernmental organizations in the implementation of development aid Projects in post-conflict development of Swat and to examine the challenges in coordination mechanism between government departments, NGOs, and community in reconstruction activities”. This research is based upon both the quantitative and qualitative data that is being gathered from the NGO representatives, government officials, and community members who were involved in post-conflict development interventions in the Swat region. A purposive sampling technique was used to select respondents from the community members/activists (25 in number) and government and NGO officials (10 in number). Based on analysis against our objectives, NGOs have faced numerous constraints such as Insecurity, Negative Perceptions about NGOs, restrictions on women's mobility, government policies and regulations, lack of coordination and networking, trust deficit, and political interference while implementing their project interventions. These findings concluded that constraints have affected project implementation to a greater extent, including women's participation, involvement of marginalized populations, and equal distribution of resources. In the Swat region, NGOs cannot openly discuss sensitive projects such as human rights, gender-based projects, or women empowerment as these issues are very sensitive to the local community due to their cultural values. The community may not allow their females to go outside their homes as this region is a male-dominated society. Similarly, lack of communication and poor networking for the arrangements of the project meetings were also the major constraints.

Keywords: national disaster management authority, millennium development goals, provincial disaster management authority, provincial reconstruction, rehabilitation and settlement authority

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Authors: Noor Taleb Ismael, Areej Abd Al Kareem Al Titi, Ala'a Fayez Jaber

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Objectives: To investigate self-perceived functional performance among adults with IDD who are Jordanian residential care and rehabilitation centers residents. Also, to investigate their functional abilities (i.e., motor, and cognitive). In addition, to determine the motor and cognitive predictors of their functional performance. Methods: The study utilized a cross-sectional descriptive design; the sample included 180 individuals with IDD (90 males and 90 females) aged 18 to 75 years. The inclusion criteria encompassed: 1) Adults with a confirmed IDD by their physician’s professional and 2) residents in Jordanian Residential Care and Rehabilitation Centers affiliated with the Jordanian Ministry of Social Development. The exclusion criteria were: 1) bedridden or totally dependent on their care providers; 2) who had an accident or acquired neurological conditions. Researchers conducted semi-structured interviews to complete the outcome measures that include the Canadian Occupational Performance Measure (COPM), the Functional Independence Measure (FIM), the Montreal Cognitive Assessment (MoCA), the Mini-Mental Status Examination (MMSE), and the sociodemographic questionnaire. Data analyses consisted of descriptive statistics, analysis of frequencies, correlation, and regression analyses. Result: Individuals with IDD showed low functional performance in all daily life areas, including self-care, productivity, and leisure; there was severe cognitive impairment and poor independence and functional performance. (COPM Performance M= 1.433, SD±.57021, COPM Satisfaction M= 1.31, SD±.54, FIM M= 3.673, SD± 1.7918). Two predictive models were validated for the COPM performance and FIM total scores. First, significant predictors of high self-perceived functional performance on COPM were high scores on FIM Motor sub scores, FIM cognitive sub scores, young age, and having a high school educational level (R2=0.603, p=0.012). Second, significant predictors of high functional capacity on FIM were a high score on the COPM performance subscale, a high MMSE score, and having a cerebral palsy (CP) diagnosis (R2=0.671, p<0.001). Conclusions: Evaluating functional performance and associated factors is important in rehabilitation to provide better services and improve health and QoL for individuals with IDD. This study suggested conducting future studies targeting integrated individuals with IDD who live with their families in the communities.

Keywords: functional performance, intellectual and developmental disabilty, cognitive abilities, motor abilities

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Authors: Susanne Manes, Anni Glaeser, Katharina Wick, Bernhard Strauss, Uwe Berger

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Introduction: Over the last decades growing rates of mental health concerns among children and adolescents have been observed. At the same time, physical well-being of children and adolescents becomes increasingly impaired as well. Schools play an important role in preventing mental and physical disorders and in promoting well-being. Self-esteem, as well as social integration, are vital influence factors for mental and physical well-being. The purpose of this study was to develop and evaluate the program 'VorteilJena' for secondary schools in Germany focusing on self-esteem and social integration to improve mental and physical well-being. Method: The school-based health promotion program was designed for students in 5th grade and higher. It consists of several short pedagogical exercises instructed by a teacher and were integrated into the regular class over the course of ten weeks. The exercises focused on fostering social integration using either tasks improving team spirit or exercises that increase tolerance and sense of belonging. Other exercises focused on strengthening the self-esteem of the students. Additionally, the program included a poster exhibition titled 'Belonging' which was put up in the school buildings. The exhibition comprised ten posters which addressed relevant risk factors and resources related to social integration and self-esteem. The study was a randomized controlled sequential study with a pre and post measurement conducted in ten German schools. A total of 1642 students (44% male) were recruited. Their age ranged from 9 to 21 years (M=12.93 years; SD= 2.11). The program was conducted in classes ranging from 5th to 12th grade. Results: The program improved wellbeing, self-esteem and social integration of the involved students compared to the control group. Differential effects depending on implementation rates or age of the students will be analyzed. Moreover, implications for future school-based health promotion programs targeting self-esteem and social integration will be discussed. Conclusion: Social integration considerably influences self-esteem and well-being of students and can be targeted by school-based programs including short and modest exercises. Since a sufficient implementation of health promotion programs is essential, the present program due to its practicability represents a good opportunity to install health promotion focusing on social integration in schools.

