Search results for: endogenous economic growth

Authors: Ramin Mehdiabadi

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Background: Breast cancer remains the most prevalent cancer diagnosis and the leading cause of cancer death among women globally, representing 11.7% of new cases and 6.9% of deaths. While the incidence and mortality of major cancers are declining in developed regions like the United States and Western Europe, underdeveloped and developing countries exhibit an increasing trend, attributed to lifestyle factors such as smoking, physical inactivity, and high-calorie diets. Objective: This study explores the intricate relationship between the mammalian transcription factor forkhead box (FoxM1) and the microRNA miR-216b-5p in various subtypes of breast cancer, aiming to deepen the understanding of their roles in tumorigenesis, metastasis, and drug resistance. Methods: Breast cancer subtypes were categorized based on key biomarkers: estrogen receptors, progesterone receptors, and human epidermal growth factor receptor 2. These include luminal A, luminal B, HER2 enriched, triple-negative, and normal-like subtypes. We focused on analyzing the expression levels of FoxM1 and miR-216b-5p, given the known role of FoxM1 in cell proliferation and its implications in cancer pathologies such as lung, gastric, and breast cancers. Concurrently, miR-216b-5p's function as a tumor suppressor was evaluated to ascertain its regulatory effects on FoxM1. Results: Preliminary data indicate a nuanced interplay between FoxM1 and miR-216b-5p, suggesting a potential inverse relationship that varies across breast cancer subtypes. This relationship underscores the dual role of these biomarkers in modulating cancer progression and response to treatments. Conclusion: The findings advocate for the potential of miR-216b-5p to serve as a prognostic biomarker and a therapeutic target, particularly in subtypes where FoxM1 is prominently expressed. Understanding these molecular interactions provides crucial insights into the personalized treatment strategies and could lead to more effective therapeutic interventions in breast cancer management. Implications: The study highlights the importance of molecular profiling in breast cancer treatment and emphasizes the need for targeted therapeutic approaches in managing diverse cancer subtypes, particularly in varying global contexts where lifestyle factors significantly impact cancer dynamics.

Keywords: breast cancer, gene expression, FoxM1, microRNA

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Authors: Meysam Saidi

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While the specific externalities and required regulatory measures in relation to Islamic banking are fairly uncertain, the business is growing across the world. Unofficial data indicate that the Islamic Finance market is growing with annual rate of 15% and it has reached 1.3 $ trillion size. This trend is associated with inherent systematic connection of Islamic financial institutions to other entities and different sectors of economies. Islamic banking has been subject of market development policies in major economies, most notably the UK. This trend highlights the need for identification of distinct risk features of Islamic banking and crafting customized regulatory measures. So far there has not been a significant systemic crisis in this market which can be attributed to its distinct nature. However, the significant growth and spread of its products worldwide necessitate an in depth study of its nature for customized congruent regulatory measures. In the post financial crisis era some market analysis and reports suggested that the Islamic banks fairly weathered the crisis. As far as heavily blamed conventional financial products such as subprime mortgage backed securities and speculative credit default swaps were concerned the immunity claim can be considered true, as Islamic financial institutions were not directly exposed to such products. Nevertheless, similar to the experience of the conventional banking industry, it can be only a matter of time for Islamic banks to face failures that can be specific to the nature of their business. Using the experience of conventional banking regulations and identifying those peculiarities of Islamic banking that need customized regulatory approach can aid to prevent major failures. Frank Knight has stated that “We perceive the world before we react to it, and we react not to what we perceive, but always to what we infer”. The debate over congruent Islamic banking regulations might not be an exception to Frank Knight’s statement but I will try to base my discussion on concrete evidences. This paper first analyzes both theoretical and actual features of Islamic banking in order to ascertain to its peculiarities in terms of market stability and other externalities. Next, the paper discusses distinct features of Islamic financial transactions and banking which might require customized regulatory measures. Finally, the paper explores how a more transparent path for the Islamic banking regulations can be drawn.

Keywords: Islamic banking, regulation, risks, capital requirements, customer protection, financial stability

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Authors: Judith Mogouong, Philippe Constant, Robert Lavallee, Claude Guertin

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The emerald ash borer (EAB) is an exotic wood borer insect native from China, which is associated with important environmental and economic damages in North America. Beetles are known to be vectors of microbial communities related to their adaptive capacities. It is now established that environmental stress factors may induce physiological events on the host trees, such as phytochemical changes. Consequently, that may affect the establishment comportment of herbivorous insect. Considering the number of insects collected on ash trees (insects’ density) as an abiotic factor related to stress damage, the aim of our study was to explore the dynamic of EAB gut microbial community genome (microbiome) when facing that factor and to monitor its diversity. Insects were trapped using specific green Lindgren© traps. A gradient of the captured insect population along the St. Lawrence River was used to create three levels of insects’ density (low, intermediate, and high). After dissection, total DNA extracted from insect guts of each level has been sent for amplicon sequencing of bacterial 16S rRNA gene and fungal ITS2 region. The composition of microbial communities among sample appeared largely diversified with the Simpson index significantly different across the three levels of density for bacteria. Add to that; bacteria were represented by seven phyla and twelve classes, whereas fungi were represented by two phyla and seven known classes. Using principal coordinate analysis (PCoA) based on Bray Curtis distances of 16S rRNA sequences, we observed a significant variation between the structure of the bacterial communities depending on insects’ density. Moreover, the analysis showed significant correlations between some bacterial taxa and the three classes of insects’ density. This study is the first to present a complete overview of the bacterial and fungal communities associated with the gut of EAB base on culture-independent methods, and to correlate those communities with a potential stress factor of the host trees.

Keywords: gut microbiome, DNA, 16S rRNA sequences, emerald ash borer

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Authors: S. Archsana, Vajira Balasuriya

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In Trincomalee of Sri Lanka, a post-conflict area, resettlement projects and policy initiatives are taking place to improve the wealth of the rural communities through promoting economic activities by way of encouraging the rural women to opt to commence and operate Micro and Small Scale (MSS) businesses. This study attempts to identify the manner in which the institutional environment could facilitate these MSS businesses owned and operated by women in the rural environment. The respondents of this study are the beneficiaries of the Divi Neguma Development Training Program (DNDTP); a project designed to aid women owned MSS businesses, in Trincomalee district. 96 women business operators, who had obtained financing facilities from the DNDTP, are taken as the sample based on fixed interval random sampling method. The study reveals that primary challenges encountered by 82% of the women business operators are lack of initial capital followed by 71% initial market finding and 35% access to technology. The low level of education and language barriers are the constraints in accessing support agencies/service providers. Institutional support; specifically management and marketing services, have a significant relationship with wealth augmentation. Institutional support at the setting-up stage of businesses are thin whereas terms and conditions of the finance facilities are perceived as ‘too challenging’. Although diversification enhances wealth of the rural women business operators, assistance from the institutional framework to prepare financial reports that are required for business expansion is skinny. The study further reveals that institutional support is very much weak in terms of providing access to new technology and identifying new market networks. A mechanism that could facilitate the institutional framework to support the rural women business operators to access new technology and untapped market segments, and assistance in preparation of legal and financial documentation is recommended.

