Search results for: disruption
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 312

Search results for: disruption

132 The Impact of Diesel Exhaust Particles on Tight Junction Proteins on Nose and Lung in a Mouse Model

Authors: Kim Byeong-Gon, Lee Pureun-Haneul, Hong Jisu, Jang An-Soo

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Background: Diesel exhaust particles (DEPs) lead to trigger airway hyperresponsiveness (AHR) and airway dysfunction or inflammation in respiratory systems. Whether tight junction protein changes can contribute to development or exacerbations of airway diseases remain to be clarified. Objective: The aim of this study was to observe the effect of DEP on tight junction proteins in one airway both nose and lung in a mouse model. Methods: Mice were treated with saline (Sham) and exposed to 100 μg/m³ DEPs 1 hour a day for 5 days a week for 4 weeks and 8 weeks in a closed-system chamber attached to a ultrasonic nebulizer. Airway hyperresponsiveness (AHR) was measured and bronchoalveolar lavage (BAL) fluid, nasal lavage (NAL) fluid, lung and nasal tissue was collected. The effects of DEP on tight junction proteins were estimated using western blot, immunohistochemical in lung and nasal tissue. Results: Airway hyperresponsiveness and number of inflammatory cells were higher in DEP exposure group than in control group, and were higher in 4 and 8 weeks model than in control group. The expression of tight junction proteins CLND4, -5, and -17 in both lung and nasal tissue were significantly increased in DEP exposure group than in the control group. Conclusion: These results suggesting that CLDN4, -5 and -17 may be involved in the airway both nose and lung, suggesting that air pollutants cause to disruption of epithelial and endothelial cell barriers. Acknowledgment: This research was supported by Korea Ministry of Environment (MOE) as 'The Environmental Health Action Program' (2016001360009) and Soonchunhyang University Research Fund.

Keywords: diesel exhaust particles, air pollutant, tight junction, Claudin, Airway inflammation

Procedia PDF Downloads 113
131 Interaction of GCN5L1 with WHAMM and KIF5B Regulates Autolysosome Tubulation

Authors: Allen Seylani

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Lysosome-dependent autophagy is a nutrient-deprivation-induced evolutionarily conserved intracellular recycling program that sequestrates intracellular cargo into autophagosomes (AP), which then fuse with lysosomes to form autolysosomes (ALs) for cargo digestion. To restore free lysosomes, autophagic lysosome reformation (ALR) is initiated by extrusion of tubular structures from autolysosomes at the final stage of autophagy, in a process called lysosomal tubulation (LT). This project aimed to investigate the molecular mechanism of GCN5L1 in LT and the following lysosomal signaling. GCN5L1 belongs to the BORC multiprotein complexes and is involved in controlling lysosomal trafficking; however, the effect of GCN5L1 on lysosome tubulation remains largely unknown. Genetic ablation of GCN5L1 in the mouse primary hepatocytes showed dramatically increased autolysosomes (ALs), decreased lysosome regeneration and absence of lysosomal tubulation. This phenotype suggests the possibility of disruption in lysosome tubulation, which results in the disturbance of the overall lysosome homeostasis. The formation of tubulars from ALs requires kinesin motor protein KIF5B. Immunoprecipitation was employed and confirmed the interaction of GCN5L1 with the ARL8B-KIF5B complex, which recruited KIF5B to ALs. At the same time, GCN5L1 interacted with WHAMM, which promotes the actin nucleation factor, which brings actin cytoskeleton to ALs and initiates LT. Furthermore, impaired LT in GCN5L1 deficient hepatocytes was restored by overexpression of GCN5L1, and this rescue effect was attenuated by knockdown of KIF5B. Additionally, lysosomal mTORC1 activity was upregulated in GCN5L1-/- hepatocytes, while inhibition of mTORC1 abrogated the GCN5L1 mediated rescue of LT in knockout hepatocytes. Altogether these findings revealed a novel mechanism of ALR, in which a simultaneous interaction of GCN5L1 with KIF5B and WHAMM is required for LT and downstream mTORC1 signaling.

Keywords: autophagy, autolysosome, GCN5L1, lysosome

Procedia PDF Downloads 127
130 Cerebrum Maturity Damage Induced by Fluoride in Suckling Mice

Authors: Hanen Bouaziz, Françoise Croute, Najiba Zeghal

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In order to investigate the toxic effects of fluoride on cerebrum maturity of suckling mice, we treated adult female mice of Swiss Albinos strain by 500 ppm NaF in their drinking water from the 15th day of pregnancy until the day 14 after delivery. All mice were sacrificed on day 14 after parturition. During treatment, levels of thiobarbituric acid reactive substances, the marker of lipid peroxidation extend, increased, while the activities of the antioxidant enzymes such as glutathione peroxidase, superoxide dismutase and catalase and the level of glutathione decreased significantly in cerebellum compared with those of the control group. These results suggested that fluoride enhanced oxidative stress, thereby disturbing the antioxidant defense of nursing pups. In addition, acetylcholinesterase activity in cerebellum was inhibited after treatment with fluoride. In cerebellum of mice, migration of neurons from the external granular layer to the internal granular layer occurred postnatally. Key guidance signals to these migrating neurons were provided by laminin, an extracellular matrix protein fixed to the surface of astrocytes. In the present study, we examined the expression and distribution of laminin in cerebellum of 14-day-old mice. Immunoreactive laminin was disappeared by postnatal day 14 in cerebellum parenchyma of control pups and was restricted to vasculature despite the continued presence of granular cells in the external granular layer. In contrast, in cerebellum of NaF treated pups, laminin was deposited in organised punctuate clusters in the molecular layer. These data indicated that the disruption of laminin distribution might play a major role in the profound derangement of neuronal migration observed in cerebellum of NaF treated pups.

Keywords: acetylcholinesterase activity, cerebellum, laminin, oxidative stress, suckling mice

Procedia PDF Downloads 371
129 The Politics of Disruption: Disrupting Polity to Influence Policy in Nigeria

Authors: Okechukwu B. C. Nwankwo

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The surge of social protests sweeping through the globe is a contemporary phenomenon. Yet the phenomenon in itself is not new. Thus, various scholars have over the years developed conceptual frameworks for evaluating it. Adopting and adapting some of these frameworks this paper begins from a purely theoretical perspective exploring the concept and content of social protest within the specific context of Nigeria. It proceeds to build a typology of the phenomenon in terms of form, actors, origin, character, organisation, goal, dynamics, outcome and a whole lot of other variables that are context relevant for evaluating it in an operationally useful manner. The centrality of the context in which protest evolves is demonstrated. Adopting Easton’s systems theory, the paper builds on the assumption that protests emerge whenever and wherever political institutions and structures prove unable or unwilling to transform inputs in form of basic demands into outputs in form of responsive policies. It argues that protests in Nigeria are simply the crystallisation of opposition in the streets. Protests are thus extra-institutional politics. This is usually the case, as elsewhere, where there is no functional institutionalised opposition. Noting that protest, disruptive or otherwise, is an influence strategy, it argues that every single protest is a new opportunity for reform, for reorganisation of state capacities, for modifying rights and obligation of citizens and government to each other. Each reform outcome is, however, only a temporal antecedent. Its extensity gives signal for the next similar protest event. Through providing evidence on how protests in Nigeria create opportunity for reform, for more accountable, more effective governance, the paper shows the positive impact of protests and its importance even in the consolidation effort for the nation’s nascent democracy. Data on protest events will be based on media reports, especially print media.

