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Authors: Dominic Sagar

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Manchester ‘King Cotton’, the first truly industrial city of the nineteenth century, passing on the baton to Detroit ‘Motor City’, is the first truly modern city. We are exploring the tales of the two cities, their rise and fall and subsequent post-industrial decline, their transitions and transformations, whilst alongside paralleling their corresponding, commercial, cultural, industrial and even agricultural, artistic and musical transactions and connections. The paper will briefly contextualize how technologies of the industrial age and modern age have been instrumental in the development of these cities and other similar cities including New York. However, the main focus of the study will be the present and more importantly the future, how globalisation and the advancements of digital technologies and industries have shaped the cities developments from AlanTuring and the making of the first programmable computer to the effect of digitalisation and digital initiatives. Manchester now has a thriving creative digital infrastructure of Digilabs, FabLabs, MadLabs and hubs, the study will reference the Smart Project and the Manchester Digital Development Association whilst paralleling similar digital and creative industrial initiatives now starting to happen in Detroit. The paper will explore other topics including the need to allow for zones of experimentation, areas to play, think and create in order develop and instigate new initiatives and ideas of production, carrying on the tradition of influential inventions throughout the history of these key cities. Other topics will be briefly touched on, such as urban farming, citing the Biospheric foundation in Manchester and other similar projects in Detroit. However, the main thread will focus on the music industries and how they are contributing to the regeneration of cities. Musically and artistically, Manchester and Detroit have been closely connected by the flow and transmission of information and transfer of ideas via ‘cars and trains and boats and planes’ through to the new ‘super highway’. From Detroit to Manchester often via New York and Liverpool and back again, these musical and artistic connections and flows have greatly affected and influenced both cities and the advancement of technology are still connecting the cities. In summary two hugely important industrial cities, subsequently both experienced massive decline in fortunes, having had their large industrial hearts ripped out, ravaged leaving dying industrial carcasses and car crashes of despair, dereliction, desolation and post-industrial wastelands vacated by a massive exodus of the cities’ inhabitants. To examine the affinity, similarity and differences between Manchester & Detroit, from their industrial importance to their post-industrial decline and their current transmutations, transformations, transient transgressions, cities in transition; contrasting how they have dealt with these problems and how they can learn from each other. With a view to framing these topics with regard to how various communities have shaped these cities and the creative industries and design [the new cotton/car manufacturing industries] are reinventing post-industrial cities, to speculate on future development of these themes in relation to Globalisation, digitalisation and how cities can function to develop solutions to communal living in cities of the future.

Keywords: cultural capital, digital developments, musical initiatives, zones of experimentation

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Authors: Mohamad F. Jamiluddin, Emeline Sarry, Ana Bejanariu, Cécile Bauche

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Introduction: Over 360 million people are chronically infected with hepatitis B virus (HBV), of whom 1 million die each year from HBV-associated liver cirrhosis or hepatocellular carcinoma. Current treatment options for chronic hepatitis B depend on interferon-α (IFNα) or nucleos(t)ide analogs, which control virus replication but rarely eliminate the virus. Treatment with PEG-IFNα leads to a sustained antiviral response in only one third of patients. After withdrawal of the drugs, the rebound of viremia is observed in the majority of patients. Furthermore, the long-term treatment is subsequently associated with the appearance of drug resistant HBV strains that is often the cause of the therapy failure. Among the new therapeutic avenues being developed, therapeutic vaccine aimed at inducing immune responses similar to those found in resolvers is of growing interest. The high prevalence of chronic hepatitis B necessitates the design of better vaccination strategies capable of eliciting broad-spectrum of cell-mediated immunity(CMI) and humoral immune response that can control chronic hepatitis B. Induction of HBV-specific T cells and B cells by therapeutic vaccination may be an innovative strategy to overcome virus persistence. Lentiviral vectors developed and optimized by THERAVECTYS, due to their ability to transduce non-dividing cells, including dendritic cells, and induce CMI response, have demonstrated their effectiveness as vaccination tools. Method: To develop a HBV therapeutic vaccine that can induce a broad but specific immune response, we generated recombinant lentiviral vector carrying IRES(Internal Ribosome Entry Site)-containing bicistronic constructs which allow the coexpression of two vaccine products, namely HBV T- cell epitope vaccine and HBV virus like particle (VLP) vaccine. HBV T-cell epitope vaccine consists of immunodominant cluster of CD4 and CD8 epitopes with spacer in between them and epitopes are derived from HBV surface protein, HBV core, HBV X and polymerase. While HBV VLP vaccine is a HBV core protein based chimeric VLP with surface protein B-cell epitopes displayed. In order to evaluate the immunogenicity, mice were immunized with lentiviral constructs by intramuscular injection. The T cell and antibody immune responses of the two vaccine products were analyzed using IFN-γ ELISpot assay and ELISA respectively to quantify the adaptive response to HBV antigens. Results: Following a single administration in mice, lentiviral construct elicited robust antigen-specific IFN-γ responses to the encoded antigens. The HBV T- cell epitope vaccine demonstrated significantly higher T cell immunogenicity than HBV VLP vaccine. Importantly, we demonstrated by ELISA that antibodies are induced against both HBV surface protein and HBV core protein when mice injected with vaccine construct (p < 0.05). Conclusion: Our results highlight that THERAVECTYS lentiviral vectors may represent a powerful platform for immunization strategy against chronic hepatitis B. Our data suggests the likely importance of Lentiviral vector based novel bicistronic construct for further study, in combination with drugs or as standalone antigens, as a therapeutic lentiviral based HBV vaccines. THERAVECTYS bicistronic HBV vaccine will be further evaluated in animal efficacy studies.

Keywords: chronic hepatitis B, lentiviral vectors, therapeutic vaccine, virus-like particle

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Authors: Chang-Hui Shen, Michelle Esposito, Andrew J. Shen, Michael Adejokun, Diana Laterman

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The packaging of DNA into nucleosomes is critical to genomic compaction, yet it can leave gene promoters inaccessible to activator proteins or transcription machinery and thus prevents transcriptional initiation. Both chromatin remodelers and histone acetylases (HATs) are the two main transcription co-activators that can reconfigure chromatin structure for transcriptional activation. Ino80p is the core component of the INO80 remodeling complex. Recently, it was shown that Ino80p dissociates from the yeast INO1 promoter after induction. However, when certain HATs were deleted or mutated, Ino80p accumulated at the promoters during gene activation. This suggests a link between HATs’ presence and Ino80p’s dissociation. However, it has yet to be demonstrated that Ino80p can be acetylated. To determine if Ino80p can be acetylated, wild-type Saccharomyces cerevisiae cells carrying Ino80p engineered with a double FLAG tag (MATa INO80-FLAG his3∆200 leu2∆0 met15∆0 trp1∆63 ura3∆0) were grown to mid log phase, as were non-tagged wild type (WT) (MATa his3∆200 leu2∆0 met15∆0 trp1∆63 ura3∆0) and ino80∆ (MATa ino80∆::TRP1 his3∆200 leu2∆0 met15∆0 trp1∆63 ura3∆0) cells as controls. Cells were harvested, and the cell lysates were subjected to immunoprecipitation (IP) with α-FLAG resin to isolate Ino80p. These eluted IP samples were subjected to SDS-PAGE and Western blot analysis. Subsequently, the blots were probed with the α-FLAG and α-acetyl lysine antibodies, respectively. For the blot probed with α-FLAG, one prominent band was shown in the INO80-FLAG cells, but no band was detected in the IP samples from the WT and ino80∆ cells. For the blot probed with the α-acetyl lysine antibody, we detected acetylated Ino80p in the INO80-FLAG strain while no bands were observed in the control strains. As such, our results showed that Ino80p can be acetylated. This acetylation can explain the co-activator’s recruitment patterns observed in current gene activation models. In yeast INO1, it has been shown that Ino80p is recruited to the promoter during repression, and then dissociates from the promoter once de-repression begins. Histone acetylases, on the other hand, have the opposite pattern of recruitment, as they have an increased presence at the promoter as INO1 de-repression commences. This Ino80p recruitment pattern significantly changes when HAT mutant strains are studied. It was observed that instead of dissociating, Ino80p accumulates at the promoter in the absence of functional HATs, such as Gcn5p or Esa1p, under de-repressing processes. As such, Ino80p acetylation may be required for its proper dissociation from the promoters. The remodelers’ dissociation mechanism may also have a wide range of implications with respect to transcriptional initiation, elongation, or even repression as it allows for increased spatial access to the promoter for the various transcription factors and regulators that need to bind in that region. Our findings here suggest a previously uncharacterized interaction between Ino80p and other co-activators recruited to promoters. As such, further analysis of Ino80p acetylation not only will provide insight into the role of epigenetic modifications in transcriptional activation, but also gives insight into the interactions occurring between co-activators at gene promoters during gene regulation.

