Search results for: reduced resource burden
203 Identification and Characterization of Novel Genes Involved in Quinone Synthesis in the Odoriferous Defensive Stink Glands of the Red Flour Beetle, Tribolium castaneum
Authors: B. Atika, S. Lehmann, E. Wimmer
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The defense strategy is very common in the insect world. Defensive substances play a wide variety of functions for beetles, such as repellents, toxicants, insecticides, and antimicrobics. Beetles react to predators, invaders, and parasitic microbes with the release of toxic and repellent substances. Defensive substances are directed against a large array of potential target organisms or may function for boiling bombardment or as surfactants. Usually, Coleoptera biosynthesize and store their defensive compounds in a complex secretory organ, known as odoriferous defensive stink glands. The red flour beetle, Tribolium castaneum (Coleoptera: Tenebrionidae), uses these glands to produce antimicrobial p-benzoquinones and 1-alkenes. In the past, the morphology of stink gland has been studied in detail in tenebrionid beetles; however, very little is known about the genes that are involved in the production of gland secretion. In this study, we studied a subset of genes that are essential for the benzoquinone production in red flour beetle. In the first phase, we selected 74 potential candidate genes from a genome-wide RNA interference (RNAi) knockdown screen named 'iBeetle.' All these 74 candidate genes were functionally characterized by RNAi-mediated gene knockdown. Therefore, they were selected for a subsequent gas chromatography-mass spectrometry (GC-MS) analysis of secretion volatiles in respective RNAi knockdown glands. 33 of them were observed to alter the phenotype of stink gland. In the GC-MS analysis, 7 candidate genes were noted to display a strongly altered gland, in terms of secretion color and chemical composition, upon knockdown, showing their key role in the biosynthesis of gland secretion. Morphologically altered stink glands were found for odorant receptor and protein kinase superfamily. Subsequent GC-MS analysis of secretion volatiles revealed reduced benzoquinone levels in LIM domain, PDZ domain, PBP/GOBP family knockdowns and a complete lack of benzoquinones in the knockdown of sulfatase-modifying factor enzyme 1, sulfate transporter family. Based on stink gland transcriptome data, we analyzed the function of sulfatase-modifying factor enzyme 1 and sulfate transporter family via RNAi-mediated gene knockdowns, GC-MS, in situ hybridization, and enzymatic activity assays. Morphologically altered stink glands were noted in knockdown of both these genes. Furthermore, GC-MS analysis of secretion volatiles showed a complete lack of benzoquinones in the knockdown of these two genes. In situ hybridization showed that these two genes are expressed around the vesicle of certain subgroup of secretory stink gland cells. Enzymatic activity assays on stink gland tissue showed that these genes are involved in p-benzoquinone biosynthesis. These results suggest that sulfatase-modifying factor enzyme 1 and sulfate transporter family play a role specifically in benzoquinone biosynthesis in red flour beetles.Keywords: Red Flour Beetle, defensive stink gland, benzoquinones, sulfate transporter, sulfatase-modifying factor enzyme 1
Procedia PDF Downloads 154202 South-Mediterranean Oaks Forests Management in Changing Climate Case of the National Park of Tlemcen-Algeria
Authors: K. Bencherif, M. Bellifa
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The expected climatic changes in North Africa are the increase of both intensity and frequencies of the summer droughts and a reduction in water availability during growing season. The exiting coppices and forest formations in the national park of Tlemcen are dominated by holm oak, zen oak and cork oak. These opened-fragmented structures don’t seem enough strong so to hope durable protection against climate change. According to the observed climatic tendency, the objective is to analyze the climatic context and its evolution taking into account the eventual behaving of the oak species during the next 20-30 years on one side and the landscaped context in relation with the most adequate sylvicultural models to choose and especially in relation with human activities on another side. The study methodology is based on Climatic synthesis and Floristic and spatial analysis. Meteorological data of the decade 1989-2009 are used to characterize the current climate. An another approach, based on dendrochronological analysis of a 120 years sample Aleppo pine stem growing in the park, is used so to analyze the climate evolution during one century. Results on the climate evolution during the 50 years obtained through climatic predictive models are exploited so to predict the climate tendency in the park. Spatially, in each forest unit of the Park, stratified sampling is achieved so to reduce the degree of heterogeneity and to easily delineate different stands using the GPS. Results from precedent study are used to analyze the anthropogenic factor considering the forecasts for the period 2025-2100, the number of warm days with a temperature over 25°C would increase from 30 to 70. The monthly mean temperatures of the maxima’s (M) and the minima’s (m) would pass respectively from 30.5°C to 33°C and from 2.3°C to 4.8°C. With an average drop of 25%, precipitations will be reduced to 411.37 mm. These new data highlight the importance of the risk fire and the water stress witch would affect the vegetation and the regeneration process. Spatial analysis highlights the forest and the agricultural dimensions of the park compared to the urban habitat and bare soils. Maps show both fragmentation state and forest surface regression (50% of total surface). At the level of the park, fires affected already all types of covers creating low structures with various densities. On the silvi cultural plan, Zen oak form in some places pure stands and this invasion must be considered as a natural tendency where Zen oak becomes the structuring specie. Climate-related changes have nothing to do with the real impact that South-Mediterranean forests are undergoing because human constraints they support. Nevertheless, hardwoods stand of oak in the national park of Tlemcen will face up to unexpected climate changes such as changing rainfall regime associated with a lengthening of the period of water stress, to heavy rainfall and/or to sudden cold snaps. Faced with these new conditions, management based on mixed uneven aged high forest method promoting the more dynamic specie could be an appropriate measure.Keywords: global warming, mediterranean forest, oak shrub-lands, Tlemcen
Procedia PDF Downloads 389201 Cicadas: A Clinician-assisted, Closed-loop Technology, Mobile App for Adolescents with Autism Spectrum Disorders
Authors: Bruno Biagianti, Angela Tseng, Kathy Wannaviroj, Allison Corlett, Megan DuBois, Kyu Lee, Suma Jacob
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Background: ASD is characterized by pervasive Sensory Processing Abnormalities (SPA) and social cognitive deficits that persist throughout the course of the illness and have been linked to functional abnormalities in specific neural systems that underlie the perception, processing, and representation of sensory information. SPA and social cognitive deficits are associated with difficulties in interpersonal relationships, poor development of social skills, reduced social interactions and lower academic performance. Importantly, they can hamper the effects of established evidence-based psychological treatments—including PEERS (Program for the Education and Enrichment of Relationship Skills), a parent/caregiver-assisted, 16-weeks social skills intervention—which nonetheless requires a functional brain capable of assimilating and retaining information and skills. As a matter of fact, some adolescents benefit from PEERS more than others, calling for strategies to increase treatment response rates. Objective: We will present interim data on CICADAS (Care Improving Cognition for ADolescents on the Autism Spectrum)—a clinician-assisted, closed-loop technology mobile application for adolescents with ASD. Via ten mobile assessments, CICADAS captures data on sensory processing abnormalities and associated cognitive deficits. These data populate a machine learning algorithm that tailors the delivery of ten neuroplasticity-based social cognitive training (NB-SCT) exercises targeting sensory processing abnormalities. Methods: In collaboration with the Autism Spectrum and Neurodevelopmental Disorders Clinic at the University of Minnesota, we conducted a fully remote, three-arm, randomized crossover trial with adolescents with ASD to document the acceptability of CICADAS and evaluate its potential as a stand-alone treatment or as a treatment enhancer of PEERS. Twenty-four adolescents with ASD (ages 11-18) have been initially randomized to 16 weeks of PEERS + CICADAS (Arm A) vs. 16 weeks of PEERS + computer games vs. 16 weeks of CICADAS alone (Arm C). After 16 weeks, the full battery of assessments has been remotely administered. Results: We have evaluated the acceptability of CICADAS by examining adherence rates, engagement patterns, and exit survey data. We found that: 1) CICADAS is able to serve as a treatment enhancer for PEERS, inducing greater improvements in sensory processing, cognition, symptom reduction, social skills and behaviors, as well as the quality of life compared to computer games; 2) the concurrent delivery of PEERS and CICADAS induces greater improvements in study outcomes compared to CICADAS only. Conclusion: While preliminary, our results indicate that the individualized assessment and treatment approach designed in CICADAS seems effective in inducing adaptive long-term learning about social-emotional events. CICADAS-induced enhancement of processing and cognition facilitates the application of PEERS skills in the environment of adolescents with ASD, thus improving their real-world functioning.Keywords: ASD, social skills, cognitive training, mobile app