Keywords: democracy, dialectics, social protest, reform

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128 Impact of Forced Displacement on Place Attachment and Home Perception of Internally Displaced Turkish Cypriots

Authors: Makbule Oktay

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Home is a significant entity in people’s lives. It is a place that provides shelter to people and a place to which one feels a sense of attachment and belonging. It is an entity that people develop feelings and meaning to it. People – place bond, or in other words place attachment, and home perception might alter as a consequence of lifetime experiences. Thus, forced displacement appears as a dramatic experience for people who lose their homes, belongings and communities. It impacts people who involuntarily leave their homes and belongings behind, experience physical, social, cultural and economic disruption and are forced to settle in an unfamiliar environment. Place attachment and home perception of internally displaced people who involuntarily leave their homes might be different from those who haven’t experience forced displacement. Although place attachment, meaning of home and forced displacement are the subjects that have been broadly studied, there is a lack of studies which question the relation between the three subjects in general and on Turkish Cypriot case in particular. Considering this, it is the aim of this paper to investigate the impact of forced displacement to internally displaced people’s attachment to a particular place and home perception. To do so, the study focuses on internally displaced Turkish Cypriots who have been internally displaced as a result of conflict. Interview and questionnaire as two of the commonly used techniques in the place attachment and home perception studies have been used in this study too. The results of the study indicate that internal displacement has an apparent impact on place attachment of forcibly displaced people. As a consequence of longstanding displacement, forcibly displaced people developed multiple attachments. Compared to people who have not experienced displacement, forcibly displaced people have low attachments. Forced displacement does not strongly impact the home perception in terms of meaning of home in longstanding displacement situations even though displacement-related meanings of home exist.

Keywords: forcibly displaced people, home perception, internal displacement, place attachment, Turkish Cypriots

Procedia PDF Downloads 173
127 Endocrine Disruptors Effects on the 20-Hydroxyecdysone Concentration and the Vitellogenin Gene Expression in Gammarus sp.

Authors: Eric Gismondi, Aurelie Bigot-Clivot

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Endocrine disruptors (EDCs) are well known to disrupt the development and the reproduction of exposed organisms. Although this point has been studied in vertebrate models, the limited knowledge of the endocrine system of invertebrates makes the evaluation of EDCs effects difficult. However, invertebrates represent the major part of aquatic ecosystems, such as amphipods Gammaridea, which are crucial for their functioning (e.g., litter degradation, food resource). Moreover, gammarids are hosts of parasites such as vertically-transmitted microsporidia (microsporidia VT), which could be confounding factors in assessment of EDC effects. Indeed, some microsporidia VT could have endocrine effects by their own present in the host since it was observed for example, a feminization of juvenile males, which become phenotypic females. This work evaluated the impact of ethinylestradiol (EE₂, estrogenic), cyproterone acetate (CPA, anti-androgenic), 4-hydroxytamoxifen (4HT, anti-estrogenic) and 17α-methyltestosterone (17MT - androgenic), on the 20-hydroxyecdysone concentration (i.e. 20HE - molt process) and the vitellogenin gene expression (i.e. reproduction) in the freshwater amphipod Gammarus pulex, after a 96h laboratory exposure. In addition, the presence of microsporidia VT was verified in order to analyze the effect of this confounding factor. Results of this study shown that, although endocrine systems of invertebrates and vertebrates are different, EDCs proved in vertebrates could also affect biological functions hormonally controlled in invertebrates. Indeed, the molt process of crustaceans was disrupted in the first stage (i.e. 20-HE concentration) and therefore, could affect, at the long term, the population dynamic. In addition, it was observed that G. pulex was differently impacted according to the gender and parasitism, which underline the importance to take into account these confounding factors to better evaluate the EDCs impact on invertebrate populations.

Keywords: endocrine disruption, gammarus sp., molt, parasitism

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126 Disrupted or Discounted Cash Flow: Impact of Digitisation on Business Valuation

Authors: Matthias Haerri, Tobias Huettche, Clemens Kustner

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This article discusses the impact of digitization on business valuation. In order to become and remain ‘digital’, investments are necessary whose return on investment (ROI) often remains vague. This uncertainty is contradictory for a valuation, that rely on predictable cash flows, fixed capital structures and the steady state. However digitisation does not make a company valuation impossible, but traditional approaches must be reconsidered. The authors identify four areas that are to be changing: (1) Tools instead of intuition - In the future, company valuation will neither be art nor science, but craft. This does not require intuition, but experience and good tools. Digital evaluation tools beyond Excel will therefore gain in importance. (2) Real-time instead of deadline - At present, company valuations are always carried out on a case-by-case basis and on a specific key date. This will change with the digitalization and the introduction of web-based valuation tools. Company valuations can thus not only be carried out faster and more efficiently, but can also be offered more frequently. Instead of calculating the value for a previous key date, current and real-time valuations can be carried out. (3) Predictive planning instead of analysis of the past - Past data will also be needed in the future, but its use will not be limited to monovalent time series or key figure analyses. With pictures of ‘black swans’ and the ‘turkey illusion’ it was made clear to us that we build forecasts on too few data points of the past and underestimate the power of chance. Predictive planning can help here. (4) Convergence instead of residual value - Digital transformation shortens the lifespan of viable business models. If companies want to live forever, they have to change forever. For the company valuation, this means that the business model valid on the valuation date only has a limited service life.