Keywords: social integration, well-being, health promotion in schools, self-esteem

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Authors: Tracey Lion-Cachet

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Eating disorders typically manifest in adolescence and are notoriously difficult to treat. There are two notable reasons for this. Firstly, research consistently demonstrates that early intervention is a critical mediator of prognosis, with early intervention leading to a better prognosis. However, because eating disorders do not originate as full-syndrome diagnoses but rather as prodromal cases, they often go undetected; by the time symptoms meet diagnostic criteria, they have become recalcitrant. Another interrelated issue is motivation to change. Research demonstrates that in the early stages of an eating disorder, adolescents are highly resistant to change, and motivation increases only once symptoms have shifted from egosyntonic to egodystonic in nature. The purpose of this project was to design a prevention model based on the social psychology paradigm of Entertainment-Education, which embeds messages within the genre of film as a means of affecting change. The resulting project was a narrative screenplay targeting teenagers/young adults from diverse backgrounds. The goals of the project were to create a film script that, if ultimately made into a film, could serve to: 1) interrupt symptom progression and improve prognosis through early intervention; 2) incorporate techniques from third-wave cognitive behavioral treatment models, acceptance and commitment therapy (ACT) and rational recovery (RR), with a focus on the effects of mindfulness as a means of informing recovery; 3) target issues to do with motivation to change by shifting the perception of eating disorders from culturally specific psychiatric illnesses to habit-based brain wiring issues. Nine licensed clinicians were asked to evaluate two excerpts taken from the final script. They subsequently provided feedback on a Likert-scale, which assessed whether the script had achieved its goals. Overall, evaluators agreed that the project’s etiological and intervention models have the potential to inspire change and serve as an effective means of prevention and treatment of eating disorders. However, one-third of the evaluators did not find the content developmentally appropriate. This is a notable limitation to the study and will need to be addressed in the larger script before the final project can potentially be targeted to a teenage and young adult audience.

Keywords: adolescents, eating disorders, pediatrics, entertainment-education, mindfulness-based intervention, prevention

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Authors: Joshua Fogel, Rivka Herzog

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Although direct-to-consumer prescription medication advertisements (DTCA) are viewed or heard in many venues, there does not appear to be any research for internet social media DTCA. We study the association of traditional media DTCA and digital media DTCA including internet social media of YouTube, Facebook, and Twitter with three different outcomes. There was one intentions outcome and two different behavior outcomes. The intentions outcome was the agreement level for seeking additional information about a prescription medication after seeing a DTCA. One behavior outcome was the agreement level for obtaining additional information about a prescription medication after seeing a DTCA. The other behavior outcome was the frequency level for obtaining additional information about a prescription medication after seeing a DTCA. Surveys were completed by 635 college students. Predictors included demographic variables, theory of planned behavior variables, health variables, and advertisements seen or heard. Also, in the behavior analyses, additional predictors of intentions and sources for seeking additional prescription drug information were included. Multivariate linear regression analyses were conducted. We found that increased age was associated with increased behavior, women were associated with increased intentions, and Hispanic race/ethnicity was associated with decreased behavior. For the theory of planned behavior variables, increased attitudes were associated with increased intentions, increased social norms were associated with increased intentions and behavior, and increased intentions were associated with increased behavior. Very good perceived health was associated with increased intentions. Advertisements seen in spam mail were associated with decreased intentions. Advertisements seen on traditional or cable television were associated with decreased behavior. Advertisements seen on television watched on the internet were associated with increased behavior. The source of seeking additional information of reading internet print content was associated with increased behavior. No internet social media advertisements were associated with either intentions or behavior. In conclusion, pharmaceutical brand managers and marketers should consider these findings when tailoring their DTCA advertising campaigns and directing their DTCA advertising budget towards young adults such as college students. They need to reconsider the current approach for traditional television DTCA and also consider dedicating a larger advertising budget toward internet television DTCA. Although internet social media is a popular place to advertise, the financial expenditures do not appear worthwhile for DTCA when targeting young adults such as college students.

Keywords: brand managers, direct-to-consumer advertising, internet, social media

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Authors: Rubina Jahan, Mohammad Zayeed Bin Alam, Sazzad Chowdhury, Sadia Chowdhury

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Access to mental health services in Bangladesh is a tale of urban privilege and rural struggle. Mental health services in the country are primarily centered in urban medical hospitals, with only 260 psychiatrists for a population of more than 162 million, while rural populations face far more severe and daunting challenges. In alignment with the World Health Organization's perspective on mental health as a basic human right and a crucial component for personal, community, and socioeconomic development; SAJIDA Foundation a value driven non-government organization in Bangladesh has introduced a Community Based Mental Health (CMHI) program to fill critical gaps in mental health care, providing accessible and affordable community-based services to protect and promote mental health, offering support for those grappling with mental health conditions. The CMHI programme is being implemented in 3 districts in Bangladesh, 2 of them are remote and most climate vulnerable areas targeting total 6,797 individual. The intervention plan involves a screening of all participants using a 10-point vulnerability assessment tool to identify vulnerable individuals. The assumption underlying this is that individuals assessed as vulnerable is primarily due to biological, psychological, social and economic factors and they are at an increased risk of developing common mental health issues. Those identified as vulnerable with high risk and emergency conditions will receive Mental Health First Aid (MHFA) and undergo further screening with GHQ-12 to be identified as cases and non-cases. The identified cases are then referred to community lay counsellors with basic training and knowledge in providing 4-6 sessions on problem solving or behavior activation. In situations where no improvement occurs post lay counselling or for individuals with severe mental health conditions, a referral process will be initiated, directing individuals to ensure appropriate mental health care. In our presentation, it will present the findings from 6-month pilot implementation focusing on the community-based screening versus outcome of the lay counseling session and barriers and facilitators of implementing community based mental health care in a resource constraint country like Bangladesh.