Keywords: acetylation, chromatin remodeler, epigenetic modification, Ino80p

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Authors: T. P. Sathishkumar, P. Navaneethakrishnan

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The research work investigates the variation of tensile properties for the sansevieria ehrenbergii fiber (SEF) and SEF reinforced polyester composites respect to various water absorption time. The experiments were conducted according to ATSM D3379-75 and ASTM D570 standards. The percentage of water absorption for composite specimens was measured according to ASTM D570 standard. The fiber of SE was cut in to 30 mm length for preparation of the composites. The simple hand lay-up method followed by compression moulding process adopted to prepare the randomly oriented SEF reinforced polyester composites at constant fiber weight fraction of 40%. The surface treatment was done on the SEFs with various chemicals such as NaOH, KMnO4, Benzoyl Peroxide, Benzoyl Chloride and Stearic Acid before preparing the composites. NaOH was used for pre-treatment of all other chemical treatments. The morphology of the tensile fractured specimens studied using the Scanning Electron Microscopic. The tensile strength of the SEF and SEF reinforced polymer composites were carried out with various water absorption time such as 4, 8, 12, 16, 20 and 24 hours respectively. The result shows that the tensile strength was drop off with increase in water absorption time for all composites. The highest tensile property of raw fiber was found due to lowest moistures content. Also the chemical bond between the cellulose and cementic materials such as lignin and wax was highest due to lowest moisture content. Tensile load was lowest and elongation was highest for the water absorbed fibers at various water absorption time ranges. During this process, the fiber cellulose inhales the water and expands the primary and secondary fibers walls. This increases the moisture content in the fibers. Ultimately this increases the hydrogen cation and the hydroxide anion from the water. In tensile testing, the water absorbed fibers shows highest elongation by stretching of expanded cellulose walls and the bonding strength between the fiber cellulose is low. The load carrying capability was stable at 20 hours of water absorption time. This could be directly affecting the interfacial bonding between the fiber/matrix and composite strength. The chemically treated fibers carry higher load and lower elongation which is due to removal of lignin, hemicellulose and wax content. The water time absorption decreases the tensile strength of the composites. The chemically SEF reinforced composites shows highest tensile strength compared to untreated SEF reinforced composites. This was due to highest bonding area between the fiber/matrix. This was proven in the morphology at the fracture zone of the composites. The intra-fiber debonding was occurred by water capsulation in the fiber cellulose. Among all, the tensile strength was found to be highest for KMnO4 treated SEF reinforced composite compared to other composites. This was due to better interfacial bonding between the fiber-matrix compared to other treated fiber composites. The percentage of water absorption of composites increased with time of water absorption. The percentage weight gain of chemically treated SEF composites at 4 hours to zero water absorption are 9, 9, 10, 10.8 and 9.5 for NaOH, BP, BC, KMnO4 and SA respectively. The percentage weight gain of chemically treated SEF composites at 24 hours to zero water absorption 5.2, 7.3, 12.5, 16.7 and 13.5 for NaOH, BP, BC, KMnO4 and SA respectively. Hence the lowest weight gain was found for KMnO4 treated SEF composites by highest percentage with lowest water uptake. However the chemically treated SEF reinforced composites is possible materials for automotive application like body panels, bumpers and interior parts, and household application like tables and racks etc.

Keywords: fibres, polymer-matrix composites (PMCs), mechanical properties, scanning electron microscopy (SEM)

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Authors: Naima Mohammadi

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The present paper critically reports on the emergency of Iranian international students in a large public university in Italy. Although the most sizeable diaspora of Iranians dates back to the 1979 revolution, a huge wave of Iranian female students travelled abroad after the Iranian Green Movement (2009) due to the intensification of gender discrimination and Islamization. To explore the experience of Iranian female students at an Italian public university, two complementary methods were adopted: a focus group and individual interviews. Focus groups yield detailed collective conversations and provide researchers with an opportunity to observe the interaction between participants, rather than between participant and researcher, which generates data. Semi-structured interviews allow participants to share their stories in their own words and speak about personal experiences and opinions. Research participants were invited to participate through a public call in a Telegram group of Iranian students. Theoretical and purposive sampling was applied to select participants. All participants were assured that full anonymity would be ensured and they consented to take part in the research. A two-hour focus group was held in English with participants in the presence and some online. They were asked to share their motivations for studying in Italy and talk about their experiences both within and outside the university context. Each of these interviews lasted from 45 to 60 minutes and was mostly carried out online and in Farsi. The focus group consisted of 8 Iranian female post-graduate students. In analyzing the data a blended approach was adopted, with a combination of deductive and inductive coding. According to research findings, although 9/11 was the beginning of the West’s challenges against Muslims, the nuclear threats of Islamic regimes promoted the toughest international sanctions against Iranians as a nation across the world. Accordingly, carrying an Iranian identity contributes to social, political, and economic exclusion. Research findings show that geopolitical factors such as international sanctions and Islamophobia, and a lack of reciprocity in terms of recognition, have created a sense of stigmatization for veiled and unveiled Iranian female students who are the largest groups of ‘non-European Muslim international students’ enrolled in Italian universities. Participants addressed how their nationality has devalued their public image and negatively impacted their self-confidence and self-realization in academia. They highlighted the experience of an unwelcoming atmosphere by different groups of people and institutes, such as receiving marked students’ badges, rejected bank account requests, failed visa processes, secondary security screening selection, and hyper-visibility of veiled students. This study corroborates the need for institutions to pay attention to geopolitical factors and religious diversity in student recruitment and provide support mechanisms and access to basic rights. Accordingly, it is suggested that Higher Education Institutions (HEIs) have a social and moral responsibility towards the discrimination and both social and academic exclusion of Iranian students.

Keywords: Iranian diaspora, female students, recognition theory, inclusive university

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Authors: Saul Ngarava, Leocadia Zhou, Nomakhaya Monde

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Water crises have the fourth most significant societal impact after weapons of mass destruction, climate change, and extreme weather conditions, ahead of natural disasters. Intricacies between women and water are central to achieving the 2030 Sustainable Development Goals (SDGs). The majority of the 1.2 billion poor people worldwide, with two-thirds being women, and mostly located in Sub Sahara Africa (SSA) and South Asia, do not have access to safe and reliable sources of water. There exist gendered differences in water security based on the division of labour associating women with water. Globally, women and girls are responsible for water collection in 80% of the households which have no water on their premises. Women spend 16 million hours a day collecting water, while men and children spend 6 million and 4 million per day, respectively, which is time foregone in the pursuit of other livelihood activities. Due to their proximity and activities concerning water, women are vulnerable to water insecurity through exposures to water-borne diseases, fatigue from physically carrying water, and exposure to sexual and physical harassment, amongst others. Proximity to treated water and their wellbeing also has an effect on their sensitivity and adaptive capacity to water insecurity. The great distances, difficult terrain and heavy lifting expose women to vulnerabilities of water insecurity. However, few studies have quantified the vulnerabilities and burdens on women, with a few taking a phenomenological qualitative approach. Vulnerability studies have also been scanty in the water security realm, with most studies taking linear forms of either quantifying exposures, sensitivities or adaptive capacities in climate change studies. The current study argues for the need for a water insecurity vulnerability assessment, especially for women into research agendas as well as policy interventions, monitoring, and evaluation. The study sought to identify and provide pathways through which female-headed households were water insecure in South Africa, the 30th driest country in the world. This was through linking the drinking water decision as well as the vulnerability frameworks. Secondary data collected during the 2016 General Household Survey (GHS) was utilised, with a sample of 5928 female-headed households. Principal Component Analysis and Structural Equation Modelling were used to analyse the data. The results show dynamic relationships between water characteristics and water treatment. There were also associations between water access and wealth status of the female-headed households. Association was also found between water access and water treatment as well as between wealth status and water treatment. The study concludes that there are dynamic relationships in water insecurity (exposure, sensitivity, and adaptive capacity) for female-headed households in South Africa. The study recommends that a multi-prong approach is required in tackling exposures, sensitivities, and adaptive capacities to water insecurity. This should include capacitating and empowering women for wealth generation, improve access to water treatment equipment as well as prioritising the improvement of infrastructure that brings piped and safe water to female-headed households.