Keywords: business valuation, corporate finance, digitisation, disruption

Procedia PDF Downloads 100
125 Advanced Biosensor Characterization of Phage-Mediated Lysis in Real-Time and under Native Conditions

Authors: Radka Obořilová, Hana Šimečková, Matěj Pastucha, Jan Přibyl, Petr Skládal, Ivana Mašlaňová, Zdeněk Farka

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Due to the spreading of antimicrobial resistance, alternative approaches to combat superinfections are being sought, both in the field of lysing agents and methods for studying bacterial lysis. A suitable alternative to antibiotics is phage therapy and enzybiotics, for which it is also necessary to study the mechanism of their action. Biosensor-based techniques allow rapid detection of pathogens in real time, verification of sensitivity to commonly used antimicrobial agents, and selection of suitable lysis agents. The detection of lysis takes place on the surface of the biosensor with immobilized bacteria, which has the potential to be used to study biofilms. An example of such a biosensor is surface plasmon resonance (SPR), which records the kinetics of bacterial lysis based on a change in the resonance angle. The bacteria are immobilized on the surface of the SPR chip, and the action of phage as the mass loss is monitored after a typical lytic cycle delay. Atomic force microscopy (AFM) is a technique for imaging of samples on the surface. In contrast to electron microscopy, it has the advantage of real-time imaging in the native conditions of the nutrient medium. In our case, Staphylococcus aureus was lysed using the enzyme lysostaphin and phage P68 from the familyPodoviridae at 37 ° C. In addition to visualization, AFM was used to study changes in mechanical properties during lysis, which resulted in a reduction of Young’s modulus (E) after disruption of the bacterial wall. Changes in E reflect the stiffness of the bacterium. These advanced methods provide deeper insight into bacterial lysis and can help to fight against bacterial diseases.

Keywords: biosensors, atomic force microscopy, surface plasmon resonance, bacterial lysis, staphylococcus aureus, phage P68

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124 Accuracy of Peak Demand Estimates for Office Buildings Using Quick Energy Simulation Tool

Authors: Mahdiyeh Zafaranchi, Ethan S. Cantor, William T. Riddell, Jess W. Everett

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The New Jersey Department of Military and Veteran’s Affairs (NJ DMAVA) operates over 50 facilities throughout the state of New Jersey, U.S. NJDMAVA is under a mandate to move toward decarbonization, which will eventually include eliminating the use of natural gas and other fossil fuels for heating. At the same time, the organization requires increased resiliency regarding electric grid disruption. These competing goals necessitate adopting the use of on-site renewables such as photovoltaic and geothermal power, as well as implementing power control strategies through microgrids. Planning for these changes requires a detailed understanding of current and future electricity use on yearly, monthly, and shorter time scales, as well as a breakdown of consumption by heating, ventilation, and air conditioning (HVAC) equipment. This paper discusses case studies of two buildings that were simulated using the QUick Energy Simulation Tool (eQUEST). Both buildings use electricity from the grid and photovoltaics. One building also uses natural gas. While electricity use data are available in hourly intervals and natural gas data are available in monthly intervals, the simulations were developed using monthly and yearly totals. This approach was chosen to reflect the information available for most NJ DMAVA facilities. Once completed, simulation results are compared to metrics recommended by several organizations to validate energy use simulations. In addition to yearly and monthly totals, the simulated peak demands are compared to actual monthly peak demand values. The simulations resulted in monthly peak demand values that were within 30% of the measured values. These benchmarks will help to assess future energy planning efforts for NJ DMAVA.

Keywords: building energy modeling, eQUEST, peak demand, smart meters

Procedia PDF Downloads 42
123 Raman Spectroscopic of Cardioprotective Mechanism During the Metabolic Inhibition of Heart Cells

Authors: A. Almohammedi, A. J. Hudson, N. M. Storey

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Following ischaemia/reperfusion injury, as in a myocardial infraction, cardiac myocytes undergo oxidative stress which leads to several potential outcomes including; necrotic or apoptotic cell death or dysregulated calcium homeostasis or disruption of the electron transport chain. Several studies have shown that nitric oxide donors protect cardiomyocytes against ischemia and reperfusion. However until present, the mechanism of cardioprotective effect of nitric oxide donor in isolated ventricular cardiomyocytes is not fully understood and has not been investigated before using Raman spectroscopy. For these reasons, the aim of this study was to develop a novel technique, pre-resonance Raman spectroscopy, to investigate the mechanism of cardioprotective effect of nitric oxide donor in isolated ventricular cardiomyocytes exposed to metabolic inhibition and re-energisation. The results demonstrated the first time that Raman microspectroscopy technique has the capability to monitor the metabolic inhibition of cardiomyocytes and to monitor the effectiveness of cardioprotection by nitric oxide donor prior to metabolic inhibition of cardiomyocytes. Metabolic inhibition and reenergisation were used in this study to mimic the low and high oxygen levels experienced by cells during ischaemic and reperfusion treatments. A laser wavelength of 488 nm used in this study has been found to provide the most sensitive means of observe the cellular mechanisms of myoglobin during nitric oxide donor preconditioning, metabolic inhibition and re-energisation and did not cause any damage to the cells. The data also highlight the considerably different cellular responses to metabolic inhibition to ischaemia. Moreover, the data has been shown the relationship between the release of myoglobin and chemical ischemia where that the release of myoglobin from the cell only occurred if a cell did not recover contractility.

Keywords: ex vivo biospectroscopy, Raman spectroscopy, biophotonics, cardiomyocytes, ischaemia / reperfusion injury, cardioprotection, nitric oxide donor

Procedia PDF Downloads 326
122 Building Transparent Supply Chains through Digital Tracing

Authors: Penina Orenstein

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In today’s world, particularly with COVID-19 a constant worldwide threat, organizations need greater visibility over their supply chains more than ever before, in order to find areas for improvement and greater efficiency, reduce the chances of disruption and stay competitive. The concept of supply chain mapping is one where every process and route is mapped in detail between each vendor and supplier. The simplest method of mapping involves sourcing publicly available data including news and financial information concerning relationships between suppliers. An additional layer of information would be disclosed by large, direct suppliers about their production and logistics sites. While this method has the advantage of not requiring any input from suppliers, it also doesn’t allow for much transparency beyond the first supplier tier and may generate irrelevant data—noise—that must be filtered out to find the actionable data. The primary goal of this research is to build data maps of supply chains by focusing on a layered approach. Using these maps, the secondary goal is to address the question as to whether the supply chain is re-engineered to make improvements, for example, to lower the carbon footprint. Using a drill-down approach, the end result is a comprehensive map detailing the linkages between tier-one, tier-two, and tier-three suppliers super-imposed on a geographical map. The driving force behind this idea is to be able to trace individual parts to the exact site where they’re manufactured. In this way, companies can ensure sustainability practices from the production of raw materials through the finished goods. The approach allows companies to identify and anticipate vulnerabilities in their supply chain. It unlocks predictive analytics capabilities and enables them to act proactively. The research is particularly compelling because it unites network science theory with empirical data and presents the results in a visual, intuitive manner.