Keywords: community-based mental health, lay counseling, rural bangladesh, treatment gap

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Authors: Salma Akter, Md. Kamal Uddin

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Ashrayan (shelter) Prakalpa – a fully subsidized ‘integrated poverty eradication program’ through the provisioning of shelter of Bangladesh Government (GoB) targeting the internally displaced and homeless. In spite of the inclusiveness (poverty alleviation, employment opportunity, Tenure ship and training) of the shelter policy, dwellers are not merely questioned by the issue of 'the quality of life' .This study demonstrates how top-down policies, ambiguous ownership status of land and dwelling environments lead to ‘everyday compromise’ by the grassroots in both subjective (satisfaction, comfort and safety) and objective (physical design elements and physical environmental elements) issues in three respective scale macro (neighborhood) meso (shelter /built environment) and micro(family). It shows that by becoming subject to Government’s resettlements policies and after becoming user of its shelter units (although locally known as ‘barracks’ rather shelter or housing), the once displaced settlers assume a curious form of spatial practice where both social and spatial often bear slippery meanings. Thus, Policy-based shelter force the dwellers frequently compromise with their provided built environments and spaces within the settlements both in overtly and covertly. Compromises are made during the production of space and forms, whereas interesting new spaces and space-making practices emerge. The settlements under study are Dakshin Chandani Mahal Ashrayan Prakalpa located at the Eastern fringe area of Khulna, Bangladesh. In terms of methodology, this research is primarily exploratory and assumes a qualitative approach. Key tools used to obtain information are policy analysis, literature review, key informant interview, focus group discussion and participant observation at the level of dwelling and settlements. Necessary drawings and photographs have been taken to promote the study objective. Findings revealed that various shortages, inadequacies and negligence of policymakers make a compromising character of displaced by the means of 'quality of life' both in objective and subjective ground. Thus the study ends up with a recommendation to the policymakers to take an initiative to ensure the quality of life of the dwellers.

Keywords: Ashrayan, compromise, displaced people, quality of life

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Authors: Giorgio Bertolazzi, Panayiotis Benos, Michele Tumminello, Claudia Coronnello

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MicroRNAs are small non-coding RNAs that post-transcriptionally regulate the expression levels of messenger RNAs. MicroRNA regulation activity depends on the recognition of binding sites located on mRNA molecules. ComiR (Combinatorial miRNA targeting) is a user friendly web tool realized to predict the targets of a set of microRNAs, starting from their expression profile. ComiR incorporates miRNA expression in a thermodynamic binding model, and it associates each gene with the probability of being a target of a set of miRNAs. ComiR algorithms were trained with the information regarding binding sites in the 3’UTR region, by using a reliable dataset containing the targets of endogenously expressed microRNA in D. melanogaster S2 cells. This dataset was obtained by comparing the results from two different experimental approaches, i.e., inhibition, and immunoprecipitation of the AGO1 protein; this protein is a component of the microRNA induced silencing complex. In this work, we tested whether including coding region binding sites in the ComiR algorithm improves the performance of the tool in predicting microRNA targets. We focused the analysis on the D. melanogaster species and updated the ComiR underlying database with the currently available releases of mRNA and microRNA sequences. As a result, we find that the ComiR algorithm trained with the information related to the coding regions is more efficient in predicting the microRNA targets, with respect to the algorithm trained with 3’utr information. On the other hand, we show that 3’utr based predictions can be seen as complementary to the coding region based predictions, which suggests that both predictions, from 3'UTR and coding regions, should be considered in a comprehensive analysis. Furthermore, we observed that the lists of targets obtained by analyzing data from one experimental approach only, that is, inhibition or immunoprecipitation of AGO1, are not reliable enough to test the performance of our microRNA target prediction algorithm. Further analysis will be conducted to investigate the effectiveness of the tool with data from other species, provided that validated datasets, as obtained from the comparison of RISC proteins inhibition and immunoprecipitation experiments, will be available for the same samples. Finally, we propose to upgrade the existing ComiR web-tool by including the coding region based trained model, available together with the 3’UTR based one.

Keywords: AGO1, coding region, Drosophila melanogaster, microRNA target prediction

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Authors: Zan Chen, D. Kwok

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The SkillsFuture Singapore’s mission to develop a responsive and forward-looking Training and Adult Education (TAE) and workforce development system is undergirded by how successful TAE providers are in their business performance and strategies that strengthen their operational efficiency and processes. Therefore, understanding the factors that drive the business performance of TAE providers is critical to the success of SkillsFuture Singapore’s initiatives. This study aims to investigate how business strategy, work autonomy, work intensity and professional development support impact the business performance of private TAE providers. Specifically, the three research questions are: (1) Are there significant relationships between the above-mentioned four factors and TAE providers’ business performance?; (2) Are there significant differences on the four factors between low and high TAE providers’ business performance groups?; and (3) To what extent and in what manner do the four factors predict TAE providers’ business performance? This was part of the first national study on organizations and professionals working in the Training and Adult Education (TAE) sector. Data from 265 private TAE providers where respondents were Chief Executive Officers representatives from the Senior Management were analyzed. The results showed that business strategy (the extent that the organization leads the way in terms of developing new products and services; uses up-to-date learning technologies; customizes its products and services to the client’s needs), work autonomy (the extent that the staff personally have an influence on how hard they work; deciding what tasks they are to do; deciding how they are to do the tasks, and deciding the quality standards to which they work) and professional development support (both monetary and non-monetary support and incentives) had positive and significant relationships with business performance. However, no significant relationship is found between work intensity and business performance. A business strategy, work autonomy and professional development support were significantly higher in the high business performance group compared to the low-performance group among the TAE providers. Results of hierarchical regression analyses controlling for the size of the TAE providers showed significant impacts of business strategy, work autonomy and professional development support on TAE providers’ business performance. Overall, the model accounted for 27% of the variance in TAE providers’ business performance. This study provides policymakers with insights into improving existing policies, designing new initiatives and implementing targeting interventions to support TAE providers. The findings also have implications on how the TAE providers could better formulate their organizational strategies and business models. Finally, limitations of study, along with directions for future research will be discussed in the paper.