Keywords: gender, principal component analysis, structural equation modelling, vulnerability, water insecurity

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

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

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

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Authors: Md Shafiqul Bari, Md Shafiqul Islam Sikdar

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This paper summarizes the current knowledge on Agroforestry practices in the Barind tract of Bangladesh. The part of greater Rajshahi, Dinajpur, Rangpur and Bogra district of Bangladesh is geographically identified as the Barind tract. The hard red soil of these areas is very significant in comparison to that of the other parts of the country. A typical dry climate with comparatively high temperature prevails in the Barind area. Scanty rainfall and excessive extraction of groundwater have created an alarming situation among the Barind people and others about irrigation to the rice field. In addition, the situation may cause an adverse impact on the people whose livelihood largely depends on agriculture. The groundwater table has been declined by at least 10 to 15 meters in some areas of the Barind tract during the last 20 years. Due to absent of forestland in the Barind tract, the soil organic carbon content can decrease more rapidly because of the higher rate of decomposition. The Barind soils are largely carbon depleted but can be brought back to carbon-carrying capacity by bringing under suitable Agroforestry systems. Agroforestry has tremendous potential for carbon sequestration not only in above C biomass but also root C biomass in deeper soil depths. Agroforestry systems habitually conserve soil organic carbon and maintain a great natural nutrient pool. Cultivation of trees with arable crops under Agroforestry systems help in improving soil organic carbon content and sequestration carbon, particularly in the highly degraded Barind lands. Agroforestry systems are a way of securing the growth of cash crops that may constitute an alternative source of income in moments of crisis. Besides being a source of fuel wood, a greater presence of trees in cropping system contributes to decreasing temperatures and to increasing rainfall, thus contrasting the negative environmental impact of climate changes. In order to fulfill the objectives of this study, two experiments were conducted. The first experiment was survey on the impact of existing agroforestry system on the livelihood security in the Barind tract of Bangladesh and the second one was the role of agroforestry system on the improvement of soil properties in a multilayered coconut orchard. Agroforestry systems have been generated a lot of employment opportunities in the Barind area. More crops mean involvement of more people in various activities like involvements in dairying, sericulture, apiculture and additional associated agro-based interventions. Successful adoption of Agroforestry practices in the Barind area has shown that the Agroforestry practitioners of this area were very sound positioned economically, and had added social status too. However, from the findings of the present study, it may be concluded that the majority rural farmers of the Barind tract of Bangladesh had a very good knowledge and medium extension contact related to agroforestry production system. It was also observed that 85 per cent farmers followed agroforestry production system and received benefits to a higher extent. Again, from the research study on orchard based mutistoried agroforestry cropping system, it was evident that there was an important effect of agroforestry cropping systems on the improvement of soil chemical properties. As a result, the agroforestry systems may be helpful to attain the development objectives and preserve the biosphere core.

Keywords: agroforestry systems, Barind tract, carbon sequestration, climate changes

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Authors: Maryam Mohammad Hadi, Heather Nesbitt, Hamzah Masood, Hashim Ahmed, Mark Emberton, John Callan, Alexander MacRobert, Anthony McHale, Nikolitsa Nomikou

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Sonodynamic therapy (SDT) utilises ultrasound in combination with sensitizers, such as porphyrins, for the production of cytotoxic reactive oxygen species (ROS) and the confined ablation of tumours. Ultrasound can be applied locally, and the acoustic waves, at frequencies between 0.5-2 MHz, are transmitted efficiently through tissue. SDT does not require highly toxic agents, and the cytotoxic effect only occurs upon ultrasound exposure at the site of the lesion. Therefore, this approach is not associated with adverse side effects. Further highlighting the benefits of SDT, no cancer cell population has shown resistance to therapy-triggered ROS production or their cytotoxic effects. This is particularly important, given the as yet unresolved issues of radiation and chemo-resistance, to the authors’ best knowledge. Another potential future benefit of this approach – considering its non-thermal mechanism of action – is its possible role as an adjuvant to immunotherapy. Substantial pre-clinical studies have demonstrated the efficacy and targeting capability of this therapeutic approach. However, SDT has yet to be fully characterised and appropriately exploited for the treatment of cancer. In this study, a formulation based on multistimulus-responsive sensitizer-containing nanoparticles that can accumulate in advanced prostate tumours and increase the therapeutic efficacy of SDT has been developed. The formulation is based on a polyglutamate-tyrosine (PGATyr) co-polymer carrying hematoporphyrin. The efficacy of SDT in this study was demonstrated using prostate cancer as the translational exemplar. The formulation was designed to respond to the microenvironment of advanced prostate tumours, such as the overexpression of the proteolytic enzymes, cathepsin-B and prostate-specific membrane antigen (PSMA), that can degrade the nanoparticles, reduce their size, improving both diffusions throughout the tumour mass and cellular uptake. The therapeutic modality was initially tested in vitro using LNCaP and PC3 cells as target cell lines. The SDT efficacy was also examined in vivo, using male SCID mice bearing LNCaP subcutaneous tumours. We have demonstrated that the PGATyr co-polymer is digested by cathepsin B and that digestion of the formulation by cathepsin-B, at tumour-mimicking conditions (acidic pH), leads to decreased nanoparticle size and subsequent increased cellular uptake. Sonodynamic treatment, at both normoxic and hypoxic conditions, demonstrated ultrasound-induced cytotoxic effects only for the nanoparticle-treated prostate cancer cells, while the toxicity of the formulation in the absence of ultrasound was minimal. Our in vivo studies in immunodeficient mice, using the hematoporphyrin-containing PGATyr nanoparticles for SDT, showed a 50% decrease in LNCaP tumour volumes within 24h, following IV administration of a single dose. No adverse effects were recorded, and body weight was stable. The results described in this study clearly demonstrate the promise of SDT to revolutionize cancer treatment. It emphasizes the potential of this therapeutic modality as a fist line treatment or in combination treatment for the elimination or downstaging of difficult to treat cancers, such as prostate, pancreatic, and advanced colorectal cancer.

Keywords: sonodynamic therapy, nanoparticles, tumour ablation, ultrasound

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Authors: Ana L. Sánchez Regla, Igor A. Rivera González, María del Pilar Monserrat Pérez Hernández

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The ability of an organization to identify and get useful information from external sources, assimilate it, transform and apply to generate products or services with added value is called absorptive capacity. Absorptive capabilities contribute to have market opportunities to firms and get a leader position with respect to others competitors. The Bioprocess Development and Research Unit (UDIBI) is a Research and Development (R&D) laboratory that belongs to the National Polytechnic Institute (IPN), which is a higher education institute in Mexico. The UDIBI was created with the purpose of carrying out R and D activities for the Transferon®, a biopharmaceutical product developed and patented by IPN. The evolution of competence and scientific and technological platform made UDIBI expand its scope by providing technological services (preclínical studies and bio-compatibility evaluation) to the national pharmaceutical industry and biopharmaceutical industry. The relevance of this study is that those industries are classified as high scientific and technological intensity, and yet, after a review of the state of the art, there is only one study of absorption capabilities in biopharmaceutical industry with a similar scope to this research; in the case of Mexico, there is none. In addition to this, UDIBI belongs to a public university and its operation does not depend on the federal budget, but on the income generated by its external technological services. This fact represents a highly remarkable case in Mexico's public higher education context. This current doctoral research (2015-2019) is contextualized within a case study, its main objective is to identify and analyze the absorptive capabilities that characterise the UDIBI that allows it had become in a one of two third authorized laboratory by the sanitary authority in Mexico for developed bio-comparability studies to bio-pharmaceutical products. The development of this work in the field is divided into two phases. In a first phase, 15 interviews were conducted with the UDIBI personnel, covering management levels, heads of services, project leaders and laboratory personnel. These interviews were structured under a questionnaire, which was designed to integrate open questions and to a lesser extent, others, whose answers would be answered on a Likert-type rating scale. From the information obtained in this phase, a scientific article was made (in review and a proposal of presentation was submitted in different academic forums. A second stage will be made from the conduct of an ethnographic study within this organization under study that will last about 3 months. On the other hand, it is intended to carry out interviews with external actors around the UDIBI (suppliers, advisors, IPN officials, including contact with an academic specialized in absorption capacities to express their comments on this thesis. The inicial findings had shown two lines: i) exist institutional, technological and organizational management elements that encourage and/or limit the creation of absorption capacities in this scientific and technological laboratory and, ii) UDIBI has had created a set of multiple transfer technology of knowledge mechanisms which have had permitted to build a huge base of prior knowledge.

Keywords: absorptive capabilities, biopharmaceutical industry, high research and development intensity industries, knowledge management, transfer of knowledge

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Authors: Katerina Krizova, Inigo Molina

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The ongoing climate change affects various natural processes resulting in significant changes in human life. Since there is still a growing human population on the planet with more or less limited resources, agricultural production became an issue and a satisfactory amount of food has to be reassured. To achieve this, agriculture is being studied in a very wide context. The main aim here is to increase primary production on a spatial unit while consuming as low amounts of resources as possible. In Europe, nowadays, the staple issue comes from significantly changing the spatial and temporal distribution of precipitation. Recent growing seasons have been considerably affected by long drought periods that have led to quantitative as well as qualitative yield losses. To cope with such kind of conditions, new techniques and technologies are being implemented in current practices. However, behind assessing the right management, there is always a set of the necessary information about plot properties that need to be acquired. Remotely sensed data had gained attention in recent decades since they provide spatial information about the studied surface based on its spectral behavior. A number of space platforms have been launched carrying various types of sensors. Spectral indices based on calculations with reflectance in visible and NIR bands are nowadays quite commonly used to describe the crop status. However, there is still the staple limit by this kind of data - cloudiness. Relatively frequent revisit of modern satellites cannot be fully utilized since the information is hidden under the clouds. Therefore, microwave remote sensing, which can penetrate the atmosphere, is on its rise today. The scientific literature describes the potential of radar data to estimate staple soil (roughness, moisture) and vegetation (LAI, biomass, height) properties. Although all of these are highly demanded in terms of agricultural monitoring, the crop moisture content is the utmost important parameter in terms of agricultural drought monitoring. The idea behind this study was to exploit the unique combination of SAR (Sentinel-1) and optical (Sentinel-2) data from one provider (ESA) to describe potential crop water stress during dry cropping season of 2019 at six winter wheat plots in the central Czech Republic. For the period of January to August, Sentinel-1 and Sentinel-2 images were obtained and processed. Sentinel-1 imagery carries information about C-band backscatter in two polarisations (VV, VH). Sentinel-2 was used to derive vegetation properties (LAI, FCV, NDWI, and SAVI) as support for Sentinel-1 results. For each term and plot, summary statistics were performed, including precipitation data and soil moisture content obtained through data loggers. Results were presented as summary layouts of VV and VH polarisations and related plots describing other properties. All plots performed along with the principle of the basic SAR backscatter equation. Considering the needs of practical applications, the vegetation moisture content may be assessed using SAR data to predict the drought impact on the final product quality and yields independently of cloud cover over the studied scene.