Keywords: data mining, supply chain, empirical research, data mapping

Procedia PDF Downloads 146
121 Comparative Correlation Investigation of Polynuclear Aromatic Hydrocarbons (PAHs) in Soils of Different Land Uses: Sources Evaluation Perspective

Authors: O. Onoriode Emoyan, E. Eyitemi Akporhonor, Charles Otobrise

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Polycyclic Aromatic Hydrocarbons (PAHs) are formed mainly as a result of incomplete combustion of organic materials during industrial, domestic activities or natural occurrence. Their toxicity and contamination of terrestrial and aquatic ecosystem have been established. Though with limited validity index, previous research has focused on PAHs isomer pair ratios of variable physicochemical properties in source identification. The objective of this investigation was to determine the empirical validity of Pearson correlation coefficient (PCC) and cluster analysis (CA) in PAHs source identification along soil samples of different land uses. Therefore, 16 PAHs grouped as endocrine disruption substances (EDSs) were determined in 10 sample stations in top and sub soils seasonally. PAHs was determined the use of Varian 300 gas chromatograph interfaced with flame ionization detector. Instruments and reagents used are of standard and chromatographic grades respectively. PCC and CA results showed that the classification of PAHs along kinetically and thermodyanamically-favoured and those derived directly from plants product through biologically mediated processes used in source signature is about the predominance PAHs are likely to be. Therefore the observed PAHs in the studied stations have trace quantities of the vast majority of the sixteen un-substituted PAHs which may ultimately inhabit the actual source signature authentication. Type and extent of bacterial metabolism, transformation products/substrates, and environmental factors such as: salinity, pH, oxygen concentration, nutrients, light intensity, temperature, co-substrates and environmental medium are hereby recommended as factors to be considered when evaluating possible sources of PAHs.

Keywords: comparative correlation, kinetically and thermodynamically-favored PAHs, pearson correlation coefficient, cluster analysis, sources evaluation

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120 Urban Water Logging Adversity: A Case Study on Disruption of Urban Landscape Due to Water Logging Problems and Probable Analytical Solutions for Urban Region on Port City Chittagong, Bangladesh

Authors: Md. Obidul Haque, Abbasi Khanm

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Port city Chittagong, the commercial capital of Bangladesh, is flourished with fascinating topography and climatic context along with basic resources for livelihood; both shape this city and become living archives of its ecologies. Chittagong has been witnessing numerous urban development measures being taken by city development authority, though some of those seem incomplete because of lack of proper planning. Due to this unplanned trail, the blessings of nature have become the reason of sufferings for city dwellers. One of which is the water clogging due to heavy rainfall, seepage, high tide, absence of well-knit underground drainage system, and so on. The problem has reached such an extent that the first monsoon rain is enough to shut down the entire city and causing immense sufferings to livestock, specially most vulnerable groups such as children and office going people. Study shows that total discharge is higher than present drainage capacity of the canals, thus, resulting in overflow, as major channels are clogged up by dumping waste or illegal encroachment, which are supposed to flush out rain water. This paper aims to address natural and manmade causes behind urban water clogging, adverse socio-environmental hazardous effects, possibilities for probable solutions on basis of local people’s experience and rational urban planning and landscape architectural proposals such as facilitating well planned drainage system, along with waste management policies etc. which can be able to intervene in these movements to activate the mighty port city’s unfulfilled potentials.

Keywords: drainage, high-tide, urban storm water logging (USWL), urban planning, water management

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119 A Computational Approach for the Prediction of Relevant Olfactory Receptors in Insects

Authors: Zaide Montes Ortiz, Jorge Alberto Molina, Alejandro Reyes

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Insects are extremely successful organisms. A sophisticated olfactory system is in part responsible for their survival and reproduction. The detection of volatile organic compounds can positively or negatively affect many behaviors in insects. Compounds such as carbon dioxide (CO2), ammonium, indol, and lactic acid are essential for many species of mosquitoes like Anopheles gambiae in order to locate vertebrate hosts. For instance, in A. gambiae, the olfactory receptor AgOR2 is strongly activated by indol, which accounts for almost 30% of human sweat. On the other hand, in some insects of agricultural importance, the detection and identification of pheromone receptors (PRs) in lepidopteran species has become a promising field for integrated pest management. For example, with the disruption of the pheromone receptor, BmOR1, mediated by transcription activator-like effector nucleases (TALENs), the sensitivity to bombykol was completely removed affecting the pheromone-source searching behavior in male moths. Then, the detection and identification of olfactory receptors in the genomes of insects is fundamental to improve our understanding of the ecological interactions, and to provide alternatives in the integrated pests and vectors management. Hence, the objective of this study is to propose a bioinformatic workflow to enhance the detection and identification of potential olfactory receptors in genomes of relevant insects. Applying Hidden Markov models (Hmms) and different computational tools, potential candidates for pheromone receptors in Tuta absoluta were obtained, as well as potential carbon dioxide receptors in Rhodnius prolixus, the main vector of Chagas disease. This study showed the validity of a bioinformatic workflow with a potential to improve the identification of certain olfactory receptors in different orders of insects.

Keywords: bioinformatic workflow, insects, olfactory receptors, protein prediction

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118 Analyzing the Food as a Form of Creativity: The Case of the Bijlmermeer in Amsterdam-Zuidoost

Authors: Marc Polo, Núria Arbonés Arán

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Amsterdam is considered one of the great European capitals, which concentrates the headquarters of various multinational companies and which, in addition, enjoys a huge tourist attraction. Its typical residential buildings next to the canals, the museums, or its striking "Red Light District" are a great focus of attraction. In 2019 almost 9 million tourists visited it, but few of them traveled to the farthest neighborhood in the city: Amsterdam-Zuidoost (Amsterdam-Southeast). This neighborhood is geographically separated from the urban core, which makes it an exclave of Amsterdam as it does not border any of the other boroughs. Bijlmermeer neighborhood is the largest of the Amsterdam-Zuidoost, and it was born in the 1960s with the expectations of becoming the city of the future. Its main architect, Siegfried Nassuth, was inspired by the Swiss Le Corbusier to design nearly 18,000 homes, most of which were in high-rise tower blocks and built together, forming a recognizable "honeycombed" pattern. For more than 40 years, a series of infrastructure and social vicissitudes have made the neighborhood outline quite different as it was expected to be. It helped also varied elements such as ethnicity, demolitions, or unoccupied apartments. The called “city of the future” became home to immigrants, drug addicts, and vandals, and the conflicts denigrated the Amsterdam-Zuidoost. This work analyzes the evolution of the Bijlmermeer from its origins and illustrates relevant international referents able to help the area. The purpose of the work is to show how different variations along the recent history didn't help enough, but how there are positive perspectives for the future taking advantage of the food as a creative issue. The research, based on academic literature, existing material in different stadiums, plus the analysis of the city imaginaries, will help to concrete relevant elements in terms of innovation, creativity, and disruption. Despite of radical renewal that is taking place, the research will demonstrate that there are still new opportunities for the old Bijlmermeer.