Keywords: business facilitation, institutional support, rural women business operators, wealth augmentation

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Authors: Andrea Corsale

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The historical and geographical regions of Banat and Crişana in Western Romania have long been characterized by a high degree of ethnic diversity. However, this traditionally complex cultural, linguistic, and religious mosaic has undergone a progressive simplification during the past century due to deportations, emigration, and assimilation, and both regions now have a large Romanian-speaking majority population. This contribution focuses on Jewish heritage in the two largest cities of these two regions, Timişoara (Banat) and Oradea (Crişana). The two cities shared some historical events but also went through different experiences, despite their relative geographic proximity. The Jewish community of Timişoara survived the Holocaust basically intact, an almost unique case in Central-Eastern Europe, but largely left the city after the war. Instead, the Jewish community of Oradea was almost completely deported and killed in Auschwitz, and a renewed post-war community gradually emigrated abroad in the following decades. The two Jewish communities are now very small in size but inherited a vast tangible and intangible heritage (synagogues, cemeteries, community buildings, characteristic architecture, memories, local traditions, and histories), partially restored and recovered in recent years. The author’s fieldwork shows that local Jewish stakeholders are aware of the potential of this heritage in terms of cultural and economic benefits, but significant weaknesses and concerns exist, as the small dimension of these communities, and their financial constraints, challenge their future role in the eventual promotion and management of this heritage, which is now basically in the hands of the non-Jewish public and private stakeholders. Projects, experiences, and views related to Jewish heritage conservation and promotion in these two contexts will be portrayed and analysed in order to contribute to a broader discussion on representations and narratives of minority heritage within cultural tourism development dynamics.

Keywords: Jewish heritage, ethnic minorities, heritage tourism, Romania

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Authors: Raphael Udeh, Luis García De Guadiana Romualdo, Xenia Dolje-Gore

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Background: Quite disturbing is the huge public health impact of COVID-19: As at today [25th March 2021, the COVID-19 global burden shows over 123 million cases and over 2.7 million deaths worldwide. Rationale: Recent evidence shows calprotectin’s potential as a therapeutic target, stating that tasquinimod, from the Quinoline-3-Carboxamide family is capable of blocking the interaction between calprotectin and TLR4. Hence preventing the cytokine release syndrome, that heralds the functional exhaustion in COVID-19. Early preclinical studies showed that tasquinimod inhibit tumor growth and prevent angiogenesis/cytokine storm. Phase I – III clinical studies in prostate cancer showed it has a good safety profile with good radiologic progression free survival but no effect on overall survival. Rationale/hypothesis: Strategic endeavors have been amplified globally to assess new therapeutic interventions for COVID-19 management – thus the clinical and antiviral efficacy of tasquinimod in COVID-19 remains to be explored. Hence the primary objective of this trial will be to evaluate the efficacy of tasquinimod in the treatment of adult patients with severe COVID-19 infections. Therefore, I hypothesise that among adults with COVID19 infection, tasquinimod will reduce the severe respiratory distress associated with COVID-19 compared to placebo, over a 28-day study period. Method: The setting is in Europe. Design – a randomized, placebo-controlled, phase II double-blinded trial. Trial lasts for 28 days from randomization, Tasquinimod capsule given as 0.5mg daily 1st fortnight, then 1mg daily 2nd fortnight. I0 outcome - assessed using six-point ordinal scale alongside eight 20 outcomes. 125 participants to be enrolled, data collection at baseline and subsequent data points, and safety reporting monitored via serological profile. Significance: This work could potentially establish tasquinimod as an effective and safe therapeutic agent for COVID-19 by reducing the severe respiratory distress, related time to recovery, time on oxygen/admission. It will also drive future research – as in larger multi-centre RCT.

Keywords: Calprotectin, COVID-19, Phase II Trial, Tasquinimod

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Authors: Fekadu Gadissa, Kassahun Tesfaye, Kifle Dagne, Mulatu Geleta

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‘Ethiopian dinich’ also called ‘Ethiopian potato’ is one of the economically important ‘orphan’ edible tuber crops indigenous to Ethiopia. We evaluated the morphological and agronomic traits performances of 174 samples from Ethiopia at multiple locations using 12 qualitative and 16 quantitative traits, recorded at the correct growth stages. We observed several morphotypes and phenotypic variations for qualitative traits along with a wide range of mean performance values for all quantitative traits. Analysis of variance for each quantitative trait showed a highly significant (p<0.001) variation among the collections with eventually non-significant variation for environment-traits interaction for all but flower length. A comparatively high phenotypic and genotypic coefficient of variation was observed for plant height, days to flower initiation, days to 50% flowering and tuber number per hill. Moreover, the variability and coefficients of variation due to genotype-environment interaction was nearly zero for all the traits except flower length. High genotypic coefficients of variation coupled with a high estimate of broad sense heritability and high genetic advance as a percent of collection mean were obtained for tuber weight per hill, number of primary branches per plant, tuber number per hill and number of plants per hill. Association of tuber yield per hectare of land showed a large magnitude of positive phenotypic and genotypic correlation with those traits. Principal components analysis revealed 76% of the total variation for the first six principal axes with high factor loadings again from tuber number per hill, number of primary branches per plant and tuber weight. The collections were grouped into four clusters with the weak region (zone) of origin based pattern. In general, there is high genetic-based variability for ‘Ethiopian dinich’ improvement and conservation. DNA based markers are recommended for further genetic diversity estimation for use in breeding and conservation.