Keywords: precision agriculture, remote sensing, Sentinel-1, SAR, water content

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Authors: Adenike Adesanya, Nonthaphat Wong, Xiang-Yun Lan, Shea Ping Yip, Chien-Ling Huang

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Background: The most challenging mutation of the oncokinase BCR-ABL protein T315I, which is commonly known as the “gatekeeper” mutation and is notorious for its strong resistance to almost all tyrosine kinase inhibitors (TKIs), especially imatinib. Therefore, this study aims to identify T315I-dependent downstream microRNA (miRNA) pathways associated with drug resistance in chronic myeloid leukemia (CML) for prognostic and therapeutic purposes. Methods: T315I-carrying K562 cell clones (K562-T315I) were generated by the CRISPR-Cas9 system. Imatinib-treated K562-T315I cells were subjected to small RNA library preparation and next-generation sequencing. Putative lncRNA-miRNA-mRNA networks were analyzed with (i) DESeq2 to extract differentially expressed miRNAs, using Padj value of 0.05 as cut-off, (ii) STarMir to obtain potential miRNA response element (MRE) binding sites of selected miRNAs on lncRNA H19, (iii) miRDB, miRTarbase, and TargetScan to predict mRNA targets of selected miRNAs, (iv) IntaRNA to obtain putative interactions between H19 and the predicted mRNAs, (v) Cytoscape to visualize putative networks, and (vi) several pathway analysis platforms – Enrichr, PANTHER and ShinyGO for pathway enrichment analysis. Moreover, mitochondria isolation and transcript quantification were adopted to determine the new mechanism involved in T315I-mediated resistance of CML treatment. Results: Verification of the CRISPR-mediated mutagenesis with digital droplet PCR detected the mutation abundance of ≥80%. Further validation showed the viability of ≥90% by cell viability assay, and intense phosphorylated CRKL protein band being detected with no observable change for BCR-ABL and c-ABL protein expressions by Western blot. As reported by several investigations into hematological malignancies, we determined a 7-fold increase of H19 expression in K562-T315I cells. After imatinib treatment, a 9-fold increment was observed. DESeq2 revealed 171 miRNAs were differentially expressed K562-T315I, 112 out of these miRNAs were identified to have MRE binding regions on H19, and 26 out of the 112 miRNAs were significantly downregulated. Adopting the seed-sequence analysis of these identified miRNAs, we obtained 167 mRNAs. 6 hub miRNAs (hsa-let-7b-5p, hsa-let-7e-5p, hsa-miR-125a-5p, hsa-miR-129-5p, and hsa-miR-372-3p) and 25 predicted genes were identified after constructing hub miRNA-target gene network. These targets demonstrated putative interactions with H19 lncRNA and were mostly enriched in pathways related to cell proliferation, senescence, gene silencing, and pluripotency of stem cells. Further experimental findings have also shown the up-regulation of mitochondrial transcript and lncRNA MALAT1 contributing to the lncRNA-miRNA-mRNA networks induced by BCR-ABL T315I mutation. Conclusions: Our results have indicated that lncRNA-miRNA regulators play a crucial role not only in leukemogenesis but also in drug resistance, considering the significant dysregulation and interactions in the K562-T315I cell model generated by CRISPR-Cas9. In silico analysis has further shown that lncRNAs H19 and MALAT1 bear several complementary miRNA sites. This implies that they could serve as a sponge, hence sequestering the activity of the target miRNAs.

Keywords: chronic myeloid leukemia, imatinib resistance, lncRNA-miRNA-mRNA, T315I mutation

Procedia PDF Downloads 126

Authors: Vincent Oghenekevbe Olughor, Olusoji Mayowa Ige

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Except for a preexisting liver disease and malnutrition, there are no predilections for low serum albumin (SA) levels in humans. At normal reference levels (4.0-6.0g/dl) SA is a universal marker for mortality and morbidity risks assessments where depletion by 1.0g/dl increases mortality risk by 137% and morbidity by 89%.It has 40 known functions contributing significantly to the sustenance of human life. A depletion in SA to <2.2g/dl, in most clinical settings worldwide, leads to loss of oncotic pressure of blood causing clinical manifestations of bipedal Oedema, in which the patients remain conscious. SA also contributes significantly to buffering of blood to a life-sustaining pH of 7.35-7.45. A drop in blood pH to <6.9 will lead to instant coma and death, which can occur after SA continues to deplete after manifestations of bipedal Oedema. In an intervention study conducted in 2014 following the discovery that “SA is depleted during malaria fever”, a Nutraceutical formulated for use as treatment adjunct to prevent SA depletions during malaria to <2.4g/dl after Efficacy testing was found to be satisfactory. There are five known types of Malaria caused by Apicomplexan parasites, Plasmodium: the most lethal being that caused by Plasmodium falciparum causing malignant tertian malaria, in which the fever was occurring every 48 hours coincides with the dumping of malaria-toxins (Hemozoin) into blood, causing contamination: blood must remain sterile. Other Apicomplexan parasites, Toxoplasma and Cryptosporidium, are opportunistic infections of HIV. Separate studies showed SA depletions in MDRTB (multidrug resistant TB), and MDRTB-HIV patients by the same mechanism discovered with malaria and such depletions will be further complicated whenever Apicomplexan parasitic infections co-exist. Both Apicomplexan parasites and the TB parasite belong to the Obligate-group of Parasites, which are parasites that replicate only inside its host; and most of them have capacities to over-consume host nutrients during parasitaemia. In MDRTB patients the body attempts repeatedly to prevent depletions in SA to critical levels in the presence of adequate nutrients and only for a while in MDRTB-HIV patients. These groups of patients will, therefore, benefit from the already tested Nutraceutical in malaria patients. The Nutraceutical bio-Powder was formulated (to BP 1988 specification) from twelve nature-based food-grade nutrients containing all dedicated nutrients for ensuring improved synthesis of Albumin by the liver. The Nutraceutical was administered daily for 38±2days in 23 children, in a prospective phase-2 clinical trial, and its impact on body weight and core blood parameters were documented at the start and end of efficacy testing period. Sixteen children who did not experience malaria-induced depletions of SA had significant SA increase; seven children who experienced malaria-induced depletions of SA had insignificant SA decrease. The Packed Cell Volume Percentage (PCV %), a measure of the Oxygen carrying capacity of blood and the amount of nutrients the body can absorb, increased in both groups. The total serum proteins (SA+ Globulins) increased or decreased within the continuum of normal. In conclusion, MDRTB and MDRTB-HIV patients will benefit from a variant of this Nutraceutical when used as treatment adjunct.

Keywords: antitrypsin-free Nutraceutical, apicomplexan parasites, no predilections for low serum albumin, toxoplasmosis

Procedia PDF Downloads 264

Authors: Liz Carmem Silva-Pereira, Raffael Alencar Mesquita Rodrigues, Francisco Helton Mendes Barbosa, Emerson de Freitas Ferreira

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Due to the Covid-19 pandemic declared in March 2020 by the World Health Organization, the way of social coexistence across the planet was affected, especially in educational processes, from the implementation of the remote modality as a teaching strategy. This teaching-learning modality caused a change in the routine and learning of basic education students, which resulted in serious consequences for the return to face-to-face teaching in 2021. 2022, at the Federal Institute of Education, Science and Technology of Pará (IFPA) – Campus Paragominas had their training process severely affected, having studied the initial half of their training in the remote modality, which compromised the carrying out of practical classes, technical visits and field classes, essential for the student formation on the environmental technician. With the objective of promoting the recomposition of these students' learning after returning to the face-to-face modality, an educational strategy was developed in the last period of the course. As teaching methodologies were used for research as an educational principle, the integrative project and the parallel recovery action applied jointly, aiming at recomposing the basic knowledge of the natural sciences, together with the technical knowledge of the environmental area applied to the course. The project assisted 58 finalist students of the environmental technical course. A research instrument was elaborated with parameters of evaluation of the environmental quality for study in 19 collection points, in the Uraim River urban hydrographic basin, in the Paragominas City – Pará – Brazilian Amazon. Students were separated into groups under the professors' and laboratory assistants’ orientation, and in the field, they observed and evaluated the places' environmental conditions and collected physical data and water samples, which were taken to the chemistry and biology laboratories at Campus Paragominas for further analysis. With the results obtained, each group prepared a technical report on the environmental conditions of each evaluated point. This work methodology enabled the practical application of theoretical knowledge received in various disciplines during the remote teaching modality, contemplating the integration of knowledge, people, skills, and abilities for the best technical training of finalist students. At the activity end, the satisfaction of the involved students in the project was evaluated, through a form, with the signing of the informed consent term, using the Likert scale as an evaluation parameter. The results obtained in the satisfaction survey were: on the use of research projects within the disciplines attended, 82% of satisfaction was obtained; regarding the revision of contents in the execution of the project, 84% of satisfaction was obtained; regarding the acquired field experience, 76.9% of satisfaction was obtained, regarding the laboratory experience, 86.2% of satisfaction was obtained, and regarding the use of this methodology as parallel recovery, 71.8% was obtained of satisfaction. In addition to the excellent performance of students in acquiring knowledge, it was possible to remedy the deficiencies caused by the absence of practical classes, technical visits, and field classes, which occurred during the execution of the remote teaching modality, fulfilling the desired educational recomposition.