Keywords: adult education, business performance, business strategy, training, work autonomy

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Authors: Alla Ovsyannikova, Oksana Rymar, Elena Shakhtshneider, Mikhail Voevoda

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In Siberia endocrinologists increasingly noted young patients with the course of diabetes mellitus differing from 1 and 2 types. Therefore we did a molecular genetic study for this group of patients to verify the monogenic forms of diabetes mellitus in them and researched the characteristics of this pathology. When confirming the monogenic form of diabetes, we performed a correction therapy for many patients (transfer from insulin to tablets), prevented specific complications, examined relatives and diagnosed their diabetes at the preclinical stage, revealed phenotypic characteristics of the pathology which led to the high significance of this work. Materials and Methods: We observed 5 patients (4 families). We diagnosed MODY (Maturity Onset Diabetes of the Young) during the molecular genetic testing (direct automatic sequencing). All patients had a full clinical examination, blood samples for biochemical research, determination of C-peptide and TSH, antibodies to b-cells, microalbuminuria, abdominal ultrasound, heart and thyroid ultrasound, examination of ophthalmologist. Results: We diagnosed 3 rare types of MODY: two women had MODY8, one man – MODY6 and man and his mother - MODY12. Patients with types 8 and 12 had clinical features. Age of onset hyperglycemia ranged from 26 to 34 years. In a patient with MODY6 fasting hyperglycemia was detected during a routine examination. Clinical symptoms, complications were not diagnosed. The patient observes a diet. In the first patient MODY8 was detected during first pregnancy, she had itchy skin and mostly postprandial hyperglycemia. Upon examination we determined glycated hemoglobin 7.5%, retinopathy, non-proliferative stage, peripheral neuropathy. She uses a basic bolus insulin therapy. The second patient with MODY8 also had clinical manifestations of hyperglycemia (pruritus, thirst), postprandial hyperglycemia and diabetic nephropathy, a stage of microalbuminuria. The patient was diagnosed autoimmune thyroiditis. She used inhibitors of DPP-4. The patient with MODY12 had an aggressive course. In the detection of hyperglycemia he had complaints of visual impairment, intense headaches, leg cramps. The patient had a history of childhood convulsive seizures of non-epileptic genesis, without organic pathology, which themselves were stopped at the age of 12 years. When we diagnosed diabetes a patient was 28 years, he had hypertriglyceridemia, atherosclerotic plaque in the carotid artery, proliferative retinopathy (lacerocoagulation). Diabetes and early myocardial infarction were observed in three cases in family. We prescribe therapy with sulfonylureas and SGLT-2 inhibitors with a positive effect. At the patient's mother diabetes began at a later age (30 years) and a less aggressive course was observed. She also has hypertriglyceridemia and uses oral hypoglycemic drugs. Conclusions: 1) When young patients with hyperglycemia have extrapancreatic pathologies and diabetic complications with a short duration of diabetes we can assume they have one of type of MODY diabetes. 2) In patients with monogenic forms of diabetes mellitus, the clinical manifestations of hyperglycemia in each succeeding generation are revealed at an earlier age. Research had increased our knowledge of the monogenic forms of diabetes. The reported study was supported by RSCF, research project No. 14-15-00496-P.

Keywords: diabetes mellitus, MODY diabetes, monogenic forms, young patients

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Authors: M. Moso-Diez, J. L. Moragues-Oregi, K. Simon-Elorz

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Innovation procurement is designed to steer the development of solutions towards concrete public sector needs as a driver for innovation from the demand side (in public services as well as in market opportunities for companies), is horizontally emerging as a new policy instrument. In 2014 the new EU public procurement directives 2014/24/EC and 2014/25/EC reinforced the support for Public Procurement for Innovation, dedicating funding instruments that can be used across all areas supported by Horizon 2020, and targeting potential buyers of innovative solutions: groups of public procurers with similar needs. Under this programme, new policy adapters and networks emerge, aiming to embed innovation criteria into new procurement processes. As these initiatives are in process, research related to is scarce. We argue that Innovation Public Procurement can arise as an innovative policy instrument to public procurement in different policy domains, in spite of existing institutional and cultural barriers (legal guarantee versus innovation). The presentation combines insights from public procurement to supply management chain management in a sustainability and innovation policy arena, as a means of providing understanding of: (1) the circumstances that emerge; (2) the relationship between public and private actors; and (3) the emerging capacities in the definition of the agenda. The policy adopters are the contracting authorities that mainly are at municipal level where they interact with the supply management chain, interconnecting sustainability and climate measures with other policy priorities such as innovation and urban planning; and through the Competitive Dialogue procedure. We found that geography and territory affect both the level of municipal budget (due to municipal income per capita) and its institutional competencies (due to demographic reasons). In spite of the relevance of institutional determinants for public procurement, other factors play an important role such as human factors as well as both public policy and private intervention. The experience is a ‘city project’ (Bilbao) in the field of brownfield decontamination. Brownfield sites typically refer to abandoned or underused industrial and commercial properties—such as old process plants, mining sites, and landfills—that are available but contain low levels of environmental contaminants that may complicate reuse or redevelopment of the land. This article concludes that Innovation Public Procurement in sustainability and climate issues should be further developed both as a policy instrument and as a policy research line that could enable further relevant changes in public procurement as well as in climate innovation.

Keywords: innovation, city projects, public policy, public procurement

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Authors: Ahmad Odeh, Ahmad Jrade

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Energy assessment is an evidently significant factor when evaluating the sustainability of structures especially at the early design stage. Today design practices revolve around the selection of material that reduces the operational energy and yet meets their displinary need. Operational energy represents a substantial part of the building lifecycle energy usage but the fact remains that embodied energy is an important aspect unaccounted for in the carbon footprint. At the moment, little or no consideration is given to embodied energy mainly due to the complexity of calculation and the various factors involved. The equipment used, the fuel needed, and electricity required for each material vary with location and thus the embodied energy will differ for each project. Moreover, the method and the technique used in manufacturing, transporting and putting in place will have a significant influence on the materials’ embodied energy. This anomaly has made it difficult to calculate or even bench mark the usage of such energies. This paper presents a model aimed at helping designers select the construction materials based on their embodied energy. Moreover, this paper presents a systematic approach that uses an efficient method of calculation and ultimately provides new insight into construction material selection. The model is developed in a BIM environment targeting the quantification of embodied energy for construction materials through the three main stages of their life: manufacturing, transportation and placement. The model contains three major databases each of which contains a set of the most commonly used construction materials. The first dataset holds information about the energy required to manufacture any type of materials, the second includes information about the energy required for transporting the materials while the third stores information about the energy required by tools and cranes needed to place an item in its intended location. The model provides designers with sets of all available construction materials and their associated embodied energies to use for the selection during the design process. Through geospatial data and dimensional material analysis, the model will also be able to automatically calculate the distance between the factories and the construction site. To remain within the sustainability criteria set by LEED, a final database is created and used to calculate the overall construction cost based on R.M.S. means cost data and then automatically recalculate the costs for any modifications. Design criteria including both operational and embodied energies will cause designers to revaluate the current material selection for cost, energy, and most importantly sustainability.