Keywords: agro-morphological traits, Ethiopian dinich, genetic diversity, variance components

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Authors: Kurias George, Ildefonso Cuesta Romeo, Clara Salueña Pérez, Jordi Sole Olle

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With the growing prevalence of wind energy there is a need, for modeling techniques to evaluate the impact of wind farms on meteorology and oceanography. This study presents an approach that utilizes the WRF (Weather Research and Forecasting )with that include a Wind Farm Parametrization model to simulate the dynamics around Parc Tramuntana project, a offshore wind farm to be located near the Gulf of Roses off the coast of Barcelona, Catalonia. The model incorporates parameterizations for wind turbines enabling a representation of the wind field and how it interacts with the infrastructure of the wind farm. Current results demonstrate that the model effectively captures variations in temeperature, pressure and in both wind speed and direction over time along with their resulting effects on power output from the wind farm. These findings are crucial for optimizing turbine placement and operation thus improving efficiency and sustainability of the wind farm. In addition to focusing on atmospheric interactions, this study delves into the wake effects within the turbines in the farm. A range of meteorological parameters were also considered to offer a comprehensive understanding of the farm's microclimate. The model was tested under different horizontal resolutions and farm layouts to scrutinize the wind farm's effects more closely. These experimental configurations allow for a nuanced understanding of how turbine wakes interact with each other and with the broader atmospheric and oceanic conditions. This modified approach serves as a potent tool for stakeholders in renewable energy, environmental protection, and marine spatial planning. environmental protection and marine spatial planning. It provides a range of information regarding the environmental and socio economic impacts of offshore wind energy projects.

Keywords: weather research and forecasting, wind turbine wake effects, environmental impact, wind farm parametrization, sustainability analysis

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Authors: Susan Ka Yee Chow

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Effective clinical preceptorship is affecting students’ competence and fostering their growth in applying theoretical knowledge and skills in clinical settings. Any difference between the expected and actual learning experience will reduce nursing students’ interest in clinical practices and having a negative consequence with their clinical performance. This cross-sectional study is an attempt to compare the differences between preferred and actual preceptorship experience of final year nursing students, and to examine the relationship between the actual preceptorship experience and perceived clinical competence of the students in a tertiary institution. Participants of the study were final year bachelor nursing students of a self-financing tertiary institution in Hong Kong. The instruments used to measure the effectiveness of clinical preceptorship was developed by the participating institution. The scale consisted of five items in a 5-point likert scale. The questions including goals development, critical thinking, learning objectives, asking questions and providing feedback to students. The “Clinical Competence Questionnaire” by Liou & Cheng (2014) was used to examine students’ perceived clinical competences. The scale consisted of 47 items categorized into four domains, namely nursing professional behaviours; skill competence: general performance; skill competence: core nursing skills and skill competence: advanced nursing skills. There were 193 questionnaires returned with a response rate of 89%. The paired t-test was used to compare the differences between preferred and actual preceptorship experiences of students. The results showed significant differences (p<0.001) for the five questions. The mean for the preferred scores is higher than the actual scores resulting statistically significance. The maximum mean difference was accepted goal and the highest mean different was giving feedback. The Pearson Correlation Coefficient was used to examine the relationship. The results showed moderate correlations between nursing professional behaviours with asking questions and providing feedback. Providing useful feedback to students is having moderate correlations with all domains of the Clinical Competence Questionnaire (r=0.269 – 0.345). It is concluded that nursing students do not have a positive perception of the clinical preceptorship. Their perceptions are significantly different from their expected preceptorship. If students were given more opportunities to ask questions in a pedagogical atmosphere, their perceived clinical competence and learning outcomes could be improved as a result.

Keywords: clinical preceptor, clinical competence, clinical practicum, nursing students

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Authors: Dmitrii Glushkov, Aleksandr G. Nigay, Olga S. Yashutina

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In recent years, due to the intensive development of the Arctic and Antarctic areas, the actual task is to develop technology for the effective utilization of solid and liquid combustible wastes in an environment with low temperatures. Firstly, such technology will help to prevent the dumping of waste into the World Ocean and reduce the risks of causing environmental damage to the Far North areas. Secondly, promising actions will help to prepare fuel compositions from the waste in the places of their production. Such kind of fuels can be used as energy resources. It will reduce waste utilization costs when transporting them to the mainland. In the present study, we suggest a solution to the problem of waste utilization by the preparation of gel fuels based on solid and liquid combustible components with the addition of the thickener. Such kind of fuels is characterized by ease of preparation, storage, transportation and use (as energy resources). The main regularities and characteristics of physical and chemical processes are established with varying parameters of gel fuels and heating sources in wide ranges. The obtained results let us conclude about the prospects of gel fuels practical application for combustible wastes utilization. Appropriate technology will be characterized by positive environmental, operational and economic effects. The composition of the gel fuels can vary in a wide range. The fuels preparation based on one type of a combustible liquid or a several liquids mixture with the finely dispersed components addition makes it possible to obtain compositions with predicted rheological, energy or environmental characteristics. Besides, gel fuels have a lower level of the fire hazard compared to common solid and liquid fuels. This makes them convenient for storage and transportation. In such conditions, it is not necessary to transport combustible wastes from the territory of the Arctic and the Antarctic to the mainland for processing, which is now quite an expensive procedure. The research was funded by the Russian Science Foundation (project No. 18-13-00031).

Keywords: combustible liquid waste, gel fuel, ignition and combustion, utilization

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Authors: Elena Masi, Adolfo Morrone

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Migration has recently become a mainstream development sector and is currently at the forefront in institutional and civil society context. However, no consensus exists on how the link between migration and development operates, that is how development is related to migration and how migration can promote development. On one hand, Official Development Assistance is recognized to be one of the levers to development. On the other hand, the debate is focusing on what should be the scope of aid programs targeting migrants groups and in general the migration process. This paper provides a descriptive analysis on how development aid for migration was allocated in the recent past, focusing on the actions that were funded and implemented by the international donor community. In the absence of an internationally shared methodology for defining the boundaries of development aid on migration, the analysis based on lexical hypotheses on the title or on the short description of initiatives funded by several Organization for Economic Co-operation and Development (OECD) countries. Moreover, the research describes and quantifies aid flows for each country according to different criteria. The terms migrant and refugee are used to identify the projects in accordance with the most internationally agreed definitions and only actions in countries of transit or of origin are considered eligible, thus excluding the amount sustained for refugees in donor countries. The results show that the percentage of projects targeting migrants, in terms of amount, has followed a growing trend from 2009 to 2016 in several European countries, and is positively correlated with the flows of migrants. Distinguishing between programs targeting migrants and programs targeting refugees, some specific national features emerge more clearly. A focus is devoted to actions targeting the root causes of migration, showing an inter-sectoral approach in international aid allocation. The analysis gives some tentative solutions to the lack of consensus on language on migration and development aid, and emphasizes the need to internationally agree on a criterion for identifying programs targeting both migrants and refugees, to make action more transparent and in order to develop effective strategies at the global level.