Keywords: amsterdam, bijlmermeer, creativity, food

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117 Oil and Development: The Case of Kuwait

Authors: Abdulaziz Abdulrahman Albahar

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This paper aims to answer the question of: is oil as a natural resource with all the wealth that it brings an economic burden? And how can resource curse be mitigated in such oil dependent nations? The case of Kuwait will be used as an example. The paper begins with an introduction of the resource curse and the Kuwaiti economy in general. Then there is an attempt to see that does the curse exist in the case for Kuwait. Furthermore, in the analysis section, an exploration on how the economy is dependent on oil and how oil is more of a burden if there is mismanagement is conducted. Later on, in answering on how to mitigate the problem of a resource curse, the case of Norway is explored. In concluding the paper, the results do show that oil rentals affects the Kuwaiti economy via 2 main channels, these are government spending that are mainly financed via oil rentals and exportation of oil based products. The surprising result was that government spending had a negative impact on GDP (gross domestic product) growth when oil rentals where instrumented on government expenditure, this is due to the issue of rent seeking in which government spending in Kuwait is financing things such as stimulus packages and raising the nominal wages. Yet, when comparing the magnitude of both oil exportation and government spending, the latter has a stronger effect on the GDP (gross domestic product) growth than the former. A resource curse doesn’t seem to exist in the case of Kuwait however, the characteristics of a curse do show in the form of rent seeking in the political sphere, the disruption of the traditional sectors like that of pearl trade and fishing markets. Yet, a curse doesn’t show due to the fact that the currency of the nation is very stable and hasn’t experienced any appreciation because of the fixed exchange rate system. Moreover, even if we can’t say that a curse exists, it is clear to see that the Kuwaiti economy is heading towards one. Whether or not it faces a resource curse will be based on how judicious the nation will be in exploiting their sovereign wealth fund and implementing diversification strategies to be less oil dependent like the vision “New Kuwait-2035” which has been underway since 2017.

Keywords: economic development, Kuwait, oil curse, dutch disease

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116 Potential Effects of Climate Change on Streamflow, Based on the Occurrence of Severe Floods in Kelantan, East Coasts of Peninsular Malaysia River Basin

Authors: Muhd. Barzani Gasim, Mohd. Ekhwan Toriman, Mohd. Khairul Amri Kamarudin, Azman Azid, Siti Humaira Haron, Muhammad Hafiz Md. Saad

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Malaysia is a country in Southeast Asia that constantly exposed to flooding and landslide. The disaster has caused some troubles such loss of property, loss of life and discomfort of people involved. This problem occurs as a result of climate change leading to increased stream flow rate as a result of disruption to regional hydrological cycles. The aim of the study is to determine hydrologic processes in the east coasts of Peninsular Malaysia, especially in Kelantan Basin. Parameterized to account for the spatial and temporal variability of basin characteristics and their responses to climate variability. For hydrological modeling of the basin, the Soil and Water Assessment Tool (SWAT) model such as relief, soil type, and its use, and historical daily time series of climate and river flow rates are studied. The interpretation of Landsat map/land uses will be applied in this study. The combined of SWAT and climate models, the system will be predicted an increase in future scenario climate precipitation, increase in surface runoff, increase in recharge and increase in the total water yield. As a result, this model has successfully developed the basin analysis by demonstrating analyzing hydrographs visually, good estimates of minimum and maximum flows and severe floods observed during calibration and validation periods.

Keywords: east coasts of Peninsular Malaysia, Kelantan river basin, minimum and maximum flows, severe floods, SWAT model

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115 Mechanism of Modeling the Level of Bcr-Abl Oncoprotein by Ubiquitin-Proteasome System in Chronic Myeloid Leukemia

Authors: Svitlana Antonenko, Gennady Telegeev

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Introductive statement: The development of chronic myeloid leukemia (CML) is caused by Bcr-Abl oncoprotein. Modern treatments with tyrosine kinase inhibitors are greatly complicated by the mutational variability of the Bcr-Abl oncoprotein, which causes drug resistance. Therefore, there is an urgent need to develop new approaches to the treatment of the disease, which will allow modeling the level of Bcr-Abl oncoprotein in the cell. Promising in this direction is the identification of proteases that can selectively promote cellular proteolysis of oncoproteins. The aim of the study was to study the effect of the interaction of Bcr-Abl with deubiquitinase USP1 on the level of oncoprotein in CML cells. Methodology: K562 cells were selected for the experiment. Сells were incubated with ML323 inhibitor for 24 hours. Precipitation of endogenous proteins from K562 cell lysate was performed using anti-Bcr-Abl antibodies. Cell lysates and precipitation results were studied by Western blot. Subcellular localization of proteins was studied by immunofluorescence analysis followed by confocal microscopy. The results were analyzed quantitatively and statistically. Major findings: The Bcr-Abl/USP1 protein complex was detected in CML cells, and it was found that inhibition of USP1 deubiquitinating activity by the compound ML323 leads to disruption of this protein complex and a decrease in the level of Bcr-Abl oncoprotein in cells. The interaction of Bcr-Abl with USP1 may result in deubiquitination of the oncoprotein, which disrupts its proteasomal degradation and leads to the accumulation of CML in cells. Conclusion: We believe that the interaction of oncoprotein with USP1 may be one of the prerequisites that contribute to malignant cell transformation due to the deubiquitination of oncoprotein, which leads to its accumulation and disease progression. A correlation was found between the deubiquitinating activity of USP1 and the level of oncoprotein in CML cells. Thus, we identify deubiquitinase USP1 as a promising therapeutic target for the development of a new strategy for the treatment of CML by modulating the level of Bcr-Abl in the cell.

Keywords: chronic myeloid leukemia, Bcr-Abl, USP1, deubiquitination Bcr-Abl, K562 cell

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114 The Legal Effects of Coronavirus (COVID-19) on the Implementation of Administrative Contracts in Saudi Arabia: Application of Emergency Circumstances Theory

Authors: Ali Obaid Alyami

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In Saudi Arabia, the pandemic of Coronavirus (COVID-19) has been affecting administrative contracts in many different ways. Lots of planned projects were stopped temporarily or implemented partially. Many contractors have suffered financial struggles and the absence of manpower. These administrative contracts are governed by Government Tenders and Procurement Law (GTPL) which was issued by a royal decree in 2019. This law addresses some challenges that could be stumbling blocks in the way of implementing a contract. One significant challenge is emergency circumstances that occur during the implementation of an administrative contract. The law provides some solutions for this disruption, but these solutions may not compensate for the whole damages that contractors suffer. This study will use the doctrinal methodology to analyze the rules of law and their application to the research problem. Most importantly, the issue that arises in this research is the possibility of governmental entities’ consideration, in administrative contracts, of the pandemic Coronavirus (COVID-19) as an emergency circumstance. This study points out the conditions for applying the theory of emergency circumstances on administrative contracts in addition to the definition of the theory and analyzing its elements. The other significant question is the limits on governmental entities to make a change in an administrative contract to achieve contractual rebalancing. GPTL and its implementing regulation set the conditions and limits of contractual rebalancing. However, this study finds that although GTPL provides rules for contractual rebalancing, there are some other mechanisms that contractors may take to fully compensate for the damages. For instance, when the loss cannot be minimized by GTPL, contractors might file lawsuits before the administrative judiciary. The study concludes that GTPL is a very comprehensive law system that stipulates specific rules for contractual rebalance and treats the emergency circumstances that obstruct the performance of administrative contracts.