Keywords: integrative project, parallel recovery, research as an educational principle, teaching-learning

Procedia PDF Downloads 34

Authors: Emre Kara, Ali Kurşun, Halil Aykul

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The lightweight sandwiches obtained with the use of various core materials such as foams, honeycomb, lattice structures etc., which have high energy absorbing capacity and high strength to weight ratio, are suitable for several applications in transport industry (automotive, aerospace, shipbuilding industry) where saving of fuel consumption, load carrying capacity increase, safety of vehicles and decrease of emission of harmful gases are very important aspects. While the sandwich structures with foams and honeycombs have been applied for many years, there is a growing interest on a new generation sandwiches with micro lattice cores. In order to produce these core structures, various production methods were created with the development of the technology. One of these production technologies is an additive manufacturing technique called selective laser sintering/melting (SLS/SLM) which is very popular nowadays because of saving of production time and achieving the production of complex topologies. The static bending and the dynamic low velocity impact tests of the sandwiches with carbon fiber/epoxy skins and the micro lattice cores produced via SLS/SLM were already reported in just a few studies. The goal of this investigation was the analysis of the flexural response of the sandwiches consisting of glass fiber reinforced plastic (GFRP) skins and the micro lattice cores manufactured via SLS under thermo-mechanical loads in order to compare the results in terms of peak load and absorbed energy values respect to the effect of core cell size, temperature and support span length. The micro lattice cores were manufactured using SLS technology that creates the product drawn by a 3D computer aided design (CAD) software. The lattice cores which were designed as body centered cubic (BCC) model having two different cell sizes (d= 2 and 2.5 mm) with the strut diameter of 0.3 mm were produced using titanium alloy (Ti6Al4V) powder. During the production of all the core materials, the same production parameters such as laser power, laser beam diameter, building direction etc. were kept constant. Vacuum Infusion (VI) method was used to produce skin materials, made of [0°/90°] woven S-Glass prepreg laminates. The combination of the core and skins were implemented under VI. Three point bending tests were carried out by a servo-hydraulic test machine with different values of support span distances (L = 30, 45, and 60 mm) under various temperature values (T = 23, 40 and 60 °C) in order to analyze the influences of support span and temperature values. The failure mode of the collapsed sandwiches has been investigated using 3D computed tomography (CT) that allows a three-dimensional reconstruction of the analyzed object. The main results of the bending tests are: load-deflection curves, peak force and absorbed energy values. The results were compared according to the effect of cell size, support span and temperature values. The obtained results have particular importance for applications that require lightweight structures with a high capacity of energy dissipation, such as the transport industry, where problems of collision and crash have increased in the last years.

Keywords: light-weight sandwich structures, micro lattice cores, selective laser sintering, transport application

Procedia PDF Downloads 313

Authors: Safa Ladhari, Alireza Saidi, Phuong Nguyen-Tri

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During health crises, such as COVID-19, using disposable protective equipment (PEs) (masks, gowns, etc.) causes long-term problems, increasing the volume of hazardous waste that must be handled safely and expensively. Therefore, producing textiles for antimicrobial and reusable materials is highly desirable to decrease the use of disposable PEs that should be treated as hazardous waste. In addition, if these items are used regularly in the workplace or for daily activities by the public, they will most likely end up in household waste. Furthermore, they may pose a high risk of contagion to waste collection workers if contaminated. Therefore, to protect the whole population in times of sanitary crisis, it is necessary to equip these materials with tools that make them resilient to the challenges of carrying out daily activities without compromising public health and the environment and without depending on them external technologies and producers. In addition, the materials frequently used for EPs are plastics of petrochemical origin. The subject of the present work is replacing petroplastics with bioplastic since it offers better biodegradability. The chosen polymer is polyhydroxybutyrate (PHB), a family of polyhydroxyalkanoates synthesized by different bacteria. It has similar properties to conventional plastics. However, it is renewable, biocompatible, and has attractive barrier properties compared to other polyesters. These characteristics make it ideal for EP protection applications. The current research topic focuses on the preparation and rapid evaluation of the biological activity of nanotechnology-based antimicrobial agents to treat textile surfaces used for PE. This work will be carried out to provide antibacterial solutions that can be transferred to a workplace application in the fight against short-term biological risks. Three main objectives are proposed during this research topic: 1) the development of suitable methods for the deposition of antibacterial agents on the surface of textiles; 2) the development of a method for measuring the antibacterial activity of the prepared textiles and 3) the study of the biodegradability of the prepared textiles. The studied textile is a non-woven fabric based on a biodegradable polymer manufactured by the electrospinning method. Indeed, nanofibers are increasingly studied due to their unique characteristics, such as high surface-to-volume ratio, improved thermal, mechanical, and electrical properties, and confinement effects. The electrospun film will be surface modified by plasma treatment and then loaded with hybrid antibacterial silver and titanium dioxide nanoparticles by the dip-coating method. This work uses simple methods with emerging technologies to fabricate nanofibers with suitable size and morphology to be used as components for protective equipment. The antibacterial agents generally used are based on silver, zinc, copper, etc. However, to our knowledge, few researchers have used hybrid nanoparticles to ensure antibacterial activity with biodegradable polymers. Also, we will exploit visible light to improve the antibacterial effectiveness of the fabric, which differs from the traditional contact mode of killing bacteria and presents an innovation of active protective equipment. Finally, this work will allow for the innovation of new antibacterial textile materials through a simple and ecological method.

Keywords: protective equipment, antibacterial textile materials, biodegradable polymer, electrospinning, hybrid antibacterial nanoparticles

Procedia PDF Downloads 49

Authors: Muna Mitchell, Akshay Parchure, Krishna Singaraju

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There is an increasing need for medium- to long-span steel bridges with complex geometry due to site restrictions in developed areas. One of the solutions to grade separations in congested areas is to use longer spans on skewed supports that avoid at-grade obstructions limiting impacts to the foundation. Where vertical clearances are also a constraint, continuous steel girders can be used to reduce superstructure depths. Combining continuous long steel spans on severe skews can resolve the constraints at a cost. The behavior of skewed girders is challenging to analyze and design with subsequent complexity during fabrication and construction. As a part of a corridor improvement project, Walter P Moore designed two 1700-foot side-by-side bridges carrying four lanes of traffic in each direction over a railroad track. The bridges consist of prestressed concrete girder approach spans and three-span continuous steel plate girder units. The roadway design added complex geometry to the bridge with horizontal and vertical curves combined with superelevation transitions within the plate girder units. The substructure at the steel units was skewed approximately 56 degrees to satisfy the existing railroad right-of-way requirements. A horizontal point of curvature (PC) near the end of the steel units required the use flared girders and chorded slab edges. Due to the flared girder geometry, the cross-frame spacing in each bay is unique. Staggered cross frames were provided based on AASHTO LRFD and NCHRP guidelines for high skew steel bridges. Skewed steel bridges develop significant forces in the cross frames and rotation in the girder websdue to differential displacements along the girders under dead and live loads. In addition, under thermal loads, skewed steel bridges expand and contract not along the alignment parallel to the girders but along the diagonal connecting the acute corners, resulting in horizontal displacement both along and perpendicular to the girders. AASHTO LRFD recommends a 95 degree Fahrenheit temperature differential for the design of joints and bearings. The live load and the thermal loads resulted in significant horizontal forces and rotations in the bearings that necessitated the use of HLMR bearings. A unique bearing layout was selected to minimize the effect of thermal forces. The span length, width, skew, and roadway geometry at the bridges also required modular bridge joint systems (MBJS) with inverted-T bent caps to accommodate movement in the steel units. 2D and 3D finite element analysis models were developed to accurately determine the forces and rotations in the girders, cross frames, and bearings and to estimate thermal displacements at the joints. This paper covers the decision-making process for developing the framing plan, bearing configurations, joint type, and analysis models involved in the design of the high-skew three-span continuous steel plate girder bridges.