Keywords: migration, official development assistance, ODA, refugees, time series

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Authors: M. Baratieri, M. Beccali, S. Corradino, B. Di Pietra, C. La Grassa, F. Monteleone, G. Morosinotto, G. Puglisi

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The energy renovation of existing buildings represents an important opportunity to increase the decarbonization and the sustainability of urban environments. In this context, the work carried out has the objective of demonstrating the technical and economic feasibility of an energy renovate of a public building destined for offices located on the island of Lampedusa in the Mediterranean Sea. By applying the Italian transpositions of European Directives 2010/31/EU and 2009/28/EC, the building has been renovated from the current energy requirements of 111.7 kWh/m² to 16.4 kWh/m². The result achieved classifies the building as nZEB (nearly Zero Energy Building) according to the Italian national definition. The analysis was carried out using in parallel a quasi-stationary software, normally used in the professional field, and a dynamic simulation model often used in the academic world. The proposed interventions cover the components of the building’s envelope, the heating-cooling system and the supply of energy from renewable sources. In these latter points, the analysis has focused more on assessing two aspects that affect the supply of renewable energy. The first concerns the use of advanced logic control systems for air conditioning units in order to increase photovoltaic self-consumption. With these adjustments, a considerable increase in photovoltaic self-consumption and a decrease in the electricity exported to the Island's electricity grid have been obtained. The second point concerned the evaluation of the building's energy classification considering the real efficiency of the heating-cooling plant. Normally the energy plants have lower operational efficiency than the designed one due to multiple reasons; the decrease in the energy classification of the building for this factor has been quantified. This study represents an important example for the evaluation of the best interventions for the energy renovation of buildings in the Mediterranean Climate and a good description of the correct methodology to evaluate the resulting improvements.

Keywords: heat pumps, HVAC systems, nZEB renovation, renewable energy sources

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Authors: Heri Hermansyah, Annisa Kurnia, A. Vania Anisya, Adi Surjosatyo, Yopi Sunarya, Rita Arbianti, Tania Surya Utami

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Lipase is one of biocatalyst which is applied commercially for the process in industries, such as bioenergy, food, and pharmaceutical industry. Nowadays, biocatalysts are preferred in industries because they work in mild condition, high specificity, and reduce energy consumption (high pressure and temperature). But, the usage of lipase for industry scale is limited by economic reason due to the high price of lipase and difficulty of the separation system. Immobilization of lipase is one of the solutions to maintain the activity of lipase and reduce separation system in the process. Therefore, we conduct a study about lipase immobilization with the adsorption-cross linking method using glutaraldehyde because this method produces high enzyme loading and stability. Lipase is immobilized on different kind of resin with the various functional group. Highest enzyme loading (76.69%) was achieved by lipase immobilized on anion macroporous which have anion functional group (OH^‑). However, highest activity (24,69 U/g support) through olive oil emulsion method was achieved by lipase immobilized on anion macroporous-chitosan which have amino (NH₂) and anion (OH^-) functional group. In addition, it also success to produce biodiesel until reach yield 50,6% through interesterification reaction and after 4 cycles stable 63.9% relative with initial yield. While for Aspergillus, niger lipase immobilized on anion macroporous-kitosan have unit activity 22,84 U/g resin and yield biodiesel higher than commercial lipase (69,1%) and after 4 cycles stable reach 70.6% relative from initial yield. This shows that optimum functional group on support for immobilization with adsorption-cross linking is the support that contains amino (NH₂) and anion (OH^-) functional group because they can react with glutaraldehyde and binding with enzyme prevent desorption of lipase from support through binding lipase with a functional group on support.

Keywords: adsorption-cross linking, immobilization, lipase, resin

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Authors: Pradip Choudhury, Tapobrata Sanyal

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Effectiveness of Jute Geotextiles (JGT) in hill slope management now stands substantiated. The reasons of its efficacy are attributed to its bio-degradability, hygroscopic property and its thickness. Usually open weave JGT is used for slope management. Thickness of JGT helps in reducing the velocity of surface run-off, thus curbing the extent of migration of soil particles detached as a result of kinetic energy of rain-drops and also of wind effects. Initially JGT acts as cover of the surface of slope thus protect movement of loose soil particles. Hygroscopic property of jute effects overland storage of the flow. JGT acts as mulch and creates a congenial micro-climate that fosters quick growth of vegetation on bio-degradation. In fact JGT plays an important role in bio-remediation of slope-erosion problems. Considering the environmental aftermath, JGT is the preferred option in developed countries for surface soil conservation against erosion. In India JGT has not been tried in low temperature zones at high altitudes where temperature goes below the freezing point (even below - 25° Celsius). The behavior of JGT in such low-temperature zones is not precisely known. The 16th BRTF of Project Himank of Border Roads Organization (BRO) has recently taken the initiative to try two varieties of JGT , ie, 292 gsm and 500 gsm at two different places for hill slope management in Leh, a high altitude place of about 2,660 mtrs and 4900 mtrs above MSL respectively in Jammu & Kashmir where erosion is caused more as a result of rapid movement of sand particles due to high wind (wind erosion. Soil particles of the region formed naturally by weathering of fragile rocks are usually loosely bonded (non-cohesive), undergo dissociation with the rise in wind force and kinetic energy of rain drops and are blown away by wind. Open weave JGT interestingly was observed to contain the dissociated soil particles within its pores and lend stability the affected soil mass to a great extent thus preventing its movement by extraneous agents such as wind. The paper delineates about climatic factors, type of JGT used and the prevailing site conditions with an attempt to analyze the mechanism of functioning of JGT in low temperature zones.

Keywords: climate, erosion, jutegeotextile, stabilize

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Authors: Mohamad Mahdi Namdari

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In today's rapidly changing and evolving business competition, companies and organizations require advanced and efficient tools to manage their markets and sales networks. Big data analysis, quick response in competitive markets, process and operations optimization, and forecasting customer behavior are among the concerns of executive managers. Artificial intelligence, as one of the emerging technologies, has provided extensive capabilities in this regard. The use of artificial intelligence in market and sales network management can lead to improved efficiency, increased decision-making accuracy, and enhanced customer satisfaction. Specifically, AI algorithms can analyze vast amounts of data, identify complex patterns, and offer strategic suggestions to improve sales performance. However, many companies are still distant from effectively leveraging this technology, and those that do face challenges in fully exploiting AI's potential in market and sales network management. It appears that the general public's and even the managerial and academic communities' lack of knowledge of this technology has caused the managerial structure to lag behind the progress and development of artificial intelligence. Additionally, high costs, fear of change and employee resistance, lack of quality data production processes, the need for updating structures and processes, implementation issues, the need for specialized skills and technical equipment, and ethical and privacy concerns are among the factors preventing widespread use of this technology in organizations. Clarifying and explaining this technology, especially to the academic, managerial, and elite communities, can pave the way for a transformative beginning. The aim of this research is to elucidate the capacities of artificial intelligence in market and sales network management, identify its opportunities and benefits, and examine the existing challenges and obstacles. This research aims to leverage AI capabilities to provide a framework for enhancing market and sales network performance for managers. The results of this research can help managers and decision-makers adopt more effective strategies for business growth and development by better understanding the capabilities and limitations of artificial intelligence.