Keywords: administrative contracts, emergency circumstances, balance of contract, administrative judiciary, government tenders, procurement law

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113 Perceptions and Governance of One Health in African Countries: A Workshop Report

Authors: Menouni Aziza, Chbihi Kaoutar, El Jaafari Samir

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There is strong evidence connecting epidemics with the disruption of the human-animal-environment interaction. Despite the fact that several cases of emerging and endemic zoonotic diseases indifferent parts of Africa have been documented, there is limited data regarding which specific interventions are effective in preventing and managing the associated risks using a One Health approach. The aim of this study is to better understand perceptions and ongoing research related to interventions in Africa through the implementation of suitable projects and policies. A bibliometric review of the scientific literature on one health studies with a focus on African countries was conducted, followed by a qualitative survey among stakeholders involved in fields related to One Health research or management in the Africa, including veterinary experts, public health professionals, environmentalists and policy makers, to learn about determinants of their perceptions, as well as barriers to and promoters of successful interventions and governance. The project was concluded with an international workshop in March 2023, where a broad range of topics relevant to One Health were discussed. 94% of the respondents were aware of the importance of the One Health approach and strongly endorse it within their respective countries. The top reported barriers to One Health development in Africa included paucity of data, weak linkages and institutional communication between the different departments and the lack of funding. Key areas of improvement identified were the impact evaluation of current initiatives, awareness raising campaigns among citizens targeted at behavioral changes, capacity building of relevant professionals and stakeholders, as well as the implementation of adequate policies and enforcement of national and continental regulations, allowing for better coordination on the African level. All One Health sectors in Africa require strong governance and leadership, as well as inter-ministerial, inter-sectoral, and interdisciplinary cooperation.

Keywords: one health, perceptions, governance, Africa

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112 “Towards Creating a Safe Future”: An Assessment of the Causes of Flooding in Nsanje District, Lower Shire Malawi

Authors: Davie Hope Moyo

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The environment is a combination of two things: resources and hazards. One of the hazards that is a result of environmental changes is the occurrence of flooding. Floods are one of the disasters that are highly feared by people because they have a huge impact on the human population and their environment. In recent years, flooding disasters in the Nsanje district are increasing in both frequency and magnitude. This study aims to understand the root causes of this phenomenon. To understand the causes of flooding, this study focused on the case of TA Ndamera in the Nsanje district, southern Malawi. People in the Nsanje district face disruption in their day-to-day life because of floods that affect their communities. When floods happen, people lose their property, land, livestock, and even lives. The study was carried out in order to have a better understanding of the root causes of floods. The findings of this study may help the government and other development agencies to put in place mitigation measures that will make Nsanje District resilient to the occurrence of future flood hazards. Data was collected from the area of TA Ndamera in order to assess the causes of flooding in the district. Interviews, transect walks, and researcher observation was done to appreciate the topography of the district and evaluate other factors that are making the people become vulnerable to the impacts of flooding in the district. It was found that flooding in the district is mainly caused by heavy rainfall in the upper shire, settlements along river banks, deforestation, and the topography of the district in general. The research study ends by providing recommendation strategies that need to be put in place to increase the resilience of the communities to future flood hazards. The research recommends the development of indigenous knowledge systems to alert people of incoming floods, construction of evacuation centers to ease pressure on schools, savings, and insurance schemes, construction of dykes, desilting rivers, and afforestation.

Keywords: disaster causes, mitigation, safety measures, Nsanje Malawi

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111 Contagion of the Global Financial Crisis and Its Impact on Systemic Risk in the Banking System: Extreme Value Theory Analysis in Six Emerging Asia Economies

Authors: Ratna Kuswardani

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This paper aims to study the impact of recent Global Financial Crisis (GFC) on 6 selected emerging Asian economies (Indonesia, Malaysia, Thailand, Philippines, Singapore, and South Korea). We first figure out the contagion of GFC from the US and Europe to the selected emerging Asian countries by studying the tail dependence of market stock returns between those countries. We apply the concept of Extreme Value Theory (EVT) to model the dependence between multiple returns series of variables under examination. We explore the factors causing the contagion between the regions. We find dependencies between markets that are influenced by their size, especially for large markets in emerging Asian countries that tend to have a higher dependency to the market in the more advanced country such as the U.S. and some countries in Europe. The results also suggest that the dependencies between market returns and bank stock returns in the same region tend to be higher than dependencies between these returns across two different regions. We extend our analysis by studying the impact of GFC on the systemic in the banking system. We also find that larger institution has more dependencies with the market stock, suggesting that larger size bank can cause disruption in the market. Further, the higher probability of extreme loss can be seen during the crisis period, which is shown by the non-linear dependency between the pre-crisis and the post-crisis period. Finally, our analysis suggests that systemic risk appears in the domestic banking systems in emerging Asia, as shown by the extreme dependencies within banks in the system. Overall, our results provide caution to policy makers and investors alike on the possible contagion of the impact of global financial crisis across different markets.

Keywords: contagion, extreme value theory, global financial crisis, systemic risk

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110 Assessing the Indicators Influencing Port Resilience: A Comprehensive Literature Review

Authors: Guo Rui, Cao Xinhu

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In recent decades, the world has endured severe challenges in light of climate change, epidemics, geopolitics, terrorism, economic uncertainties, as well as regional conflicts and rivalries. The appropriate use of critical infrastructures (Cis) is confronted. Ports, as typical Cis cover more than 80% of the global freight movement. Within this context, even the minimal disruption of port operations could cause malfunction of the holistic supply chain network and substantial economic losses. Hence, it is crucial to evaluate port performance from the perspective of resilience. Research on resilience and risk/safety management has been increasing, however, it needs more attention, as it could prevent potential socio-economic losses and inspire decision-makers to make resilience-based decisions to answer the challenges, such as COVID-19. To facilitate better moves from decision-makers, ports need to identify proper factors influencing port resilience. Inappropriately influenced factor selection could have a cascading effect on undesirable port performances. Thus, a systematic evaluation of factors is essential to stimulate the improvement process of port resilience investigation. This study zooms into container ports considering their critical role in international trade and global supply chains. 440 articles are selected after relevance ranking, and consequently, 62 articles are scrutinized after the title and abstract screening. Forty-one articles are included for bibliographic analysis in the end. It is found that there is no standardized index system to measure port resilience. And most studies evaluate port resilience merely in the recovery phase. Only two articles cover absorption, adaption and recovery state. However, no literature involves the prevention state. Hence, a uniform resilience index system is expected with a clear resilience definition. And port safety and security should also be considered while evaluating port resilience.