Keywords: building information modelling, energy, life cycle analysis, sustainablity

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Authors: Srijata Mitra, Mobina Parveen, Pranab Roy, Narayan Chandra Chattopadhyay

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Chlorinated hydrocarbon can be a major pollution problem in groundwater as well as soil. Many people interact with these chemicals on daily accidentally or by professionally in the laboratory. One of the most common sources for Chlorinated hydrocarbon contamination of soil and groundwater are industrial effluents. The wide use and discharge of Trichloroethylene (TCE), a volatile chlorohydrocarbon from chemical industry, led to major water pollution in rural areas. TCE is an mainly used as an industrial metal degreaser in industries. Biotransformation of TCE to the potent carcinogen vinyl chloride (VC) by consortia of anaerobic bacteria might have role for the above purpose. For these reasons, the aim of current study was to isolate and characterized the genes involved in TCE metabolism and also to investigate the in silico study of those genes. To our knowledge, only one aromatic dioxygenase system, the toluene dioxygenase in Pseudomonas putida F1 has been shown to be involved in TCE degradation. This is first instance where Bacillus cereus group being used in biodegradation of trichloroethylene. A novel bacterial strain 2479 was isolated from oil depot site at Rajbandh, Durgapur (West Bengal, India) by enrichment culture technique. It was identified based on polyphasic approach and ribotyping. The bacterium was gram positive, rod shaped, endospore forming and capable of degrading trichloroethylene as the sole carbon source. On the basis of phylogenetic data and Fatty Acid Methyl Ester Analysis, strain 2479 should be placed within the genus Bacillus and species cereus. However, the present isolate (strain 2479) is unique and sharply different from the usual Bacillus strains in its biodegrading nature. Fujiwara test was done to estimate that the strain 2479 could degrade TCE efficiently. The gene for TCE biodegradation was PCR amplified from genomic DNA of Bacillus cereus 2479 by using todC1 gene specific primers. The 600bp amplicon was cloned into expression vector pUC I8 in the E. coli host XL1-Blue and expressed under the control of lac promoter and nucleotide sequence was determined. The gene sequence was deposited at NCBI under the Accession no. GU183105. In Silico approach involved predicting the physico-chemical properties of deduced Tce1 protein by using ProtParam tool. The tce1 gene contained 342 bp long ORF encoding 114 amino acids with a predicted molecular weight 12.6 kDa and the theoretical pI value of the polypeptide was 5.17, molecular formula: C559H886N152O165S8, total number of atoms: 1770, aliphatic index: 101.93, instability index: 28.60, Grand Average of Hydropathicity (GRAVY): 0.152. Three differentially expressed proteins (97.1, 40 and 30 kDa) were directly involved in TCE biodegradation, found to react immunologically to the antibodies raised against TCE inducible proteins in Western blot analysis. The present study suggested that cloned gene product (TCE1) was capable of degrading TCE as verified chemically.

Keywords: cloning, Bacillus cereus, in silico analysis, TCE

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Authors: Annamarie Rannou, Horace Bartilow

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Global concerns about xenophobic activity are on the rise across developed and developing countries. And yet, social science scholarship has almost exclusively examined xenophobia as a prejudice of advanced western nations. This research argues that the fields of study related to xenophobia must be re-conceptualized within a framework of ethnicity in order to level the playing field for cross-regional inquiry. This study develops a new concept of ethnic xenophobia and integrates existing explanations of anti-migrant expression into theories of ethnic threat. We argue specifically that political elites convert economic, political, and social threats at the national level into ethnic xenophobic activity in order to gain or maintain political advantage among their native selectorate. We expand on Stuart Kaufman’s theory of symbolic politics to underscore the methods of mobilization used against migrants and the power of elite discourse in moments of national crises. An original dataset is used to examine over 35,000 cases of ethnic xenophobic activity targeting refugees. Wordscores software is used to develop a unique measure of anti-migrant elite rhetoric which captures the symbolic discourse of elites in their mobilization of ethnic xenophobic activism. We use a Structural Equation Model (SEM) to test the causal pathways of the theory across seventy-two developed and developing countries from 1990 to 2016. A framework of Most Different Systems Design (MDSD) is also applied to two pairs of developed-developing country cases, including Kenya and the Netherlands and Lebanon and the United States. This study sheds tremendous light on an underrepresented area of comparative research in migration studies. It shows that the causal elements of anti-migrant activity are far more similar than existing research suggests which has major implications for policy makers, practitioners, and academics in fields of migration protection and advocacy. It speaks directly to the mobilization of myths surrounding refugees, in particular, and the nationalization of narratives of migration that may be neutralized by the development of deeper associational relationships between natives and migrants.