Keywords: artificial intelligence, market management, sales network, big data analysis, decision-making, digital marketing

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Authors: Y. Fandja, O. Colot, M. Croquet

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Small and medium-sized firms (SMEs) face difficulties in accessing bank credit. Bank credit is actually the main source of external financing for SMEs. In general, SMEs are risky businesses because of the potential opacity maintained by the leader in the management of affairs, the agency conflicts between business owners and third-party funders and the potential opportunism of the leader due to the incompleteness of the contracts. These elements accentuate the problems of information asymmetries between SMEs and bankers leading to capital rationing. Moreover, the last economic crisis reinforced this rationing of capital. However, a long-term relationship between SMEs and their bank would enable the latter to accumulate a set of relevant information allowing the reduction of information asymmetry and, consequently, the reduction of credit rationing. The objective of this research is to investigate the lived experience of SMEs loan officers in their relationships with their clients in order to understand how these relationships can affect the financing structure of these SMEs. To carry out this research, an Interpretative Phenomenological Analysis is implemented. This approach is part of the constructivist paradigm and refers to the subjective narratives of the individual rather than to an objective description of the facts. The role of the researcher is to explore the lived experience of the interviewees and to try to understand the meaning they give to this experience. Currently, several sixty-minute semi-structured interviews with loan officers for SMEs have been conducted. The analysis of the content of these interviews brought out three main themes. First, the relationship between the credit officer and the company manager is complex because the credit officer is not aware of establishing a personal relationship with his client. Second; the emotional involvement in the bank financing decision is present and third, the trust in the relationship between the credit officer and his client is very important. The originality of this research is to use the interpretative phenomenological analysis more specific to psychology and sociology in order to approach in a different way the problem of the financing of SMEs through their particular relations with the bankers.

Keywords: financing structure, interpretative phenomenological analysis, relationship financing, SME

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Authors: Israel Ekanade, Richard Molapo, Patrick Dzimiri, Isaac Ndlovu

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This study aims to unravel the myth behind animosity towards foreign nationals in South Africa. Systemic violence against foreign African nationals since 2008 to date necessitates critical research with regards to migration issues connected to social upheavals. Extensive research ubiquitously tagged black-on-black violence as xenophobia or Afrophobia. In all, escalation of violence indicates a connotation of belonging. With unemployment rates approaching a crescendo, other vices have also soared in the same regard. As a result, this present generation seems cynical as the South African state has not fulfilled her obligations towards the indigent population; a situation pitching locals against foreigners. Locals have repeatedly blamed African foreign nationals for the economic downturn, using service delivery strikes to express their grievances. These strikes have continued unabatedly over the years but February 2017 marked a turning point in ‘insider-outsider’ relations as the strike was now turned to an anti-immigrant march resulting into widespread violence as the police failed to restore normalcy at some point. Over time, migration has been a harbinger of violence against the foreign black population in South Africa. Our paper encourages the state and civil society to invent new peace-building mechanisms to reduce xenophobic orchestrated violence. Our paper also contends that since the political class has hijacked the situation by using the youths for political propaganda during crises periods, a re-education of the political class and a culture of tolerance is inevitable for peace and harmony between locals and foreigners in post-apartheid South Africa.

Keywords: anti-immigrant march, politics of belonging, service delivery strikes, South Africa

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Authors: Soojin Kim, Yongjae Kim

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Continuous economic downturn and ongoing budget cuts poses higher education with profound challenges which has a direct impact on the collegiate athletic programs. In response to the ever-changing landscape of the fiscal environment, universities seek to boost revenues, resorting to alternative sources of funding. In particular, athletic programs have become increasingly dependent on financial support from their alumni and boosters, which is how athletic departments attempt to offset budget shortfalls and make capital improvements. Although there currently exists three major divisions within National Collegiate Athletic Association (NCAA), the majority of the sport management studies on college sport tend to focus on Division I level. Particularly within the donor motivation literature, a plethora of donor motivation studies exist, but mainly on NCAA Division I athletic programs. Since each athletic department functions differently in a number of different dimensions, while institutional difference can also have a huge impact on athletic donor motivations, the current study attempts to fill this gap that exists in the literature. As such, the purpose of this study was to (I) reexamine the factor structure of the Athletic Donor motivation scale; and (II) identify the prominent athletic donor motives in a NCAA Division II athletic program. For the purpose of this study, a total of 232 actual donors were used for analysis. A confirmatory factor analysis (CFA) was employed to test construct validity, and the reliability of the scale was assessed using Composite Reliability. To identify the prominent motivational factors, the means and standard deviations were examined. Results of this study indicated that Vicarious Achievement, Philanthropy, and Commitment are the three primary motivational factors, while Tangible Benefits, was consistently found as an important motive in prior studies was found low. Such findings highlight the key difference and suggest different salient motivations exist that are specific to the context.

Keywords: college athletics, donor, motivation, NCAA

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Authors: Konstantinos Tolidis

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The mountains are amongst the most fragile environments in the world. The world’s mountain areas cover 24% of the Earth’s land surface and are home to 12% of the global population. A further 14% of the global population is estimated to live in the vicinity of their surrounding areas. As urbanization continues to increase in the world, the mountains are also key centers for recreation and tourism; their attraction is often heightened by their remarkably high levels of biodiversity. Due to the fact that the features in mountain areas vary spatially (development degree, human geography, socio-economic reality, relations of dependency and interaction with other areas-regions), the spatial planning on these areas consists of a crucial process for preserving the natural, cultural and human environment and consists of one of the major processes of an integrated spatial policy. This research has been focused on the spatial decision problem of land use allocation optimization which is an ordinary planning problem on the mountain areas. It is a matter of fact that such decisions must be made not only on what to do, how much to do, but also on where to do, adding a whole extra class of decision variables to the problem when combined with the consideration of spatial optimization. The utility of optimization as a normative tool for spatial problem is widely recognized. However, it is very difficult for planners to quantify the weights of the objectives especially when these are related to mountain areas. Furthermore, the land use allocation optimization problems at mountain areas must be addressed not only by taking into account the general development objectives but also the spatial objectives (e.g. compactness, compatibility and accessibility, etc). Therefore, the main research’s objective was to approach the land use allocation problem by utilizing a hybrid meta-heuristic optimization technique tailored to the mountain areas’ spatial characteristics. The results indicates that the proposed methodological approach is very promising and useful for both generating land use alternatives for further consideration in land use allocation decision-making and supporting spatial management plans at mountain areas.