Keywords: port resilience, port safety and security, literature review, index system, port performance

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109 Monitoring of Endocrine Disruptors in Surface Waters and Sediment from the River Nile (Egypt) by Yeast Assays

Authors: Alaa G. M. Osman, Khaled Y. AbouelFadl, Angela Krüger, Werner Kloas

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In Egypt, no previous records are available regarding possible multiple hormonal activities in the aquatic systems and especially the river Nile. In this paper, the in vitro yeast estrogen screen (YES) and yeast androgen screen (YAS) were used to assess the multiple hormonal activities in surface waters and sediment from the Egyptian river Nile for the first time. This study sought to determine if river Nile water caused changes in gonadal histology of Nile tilapia (Oreochromis niloticus niloticus). All water samples exhibited extremely low levels of estrogenicity. Estrogenicity was not detected nearly in any of the sediment samples. Unlike the estrogenicity, significant androgenic activities were recorded in the water and sediment samples along the Nile course. The present study reports for the first time quantified anti-estrogenic and anti-androgenic activities with high levels in both water and sediment of the river Nile. The greatest anti-estrogenic and anti-androgenic activities were observed in sample from downstream river Nile. These results indicated that the anti-estrogenic and anti-androgenic activities along the Nile course were great and the pollution of the sites at the downstream was more serious than the upstream sites due to industrial activities at theses sites. Good correlations were observed among some hormonal activities, suggesting coexistence of these contaminants in the environmental matrices. There were no signs of sexual disruption in any of the gonads analysed from either male or female Nile tilapia, demonstrating that any hormonal activity present along the Nile course was not sufficient to induce adverse effects on reproductive development. Further investiga¬tion is necessary to identify the chemicals responsible for the hormonal activities in the river Nile and to examine the effect of very low levels of hormonally active chemicals on gonadal histology, as well as in the development of more sensitive biomarkers.

Keywords: multiple hormonal activities, YES, YAS, river Nile, Nile tilapia, gonadal histology

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108 ‘An Invisible Labyrinth of Time’: Temporal Disjunction in J.M. Coetzee’s Dusklands

Authors: Barbara Janari

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This paper focuses on temporality in J.M. Coetzee’s first novel, Dusklands, to argue that the novel’s fractured, disjointed temporality is intricately linked to the representations of the war in Vietnam and the colonial project in South Africa. The disrupted temporalities in the novel eschew chronological plots and linear time in favour of narratives that subvert the notion of historical progress to suggest instead the coextensive, multivalent ways in which the past and present interpenetrate one another. The disruption of temporal flow in the novel is evident in its form – the novel comprises two novellas that are juxtaposed, with the first part (‘The Vietnam War’) set centuries before the second part (‘The Narrative of Jacobus Coetzee’). The juxtaposition of the two novellas suggests history’s sometimes overlapping and lateral, rather than linear, movement. The novel’s form is extended in its montage narrative structure, which works to extend its temporal range. The temporal disjunction is reinforced, firstly, by Coetzee’s textual strategies, which include the subversion and critique of realism, parody, repetition, and the narrative technique of montage, and secondly, by the novel’s thematic concerns, which focus on the ways in which American domination can be linked to the colonial quest from earlier times. The complex structure of various strands and levels of authorship slows down the narrative’s temporal flow, requiring the reader to spend a fair amount of time unraveling the various parts of the narrative and relating them to each other. The structure epitomizes reflexive referencing, in which the reader can only make sense of the narrative by going back and forth and connecting various parts of it. The narrative structure also emphasizes the underlying similarities in the brutality that marked these two distinct historical events, epitomized by the drive towards subjection and domination by the novel’s two protagonists, Eugene Dawn and Jacobus Coetzee. The links and overlapping strands between the two novellas emphasize the ways in which the historical truth of colonial discourse becomes as much a myth as the propaganda program in Vietnam.

Keywords: disjunction, juxtaposition, montage, temporality

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107 Host Cell Membrane Lipid Rafts Are Required for Influenza A Virus Adsorption to Host Cell Surface

Authors: Dileep K. Verma, Sunil K. Lal

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Influenza still remains one of the most challenging diseases posing significant threat to public health causing seasonal epidemics and pandemics. Previous studies suggest that influenza hemagglutinin is essential for viral attachment to host sialic acid receptors and concentrate in lipid rafts for efficient viral fusion. Studies also reported selective nature of Influenza virus to utilize rafts micro-domain for efficient virus assembly and budding. However, the detailed mechanism of Influenza A Virus (IAV) binding to host cell membrane and entry inside the host remains elusive. In the present study, we investigated if host membrane lipid rafts play any significant role in early life cycle events of influenza A virus. Role of host lipid rafts was studied using raft disruption method by extraction of cholesterol and Methyl-β-Cyclodextrin was used to remove membrane cholesterol. We observed co-localization of Influenza A Virus to lipid rafts by visualization of known lipid raft marker GM1 on host cell membrane. Co-localization suggest direct involvement of these micro-domain in initiation of IAV life cycle. We found significant reduction in influenza A virus adsorption in raft disrupted target host cells indicating poor binding and attachment in absence of coherent membrane rafts. Taken together, the results of present study provide evidence for critical involvement of host lipid rafts and its constituents in adsorption process of Influenza A Virus and suggests crucial involvement in other early events of IAV life cycle. The present study opens a new domain to study influenza virus-host interaction and to combat flu at the very early steps of viral life cycle.