Keywords: refugees, ethnicity, symbolic politics, elites, migration, comparative politics

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Authors: Tomasz Stenzel, Daria Dziewulska, Ewa Łukaszuk, Joy Custer, Simona Kraberger, Arvind Varsani

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Viral diseases, especially those leading to impairment of the immune system, are among the most important problems in avian pathology. However, there is not much data available on this subject other than commercial poultry bird species. Recently, increasing attention has been paid to racing pigeons, which have been refined for many years in terms of their ability to return to their place of origin. Currently, these birds are used for races at distances from 100 to 1000 km, and winning pigeons are highly valuable. The rearing system of racing pigeons contradicts the principles of biosecurity, as birds originating from various breeding facilities are commonly transported and reared in “One Loft Race” (OLR) facilities. This favors the spread of multiple infections and provides conditions for the development of novel variants of various pathogens through recombination. One of the most significant viruses occurring in this avian species is the pigeon circovirus (PiCV), which is detected in ca. 70% of pigeons. Circoviruses are characterized by vast genetic diversity which is due to, among other things, the recombination phenomenon. It consists of an exchange of fragments of genetic material among various strains of the virus during the infection of one organism. The rate and intensity of the development of PiCV recombinants have not been determined so far. For this reason, an experiment was performed to investigate the frequency of development of novel PiCV recombinants in racing pigeons kept in OLR-type conditions. 15 racing pigeons originating from 5 different breeding facilities, subclinically infected with various PiCV strains, were housed in one room for eight weeks, which was supposed to mimic the conditions of OLR rearing. Blood and swab samples were collected from birds every seven days to recover complete PiCV genomes that were amplified through Rolling Circle Amplification (RCA), cloned, sequenced, and subjected to bioinformatic analyses aimed at determining the genetic diversity and the dynamics of recombination phenomenon among the viruses. In addition, virus shedding rate/level of viremia, expression of the IFN-γ and interferon-related genes, and anti-PiCV antibodies were determined to enable the complete analysis of the course of infection in the flock. Initial results have shown that 336 full PiCV genomes were obtained, exhibiting nucleotide similarity ranging from 86.6 to 100%, and 8 of those were recombinants originating from viruses of different lofts of origin. The first recombinant appeared after seven days of experiment, but most of the recombinants appeared after 14 and 21 days of joint housing. The level of viremia and virus shedding was the highest in the 2nd week of the experiment and gradually decreased to the end of the experiment, which partially corresponded with Mx 1 gene expression and antibody dynamics. The results have shown that the OLR pigeon-rearing system could play a significant role in spreading infectious agents such as circoviruses and contributing to PiCV evolution through recombination. Therefore, it is worth considering whether a popular gambling game such as pigeon racing is sensible from both animal welfare and epidemiological point of view.

Keywords: pigeon circovirus, recombination, evolution, one loft race

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Authors: Annette Cosgrove

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The objectives of this research study is to examine the impact of professional development in Technology Enhanced Learning (TEL) and the digitisation of learning in teaching communities across multiple higher education sites in the ATU (Atlantic Technological University *) ( 2020-2025), including the proposal of an evidence based digital teaching model for use in a future pandemic. The research strategy undertaken for this PhD Study is a multi-site study using mixed methods. Qualitative & quantitative methods are being used in the study to collect data. A pilot study was carried out initially , feedback collected and the research instrument was edited to reflect this feedback, before being administered. The purpose of the staff questionnaire is to evaluate the impact of professional development in the area of TEL, and to capture the practitioners views on the perceived impact on their teaching practice in the higher education sector across ATU (West of Ireland – 5 Higher education locations ). The phenomenon being explored is ‘ the impact of professional development in the area of technology enhanced learning and on teaching practice in a higher education institution.’ The research methodology chosen for this study is an Action based Research Study. The researcher has chosen this approach as it is a prime strategy for developing educational theory and enhancing educational practice . This study includes quantitative and qualitative methods to elicit data which will quantify the impact that continuous professional development in the area of digital teaching practice and technologies has on the practitioner’s teaching practice in higher education. The research instruments / data collection tools for this study include a lecturer survey with a targeted TEL Practice group ( Pre and post covid experience) and semi-structured interviews with lecturers.. This research is currently being conducted across the ATU multisite campus and targeting Higher education lecturers that have completed formal CPD in the area of digital teaching. ATU, a west of Ireland university is the focus of the study , The research questionnaire has been deployed, with 75 respondents to date across the ATU - the primary questionnaire and semi- formal interviews are ongoing currently – the purpose being to evaluate the impact of formal professional development in the area of TEL and its perceived impact on the practitioners teaching practice in the area of digital teaching and learning . This paper will present initial findings, reflections and data from this ongoing research study.

Keywords: TEL, DTL, digital teaching, digital assessment

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Authors: Alena Semeradtova, Marcel Stofik, Lucie Mareckova, Petr Maly, Ondrej Stanek, Jan Maly

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Recently, novel strategies based on so-called molecular evolution were shown to be effective for the production of various peptide ligand libraries with high affinities to molecular targets of interest comparable or even better than monoclonal antibodies. The major advantage of these peptide scaffolds is mainly their prevailing low molecular weight and simple structure. This study describes a new high-affinity binding molecules based immunesensor using a simple optical system for human serum albumin (HSA) detection as a model molecule. We present a comparison of two variants of recombinant binders based on albumin binding domain of the protein G (ABD) performed on micropatterned glass chip. Binding domains may be tailored to any specific target of interest by molecular evolution. Micropatterened glass chips were prepared using UV-photolithography on chromium sputtered glasses. Glass surface was modified by (3-aminopropyl)trietoxysilane and biotin-PEG-acid using EDC/NHS chemistry. Two variants of high-affinity binding molecules were used to detect target molecule. Firstly, a variant is based on ABD domain fused with TolA chain. This molecule is in vivo biotinylated and each molecule contains one molecule of biotin and one ABD domain. Secondly, the variant is ABD domain based on streptavidin molecule and contains four gaps for biotin and four ABD domains. These high-affinity molecules were immobilized to the chip surface via biotin-streptavidin chemistry. To eliminate nonspecific binding 1% bovine serum albumin (BSA) or 6% fetal bovine serum (FBS) were used in every step. For both variants range of measured concentrations of fluorescently labelled HSA was 0 – 30 µg/ml. As a control, we performed a simultaneous assay without high-affinity binding molecules. Fluorescent signal was measured using inverse fluorescent microscope Olympus IX 70 with COOL LED pE 4000 as a light source, related filters, and camera Retiga 2000R as a detector. The fluorescent signal from non-modified areas was substracted from the signal of the fluorescent areas. Results were presented in graphs showing the dependence of measured grayscale value on the log-scale of HSA concentration. For the TolA variant the limit of detection (LOD) of the optical immunosensor proposed in this study is calculated to be 0,20 µg/ml for HSA detection in 1% BSA and 0,24 µg/ml in 6% FBS. In the case of streptavidin-based molecule, it was 0,04 µg/ml and 0,07 µg/ml respectively. The dynamical range of the immunosensor was possible to estimate just in the case of TolA variant and it was calculated to be 0,49 – 3,75 µg/ml and 0,73-1,88 µg/ml respectively. In the case of the streptavidin-based the variant we didn´t reach the surface saturation even with the 480 ug/ml concentration and the upper value of dynamical range was not estimated. Lower value was calculated to be 0,14 µg/ml and 0,17 µg/ml respectively. Based on the obtained results, it´s clear that both variants are useful for creating the bio-recognizing layer on immunosensors. For this particular system, it is obvious that the variant based on streptavidin molecule is more useful for biosensing on glass planar surfaces. Immunosensors based on this variant would exhibit better limit of detection and wide dynamical range.