Keywords: multiobjective land use allocation, mountain areas, spatial planning, spatial decision making, meta-heuristic methods

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Authors: Weichao Yu, Kai Wen, Weihe Huang, Yang Yang, Jing Gong

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Metal-loss corrosion is a major threat to the safety and integrity of gas pipelines as it may result in the burst failures which can cause severe consequences that may include enormous economic losses as well as the personnel casualties. Therefore, it is important to ensure the corroding pipeline integrity and efficiency, considering the value of wall thickness, which plays an important role in the failure probability of corroding pipeline. Actually, the wall thickness is controlled during pipe purchase stage. For example, the API_SPEC_5L standard regulates the allowable tolerance of the wall thickness from the specified value during the pipe purchase. The allowable wall thickness tolerance will be used to determine the wall thickness distribution characteristic such as the mean value, standard deviation and distribution. Taking the uncertainties of the input variables in the burst limit-state function into account, the reliability approach rather than the deterministic approach will be used to evaluate the failure probability. Moreover, the cost of pipe purchase will be influenced by the allowable wall thickness tolerance. More strict control of the wall thickness usually corresponds to a higher pipe purchase cost. Therefore changing the wall thickness tolerance will vary both the probability of a burst failure and the cost of the pipe. This paper describes an approach to optimize the wall thickness tolerance considering both the safety and economy of corroding pipelines. In this paper, the corrosion burst limit-state function in Annex O of CSAZ662-7 is employed to evaluate the failure probability using the Monte Carlo simulation technique. By changing the allowable wall thickness tolerance, the parameters of the wall thickness distribution in the limit-state function will be changed. Using the reliability approach, the corresponding variations in the burst failure probability will be shown. On the other hand, changing the wall thickness tolerance will lead to a change in cost in pipe purchase. Using the variation of the failure probability and pipe cost caused by changing wall thickness tolerance specification, the optimal allowable tolerance can be obtained, and used to define pipe purchase specifications.

Keywords: allowable tolerance, corroding pipeline segment, operation cost, production cost, reliability approach

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Authors: M. G. Cattaneo

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The non-effectiveness of certain codified human rights is particularly apparent with reference to the lack of access to essential drugs in developing countries, which represents a breach of the human right to receive adequate health assistance. This paper underlines the conflict and the legal contradictions between human rights, namely health rights, international Intellectual Property Rights, in particular patent law, as well as international trade law. The paper discusses the crucial links between R&D costs for innovation, patents and new medical drugs, with the goal of reformulating the hierarchies of priorities and of interests at stake in the international intellectual property (IP) law system. Different from what happens today, International patent law should be a legal instrument apt at rebalancing an axiological asymmetry between the (conflicting) needs at stake The core argument in the paper is the proposal of an alternative pathway, namely a feasible proposal for a patent law reform. IP laws tend to balance the benefits deriving from innovation with the costs of the provided monopoly, but since developing countries and industrialized countries are in completely different political and economic situations, it is necessary to (re)modulate such exchange according to the different needs. Based on this critical analysis, the paper puts forward a proposal, called Trading Time for Space (TTS), whereby a longer time for patent exclusive life in western countries (Time) is offered to the patent holder company, in exchange for the latter selling the medical drug at cost price in developing countries (Space). Accordingly, pharmaceutical companies should sell drugs in developing countries at the cost price, or alternatively grant a free license for the sale in such countries, without any royalties or fees. However, such social service shall be duly compensated. Therefore, the consideration for such a service shall be an extension of the temporal duration of the patent’s exclusive in the country of origin that will compensate the reduced profits caused by the supply at the price cost in developing countries.

Keywords: global health, global justice, patent law reform, access to drugs

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Authors: Scott Nielsen, Luca Longanesi, Chris Chuck

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Palm oil is obtained from the flesh and kernel of the fruit of oil palms and is the most productive and inexpensive oil crop. The global demand for palm oil is approximately 75 million metric tonnes, a 29% increase in global production of palm oil since 2016. This expansion of oil palm cultivation has resulted in mass deforestation, vast biodiversity destruction and increasing net greenhouse gas emissions. One possible alternative is to produce a saturated oil, similar to palm, from microbes such as oleaginous yeast. The yeasts can be cultured on sugars derived from second-generation sources and do not compete with tropical forests for land. One highly promising oleaginous yeast for this application is Metschnikowia pulcherrima. However, recent techno-economic modeling has shown that cell lysis and standard lipid extraction are major contributors to the cost of the oil. Typical cell disruption techniques to extract either single cell oils or proteins have been based around bead-beating, homogenization and acid lysis. However, these can have a detrimental effect on lipid quality and are energy-intensive. In this study, a vortex separator, which produces high sheer with minimal energy input, was investigated as a potential low energy method of lysing cells. This was compared to four more traditional methods (thermal lysis, acid lysis, alkaline lysis, and osmotic lysis). For each method, the yeast loading was also examined at 1 g/L, 10 g/L and 100 g/L. The quality of the cell disruption was measured by optical cell density, cell counting and the particle size distribution profile comparison over a 2-hour period. This study demonstrates that the vortex separator is highly effective at lysing the cells and could potentially be used as a simple apparatus for lipid recovery in an oleaginous yeast process. The further development of this technology could potentially reduce the overall cost of microbial lipids in the future.