Keywords: lipid raft, adsorption, cholesterol, methyl-β-cyclodextrin, GM1

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106 Environmental Problems (with Examples from Georgia)

Authors: Ana Asratashvili

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One of the main issues of state’s economic policy is the environmental problems. The development of society is implementing by the connection with nature. A human being needs different material resources which must be got by the influence on the nature. This relationship between nature and society is complicated and controversial and it was changing from time to time according to human’s evolution. The imprudent and unreasonable usage of natural resources, scientific-technological revolution and the hard pollution of nature related to it caused the disruption of environmental balance between nature and society which has been made for ages and destructively acted on society and environment. Environmental protection is one of the major issues of the European Union all over the world. The aim of EU environmental policy is to improve ecological conditions. Besides, it aims encouraging of careful and rational usage of natural resources. At the same time, the union tries to raise problems related to environmental protection at the international level. After that when scientists concluded anthropogenic impact of human on the nature causes climate changes, the special attention was paid to the environmental protection by developed countries. Global warming will cause floods, storms, draughts and desertification and to solve these results presumably will cost 20% of World GDP by 2050 for developed countries, if, of course, it does not make strict environmental policy. EU member countries have pretty strict environmental standards. Their defense is observed by different state institutions. According to impacts on nature throughout the world the most polluted fumes are made by electricity facilities (44%), transport (20%), industry (18%), domestic and service sector (17%). The special concern to the issues related to the importance of environment by environmentalists is caused by low self-esteem of population about the problems of environment. According to their mind, population is engaged with daily difficulties so that they don’t react much on environmental problems. Correspondingly, the main task for environmental organizations is to inform population and raise self-esteem about environmental issues.

Keywords: economic policy, environment, technological revolution, pollution, environmental, standards, self-esteem

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105 Analyzing the Performance of Different Cost-Based Methods for the Corrective Maintenance of a System in Thermal Power Plants

Authors: Demet Ozgur-Unluakin, Busenur Turkali, S. Caglar Aksezer

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Since the age of industrialization, maintenance has always been a very crucial element for all kinds of factories and plants. With today’s increasingly developing technology, the system structure of such facilities has become more complicated, and even a small operational disruption may return huge losses in profits for the companies. In order to reduce these costs, effective maintenance planning is crucial, but at the same time, it is a difficult task because of the complexity of systems. The most important aspect of correct maintenance planning is to understand the structure of the system, not to ignore the dependencies among the components and as a result, to model the system correctly. In this way, it will be better to understand which component improves the system more when it is maintained. Undoubtedly, proactive maintenance at a scheduled time reduces costs because the scheduled maintenance prohibits high losses in profits. But the necessity of corrective maintenance, which directly affects the situation of the system and provides direct intervention when the system fails, should not be ignored. When a fault occurs in the system, if the problem is not solved immediately and proactive maintenance time is awaited, this may result in increased costs. This study proposes various maintenance methods with different efficiency measures under corrective maintenance strategy on a subsystem of a thermal power plant. To model the dependencies between the components, dynamic Bayesian Network approach is employed. The proposed maintenance methods aim to minimize the total maintenance cost in a planning horizon, as well as to find the most appropriate component to be attacked on, which improves the system reliability utmost. Performances of the methods are compared under corrective maintenance strategy. Furthermore, sensitivity analysis is also applied under different cost values. Results show that all fault effect methods perform better than the replacement effect methods and this conclusion is also valid under different downtime cost values.

Keywords: dynamic Bayesian networks, maintenance, multi-component systems, reliability

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104 The Angiogenic Activity of α-Mangostin in the Development of Zebrafish Embryo In Vivo

Authors: Titis Indah Adi Rahayu

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Angiogenesis is the process of generating new capillary from pre-existing blood vessels. VEGFA is a major regulator in angiogenesis that binds and activates two tyrosine kinase receptors, VEGFR1 (Flt-1) and VEGFR2 (Flk-1/KDR) which regulate pathological and physiological angiogenesis. Disruption of VEGFA and VEGFR2 regulation lead to many diseases. The study of α-Mangostin (derivate of xanthone) as anti-oxidant and anti inflammation has been explored recently and both of them have relation to vasculature however the effect of α-Mangostin in blood vessel formation in healthy tissue in vivo has not been studied. Zebrafish is a powerful model in studying angiogenesis and shared many advantages that is a viable whole animal model for screening small molecules that affect blood vessel formation. Therefore the aim of this study is to evaluate angiogenic activity of α-Mangostin in healthy tissue in vivo in zebrafish embryo in relation of patterning blood vessel. Blood vessel patterning is highly characteristic in the developing of zebrafish embryo and the subintestinal vessel (SIV) can be stained and visualized microscopically as a primary screen for α-Mangostin that effect angiogenesis. The zebrafish embryos are divided into 2 groups. Group one consists of the zebrafish embryos at 1 dpf for 4 days which are tested to α-Mangostin in several concentration 2 µM, 4 µM, 6 µM, 8 µM and 10 µM whereas in group two the zebrafish larva at 4 dpf are exposed to α-Mangostin 1,75 µM, 2,3 µM, 2,9 µM, 3,8 µM dan 5 µM for 2 days. DMSO is served as a control for each group. The level expression of vegfa and vegfr2 are observed quantitatively using real time q-PCR and patterning of SIV are then analized via alkaline phospatase staining. Result shows that the level expression of vegfa and vegfr2 is repressed quantitatively as shown in real time q-PCR in the group of 1-4 days of α-Mangostin exposure where it is increased in the group of 4-6 days of α-Mangostin exposure. The result is then compared to alkaline phospatase staining of SIV using stereo microscope. It indicates that α-Mangostin does not disturb the patterning of SIV formation in zebrafish.

Keywords: angiogenesis, Danio rerio, α-Mangostin, SIV, vegfa, vegfr2

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103 Development of a Robust Protein Classifier to Predict EMT Status of Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (CESC) Tumors

Authors: ZhenlinJu, Christopher P. Vellano, RehanAkbani, Yiling Lu, Gordon B. Mills

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The epithelial–mesenchymal transition (EMT) is a process by which epithelial cells acquire mesenchymal characteristics, such as profound disruption of cell-cell junctions, loss of apical-basolateral polarity, and extensive reorganization of the actin cytoskeleton to induce cell motility and invasion. A hallmark of EMT is its capacity to promote metastasis, which is due in part to activation of several transcription factors and subsequent downregulation of E-cadherin. Unfortunately, current approaches have yet to uncover robust protein marker sets that can classify tumors as possessing strong EMT signatures. In this study, we utilize reverse phase protein array (RPPA) data and consensus clustering methods to successfully classify a subset of cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) tumors into an EMT protein signaling group (EMT group). The overall survival (OS) of patients in the EMT group is significantly worse than those in the other Hormone and PI3K/AKT signaling groups. In addition to a shrinkage and selection method for linear regression (LASSO), we applied training/test set and Monte Carlo resampling approaches to identify a set of protein markers that predicts the EMT status of CESC tumors. We fit a logistic model to these protein markers and developed a classifier, which was fixed in the training set and validated in the testing set. The classifier robustly predicted the EMT status of the testing set with an area under the curve (AUC) of 0.975 by Receiver Operating Characteristic (ROC) analysis. This method not only identifies a core set of proteins underlying an EMT signature in cervical cancer patients, but also provides a tool to examine protein predictors that drive molecular subtypes in other diseases.

Keywords: consensus clustering, TCGA CESC, Silhouette, Monte Carlo LASSO

Procedia PDF Downloads 437