Procedia PDF Downloads 213200 Sustainable Urban Growth of Neighborhoods: A Case Study of Alryad-Khartoum
Authors: Zuhal Eltayeb Awad
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Alryad neighborhood is located in Khartoum town– the administrative center of the Capital of Sudan. The neighborhood is one of the high-income residential areas with villa type development of low-density. It was planned and developed in 1972 with large plots (600-875m²), wide crossing roads and balanced environment. Recently the area transformed into more compact urban form of high density, mixed-use integrated development with more intensive use of land; multi-storied apartments. The most important socio-economic process in the neighborhood has been the commercialization and deinitialization of the area in connect with the displacement of the residential function. This transformation affected the quality of the neighborhood and the inter-related features of the built environment. A case study approach was chosen to gather the necessary qualitative and quantitative data. A detailed survey on existing development pattern was carried out over the whole area of Alryad. Data on the built and social environment of the neighborhoods were collected through observations, interviews and secondary data sources. The paper reflected a theoretical and empirical interest in the particular characteristics of compact neighborhood with high density, and mixed land uses and their effect on social wellbeing of the residents all in the context of the sustainable development. The research problem is focused on the challenges of transformation that associated with compact neighborhood that created multiple urban problems, e.g., stress of essential services (water supply, electricity, and drainage), congestion of streets and demand for parking. The main objective of the study is to analyze the transformation of this area from residential use to commercial and administrative use. The study analyzed the current situation of the neighborhood compared to the five principles of sustainable neighborhood prepared by UN Habitat. The study found that the neighborhood is experienced changes that occur to inner-city residential areas and the process of change of the neighborhood was originated by external forces due to the declining economic situation of the whole country. It is evident that non-residential uses have taken place uncontrolled, unregulated and haphazardly that led to damage the residential environment and deficiency in infrastructure. The quality of urban life and in particular on levels of privacy was reduced, the neighborhood changed gradually to be a central business district that provides services to the whole Khartoum town. The change of house type may be attributed to a demand-led housing market and absence of policy. The results showed that Alryad is not fully sustainable and self-contained, street network characteristics and mixed land-uses development are compatible with the principles of sustainability. The area of streets represents 27.4% of the total area of the neighborhood. Residential density is 4,620 people/ km², that is lower than the recommendations, and the limited block land-use specialization is higher than 10% of the blocks. Most inhabitants have a high income so that there is no social mix in the neighborhood. The study recommended revision of the current zoning regulations in order to control and regulate undesirable development in the neighborhood and provide new solutions which allow promoting the neighborhood sustainable development.Keywords: compact neighborhood, land uses, mixed use, residential area, transformation
Procedia PDF Downloads 129199 Dynamics of Protest Mobilization and Rapid Demobilization in Post-2001 Afghanistan: Facing Enlightening Movement
Authors: Ali Aqa Mohammad Jawad
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Taking a relational approach, this paper analyzes the causal mechanisms associated with successful mobilization and rapid demobilization of the Enlightening Movement in post-2001 Afghanistan. The movement emerged after the state-owned Da Afghan Bereshna Sherkat (DABS) decided to divert the route for the Turkmenistan-Uzbekistan-Tajikistan-Afghanistan-Pakistan (TUTAP) electricity project. The grid was initially planned to go through the Hazara-inhabited province of Bamiyan, according to Afghanistan’s Power Sector Master Plan. The reroute served as an aide-mémoire of historical subordination to other ethno-religious groups for the Hazara community. It was also perceived as deprivation from post-2001 development projects, financed by international aid. This torched the accumulated grievances, which then gave birth to the Enlightening Movement. The movement had a successful mobilization. However, it demobilized after losing much of its mobilizing capabilities through an amalgamation of external and internal relational factors. The successful mobilization yet rapid demobilization constitutes the puzzle of this paper. From the theoretical perspective, this paper is significant as it establishes the applicability of contentious politics theory to protest mobilizations that occurred in Afghanistan, a context-specific, characterized by ethnic politics. Both primary and secondary data are utilized to address the puzzle. As for the primary resources, media coverage, interviews, reports, public media statements of the movement, involved in contentious performances, and data from Social Networking Services (SNS) are used. The covered period is from 2001-2018. As for the secondary resources, published academic articles and books are used to give a historical account of contentious politics. For data analysis, a qualitative comparative historical method is utilized to uncover the causal mechanisms associated with successful mobilization and rapid demobilization of the Movement. In this pursuit, both mobilization and demobilization are considered as larger political processes that could be decomposed to constituent mechanisms. Enlightening Movement’s framing and campaigns are first studied to uncover the associated mechanisms. Then, to avoid introducing some ad hoc mechanisms, the recurrence of mechanisms is checked against another case. Mechanisms qualify as robust if they are “recurrent” in different episodes of contention. Checking the recurrence of causal mechanisms is vital as past contentious events tend to reinforce future events. The findings of this paper suggest that the public sphere in Afghanistan is drastically different from Western democracies known as the birthplace of social movements. In Western democracies, when institutional politics did not respond, movement organizers occupied the public sphere, undermining the legitimacy of the government. In Afghanistan, the public sphere is ethicized. Considering the inter- and intra-relational dynamics of ethnic groups in Afghanistan, the movement reduced to an erosive inter- and intra-ethnic conflict. This undermined the cohesiveness of the movement, which then kicked-off its demobilization process.Keywords: enlightening movement, contentious politics, mobilization, demobilization
Procedia PDF Downloads 194198 Improving a Stagnant River Reach Water Quality by Combining Jet Water Flow and Ultrasonic Irradiation
Authors: A. K. Tekile, I. L. Kim, J. Y. Lee
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Human activities put freshwater quality under risk, mainly due to expansion of agriculture and industries, damming, diversion and discharge of inadequately treated wastewaters. The rapid human population growth and climate change escalated the problem. External controlling actions on point and non-point pollution sources are long-term solution to manage water quality. To have a holistic approach, these mechanisms should be coupled with the in-water control strategies. The available in-lake or river methods are either costly or they have some adverse effect on the ecological system that the search for an alternative and effective solution with a reasonable balance is still going on. This study aimed at the physical and chemical water quality improvement in a stagnant Yeo-cheon River reach (Korea), which has recently shown sign of water quality problems such as scum formation and fish death. The river water quality was monitored, for the duration of three months by operating only water flow generator in the first two weeks and then ultrasonic irradiation device was coupled to the flow unit for the remaining duration of the experiment. In addition to assessing the water quality improvement, the correlation among the parameters was analyzed to explain the contribution of the ultra-sonication. Generally, the combined strategy showed localized improvement of water quality in terms of dissolved oxygen, Chlorophyll-a and dissolved reactive phosphate. At locations under limited influence of the system operation, chlorophyll-a was highly increased, but within 25 m of operation the low initial value was maintained. The inverse correlation coefficient between dissolved oxygen and chlorophyll-a decreased from 0.51 to 0.37 when ultrasonic irradiation unit was used with the flow, showing that ultrasonic treatment reduced chlorophyll-a concentration and it inhibited photosynthesis. The relationship between dissolved oxygen and reactive phosphate also indicated that influence of ultra-sonication was higher than flow on the reactive phosphate concentration. Even though flow increased turbidity by suspending sediments, ultrasonic waves canceled out the effect due to the agglomeration of suspended particles and the follow-up settling out. There has also been variation of interaction in the water column as the decrease of pH and dissolved oxygen from surface to the bottom played a role in phosphorus release into the water column. The variation of nitrogen and dissolved organic carbon concentrations showed mixed trend probably due to the complex chemical reactions subsequent to the operation. Besides, the intensive rainfall and strong wind around the end of the field trial had apparent impact on the result. The combined effect of water flow and ultrasonic irradiation was a cumulative water quality improvement and it maintained the dissolved oxygen and chlorophyll-a requirement of the river for healthy ecological interaction. However, the overall improvement of water quality is not guaranteed as effectiveness of ultrasonic technology requires long-term monitoring of water quality before, during and after treatment. Even though, the short duration of the study conducted here has limited nutrient pattern realization, the use of ultrasound at field scale to improve water quality is promising.Keywords: stagnant, ultrasonic irradiation, water flow, water quality