Keywords: palm oil substitute, metschnikowia pulcherrima, cell disruption, cell lysis

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Authors: Masaki Ohno, Cervinia Manalo, Tetsuji Okuda, Satoshi Nakai, Wataru Nishijima

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Reverse osmosis (RO) membranes have been widely used for desalination to purify water for drinking and other purposes. Although at present most RO membranes have no resistance to chlorine, chlorine-resistant membranes are being developed. Therefore, direct chlorine treatment or chlorine washing will be an option in preventing biofouling on chlorine-resistant membranes. Furthermore, if particle accumulation control is possible by using chlorine washing, expensive pretreatment for particle removal can be removed or simplified. The objective of this study was to determine the effective hypochlorite washing condition required for controlling biofilm formation and inorganic particle accumulation on RO membrane in a continuous flow channel with RO membrane and spacer. In this study, direct chlorine washing was done by soaking fouled RO membranes in hypochlorite solution and fluorescence intensity was used to quantify biofilm on the membrane surface. After 48 h of soaking the membranes in high fouling potential waters, the fluorescence intensity decreased to 0 from 470 using the following washing conditions: 10 mg/L chlorine concentration, 2 times/d washing interval, and 30 min washing time. The chlorine concentration required to control biofilm formation decreased as the chlorine concentration (0.5–10 mg/L), the washing interval (1–4 times/d), or the washing time (1–30 min) increased. For the sample solutions used in the study, 10 mg/L chlorine concentration with 2 times/d interval, and 5 min washing time was required for biofilm control. The optimum chlorine washing conditions obtained from soaking experiments proved to be applicable also in controlling biofilm formation in continuous flow experiments. Moreover, chlorine washing employed in controlling biofilm with suspended particles resulted in lower amounts of organic (0.03 mg/cm²) and inorganic (0.14 mg/cm²) deposits on the membrane than that for sample water without chlorine washing (0.14 mg/cm² and 0.33 mg/cm², respectively). The amount of biofilm formed was 79% controlled by continuous washing with 10 mg/L of free chlorine concentration, and the inorganic accumulation amount decreased by 58% to levels similar to that of pure water with kaolin (0.17 mg/cm²) as feed water. These results confirmed the acceleration of particle accumulation due to biofilm formation, and that the inhibition of biofilm growth can almost completely reduce further particle accumulation. In addition, effective hypochlorite washing condition which can control both biofilm formation and particle accumulation could be achieved.

Keywords: reverse osmosis, washing condition optimization, hypochlorous acid, biofouling control

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Authors: Roberto Coppo, Francesca Orso, Daniela Dettori, Elena Quaglino, Lei Nie, Mehran M. Sadeghi, Daniela Taverna

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Malignant melanoma is currently the fifth most common cancer in the white population and it is fatal in its metastatic stage. Several research studies in recent years have provided evidence that cancer initiation and progression are driven by genetic alterations of the tumor and paracrine interactions between tumor and microenvironment. Scattered data show that the Endothelial and Smooth muscle cell-Derived Neuropilin-like molecule (ESDN) controls cell proliferation and movement of stroma and tumor cells. To investigate the role of ESDN in the tumor microenvironment during melanoma progression, murine melanoma cells (B16 or B16-F10) were injected in ESDN knockout mice in order to evaluate how the absence of ESDN in stromal cells could influence melanoma progression. While no effect was found on primary tumor growth, increased cell extravasation and lung metastasis formation was observed in ESDN knockout mice compared to wild type controls. In order to understand how cancer cells cross the endothelial barrier during metastatic dissemination in an ESDN-null microenvironment, structure, and permeability of lung blood vessels were analyzed. Interestingly, ESDN knockout mice showed structurally altered and more permeable vessels compared to wild type animals. Since cell surface molecules mediate the process of tumor cell extravasation, the expression of a panel of extravasation-related ligands and receptors was analyzed. Importantly, modulations of N-cadherin, E-selectin, ICAM-1 and VAP-1 were observed in ESDN knockout endothelial cells, suggesting the presence of a favorable tumor microenvironment which facilitates melanoma cell extravasation and metastasis formation in the absence of ESDN. Furthermore, a potential contribution of immune cells in tumor dissemination was investigated. An increased recruitment of macrophages in the lungs of ESDN knockout mice carrying subcutaneous B16-F10 tumors was found. In conclusion, our data suggest a functional role of ESDN in the tumor microenvironment during melanoma progression and the identification of the mechanisms that regulate tumor cell extravasation could lead to the development of new therapies to reduce metastasis formation.

Keywords: melanoma, tumor microenvironment, extravasation, cell surface molecules

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Authors: Desiree Vandenberghe, Johan Albrecht

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Non-communicable diseases (NCDs) are responsible for the vast majority of deaths in the European Union (EU) and represent a large share of total health care spending. A future increase in this health and financial burden is likely to be driven by population ageing, lifestyle changes and technological advances in medicine. Without adequate prevention measures, this burden can severely threaten population health and economic development. To tackle this challenge, a correct assessment of the current burden of NCDs is required, as well as a projection of potential increases of this burden. The contribution of this paper is to offer perspective on the evolution of the NCD burden towards the future and to give an indication of the potential of prevention policy. A Non-Homogenous, Semi-Markov model for the EU was constructed, which allowed for a projection of the cost burden for the four main NCDs (cancer, cardiovascular disease, chronic respiratory disease and diabetes mellitus) towards 2030 and 2050. This simulation is done based on multiple baseline scenarios that vary in demand and supply factors such as health status, population structure, and technological advances. Finally, in order to assess the potential of preventive measures to curb the cost explosion of NCDs, a simulation is executed which includes increased efforts for preventive health care measures. According to the Markov model, by 2030 and 2050, total costs (direct and indirect costs) in the EU could increase by 30.1% and 44.1% respectively, compared to 2015 levels. An ambitious prevention policy framework for NCDs will be required if the EU wants to meet this challenge of rising costs. To conclude, significant cost increases due to Non-Communicable Diseases are likely to occur due to demographic and lifestyle changes. Nevertheless, an ambitious prevention program throughout the EU can aid in making this cost burden manageable for future generations.

Keywords: non-communicable diseases, preventive health care, health policy, Markov model, scenario analysis

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Authors: Luis Amador Jimenez, Md. Shohel Amin

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Pavement performance models are based on projections of observed traffic loads, which makes uncertain to study funding strategies in the long run if history does not repeat. Neural networks can be used to estimate deterioration rates but the learning rate and momentum have not been properly investigated, in addition, economic evolvement could change traffic flows. This study addresses both issues through a case study for roads of Montreal that simulates traffic for a period of 50 years and deals with the measurement error of the pavement deterioration model. Travel demand models are applied to simulate annual average daily traffic (AADT) every 5 years. Accumulated equivalent single axle loads (ESALs) are calculated from the predicted AADT and locally observed truck distributions combined with truck factors. A back propagation Neural Network (BPN) method with a Generalized Delta Rule (GDR) learning algorithm is applied to estimate pavement deterioration models capable of overcoming measurement errors. Linear programming of lifecycle optimization is applied to identify M&R strategies that ensure good pavement condition while minimizing the budget. It was found that CAD 150 million is the minimum annual budget to good condition for arterial and local roads in Montreal. Montreal drivers prefer the use of public transportation for work and education purposes. Vehicle traffic is expected to double within 50 years, ESALS are expected to double the number of ESALs every 15 years. Roads in the island of Montreal need to undergo a stabilization period for about 25 years, a steady state seems to be reached after.