Keywords: complex geometry, continuous steel plate girders, finite element structural analysis, high skew, HLMR bearings, modular joint

Procedia PDF Downloads 150

Authors: Karen L. Lindsay, Sonja Entringer, Claudia Buss, Pathik D. Wadhwa

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Maternal nutrition and stress are independently recognized as among the most important factors that influence prenatal biology, with implications for fetal development and poor pregnancy outcomes. While there is substantial evidence from non-pregnancy human and animal studies that a complex, bi-directional relationship exists between nutrition and stress, to the author’s best knowledge, their interaction in the context of pregnancy has been significantly understudied. The aim of this study is to assess the interaction between maternal psychological stress and diet quality across pregnancy and its effects on biomarkers of prenatal insulin resistance and inflammation. This is a prospective longitudinal study of N=235 women carrying a healthy, singleton pregnancy, recruited from prenatal clinics of the University of California, Irvine Medical Center. Participants completed a 4-day ambulatory assessment in early, middle and late pregnancy, which included multiple daily electronic diary entries using Ecological Momentary Assessment (EMA) technology on a dedicated study smartphone. The EMA diaries gathered moment-level data on maternal perceived stress, negative mood, positive mood and quality of social interactions. The numerical scores for these variables were averaged across each study time-point and converted to Z-scores. A single composite variable for 'STRESS' was computed as follows: (Negative mood+Perceived stress)–(Positive mood+Social interaction quality). Dietary intakes were assessed by three 24-hour dietary recalls conducted within two weeks of each 4-day assessment. Daily nutrient and food group intakes were averaged across each study time-point. The Alternative Healthy Eating Index adapted for pregnancy (AHEI-P) was computed for early, middle and late pregnancy as a validated summary measure of diet quality. At the end of each 4-day ambulatory assessment, women provided a fasting blood sample, which was assayed for levels of glucose, insulin, Interleukin (IL)-6 and Tumor Necrosis Factor (TNF)-α. Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) was computed. Pearson’s correlation was used to explore the relationship between maternal STRESS and AHEI-P within and between each study time-point. Linear regression was employed to test the association of the stress-diet interaction (STRESS*AHEI-P) with the biological markers HOMA-IR, IL-6 and TNF-α at each study time-point, adjusting for key covariates (pre-pregnancy body mass index, maternal education level, race/ethnicity). Maternal STRESS and AHEI-P were significantly inversely correlated in early (r=-0.164, p=0.018) and mid-pregnancy (-0.160, p=0.019), and AHEI-P from earlier gestational time-points correlated with later STRESS (early AHEI-P x mid STRESS: r=-0.168, p=0.017; mid AHEI-P x late STRESS: r=-0.142, p=0.041). In regression models, the interaction term was not associated with HOMA-IR or IL-6 at any gestational time-point. The stress-diet interaction term was significantly associated with TNF-α according to the following patterns: early AHEI-P*early STRESS vs early TNF-α (p=0.005); early AHEI-P*early STRESS vs mid TNF-α (p=0.002); early AHEI-P*mid STRESS vs mid TNF-α (p=0.005); mid AHEI-P*mid STRESS vs mid TNF-α (p=0.070); mid AHEI-P*late STRESS vs late TNF-α (p=0.011). Poor diet quality is significantly related to higher psychosocial stress levels in pregnant women across gestation, which may promote inflammation via TNF-α. Future prenatal studies should consider the combined effects of maternal stress and diet when evaluating either one of these factors on pregnancy or infant outcomes.

Keywords: diet quality, inflammation, insulin resistance, nutrition, pregnancy, stress, tumor necrosis factor-alpha

Procedia PDF Downloads 162

Authors: James Brown, Stella Kortekaas, Ian Finnie, George Zhang, Christine Devine, Neil Healy

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The use of GIS as an analysis tool for engineering decision making is now best practice in the offshore industry. GIS enables multidisciplinary data integration, analysis and visualisation which allows the presentation of large and intricate datasets in a simple map-interface accessible to all project stakeholders. Presenting integrated geoscience and geotechnical data in GIS enables decision makers to be well-informed. This paper is a successful case study of how GIS spatial analysis techniques were applied to help select the most favourable pipeline route. Routing a pipeline through any natural environment has numerous obstacles, whether they be topographical, geological, engineering or financial. Where the pipeline is subjected to external hydrostatic water pressure and is carrying pressurised hydrocarbons, the requirement to safely route the pipeline through hazardous terrain becomes absolutely paramount. This study illustrates how the application of modern, GIS-based pipeline routing techniques enabled the identification of a single most-favourable pipeline route crossing of a challenging seabed terrain. Conventional approaches to pipeline route determination focus on manual avoidance of primary constraints whilst endeavouring to minimise route length. Such an approach is qualitative, subjective and is liable to bias towards the discipline and expertise that is involved in the routing process. For very short routes traversing benign seabed topography in shallow water this approach may be sufficient, but for deepwater geohazardous sites, the need for an automated, multi-criteria, and quantitative approach is essential. This study combined multiple routing constraints using modern least-cost-routing algorithms deployed in GIS, hitherto unachievable with conventional approaches. The least-cost-routing procedure begins with the assignment of geocost across the study area. Geocost is defined as a numerical penalty score representing hazard posed by each routing constraint (e.g. slope angle, rugosity, vulnerability to debris flows) to the pipeline. All geocosted routing constraints are combined to generate a composite geocost map that is used to compute the least geocost route between two defined terminals. The analyses were applied to select the most favourable pipeline route for a potential gas development in deep water. The study area is geologically complex with a series of incised, potentially active, canyons carved into a steep escarpment, with evidence of extensive debris flows. A similar debris flow in the future could cause significant damage to a poorly-placed pipeline. Protruding inter-canyon spurs offer lower-gradient options for ascending an escarpment but the vulnerability of periodic failure of these spurs is not well understood. Close collaboration between geoscientists, pipeline engineers, geotechnical engineers and of course the gas export pipeline operator guided the analyses and assignment of geocosts. Shorter route length, less severe slope angles, and geohazard avoidance were the primary drivers in identifying the most favourable route.

Keywords: geocost, geohazard, pipeline route determination, pipeline route optimisation, spatial analysis

Procedia PDF Downloads 365

Authors: Betül Gelengül Eki̇mci̇, Semra Günay Aktaş

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Festive, habitual activities celebrated on the specified date by a local community, are conducive to recognition of the region. The main function of festive events is to help gathering people via an annual celebration to create an atmosphere of understanding and the opportunity to participate in the joy of life. At the same time, festive events may serve as special occasions on which immigrants return home to celebrate with their family and community, reaffirming their identity and link to the community’s traditions. Festivals also support the local economy by bringing in different visitors to the region. The tradition of “Beet Brewing-Molasses Production,” which is held in İdrisyayla Village is an intangible cultural heritage with customs, traditions, and rituals carrying impacts of cuisine culture of Rumelian immigrants in the Ottoman. After the harvest of the beet plant in the autumn season of the year, Beet Brewing Molasses syrup is made by traditional production methods with co-op of the local community. Festive occurring brewing paste made process provided transmission of knowledge and experience to the young generations. Making molasses, which is a laborious process, is accompanied by folk games such as "sayacı," which is vital element of the festive performed in İdrisyayla. Performance provides enjoyable time and supporting motivation. Like other forms of intangible cultural heritage, “Beet Brewing-Molasses Festive in İdrasyayla is threatened by rapid urbanisation, young generation migration, industrialisation and environmental change. The festive events are threatened with gradual disappearance due to changes communities undergo in modern societies because it depends on the broad participation of practitioners. Ensuring the continuity of festive events often requires the mobilization of large numbers of individuals and the social, political and legal institutions and mechanisms of society. In 2015, Intangible cultural heritage research project with the title of "İdrisyayla Molasses Process" managed by the Eskişehir Governorship, City Directorate of Culture and Tourism and Anadolu University, project members took part in the festival organization to promote sustainability, making it visible, to encourage the broadest public participation possible, to ensure public awareness on the cultural importance. To preserve the originality of and encourage participation in the festive İdrisyayla, local associations, researchers and institutions created foundation and supports festive events, such as "sayacı" folk game, which is vital element of the festive performed in İdrisyayla. Practitioners find new opportunity to market İdrisyayla Molasses production. Publicity program through the press and exhibition made it possible to stress the cultural importance of the festive in İdrisyayla Village. The research reported here used a survey analysis to evaluate an affect of the festive after the spirit of the 2015 Festive in İdrisyayla Village. Particular attention was paid to the importance of the cultural aspects of the festival. Based on a survey of more than a hundred festival attendees, several recommendations are made to festival planners. Results indicate that the variety of festive activities and products offered for sale very important to attendees. The local participants care product sales rather than cultural heritage.