Procedia PDF Downloads 193197 Managing Crowds at Sports Mega Events: Examining the Impact of ‘Fan Parks’ at International Football Tournaments between 2002 and 2016
Authors: Joel Rookwood
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Sports mega events have become increasingly significant in sporting, political and economic terms, with analysis often focusing on issues including resource expenditure, development, legacy and sustainability. Transnational tournaments can inspire interest from a variety of demographics, and the operational management of such events can involve contributions from a range of personnel. In addition to television audiences events also attract attending spectators, and in football contexts the temporary migration of fans from potentially rival nations and teams can present event organising committees and security personnel with various challenges in relation to crowd management. The behaviour, interaction and control of supporters has previously led to incidents of disorder and hooliganism, with damage to property as well as injuries and deaths proving significant consequences. The Heysel tragedy at the 1985 European Cup final in Brussels is a notable example, where 39 fans died following crowd disorder and mismanagement. Football disasters and disorder, particularly in the context of international competition, have inspired responses from police, law makers, event organisers, clubs and associations, including stadium improvements, legislative developments and crowd management practice to improve the effectiveness of spectator safety. The growth and internationalisation of fandom and developments in event management and tourism have seen various responses to the evolving challenges associated with hosting large numbers of visiting spectators at mega events. In football contexts ‘fan parks’ are a notable example. Since the first widespread introduction in European football competitions at the 2006 World Cup finals in Germany, these facilities have become a staple element of such mega events. This qualitative, longitudinal, multi-continent research draws on extensive semi-structured interview and observation data. As a frame of reference, this work considers football events staged before and after the development of fan parks. Research was undertaken at four World Cup finals (Japan 2002, Germany 2006, South Africa 2010 and Brazil 2014), four European Championships (Portugal 2004, Switzerland/Austria 2008, Poland/Ukraine 2012 and France 2016), four other confederation tournaments (Ghana 2008, Qatar 2011, USA 2011 and Chile 2015), and four European club finals (Istanbul 2005, Athens 2007, Rome 2009 and Basle 2016). This work found that these parks are typically temporarily erected, specifically located zones where supporters congregate together irrespective of allegiances to watch matches on large screens, and partake in other forms of organised on-site entertainment. Such facilities can also allow organisers to control the behaviour, confine the movement and monitor the alcohol consumption of supporters. This represents a notable shift in policy from previous football tournaments, when the widely assumed causal link between alcohol and hooliganism which frequently shaped legislative and police responses to disorder, also dissuaded some authorities from permitting fans to consume alcohol in and around stadia. It also reflects changing attitudes towards modern football fans. The work also found that in certain contexts supporters have increasingly engaged with such provision which impacts fan behaviour, but that this is relative to factors including location, facilities, management and security.Keywords: event, facility, fan, management, park
Procedia PDF Downloads 312196 Synthetic Method of Contextual Knowledge Extraction
Authors: Olga Kononova, Sergey Lyapin
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Global information society requirements are transparency and reliability of data, as well as ability to manage information resources independently; particularly to search, to analyze, to evaluate information, thereby obtaining new expertise. Moreover, it is satisfying the society information needs that increases the efficiency of the enterprise management and public administration. The study of structurally organized thematic and semantic contexts of different types, automatically extracted from unstructured data, is one of the important tasks for the application of information technologies in education, science, culture, governance and business. The objectives of this study are the contextual knowledge typologization, selection or creation of effective tools for extracting and analyzing contextual knowledge. Explication of various kinds and forms of the contextual knowledge involves the development and use full-text search information systems. For the implementation purposes, the authors use an e-library 'Humanitariana' services such as the contextual search, different types of queries (paragraph-oriented query, frequency-ranked query), automatic extraction of knowledge from the scientific texts. The multifunctional e-library «Humanitariana» is realized in the Internet-architecture in WWS-configuration (Web-browser / Web-server / SQL-server). Advantage of use 'Humanitariana' is in the possibility of combining the resources of several organizations. Scholars and research groups may work in a local network mode and in distributed IT environments with ability to appeal to resources of any participating organizations servers. Paper discusses some specific cases of the contextual knowledge explication with the use of the e-library services and focuses on possibilities of new types of the contextual knowledge. Experimental research base are science texts about 'e-government' and 'computer games'. An analysis of the subject-themed texts trends allowed to propose the content analysis methodology, that combines a full-text search with automatic construction of 'terminogramma' and expert analysis of the selected contexts. 'Terminogramma' is made out as a table that contains a column with a frequency-ranked list of words (nouns), as well as columns with an indication of the absolute frequency (number) and the relative frequency of occurrence of the word (in %% ppm). The analysis of 'e-government' materials showed, that the state takes a dominant position in the processes of the electronic interaction between the authorities and society in modern Russia. The media credited the main role in these processes to the government, which provided public services through specialized portals. Factor analysis revealed two factors statistically describing the used terms: human interaction (the user) and the state (government, processes organizer); interaction management (public officer, processes performer) and technology (infrastructure). Isolation of these factors will lead to changes in the model of electronic interaction between government and society. In this study, the dominant social problems and the prevalence of different categories of subjects of computer gaming in science papers from 2005 to 2015 were identified. Therefore, there is an evident identification of several types of contextual knowledge: micro context; macro context; dynamic context; thematic collection of queries (interactive contextual knowledge expanding a composition of e-library information resources); multimodal context (functional integration of iconographic and full-text resources through hybrid quasi-semantic algorithm of search). Further studies can be pursued both in terms of expanding the resource base on which they are held, and in terms of the development of appropriate tools.Keywords: contextual knowledge, contextual search, e-library services, frequency-ranked query, paragraph-oriented query, technologies of the contextual knowledge extraction
Procedia PDF Downloads 359195 The Analgesic Effect of Electroacupuncture in a Murine Fibromyalgia Model
Authors: Bernice Jeanne Lottering, Yi-Wen Lin