Keywords: high affinity binding molecules, human serum albumin, optical immunosensor, protein G, UV-photolitography

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Authors: Samuel Holder

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Mass incarceration in the United States is a human rights issue, not merely a civil rights problem. It is a human rights problem not only because the United States has a high rate of incarceration, but more importantly because of who is jailed, for what purpose they are jailed and, ultimately, the manner in which they are jailed. To sustain the scale of the criminal justice system, one of the darker policies involves a multi-tiered strategy of fee- and fine-collection, targeting, usually, the most vulnerable and poor, many of whom run into the law via small offenses that do not rise to the level of felonies. This paper advances the notion that this debt collection-to-incarceration pipeline is tantamount to a modern-day debtors’ prison system. This article seeks to confront the thorny issue of incarceration via criminal justice debt from a human rights and cause-lawyering position. It will argue that a two-pronged cause-lawyering strategy: the first focused on traditional litigation along constitutional grounds, and the second, an advocacy approach rooted in grassroots campaigns, designed to shift the normative operation and understanding of the rights of marginalized and racialized offenders. Ultimately, the argument suggests that this approach will be effective in combatting the (often highly privatized) criminal justice debt system and bring the roles of 'incapacitation, rehabilitation, deterrence, and retribution' back into the criminal justice legal conversation. Part I contextualizes and historicizes the role of fees, penalties, and fines in American criminal justice. Part II examines the emergence of private industry in the criminal justice system, and its role in the acceleration of profit-driven criminal justice debt collection and incarceration. Part III addresses the failures of the federal and state law and legislation in combatting predatory incarceration and debt collection in the criminal justice system, particularly as waged against the indigent and/or ethnically or racially marginalized. Part IV examines the potential for traditional cause-lawyering litigation along constitutional grounds, using case studies across contexts for illustration. Finally, Part V will review the radical cause-lawyer’s role in the normative struggle in redefining prisoners’ rights and the rights of the marginalized (and racialized) as they intersect at the crossroads of criminal justice debt. This paper will conclude with recommendations for litigation and advocacy, drawing on hypotheses advanced, and informed by case studies from a variety of both national and international jurisdictions.

Keywords: cause-lawyering, criminal justice debt, human rights, judicial fees

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Authors: Selisha A. Sooklal, Phelelani Mpangase, Shaun Aron, Karl Rumbold

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Organically bound fluorine (C-F bond) is extremely rare in nature. Despite this, the first fluorinated secondary metabolite, fluoroacetate, was isolated from the plant Dichapetalum cymosum (commonly known as Gifblaar). However, the enzyme responsible for fluorination (fluorinase) in Gifblaar was never isolated and very little progress has been achieved in understanding this process in higher plants. Fluorinated compounds have vast applications in the pharmaceutical, agrochemical and fine chemicals industries. Consequently, an enzyme capable of catalysing a C-F bond has great potential as a biocatalyst in the industry considering that the field of fluorination is virtually synthetic. As with any biocatalyst, a range of these enzymes are required. Therefore, it is imperative to expand the exploration for novel fluorinases. This study aimed to gain molecular insights into secondary metabolite biosynthesis in Gifblaar using a high-throughput sequencing-based approach. Mechanical wounding studies were performed using Gifblaar leaf tissue in order to induce expression of the fluorinase. The transcriptome of the wounded and unwounded plant was then sequenced on the Illumina HiSeq platform. A total of 26.4 million short sequence reads were assembled into 77 845 transcripts using Trinity. Overall, 68.6 % of transcripts were annotated with gene identities using public databases (SwissProt, TrEMBL, GO, COG, Pfam, EC) with an E-value threshold of 1E-05. Sequences exhibited the greatest homology to the model plant, Arabidopsis thaliana (27 %). A total of 244 annotated transcripts were found to be differentially expressed between the wounded and unwounded plant. In addition, secondary metabolic pathways present in Gifblaar were successfully reconstructed using Pathway tools. Due to lack of genetic information for plant fluorinases, a transcript failed to be annotated as a fluorinating enzyme. Thus, a local database containing the 5 existing bacterial fluorinases was created. Fifteen transcripts having homology to partial regions of existing fluorinases were found. In efforts to obtain the full coding sequence of the Gifblaar fluorinase, primers were designed targeting the regions of homology and genome walking will be performed to amplify the unknown regions. This is the first genetic data available for Gifblaar. It has provided novel insights into the mechanisms of metabolite biosynthesis and will allow for the discovery of the first eukaryotic fluorinase.