Keywords: pavement management system, traffic simulation, backpropagation neural network, performance modeling, measurement errors, linear programming, lifecycle optimization

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Authors: Rabah Iratni, Husain El Hasasna, Khawlah Athamneh, Halima Al Sameri, Nehla Benhalilou, Asma Al Rashedi

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Background: Cancer therapies have witnessed great advances in the recent past, however, cancer continues to be a leading cause of death, with colorectal cancer being the fourth cause of cancer-related deaths. Colorectal cancer affects both sexes equally with poor survival rate once it metastasizes. Phytochemicals, which are plant derived compounds, have been on a steady rise as anti-cancer drugs due to the accumulation of evidences that support their potential. Here, we investigated the anticancer effect of Rhus coriaria on colon cancer cells. Material and Method: Human colon cancer HT-29 cell line was used. Protein expression and protein phosphorylation were examined using Western blotting. Transcription activity was measure using Quantitative RT-PCR. Human tumoral clonogenic assay was used to assess cell survival. Senescence was assessed by the senescence-associated beta-galactosidase assay. Results: Rhus coriaria extract (RCE) was found to significantly inhibit the viability and colony growth of human HT-29 colon cancer cells. RCE induced senescence and cell cycle arrest at G1 phase. These changes were concomitant with upregulation of p21, p16, downregulation of cyclin D1, p27, c-myc and expression of Senescence-associated-β-Galactosidase activity. Moreover, RCE induced non-canonical beclin-1independent autophagy and subsequent apoptotic cell death through activation of activation caspase 8 and caspase 7. The blocking of autophagy by 3-methyladenine (3-MA) or chloroquine (CQ) reduced RCE-induced cell death. Further, RCE induced DNA damage, reduced mutant p53 protein level and downregulated phospho-AKT and phospho-mTOR, events that preceded autophagy. Mechanistically, we found that RCE inhibited the AKT and mTOR pathway, a regulator of autophagy, by promoting the proteasome-dependent degradation of both AKT and mTOR proteins. Conclusion: Our findings provide strong evidence that Rhus coriaria possesses strong anti-colon cancer activity through induction of senescence and autophagic cell death, making it a promising alternative or adjunct therapeutic candidate against colon cancer.

Keywords: autophagy, proteasome degradation, senescence, mTOR, apoptosis, Beclin-1

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Authors: Tanvir A. Uddin, Blake Goud

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Emerging trends in FinTech-enabled alternative finance, which includes channels and instruments emerging outside the traditional financial system, heralds unprecedented opportunities to improve financial intermediation and increase access to finance. With widespread criticism of the mainstream Islamic banking and finance sector as either mimicking the conventional system, failing to achieve inclusive growth or both, industry stakeholders are turning to technology to show that finance can be done differently. This paper will outline the critical elements for successful deployment of technology to maximize benefit and minimize potential for harm from introduction of Islamic FinTech and propose recommendations for Islamic financial institutions, FinTech companies, regulators and other stakeholders who are integrating or who are considering introducing FinTech solutions. The paper will present an overview of literature, present relevant case studies and summarize the lessons from interviews conducted with Islamic FinTech founders from around the world. With growing central bank concerns about leveraged loans and ballooning private credit markets globally (estimated at $1.4 trillion), current and future Islamic FinTech operators are at risk of contributing to the problems they aim to solve by operating in a 'shadow banking' system. The paper will show that by systematising a robust theory of change linked to positive outcomes, utilising objective impact frameworks (e.g., the Impact Measurement Project) and instilling a risk management culture that is proactive about potential social harm (e.g., irresponsible lending), FinTech can enable the Islamic finance industry to support positive social impact and minimize harm in support of the maqasid. The adoption of FinTech within the Islamic finance context is still at a nascent stage and the recommendations we provide based on the limited experience to date will help address some of the major cross-cutting issues related to FinTech. Further research will be needed to elucidate in more detail issues relating to individual sectors and countries within the broader global Islamic finance industry.

Keywords: alternative finance, FinTech, Islamic finance, maqasid, theory of change

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Authors: Eliane Cristina De Carvalho Mendoza Meza

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The Brazilian Federal Constitution from 1988 innovated with decentralized management, sharing the decision process among the federal government, states, and municipality (federalism). This innovation gave the opportunity to the civil society participates in the public policy agenda, including the municipal one; the state recognized that new actors were needed now it has been one more actor and not the only one. It was in this context that the woman’s Policy Secretaries were created in the three levels of government: federal, state and municipal. It intend to reduce the historical and social differences between men and women, especially in the poorest municipalities, working in a network basis with other secretaries, governmental institutions and non-governmental organizations to promote actions that can result in benefits and empowerment for women. In addition, they promote actions to protect them from domestic violence and to help them to learn how generate income. It was not a calm process, women have been fighting for their rights since the 1970s and despite the gender equality was recognized in the Federal Constitution of 1988, just in 2013 it was possible to see a real growth in the creation of municipal Women’s Policy Secretary. In 2009, just 6.5% of the cities in Brazil had implemented the Secretary; in 2013, it was 11%. The municipality realized that the gender issue was in reality a public problem, so the municipal agenda incorporated it and transformed in public policy, creating the municipal Women’s Policy Secretary. The introduction of a gender policy in Brazilian municipalities shows us that the female citizens are treated as political subjects and it is the first step to try to compensate inequality between men and women in the local level. It becomes more important when the Brazilian federalism is analyzed. In Brazil, the federal government controls the municipalities’ budgets to implement federal public policies and others federal interests, so having a public policy of gender approved by the actors in the local government with so little freedom to manage is something very important. It is necessary mark some points: taking a gender policy to the poorest cities is a form to protect all citizens with no distinction, men and women, as recommended in the Federal Constitution; not all problems in a city center in the municipal agenda, this only happens when a problem is perceived as an issue, it means the women situation was perceived as important, so that it became a public policy; at least, the gender public policy intend to emancipate and contemplate the empowerment of women.

Keywords: federalism, gender, municipal agenda, social participation

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Authors: Shujun Xie, Shirong Zhang, Shenglin Ma

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

Keywords: inflammasome, afatinib, inflammation, tyrosine kinase inhibitor

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