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Introduction: Chronic pain has a definitive lack of objective parameters in the measurement and treatment efficacy of diseases such as Fibromyalgia (FM). Persistent widespread pain and generalized tenderness are the characteristic symptoms affecting a large majority of the global population, particularly females. This disease has indicated a refractory tendency to conventional treatment ventures, largely resultant from a lack of etiological and pathogenic understanding of the disease development. Emerging evidence indicates that the central nervous system (CNS) plays a critical role in the amplification of pain signals and the neurotransmitters associated therewith. Various stimuli have been found to activate the channels existent on nociceptor terminals, thereby actuating nociceptive impulses along the pain pathways. The transient receptor potential vanalloid 1 (TRPV1) channel functions as a molecular integrator for numerous sensory inputs, such as nociception, and was explored in the current study. Current intervention approaches face a multitude challenges, ranging from effective therapeutic interventions to the limitation of pathognomonic criteria resultant from incomplete understanding and partial evidence on the mechanisms of action of FM. It remains unclear whether electroacupuncture (EA) plays an integral role in the functioning of the TRPV1 pathway, and whether or not it can reduce the chronic pain induced by FM. Aims: The aim of this study was to explore the mechanisms underlying the activation and modulation of the TRPV1 channel pathway in a cold stress model of FM applied to a murine model. Furthermore, the effect of EA in the treatment of mechanical and thermal pain, as expressed in FM was also to be investigated. Methods: 18 C57BL/6 wild type and 6 TRPV1 knockout (KO) mice, aged 8-12 weeks, were exposed to an intermittent cold stress-induced fibromyalgia-like pain model, with or without EA treatment at ZusanLi ST36 (2Hz/20min) on day 3 to 5. Von Frey and Hargreaves behaviour tests were implemented in order to analyze the mechanical and thermal pain thresholds on day 0, 3 and 5 in control group (C), FM group (FM), FM mice with EA treated group (FM + EA) and FM in KO group. Results: An increase in mechanical and thermal hyperalgesia was observed in the FM, EA and KO groups when compared to the control group. This initial increase was reduced in the EA group, which directs focus at the treatment efficacy of EA in nociceptive sensitization, and the analgesic effect EA has attenuating FM associated pain. Discussion: An increase in the nociceptive sensitization was observed through higher withdrawal thresholds in the von Frey mechanical test and the Hargreaves thermal test. TRPV1 function in mice has been scientifically associated with these nociceptive conduits, and the increased behaviour test results suggest that TRPV1 upregulation is central to the FM induced hyperalgesia. This data was supported by the decrease in sensitivity observed in results of the TRPV1 KO group. Moreover, the treatment of EA showed a decrease in this FM induced nociceptive sensitization, suggesting TRPV1 upregulation and overexpression can be attenuated by EA at bilateral ST36. This evidence compellingly implies that the analgesic effect of EA is associated with TRPV1 downregulation.Keywords: fibromyalgia, electroacupuncture, TRPV1, nociception
Procedia PDF Downloads 139194 Biochemical Effects of Low Dose Dimethyl Sulfoxide on HepG2 Liver Cancer Cell Line
Authors: Esra Sengul, R. G. Aktas, M. E. Sitar, H. Isan
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Hepatocellular carcinoma (HCC) is a hepatocellular tumor commonly found on the surface of the chronic liver. HepG2 is the most commonly used cell type in HCC studies. The main proteins remaining in the blood serum after separation of plasma fibrinogen are albumin and globulin. The fact that the albumin showed hepatocellular damage and reflect the synthesis capacity of the liver was the main reason for our use. Alpha-Fetoprotein (AFP) is an albumin-like structural embryonic globulin found in the embryonic cortex, cord blood, and fetal liver. It has been used as a marker in the follow-up of tumor growth in various malign tumors and in the efficacy of surgical-medical treatments, so it is a good protein to look at with albumins. We have seen the morphological changes of dimethyl sulfoxide (DMSO) on HepG2 and decided to investigate its biochemical effects. We examined the effects of DMSO, which is used in cell cultures, on albumin, AFP and total protein at low doses. Material Method: Cell Culture: Medium was prepared in cell culture using Dulbecco's Modified Eagle Media (DMEM), Fetal Bovine Serum Dulbecco's (FBS), Phosphate Buffered Saline and trypsin maintained at -20 ° C. Fixation of Cells: HepG2 cells, which have been appropriately developed at the end of the first week, were fixed with acetone. We stored our cells in PBS at + 4 ° C until the fixation was completed. Area Calculation: The areas of the cells are calculated in the ImageJ (IJ). Microscope examination: The examination was performed with a Zeiss Inverted Microscope. Daytime photographs were taken at 40x, 100x 200x and 400x. Biochemical Tests: Protein (Total): Serum sample was analyzed by a spectrophotometric method in autoanalyzer. Albumin: Serum sample was analyzed by a spectrophotometric method in autoanalyzer. Alpha-fetoprotein: Serum sample was analyzed by ECLIA method. Results: When liver cancer cells were cultured in medium with 1% DMSO for 4 weeks, a significant difference was observed when compared with the control group. As a result, we have seen that DMSO can be used as an important agent in the treatment of liver cancer. Cell areas were reduced in the DMSO group compared to the control group and the confluency ratio increased. The ability to form spheroids was also significantly higher in the DMSO group. Alpha-fetoprotein was lower than the values of an ordinary liver cancer patient and the total protein amount increased to the reference range of the normal individual. Because the albumin sample was below the specimen value, the numerical results could not be obtained on biochemical examinations. We interpret all these results as making DMSO a caretaking aid. Since each one was not enough alone we used 3 parameters and the results were positive when we refer to the values of a normal healthy individual in parallel. We hope to extend the study further by adding new parameters and genetic analyzes, by increasing the number of samples, and by using DMSO as an adjunct agent in the treatment of liver cancer.Keywords: hepatocellular carcinoma, HepG2, dimethyl sulfoxide, cell culture, ELISA
Procedia PDF Downloads 135193 Treatment Process of Sludge from Leachate with an Activated Sludge System and Extended Aeration System
Authors: A. Chávez, A. Rodríguez, F. Pinzón
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Society is concerned about measures of environmental, economic and social impacts generated in the solid waste disposal. These places of confinement, also known as landfills, are locations where problems of pollution and damage to human health are reduced. They are technically designed and operated, using engineering principles, storing the residue in a small area, compact it to reduce volume and covering them with soil layers. Problems preventing liquid (leachate) and gases produced by the decomposition of organic matter. Despite planning and site selection for disposal, monitoring and control of selected processes, remains the dilemma of the leachate as extreme concentration of pollutants, devastating soil, flora and fauna; aggressive processes requiring priority attention. A biological technology is the activated sludge system, used for tributaries with high pollutant loads. Since transforms biodegradable dissolved and particulate matter into CO2, H2O and sludge; transform suspended and no Settleable solids; change nutrients as nitrogen and phosphorous; and degrades heavy metals. The microorganisms that remove organic matter in the processes are in generally facultative heterotrophic bacteria, forming heterogeneous populations. Is possible to find unicellular fungi, algae, protozoa and rotifers, that process the organic carbon source and oxygen, as well as the nitrogen and phosphorus because are vital for cell synthesis. The mixture of the substrate, in this case sludge leachate, molasses and wastewater is maintained ventilated by mechanical aeration diffusers. Considering as the biological processes work to remove dissolved material (< 45 microns), generating biomass, easily obtained by decantation processes. The design consists of an artificial support and aeration pumps, favoring develop microorganisms (denitrifying) using oxygen (O) with nitrate, resulting in nitrogen (N) in the gas phase. Thus, avoiding negative effects of the presence of ammonia or phosphorus. Overall the activated sludge system includes about 8 hours of hydraulic retention time, which does not prevent the demand for nitrification, which occurs on average in a value of MLSS 3,000 mg/L. The extended aeration works with times greater than 24 hours detention; with ratio of organic load/biomass inventory under 0.1; and average stay time (sludge age) more than 8 days. This project developed a pilot system with sludge leachate from Doña Juana landfill - RSDJ –, located in Bogota, Colombia, where they will be subjected to a process of activated sludge and extended aeration through a sequential Bach reactor - SBR, to be dump in hydric sources, avoiding ecological collapse. The system worked with a dwell time of 8 days, 30 L capacity, mainly by removing values of BOD and COD above 90%, with initial data of 1720 mg/L and 6500 mg/L respectively. Motivating the deliberate nitrification is expected to be possible commercial use diffused aeration systems for sludge leachate from landfills.Keywords: sludge, landfill, leachate, SBR
Procedia PDF Downloads 270192 Collagen/Hydroxyapatite Compositions Doped with Transitional Metals for Bone Tissue Engineering Applications