Keywords: biocatalyst, fluorinase, gifblaar, transcriptome

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Authors: Farahnaz Sadat Golestan Hashemi, Mohd Razi Ismail, Mohd Y. Rafii

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Clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein (Cas) system can facilitate targeted genome editing in organisms. Dual or single guide RNA (gRNA) can program the Cas9 nuclease to cut target DNA in particular areas; thus, introducing concise mutations either via error-prone non-homologous end-joining repairing or via incorporating foreign DNAs by homologous recombination between donor DNA and target area. In spite of high demand of such promising technology, developing a well-organized procedure in order for reliable mining of potential target sites for gRNAs in large genomic data is still challenging. Hence, we aimed to perform high-throughput detection of target sites by specific PAMs for not only common Streptococcus pyogenes (SpCas9) but also for Neisseria meningitides (NmCas9) CRISPR-Cas systems. Previous research confirmed the successful application of such RNA-guided Cas9 orthologs for effective gene targeting and subsequently genome manipulation. However, Cas9 orthologs need their particular PAM sequence for DNA cleavage activity. Activity levels are based on the sequence of the protospacer and specific combinations of favorable PAM bases. Therefore, based on the specific length and sequence of PAM followed by a constant length of the target site for the two orthogonals of Cas9 protein, we created a reliable procedure to explore possible gRNA sequences. To mine CRISPR target sites, four different searching modes of sgRNA binding to target DNA strand were applied. These searching modes are as follows i) coding strand searching, ii) anti-coding strand searching, iii) both strand searching, and iv) paired-gRNA searching. Finally, a complete list of all potential gRNAs along with their locations, strands, and PAMs sequence orientation can be provided for both SpCas9 as well as another potential Cas9 ortholog (NmCas9). The artificial design of potential gRNAs in a genome of interest can accelerate functional genomic studies. Consequently, the application of such novel genome editing tool (CRISPR/Cas technology) will enhance by presenting increased versatility and efficiency.

Keywords: CRISPR/Cas9 genome editing, gRNA mining, SpCas9, NmCas9

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Authors: Jinming Du

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With the COVID-19 pandemic beginning in 2020, many higher education institutions and education systems are turning to hybrid or fully distance online courses to maintain social distance and provide a safe virtual space for learning and teaching. However, the majority of faculty members were not well prepared for the shift to blended or distance learning. Communication frustrations are prevalent in both hybrid and full-distance courses. A systematic literature review was conducted by a comprehensive analysis of 1688 publications that focused on the application of the adoption of chatbots in education. This study aimed to explore instructors' experiences with chatbots in online and blended undergraduate English courses. Language learners are overwhelmed by the variety of information offered by many online sites. The recently emerged chatbots (e.g.: ChatGPT) are slightly superior in performance as compared to those traditional through previous technologies such as tapes, video recorders, and websites. The field of chatbots has been intensively researched, and new methods have been developed to demonstrate how students can best learn and practice a new language in the target language. However, it is believed that among the many areas where chatbots are applied, while chatbots have been used as effective tools for communicating with business customers, in consulting and targeting areas, and in the medical field, chatbots have not yet been fully explored and implemented in the field of language education. This issue is challenging enough for language teachers; they need to study and conduct research carefully to clarify it. Pedagogical chatbots may alleviate the perception of a lack of communication and feedback from instructors by interacting naturally with students through scaffolding the understanding of those learners, much like educators do. However, educators and instructors lack the proficiency to effectively operate this emerging AI chatbot technology and require comprehensive study or structured training to attain competence. There is a gap between language teachers’ perceptions and recent advances in the application of AI chatbots to language learning. The results of the study found that although the teachers felt that the chatbots did the best job of giving feedback, the teachers needed additional training to be able to give better instructions and to help them assist in teaching. Teachers generally perceive the utilization of chatbots to offer substantial assistance to English language instruction.

Keywords: artificial intelligence in education, chatbots, education and technology, education system, pedagogical chatbot, chatbots and language education

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Authors: Mohamed Raouf Benmakrelouf, Joseph Rynkiewicz

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Targeted maximum likelihood estimation (TMLE) is well-established method for causal effect estimation with desirable statistical properties. TMLE is a doubly robust maximum likelihood based approach that includes a secondary targeting step that optimizes the target statistical parameter. A causal interpretation of the statistical parameter requires assumptions of the Rubin causal framework. The causal effect of binary variable, E, on outcomes, Y, is defined in terms of comparisons between two potential outcomes as E[YE=1 − YE=0]. Our aim in this paper is to present an adaptation of TMLE methodology to estimate the causal effect of a non-binary categorical variable, providing a large application. We propose coding on the initial data in order to operate a binarization of the interest variable. For each category, we get a transformation of the non-binary interest variable into a binary variable, taking value 1 to indicate the presence of category (or group of categories) for an individual, 0 otherwise. Such a dummy variable makes it possible to have a pair of potential outcomes and oppose a category (or a group of categories) to another category (or a group of categories). Let E be a non-binary interest variable. We propose a complete disjunctive coding of our variable E. We transform the initial variable to obtain a set of binary vectors (dummy variables), E = (Ee : e ∈ {1, ..., |E|}), where each vector (variable), Ee, takes the value of 0 when its category is not present, and the value of 1 when its category is present, which allows to compute a pairwise-TMLE comparing difference in the outcome between one category and all remaining categories. In order to illustrate the application of our strategy, first, we present the implementation of TMLE to estimate the causal effect of non-binary variable on outcome using simulated data. Secondly, we apply our TMLE adaptation to survey data from the French Political Barometer (CEVIPOF), to estimate the causal effect of education level (A five-level variable) on a potential vote in favor of the French extreme right candidate Jean-Marie Le Pen. Counterfactual reasoning requires us to consider some causal questions (additional causal assumptions). Leading to different coding of E, as a set of binary vectors, E = (Ee : e ∈ {2, ..., |E|}), where each vector (variable), Ee, takes the value of 0 when the first category (reference category) is present, and the value of 1 when its category is present, which allows to apply a pairwise-TMLE comparing difference in the outcome between the first level (fixed) and each remaining level. We confirmed that the increase in the level of education decreases the voting rate for the extreme right party.

Keywords: statistical inference, causal inference, super learning, targeted maximum likelihood estimation

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