Keywords: agritourism, cultural tourism, festival, sustainable cultural heritage

Procedia PDF Downloads 194

Authors: C. Bel, J. Nevado, F. Ciceri, M. Ropacki, T. Hoffmann, P. Lapunzina, C. Buesa

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Background: The Phelan-McDermid syndrome (PMS) is a genetic disorder caused by the deletion of the terminal region of chromosome 22 or mutation of the SHANK3 gene. Shank3 disruption in mice leads to dysfunction of synaptic transmission, which can be restored by epigenetic regulation with both Lysine Specific Demethylase 1 (LSD1) inhibitors. PMS subjects result in a variable degree of intellectual disability, delay or absence of speech, autistic spectrum disorders symptoms, low muscle tone, motor delays and epilepsy. Vafidemstat is an LSD1 inhibitor in Phase II clinical development with a well-established and favorable safety profile, and data supporting the restoration of memory and cognition defects as well as reduction of agitation and aggression in several animal models and clinical studies. Therefore, vafidemstat has the potential to become a first-in-class precision medicine approach to treat PMS patients. Aims: The goal of this research is to perform an observational trial to psychometrically characterize individuals carrying deletions in SHANK3 and build a foundation for subsequent precision psychiatry clinical trials with vafidemstat. Methodology: This study is characterizing the clinical profile of 20 to 40 subjects, > 16-year-old, with genotypically confirmed PMS diagnosis. Subjects will complete a battery of neuropsychological scales, including the Repetitive Behavior Questionnaire (RBQ), Vineland Adaptive Behavior Scales, Escala de Observación para el Diagnostico del Autismo (Autism Diagnostic Observational Scale) (ADOS)-2, the Battelle Developmental Inventory and the Behavior Problems Inventory (BPI). Results: By March 2021, 19 patients have been enrolled. Unsupervised hierarchical clustering of the results obtained so far identifies 3 groups of patients, characterized by different profiles of cognitive and behavioral scores. The first cluster is characterized by low Battelle age, high ADOS and low Vineland, RBQ and BPI scores. Low Vineland, RBQ and BPI scores are also detected in the second cluster, which in contrast has high Battelle age and low ADOS scores. The third cluster is somewhat in the middle for the Battelle, Vineland and ADOS scores while displaying the highest levels of aggression (high BPI) and repeated behaviors (high RBQ). In line with the observation that female patients are generally affected by milder forms of autistic symptoms, no male patients are present in the second cluster. Dividing the results by gender highlights that male patients in the third cluster are characterized by a higher frequency of aggression, whereas female patients from the same cluster display a tendency toward higher repetitive behavior. Finally, statistically significant differences in deletion sizes are detected comparing the three clusters (also after correcting for gender), and deletion size appears to be positively correlated with ADOS and negatively correlated with Vineland A and C scores. No correlation is detected between deletion size and the BPI and RBQ scores. Conclusions: Precision medicine may open a new way to understand and treat Central Nervous System disorders. Epigenetic dysregulation has been proposed to be an important mechanism in the pathogenesis of schizophrenia and autism. Vafidemstat holds exciting therapeutic potential in PMS, and this study will provide data regarding the optimal endpoints for a future clinical study to explore vafidemstat ability to treat shank3-associated psychiatric disorders.

Keywords: autism, epigenetics, LSD1, personalized medicine

Procedia PDF Downloads 136

Authors: Manuel I. Capel, Antonio Tomeu, Alberto Salguero

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Tumor growth from a transformed cancer-cell up to a clinically apparent mass spans through a range of spatial and temporal magnitudes. Through computer simulations, Cellular Automata (CA) can accurately describe the complexity of the development of tumors. Tumor development prognosis can now be made -without making patients undergo through annoying medical examinations or painful invasive procedures- if we develop appropriate CA-based software tools. In silico testing mainly refers to Computational Biology research studies of application to clinical actions in Medicine. To establish sound computer-based models of cellular behavior, certainly reduces costs and saves precious time with respect to carrying out experiments in vitro at labs or in vivo with living cells and organisms. These aim to produce scientifically relevant results compared to traditional in vitro testing, which is slow, expensive, and does not generally have acceptable reproducibility under the same conditions. For speeding up computer simulations of cellular models, specific literature shows recent proposals based on the CA approach that include advanced techniques, such the clever use of supporting efficient data structures when modeling with deterministic stochastic cellular automata. Multiparadigm and multiscale simulation of tumor dynamics is just beginning to be developed by the concerned research community. The use of stochastic cellular automata (SCA), whose parallel programming implementations are open to yield a high computational performance, are of much interest to be explored up to their computational limits. There have been some approaches based on optimizations to advance in multiparadigm models of tumor growth, which mainly pursuit to improve performance of these models through efficient memory accesses guarantee, or considering the dynamic evolution of the memory space (grids, trees,…) that holds crucial data in simulations. In our opinion, the different optimizations mentioned above are not decisive enough to achieve the high performance computing power that cell-behavior simulation programs actually need. The possibility of using multicore and GPU parallelism as a promising multiplatform and framework to develop new programming techniques to speed-up the computation time of simulations is just starting to be explored in the few last years. This paper presents a model that incorporates parallel processing, identifying the synchronization necessary for speeding up tumor growth simulations implemented in Java and C++ programming environments. The speed up improvement that specific parallel syntactic constructs, such as executors (thread pools) in Java, are studied. The new tumor growth parallel model is proved using implementations with Java and C++ languages on two different platforms: chipset Intel core i-X and a HPC cluster of processors at our university. The parallelization of Polesczuk and Enderling model (normally used by researchers in mathematical oncology) proposed here is analyzed with respect to performance gain. We intend to apply the model and overall parallelization technique presented here to solid tumors of specific affiliation such as prostate, breast, or colon. Our final objective is to set up a multiparadigm model capable of modelling angiogenesis, or the growth inhibition induced by chemotaxis, as well as the effect of therapies based on the presence of cytotoxic/cytostatic drugs.

Keywords: cellular automaton, tumor growth model, simulation, multicore and manycore programming, parallel programming, high performance computing, speed up

Procedia PDF Downloads 212

Authors: Yung-Chih Kuo, Che-Yu Lin, Jay-Shake Li, Yung-I Lou

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Curcumin (CRM) and nerve growth factor (NGF) were entrapped in liposomes (LIP) with cardiolipin (CL) to downregulate the phosphorylation of mitogen-activated protein kinases for Alzheimer’s disease (AD) management. AD belongs to neurodegenerative disorder with a gradual loss of memory, yielding irreversible dementia. CL-conjugated LIP loaded with CRM (CRM-CL/LIP) and that with NGF (NGF-CL/LIP) were applied to AD models of SK-N-MC cells and Wistar rats with an insult of β-amyloid peptide (Aβ). Lipids comprising 1,2-dipalmitoyl-sn-glycero-3- phosphocholine (Avanti Polar Lipids, Alabaster, AL), 1',3'-bis[1,2- dimyristoyl-sn-glycero-3-phospho]-sn-glycerol (CL; Avanti Polar Lipids), 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N- [methoxy(polyethylene glycol)-2000] (Avanti Polar Lipids), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[carboxy(polyethylene glycol)-2000] (Avanti Polar Lipids) and CRM (Sigma–Aldrich, St. Louis, MO) were dissolved in chloroform (J. T. Baker, Phillipsburg, NJ) and condensed using a rotary evaporator (Panchum, Kaohsiung, Taiwan). Human β-NGF (Alomone Lab, Jerusalem, Israel) was added in the aqueous phase. Wheat germ agglutinin (WGA; Medicago AB, Uppsala, Sweden) was grafted on LIP loaded with CRM for (WGA-CRM-LIP) and CL-conjugated LIP loaded with CRM (WGA-CRM-CL/LIP) using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (Sigma–Aldrich) and N-hydroxysuccinimide (Alfa Aesar, Ward Hill, MA). The protein samples of SK-N-MC cells (American Type Tissue Collection, Rockville, MD) were used for sodium dodecyl sulfate (Sigma–Aldrich) polyacrylamide gel (Sigma–Aldrich) electrophoresis. In animal study, the LIP formulations were administered by intravenous injection via a tail vein of male Wistar rats (250–280 g, 8 weeks, BioLasco, Taipei, Taiwan), which were housed in the Animal Laboratory of National Chung Cheng University in accordance with the institutional guidelines and the guidelines of Animal Protection Committee under the Council of Agriculture of the Republic of China. We found that CRM-CL/LIP could inhibit the expressions of phosphorylated p38 (p-p38), p-Jun N-terminal kinase (p-JNK), and p-tau protein at serine 202 (p-Ser202) to retard the neuronal apoptosis. Free CRM and released CRM from CRM-LIP and CRM-CL/LIP were not in a straightforward manner to effectively inhibit the expression of p-p38 and p-JNK in the cytoplasm. In addition, NGF-CL/LIP enhanced the quantities of p-neurotrophic tyrosine kinase receptor type 1 (p-TrkA) and p-extracellular-signal-regulated kinase 5 (p-ERK5), preventing the Aβ-induced degeneration of neurons. The membrane fusion of NGF-LIP activated the ERK5 pathway and the targeting capacity of NGF-CL/LIP enhanced the possibility of released NGF to affect the TrkA level. Moreover, WGA-CRM-LIP improved the permeation of CRM across the blood–brain barrier (BBB) and significantly reduced the Aβ plaque deposition and malondialdehyde level and increased the percentage of normal neurons and cholinergic function in the hippocampus of AD rats. This was mainly because the encapsulated CRM was protected by LIP against a rapid degradation in the blood. Furthermore, WGA on LIP could target N-acetylglucosamine on endothelia and increased the quantity of CRM transported across the BBB. In addition, WGA-CRM-CL/LIP could be effective in suppressing the synthesis of acetylcholinesterase and reduced the decomposition of acetylcholine for better neurotransmission. Based on the in vitro and in vivo evidences, WGA-CRM-CL/LIP can rescue neurons from apoptosis in the brain and can be a promising drug delivery system for clinical AD therapy.