Authors: D. Ficai, A. Ficai, D. Gudovan, I. A. Gudovan, I. Ardelean, R. Trusca, E. Andronescu, V. Mitran, A. Cimpean
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In the last years, scientists struggled hardly to mimic bone structures to develop implants and biostructures which present higher biocompatibility and reduced rejection rate. One way to obtain this goal is to use similar materials as that of bone, namely collagen/hydroxyapatite composite materials. However, it is very important to tailor both compositions but also the microstructure of the bone that would ensure both the optimal osteointegartion and the mechanical properties required by the application. In this study, new collagen/hydroxyapatites composite materials doped with Cu, Li, Mn, Zn were successfully prepared. The synthesis method is described below: weight the Ca(OH)₂ mass, i.e., 7,3067g, and ZnCl₂ (0.134g), CuSO₄ (0.159g), LiCO₃ (0.133g), MnCl₂.4H₂O (0.1971g), and suspend in 100ml distilled water under magnetic stirring. The solution thus obtained is added a solution of NaH₂PO₄*H2O (8.247g dissolved in 50ml distilled water) under slow dropping of 1 ml/min followed by adjusting the pH to 9.5 with HCl and finally filter and wash until neutral pH. The as-obtained slurry was dried in the oven at 80°C and then calcined at 600°C in order to ensure a proper purification of the final product of organic phases, also inducing a proper sterilization of the mixture before insertion into the collagen matrix. The collagen/hydroxyapatite composite materials are tailored from morphological point of view to optimize their biocompatibility and bio-integration against mechanical properties whereas the addition of the dopants is aimed to improve the biological activity of the samples. The addition of transitional metals can improve the biocompatibility and especially the osteoblasts adhesion (Mn²⁺) or to induce slightly better osteoblast differentiation of the osteoblast, Zn²⁺ being a cofactor for many enzymes including those responsible for cell differentiation. If the amount is too high, the final material can become toxic and lose all of its biocompatibility. In order to achieve a good biocompatibility and not reach the cytotoxic effect, the amount of transitional metals added has to be maintained at low levels (0.5% molar). The amount of transitional metals entering into the elemental cell of HA will be verified using inductively-coupled plasma mass spectrometric system. This highly sensitive technique is necessary, because, at such low levels of transitional metals, the difference between biocompatible and cytotoxic is a very thin line, thus requiring proper and thorough investigation using a precise technique. In order to determine the structure and morphology of the obtained composite materials, IR spectroscopy, X-Ray diffraction (XRD), scanning electron microscopy (SEM), and Energy Dispersive X-Ray Spectrometry (EDS) were used. Acknowledgment: The present work was possible due to the EU-funding grant POSCCE-A2O2.2.1-2013-1, Project No. 638/12.03.2014, code SMIS-CSNR 48652. The financial contribution received from the national project “Biomimetic porous structures obtained by 3D printing developed for bone tissue engineering (BIOGRAFTPRINT), No. 127PED/2017 is also highly acknowledged.Keywords: collagen, composite materials, hydroxyapatite, bone tissue engineering
Procedia PDF Downloads 206191 To Examine Perceptions and Associations of Shock Food Labelling and to Assess the Impact on Consumer Behaviour: A Quasi-Experimental Approach
Authors: Amy Heaps, Amy Burns, Una McMahon-Beattie
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Shock and fear tactics have been used to encourage consumer behaviour change within the UK regarding lifestyle choices such as smoking and alcohol abuse, yet such measures have not been applied to food labels to encourage healthier purchasing decisions. Obesity levels are continuing to rise within the UK, despite efforts made by government and charitable bodies to encourage consumer behavioural changes, which will have a positive influence on their fat, salt, and sugar intake. We know that taking extreme measures to shock consumers into behavioural changes has worked previously; for example, the anti-smoking television adverts and new standardised cigarette and tobacco packaging have reduced the numbers of the UK adult population who smoke or encouraged those who are currently trying to quit. The USA has also introduced new front-of-pack labelling, which is clear, easy to read, and includes concise health warnings on products high in fat, salt, or sugar. This model has been successful, with consumers reducing purchases of products with these warning labels present. Therefore, investigating if shock labels would have an impact on UK consumer behaviour and purchasing decisions would help to fill the gap within this research field. This study aims to develop an understanding of consumer’s initial responses to shock advertising with an interest in the perceived impact of long-term effect shock advertising on consumer food purchasing decisions, behaviour, and attitudes and will achieve this through a mixed methodological approach taken with a sample size of 25 participants ages ranging from 22 and 60. Within this research, shock mock labels were developed, including a graphic image, health warning, and get-help information. These labels were made for products (available within the UK) with large market shares which were high in either fat, salt, or sugar. The use of online focus groups and mouse-tracking experiments results helped to develop an understanding of consumer’s initial responses to shock advertising with interest in the perceived impact of long-term effect shock advertising on consumer food purchasing decisions, behaviour, and attitudes. Preliminary results have shown that consumers believe that the use of graphic images, combined with a health warning, would encourage consumer behaviour change and influence their purchasing decisions regarding those products which are high in fat, salt and sugar. Preliminary main findings show that graphic mock shock labels may have an impact on consumer behaviour and purchasing decisions, which will, in turn, encourage healthier lifestyles. Focus group results show that 72% of participants indicated that these shock labels would have an impact on their purchasing decisions. During the mouse tracking trials, this increased to 80% of participants, showing that more exposure to shock labels may have a bigger impact on potential consumer behaviour and purchasing decision change. In conclusion, preliminary results indicate that graphic shock labels will impact consumer purchasing decisions. Findings allow for a deeper understanding of initial emotional responses to these graphic labels. However, more research is needed to test the longevity of these labels on consumer purchasing decisions, but this research exercise is demonstrably the foundation for future detailed work.Keywords: consumer behavior, decision making, labelling legislation, purchasing decisions, shock advertising, shock labelling
Procedia PDF Downloads 67190 Maintaining Energy Security in Natural Gas Pipeline Operations by Empowering Process Safety Principles Through Alarm Management Applications
Authors: Huseyin Sinan Gunesli
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Process Safety Management is a disciplined framework for managing the integrity of systems and processes that handle hazardous substances. It relies on good design principles, well-implemented automation systems, and operating and maintenance practices. Alarm Management Systems play a critically important role in the safe and efficient operation of modern industrial plants. In that respect, Alarm Management is one of the critical factors feeding the safe operations of the plants in the manner of applying effective process safety principles. Trans Anatolian Natural Gas Pipeline (TANAP) is part of the Southern Gas Corridor, which extends from the Caspian Sea to Italy. TANAP transports Natural Gas from the Shah Deniz gas field of Azerbaijan, and possibly from other neighboring countries, to Turkey and through Trans Adriatic Pipeline (TAP) Pipeline to Europe. TANAP plays a crucial role in maintaining Energy Security for the region and Europe. In that respect, the application of Process Safety principles is vital to deliver safe, reliable and efficient Natural Gas delivery to Shippers both in the region and Europe. Effective Alarm Management is one of those Process Safety principles which feeds safe operations of the TANAP pipeline. Alarm Philosophy was designed and implemented in TANAP Pipeline according to the relevant standards. However, it is essential to manage the alarms received in the control room effectively to maintain safe operations. In that respect, TANAP has commenced Alarm Management & Rationalization program as of February 2022 after transferring to Plateau Regime, reaching the design parameters. While Alarm Rationalization started, there were more than circa 2300 alarms received per hour from one of the compressor stations. After applying alarm management principles such as reviewing and removal of bad actors, standing, stale, chattering, fleeting alarms, comprehensive review and revision of alarm set points through a change management principle, conducting alarm audits/design verification and etc., it has been achieved to reduce down to circa 40 alarms per hour. After the successful implementation of alarm management principles as specified above, the number of alarms has been reduced to industry standards. That significantly improved operator vigilance to focus on mainly important and critical alarms to avoid any excursion beyond safe operating limits leading to any potential process safety events. Following the ‟What Gets Measured, Gets Managed” principle, TANAP has identified key Performance Indicators (KPIs) to manage Process Safety principles effectively, where Alarm Management has formed one of the key parameters of those KPIs. However, review and analysis of the alarms were performed manually. Without utilizing Alarm Management Software, achieving full compliance with international standards is almost infeasible. In that respect, TANAP has started using one of the industry-wide known Alarm Management Applications to maintain full review and analysis of alarms and define actions as required. That actually significantly empowered TANAP’s process safety principles in terms of Alarm Management.Keywords: process safety principles, energy security, natural gas pipeline operations, alarm rationalization, alarm management, alarm management application
Procedia PDF Downloads 103189 Optimization of Perfusion Distribution in Custom Vascular Stent-Grafts Through Patient-Specific CFD Models
Authors: Scott M. Black, Craig Maclean, Pauline Hall Barrientos, Konstantinos Ritos, Asimina Kazakidi
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Aortic aneurysms and dissections are leading causes of death in cardiovascular disease. Both inevitably lead to hemodynamic instability without surgical intervention in the form of vascular stent-graft deployment. An accurate description of the aortic geometry and blood flow in patient-specific cases is vital for treatment planning and long-term success of such grafts, as they must generate physiological branch perfusion and in-stent hemodynamics. The aim of this study was to create patient-specific computational fluid dynamics (CFD) models through a multi-modality, multi-dimensional approach with boundary condition optimization to predict branch flow rates and in-stent hemodynamics in custom stent-graft configurations. Three-dimensional (3D) thoracoabdominal aortae were reconstructed from four-dimensional flow-magnetic resonance imaging (4D Flow-MRI) and computed tomography (CT) medical images. The former employed a novel approach to generate and enhance vessel lumen contrast via through-plane velocity at discrete, user defined cardiac time steps post-hoc. To produce patient-specific boundary conditions (BCs), the aortic geometry was reduced to a one-dimensional (1D) model. Thereafter, a zero-dimensional (0D) 3-Element Windkessel model (3EWM) was coupled to each terminal branch to represent the distal vasculature. In this coupled 0D-1D model, the 3EWM parameters were optimized to yield branch flow waveforms which are representative of the 4D Flow-MRI-derived in-vivo data. Thereafter, a 0D-3D CFD model was created, utilizing the optimized 3EWM BCs and a 4D Flow-MRI-obtained inlet velocity profile. A sensitivity analysis on the effects of stent-graft configuration and BC parameters was then undertaken using multiple stent-graft configurations and a range of distal vasculature conditions. 4D Flow-MRI granted unparalleled visualization of blood flow throughout the cardiac cycle in both the pre- and postsurgical states. Segmentation and reconstruction of healthy and stented regions from retrospective 4D Flow-MRI images also generated 3D models with geometries which were successfully validated against their CT-derived counterparts. 0D-1D coupling efficiently captured branch flow and pressure waveforms, while 0D-3D models also enabled 3D flow visualization and quantification of clinically relevant hemodynamic parameters for in-stent thrombosis and graft limb occlusion. It was apparent that changes in 3EWM BC parameters had a pronounced effect on perfusion distribution and near-wall hemodynamics. Results show that the 3EWM parameters could be iteratively changed to simulate a range of graft limb diameters and distal vasculature conditions for a given stent-graft to determine the optimal configuration prior to surgery. To conclude, this study outlined a methodology to aid in the prediction post-surgical branch perfusion and in-stent hemodynamics in patient specific cases for the implementation of custom stent-grafts.Keywords: 4D flow-MRI, computational fluid dynamics, vascular stent-grafts, windkessel
Procedia PDF Downloads 181188 Surviral: An Agent-Based Simulation Framework for Sars-Cov-2 Outcome Prediction
Authors: Sabrina Neururer, Marco Schweitzer, Werner Hackl, Bernhard Tilg, Patrick Raudaschl, Andreas Huber, Bernhard Pfeifer
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History and the current outbreak of Covid-19 have shown the deadly potential of infectious diseases. However, infectious diseases also have a serious impact on areas other than health and healthcare, such as the economy or social life. These areas are strongly codependent. Therefore, disease control measures, such as social distancing, quarantines, curfews, or lockdowns, have to be adopted in a very considerate manner. Infectious disease modeling can support policy and decision-makers with adequate information regarding the dynamics of the pandemic and therefore assist in planning and enforcing appropriate measures that will prevent the healthcare system from collapsing. In this work, an agent-based simulation package named “survival” for simulating infectious diseases is presented. A special focus is put on SARS-Cov-2. The presented simulation package was used in Austria to model the SARS-Cov-2 outbreak from the beginning of 2020. Agent-based modeling is a relatively recent modeling approach. Since our world is getting more and more complex, the complexity of the underlying systems is also increasing. The development of tools and frameworks and increasing computational power advance the application of agent-based models. For parametrizing the presented model, different data sources, such as known infections, wastewater virus load, blood donor antibodies, circulating virus variants and the used capacity for hospitalization, as well as the availability of medical materials like ventilators, were integrated with a database system and used. The simulation result of the model was used for predicting the dynamics and the possible outcomes and was used by the health authorities to decide on the measures to be taken in order to control the pandemic situation. The survival package was implemented in the programming language Java and the analytics were performed with R Studio. During the first run in March 2020, the simulation showed that without measures other than individual personal behavior and appropriate medication, the death toll would have been about 27 million people worldwide within the first year. The model predicted the hospitalization rates (standard and intensive care) for Tyrol and South Tyrol with an accuracy of about 1.5% average error. They were calculated to provide 10-days forecasts. The state government and the hospitals were provided with the 10-days models to support their decision-making. This ensured that standard care was maintained for as long as possible without restrictions. Furthermore, various measures were estimated and thereafter enforced. Among other things, communities were quarantined based on the calculations while, in accordance with the calculations, the curfews for the entire population were reduced. With this framework, which is used in the national crisis team of the Austrian province of Tyrol, a very accurate model could be created on the federal state level as well as on the district and municipal level, which was able to provide decision-makers with a solid information basis. This framework can be transferred to various infectious diseases and thus can be used as a basis for future monitoring.Keywords: modelling, simulation, agent-based, SARS-Cov-2, COVID-19
Procedia PDF Downloads 174187 Food Consumption and Adaptation to Climate Change: Evidence from Ghana
Authors: Frank Adusah-Poku, John Bosco Dramani, Prince Boakye Frimpong
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Climate change is considered a principal threat to human existence and livelihood. The persistence and intensity of droughts and floods in recent years have adversely affected food production systems and value chains, making it impossible to end global hunger by 2030. Thus, this study aims to examine the effect of climate change on food consumption for both farm and non-farm households in Ghana. An important focus of the analysis is to investigate how climate change affects alternative dimensions of food security, examine the extent to which these effects vary across heterogeneous groups, and explore the channels through which climate change affects food consumption. Finally, we conducted a pilot study to understand the significance of farm and non-farm diversification measures in reducing the harmful impact of climate change on farm households. The approach of this article is to use two secondary and one primary datasets. The first secondary dataset is the Ghana Socioeconomic Panel Survey (GSPS). The GSPS is a household panel dataset collected during the period 2009 to 2019. The second dataset is monthly district rainfall and temperature gridded data from the Ghana Meteorological Agency. This data was matched to the GSPS dataset at the district level. Finally, the primary data was obtained from a survey of farm and non-farm adaptation practices used by farmers in three regions in Northern Ghana. The study employed the household fixed effects model to estimate the effect of climate change (measured by temperature and rainfall) on food consumption in Ghana. Again, it used the spatial and temporal variation in temperature and rainfall across the districts in Ghana to estimate the household-level model. Evidence of potential mechanisms through which climate change affects food consumption was explored using two steps. First, the potential mechanism variables were regressed on temperature, rainfall, and the control variables. In the second and final step, the potential mechanism variables were included as extra covariates in the first model. The results revealed that extreme average temperature and drought had caused a decrease in food consumption as well as reduced the intake of important food nutrients such as carbohydrates, protein and vitamins. The results further indicated that low rainfall increased food insecurity among households with no education compared with those with primary and secondary education. Again, non-farm activity and silos have been revealed as the transmission pathways through which the effect of climate change on farm households can be moderated. Finally, the results indicated over 90% of the small-holder farmers interviewed had no farm diversification adaptation strategies for climate change, and a little over 50% of the farmers owned unskilled or manual non-farm economic ventures. This makes it very difficult for the majority of the farmers to withstand climate-related shocks. These findings suggest that achieving the Sustainable Development Goal of Zero Hunger by 2030 needs an integrated approach, such as reducing the over-reliance on rainfed agriculture, educating farmers, and implementing non-farm interventions to improve food consumption in Ghana.Keywords: climate change, food consumption, Ghana, non-farm activity