Keywords: Alzheimer’s disease, β-amyloid, liposome, mitogen-activated protein kinase

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Authors: M. M. Hassani, S. Ammann, F. K. Wittel, P. Niemz, H. J. Herrmann

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Application of engineered wood, especially in the form of glued-laminated timbers has increased significantly. Recent progress in plywood made of high strength and high stiffness hardwoods, like European beech, gives designers in general more freedom by increased dimensional stability and load-bearing capacity. However, the strong hygric dependence of basically all mechanical properties renders many innovative ideas futile. The tendency of hardwood for higher moisture sorption and swelling coefficients lead to significant residual stresses in glued-laminated configurations, cross-laminated patterns in particular. These stress fields cause initiation and evolution of cracks in the bond-lines resulting in: interfacial de-bonding, loss of structural integrity, and reduction of load-carrying capacity. Subsequently, delamination of glued-laminated timbers made of hardwood elements can be considered as the dominant failure mechanism in such composite elements. In addition, long-term creep and mechano-sorption under changing environmental conditions lead to loss of stiffness and can amplify delamination growth over the lifetime of a structure even after decades. In this study we investigate the delamination process of adhesively bonded hardwood (European beech) elements subjected to changing climatic conditions. To gain further insight into the long-term performance of adhesively bonded elements during the design phase of new products, the development and verification of an authentic moisture-dependent constitutive model for various species is of great significance. Since up to now, a comprehensive moisture-dependent rheological model comprising all possibly emerging deformation mechanisms was missing, a 3D orthotropic elasto-plastic, visco-elastic, mechano-sorptive material model for wood, with all material constants being defined as a function of moisture content, was developed. Apart from the solid wood adherends, adhesive layer also plays a crucial role in the generation and distribution of the interfacial stresses. Adhesive substance can be treated as a continuum layer constructed from finite elements, represented as a homogeneous and isotropic material. To obtain a realistic assessment on the mechanical performance of the adhesive layer and a detailed look at the interfacial stress distributions, a generic constitutive model including all potentially activated deformation modes, namely elastic, plastic, and visco-elastic creep was developed. We focused our studies on the three most common adhesive systems for structural timber engineering: one-component polyurethane adhesive (PUR), melamine-urea-formaldehyde (MUF), and phenol-resorcinol-formaldehyde (PRF). The corresponding numerical integration approaches, with additive decomposition of the total strain are implemented within the ABAQUS FEM environment by means of user subroutine UMAT. To predict the true stress state, we perform a history dependent sequential moisture-stress analysis using the developed material models for both wood substrate and adhesive layer. Prediction of the delamination process is founded on the fracture mechanical properties of the adhesive bond-line, measured under different levels of moisture content and application of the cohesive interface elements. Finally, we compare the numerical predictions with the experimental observations of de-bonding in glued-laminated samples under changing environmental conditions.

Keywords: engineered wood, adhesive, material model, FEM analysis, fracture mechanics, delamination

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Authors: Berrachid Dounia, Bellihi Hassan

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The financial crisis made a barrier in front of small projects that are looking for funding, but in the other hand it has had at least an interesting side effect which is the rise of alternative and increasingly creative forms of financing. The traditional forms of financing has known a recession due to the new difficult situation of economical recession that all parts of the world have known. Having an innovating idea that has an effect on both sides, the economic one and social one is very beneficial for those who wants to get rid of the economical crisis. In this case, entrepreneurs who want to be successful are looking for the means of financing that are going to get their projects to the reality. The financing could be various, whether the entrepreneur can use his own resources, or go to the three “Fs”(Family, friends, and fools),look for Angel Investors, or try for the academic solution like universities and private incubators, but sometimes, entrepreneurs feels uncomfortable about those means and start looking to newer, less traditional forms of financing their projects. In the last few years, people have shown a great interest to the use of internet for many reasons (information, social networking, communication, entertainment, transaction, etc.). The use of internet facilitates relations between people and eases the maintenance of existing relationships ,it increases also the number of exchanges which leads to a “collective creativity”, moreover, internet gives an opportunity to create new tool for mobilizing civil society, which makes the participation in a project company much easier. The new atmosphere of business forces the project leaders to look for new solution of financing that cut out the financial intermediaries. Using platforms in order to finance projects is an alternative that is changing the traditional solutions of financing projects. New creative ways of lending money appears like Peer to Peer (person to person or P2P)lending. This digital directly intermediary got his origins from microcredit principles. Crowdfunding also, like P2P, involves getting individuals to pool their resources to finance a project without a typical financial intermediary. For Lambert and Schwienbacher "Crowdfunding involves an open call, essentially through the Internet, for the provision of financial resources either in the form of donations (without rewards) or in exchange for some form of reward and/or voting rights in order to support initiatives for specific purposes". The idea of this proposal for investors and entrepreneurs is to encourage small contributions from a large number of funders "the crowd" in order to raise money to fund projects. All those conditions made from crowdfunding a useful alternative to project leaders, and especially the ones who are carrying special ideas that need special funds. As mentioned before by Laflamme. S. et Lafortune. S. internet is a tool for mobilizing civil society. In our case, the crowdfunding is the tool that funds social entrepreneurship, in the case of not for profit organizations, it focuses his attention on social problems which could be resolved by mobilizing different resources, creating innovative initiatives, and building new social arrangements which call up the civil society. Social entrepreneurs are mostly the ones who goes onto crowdfunding web site, so they propose the amount which is expected to realize their project and then they receive the funds from crowd funders. Something the crowd funders expect something in return, like a product from the business (a sample from a product (case of a cooperative) or a CD (in the case of films or songs)), but not their money back. Thus, we cannot say that their lands are donations, because a donator did not expect anything back. However, in order to encourage "crowd-funders", rewards motivates people to get interested by projects and made some money from internet. The operation of crowd funding is making all parts satisfied investors, entrepreneurs and also crowdfunding sites owners. This paper aims to give a view of the mechanism of crowdfunding, by clarifying the techniques and its different categories, and social entrepreneurship as a sponsor of social development. Also, it aims to show how this alternative of financing could be beneficial for social entrepreneurs and how it is bringing a solution to fund social projects. The article concludes with a discussion of the contribution of crowdfunding in social entrepreneurship especially in the Moroccan context.

Keywords: crowd-funding, social entrepreneurship, projects funding, financing

Procedia PDF Downloads 351

Authors: Mohamed Sameer Mughal, Andrew D. Ross, Damian J. Fearon

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Background: The fast-paced changing landscape of UK Higher Education Institution (HEIs) is poised by changes and challenges affecting Middle Managers (MM) in their job roles. MM contribute to the success of HEIs by balancing the equilibrium and pass organization strategies from senior staff towards operationalization directives to junior staff. However, this study showcased from the data analyzed during the semi structured interviews; MM job role is becoming more complex due to changes and challenges creating colossal pressures and workloads in day-to-day working. Current development programmes provisions by Human Resources (HR) departments in such HEIs are not feasible, applicable, and matching the true essence and requirements of MM who suggest that programmes offered by HR are too generic to suit their precise needs and require tailor made espousal to work effectively in their pertinent job roles. Methodologies: This study aims to capture demands of MM Development Needs (DN) by means of a conceptual model as conclusive part of the research that is divided into 2 phases. Phase 1 initiated by carrying out 2 pilot interviews with a retired Emeritus status professor and HR programmes development coordinator. Key themes from the pilot and literature review subsidized into formulation of 22 set of questions (Kvale and Brinkmann) in form of interviewing questionnaire during qualitative data collection. Data strategy and collection consisted of purposeful sampling of 12 semi structured interviews (n=12) lasting approximately an hour for all participants. The MM interviewed were at faculty and departmental levels which included; deans (n=2), head of departments (n=4), subject leaders (n=2), and lastly programme leaders (n=4). Participants recruitment was carried out via emails and snowballing technique. The interviews data was transcribed (verbatim) and managed using Computer Assisted Qualitative Data Analysis using Nvivo ver.11 software. Data was meticulously analyzed using Miles and Huberman inductive approach of positivistic style grounded theory, whereby key themes and categories emerged from the rich data collected. The data was precisely coded and classified into case studies (Robert Yin); with a main case study, sub cases (4 classes of MM) and embedded cases (12 individual MMs). Major Findings: An interim conceptual model emerged from analyzing the data with main concepts that included; key performance indicators (KPI’s), HEI effectiveness and outlook, practices, processes and procedures, support mechanisms, student events, rules, regulations and policies, career progression, reporting/accountability, changes and challenges, and lastly skills and attributes. Conclusion: Dynamic elements affecting MM includes; increase in government pressures, student numbers, irrelevant development programmes, bureaucratic structures, transparency and accountability, organization policies, skills sets… can only be confronted by employing structured development programmes originated by HR that are not provided generically. Future Work: Stage 2 (Quantitative method) of the study plans to validate the interim conceptual model externally through fully completed online survey questionnaire (Bram Oppenheim) from external HEIs (n=150). The total sample targeted is 1500 MM. Author contribution focuses on enhancing management theory and narrow the gap between by HR and MM development programme provision.

Keywords: development needs (DN), higher education institutions (HEIs), human resources (HR), middle managers (MM)

Procedia PDF Downloads 208