Procedia PDF Downloads 6186 Brittle Fracture Tests on Steel Bridge Bearings: Application of the Potential Drop Method
Authors: Natalie Hoyer
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Usually, steel structures are designed for the upper region of the steel toughness-temperature curve. To address the reduced toughness properties in the temperature transition range, additional safety assessments based on fracture mechanics are necessary. These assessments enable the appropriate selection of steel materials to prevent brittle fracture. In this context, recommendations were established in 2011 to regulate the appropriate selection of steel grades for bridge bearing components. However, these recommendations are no longer fully aligned with more recent insights: Designing bridge bearings and their components in accordance with DIN EN 1337 and the relevant sections of DIN EN 1993 has led to an increasing trend of using large plate thicknesses, especially for long-span bridges. However, these plate thicknesses surpass the application limits specified in the national appendix of DIN EN 1993-2. Furthermore, compliance with the regulations outlined in DIN EN 1993-1-10 regarding material toughness and through-thickness properties requires some further modifications. Therefore, these standards cannot be directly applied to the material selection for bearings without additional information. In addition, recent findings indicate that certain bridge bearing components are subjected to high fatigue loads, necessitating consideration in structural design, material selection, and calculations. To address this issue, the German Center for Rail Traffic Research initiated a research project aimed at developing a proposal to enhance the existing standards. This proposal seeks to establish guidelines for the selection of steel materials for bridge bearings to prevent brittle fracture, particularly for thick plates and components exposed to specific fatigue loads. The results derived from theoretical analyses, including finite element simulations and analytical calculations, are verified through component testing on a large-scale. During these large-scale tests, where a brittle failure is deliberately induced in a bearing component, an artificially generated defect is introduced into the specimen at the predetermined hotspot. Subsequently, a dynamic load is imposed until the crack initiation process transpires, replicating realistic conditions akin to a sharp notch resembling a fatigue crack. To stop the action of the dynamic load in time, it is important to precisely determine the point at which the crack size transitions from stable crack growth to unstable crack growth. To achieve this, the potential drop measurement method is employed. The proposed paper informs about the choice of measurement method (alternating current potential drop (ACPD) or direct current potential drop (DCPD)), presents results from correlations with created FE models, and may proposes a new approach to introduce beach marks into the fracture surface within the framework of potential drop measurement.Keywords: beach marking, bridge bearing design, brittle fracture, design for fatigue, potential drop
Procedia PDF Downloads 42185 Application of Discrete-Event Simulation in Health Technology Assessment: A Cost-Effectiveness Analysis of Alzheimer’s Disease Treatment Using Real-World Evidence in Thailand
Authors: Khachen Kongpakwattana, Nathorn Chaiyakunapruk
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Background: Decision-analytic models for Alzheimer’s disease (AD) have been advanced to discrete-event simulation (DES), in which individual-level modelling of disease progression across continuous severity spectra and incorporation of key parameters such as treatment persistence into the model become feasible. This study aimed to apply the DES to perform a cost-effectiveness analysis of treatment for AD in Thailand. Methods: A dataset of Thai patients with AD, representing unique demographic and clinical characteristics, was bootstrapped to generate a baseline cohort of patients. Each patient was cloned and assigned to donepezil, galantamine, rivastigmine, memantine or no treatment. Throughout the simulation period, the model randomly assigned each patient to discrete events including hospital visits, treatment discontinuation and death. Correlated changes in cognitive and behavioral status over time were developed using patient-level data. Treatment effects were obtained from the most recent network meta-analysis. Treatment persistence, mortality and predictive equations for functional status, costs (Thai baht (THB) in 2017) and quality-adjusted life year (QALY) were derived from country-specific real-world data. The time horizon was 10 years, with a discount rate of 3% per annum. Cost-effectiveness was evaluated based on the willingness-to-pay (WTP) threshold of 160,000 THB/QALY gained (4,994 US$/QALY gained) in Thailand. Results: Under a societal perspective, only was the prescription of donepezil to AD patients with all disease-severity levels found to be cost-effective. Compared to untreated patients, although the patients receiving donepezil incurred a discounted additional costs of 2,161 THB, they experienced a discounted gain in QALY of 0.021, resulting in an incremental cost-effectiveness ratio (ICER) of 138,524 THB/QALY (4,062 US$/QALY). Besides, providing early treatment with donepezil to mild AD patients further reduced the ICER to 61,652 THB/QALY (1,808 US$/QALY). However, the dominance of donepezil appeared to wane when delayed treatment was given to a subgroup of moderate and severe AD patients [ICER: 284,388 THB/QALY (8,340 US$/QALY)]. Introduction of a treatment stopping rule when the Mini-Mental State Exam (MMSE) score goes below 10 to a mild AD cohort did not deteriorate the cost-effectiveness of donepezil at the current treatment persistence level. On the other hand, none of the AD medications was cost-effective when being considered under a healthcare perspective. Conclusions: The DES greatly enhances real-world representativeness of decision-analytic models for AD. Under a societal perspective, treatment with donepezil improves patient’s quality of life and is considered cost-effective when used to treat AD patients with all disease-severity levels in Thailand. The optimal treatment benefits are observed when donepezil is prescribed since the early course of AD. With healthcare budget constraints in Thailand, the implementation of donepezil coverage may be most likely possible when being considered starting with mild AD patients, along with the stopping rule introduced.Keywords: Alzheimer's disease, cost-effectiveness analysis, discrete event simulation, health technology assessment
Procedia PDF Downloads 129184 Leading, Teaching and Learning “in the Middle”: Experiences, Beliefs, and Values of Instructional Leaders, Teachers, and Students in Finland, Germany, and Canada
Authors: Brandy Yee, Dianne Yee
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Through the exploration of the lived experiences, beliefs and values of instructional leaders, teachers and students in Finland, Germany and Canada, we investigated the factors which contribute to developmentally responsive, intellectually engaging middle-level learning environments for early adolescents. Student-centred leadership dimensions, effective instructional practices and student agency were examined through the lens of current policy and research on middle-level learning environments emerging from the Canadian province of Manitoba. Consideration of these three research perspectives in the context of early adolescent learning, placed against an international backdrop, provided a previously undocumented perspective on leading, teaching and learning in the middle years. Aligning with a social constructivist, qualitative research paradigm, the study incorporated collective case study methodology, along with constructivist grounded theory methods of data analysis. Data were collected through semi-structured individual and focus group interviews and document review, as well as direct and participant observation. Three case study narratives were developed to share the rich stories of study participants, who had been selected using maximum variation and intensity sampling techniques. Interview transcript data were coded using processes from constructivist grounded theory. A cross-case analysis yielded a conceptual framework highlighting key factors that were found to be significant in the establishment of developmentally responsive, intellectually engaging middle-level learning environments. Seven core categories emerged from the cross-case analysis as common to all three countries. Within the visual conceptual framework (which depicts the interconnected nature of leading, teaching and learning in middle-level learning environments), these seven core categories were grouped into Essential Factors (student agency, voice and choice), Contextual Factors (instructional practices; school culture; engaging families and the community), Synergistic Factors (instructional leadership) and Cornerstone Factors (education as a fundamental cultural value; preservice, in-service and ongoing teacher development). In addition, sub-factors emerged from recurring codes in the data and identified specific characteristics and actions found in developmentally responsive, intellectually engaging middle-level learning environments. Although this study focused on 12 schools in Finland, Germany and Canada, it informs the practice of educators working with early adolescent learners in middle-level learning environments internationally. The authentic voices of early adolescent learners are the most important resource educators have to gauge if they are creating effective learning environments for their students. Ongoing professional dialogue and learning is essential to ensure teachers are supported in their work and develop the pedagogical practices needed to meet the needs of early adolescent learners. It is critical to balance consistency, coherence and dependability in the school environment with the necessary flexibility in order to support the unique learning needs of early adolescents. Educators must intentionally create a school culture that unites teachers, students and their families in support of a common purpose, as well as nurture positive relationships between the school and its community. A large, urban school district in Canada has implemented a school cohort-based model to begin to bring developmentally responsive, intellectually engaging middle-level learning environments to scale.Keywords: developmentally responsive learning environments, early adolescents, middle level learning, middle years, instructional leadership, instructional practices, intellectually engaging learning environments, leadership dimensions, student agency
Procedia PDF Downloads 304183 Supplementation of Yeast Cell Wall on Growth Performance in Broiler Reared under High Ambient Temperature
Authors: Muhammad Shahzad Hussain
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Two major problems are facing generally by conventional poultry farming that is disease outbreaks and poor performance, which results due to improper management. To enhance the growth performance and efficiency of feed and reduce disease outbreaks, antibiotic growth promoters (AGPs) which are antibiotics at sub-therapeutic levels, are extensively used in the poultry industry. European Union has banned the use of antibiotics due to their presence in poultry products, development of antibiotic-resistant pathogens, and disturbance of normal gut microbial ecology. These residues cause serious health concerns and produce antibiotic resistance in pathogenic microbes in human beings. These issues strengthen the need for the withdrawal of AGPs from poultry feed. Nowadays, global warming is a major issue, and it is more critical in tropical areas like Pakistan, where heat stress is already a major problem. Heat stress leads to poor production performance, high mortality, immuno-suppression, and concomitant diseases outbreak. The poultry feed industry in Pakistan, like other countries of the world, has been facing shortages and high prices of local as well as imported feed ingredients. Prebiotics are potential replacer for AGP as prebiotics has properties to enhance the production potential and reduce the growth of harmful bacteria as well as stimulate the growth/activity of beneficial bacteria. The most commonly used prebiotics in poultry includes mannan oligosaccharide (MOS). MOS is an essential component of the yeast cell wall (YCW) (Saccharomyces cerevisiae); therefore, the YCW wall possesses prebiotic properties. The use of distillery yeast wall (YCW) has the potential to replace conventional AGPs and to reduce mortality due to heat stress as well as to bind toxins in the feed. The dietary addition of YCW has not only positive effects on production performance in poultry during normal conditions but during stressful conditions. A total of 168-day-old broilers were divided into 6 groups, each of which has 28 birds with 4 replicates (n=7).Yeast cell wall (YCW) supplementation @ 0%, 1%, 1.5%, 2%, 2.5%, 3% from day 0 to 35. Heat stress was exposed from day 21 to 35 at 30±1.1ᵒC with relative humidity 65±5%. Zootechnical parameters like body weight, FCR, Organ development, and histomorphometric parameters were studied. A significant weight gain was observed at group C supplemented @ 1.5% YCW during the fifth week. Significant organ weight gain of Gizzard, spleen, small intestine, and cecum was observed at group C supplemented @ 1.5% YCW. According to morphometric indices Duodenum, Jejunum, and Ileum has significant villus height, while Jejunum and Ileum have also significant villus surface area in the group supplemented with 1.5% YCW. IEL count was only decreased in 1.5% YCW-fed group in jejunum and ileum, not in duodenum, that was less in 2% YCW-supplemented group. Dietary yeast cell wall of saccharomyces cerevisiae partially reduced the effects of high ambient temperature in terms of better growth and modified gut histology and components of mucosal immune response to better withstand heat stress in broilers.Keywords: antibiotics, AGPs, broilers, MOS, prebiotics, YCW
Procedia PDF Downloads 95182 Multi-Modality Brain Stimulation: A Treatment Protocol for Tinnitus
Authors: Prajakta Patil, Yash Huzurbazar, Abhijeet Shinde
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Aim: To develop a treatment protocol for the management of tinnitus through multi-modality brain stimulation. Methodology: Present study included 33 adults with unilateral (31 subjects) and bilateral (2 subjects) chronic tinnitus with and/or without hearing loss independent of their etiology. The Treatment protocol included 5 consecutive sessions with follow-up of 6 months. Each session was divided into 3 parts: • Pre-treatment: a) Informed consent b) Pitch and loudness matching. • Treatment: Bimanual paper pen task with tinnitus masking for 30 minutes. • Post-treatment: a) Pitch and loudness matching b) Directive counseling and obtaining feedback. Paper-pen task is to be performed bimanually that included carrying out two different writing activities in different context. The level of difficulty of the activities was increased in successive sessions. Narrowband noise of a frequency same as that of tinnitus was presented at 10 dBSL of tinnitus for 30 minutes simultaneously in the ear with tinnitus. Result: The perception of tinnitus was no longer present in 4 subjects while in remaining subjects it reduced to an intensity that its perception no longer troubled them without causing residual facilitation. In all subjects, the intensity of tinnitus decreased by an extent of 45 dB at an average. However, in few subjects, the intensity of tinnitus also decreased by more than 45 dB. The approach resulted in statistically significant reductions in Tinnitus Functional Index and Tinnitus Handicap Inventory scores. The results correlate with pre and post treatment score of Tinnitus Handicap Inventory that dropped from 90% to 0%. Discussion: Brain mapping(qEEG) Studies report that there is multiple parallel overlapping of neural subnetworks in the non-auditory areas of the brain which exhibits abnormal, constant and spontaneous neural activity involved in the perception of tinnitus with each subnetwork and area reflecting a specific aspect of tinnitus percept. The paper pen task and directive counseling are designed and delivered respectively in a way that is assumed to induce normal, rhythmically constant and premeditated neural activity and mask the abnormal, constant and spontaneous neural activity in the above-mentioned subnetworks and the specific non-auditory area. Counseling was focused on breaking the vicious cycle causing and maintaining the presence of tinnitus. Diverting auditory attention alone is insufficient to reduce the perception of tinnitus. Conscious awareness of tinnitus can be suppressed when individuals engage in cognitively demanding tasks of non-auditory nature as the paper pen task used in the present study. To carry out this task selective, divided, sustained, simultaneous and split attention act cumulatively. Bimanual paper pen task represents a top-down activity which underlies brain’s ability to selectively attend to the bimanual written activity as a relevant stimulus and to ignore tinnitus that is the irrelevant stimuli in the present study. Conclusion: The study suggests that this novel treatment approach is cost effective, time saving and efficient to vanish the tinnitus or to reduce the intensity of tinnitus to a negligible level and thereby eliminating the negative reactions towards tinnitus.Keywords: multi-modality brain stimulation, neural subnetworks, non-auditory areas, paper-pen task, top-down activity
Procedia PDF Downloads 147181 Longitudinal Examination of Depressive Symptoms among U.S. Parents who Gave Birth During the COVID-19 Pandemic
Authors: Amy Claridge, Tishra Beeson
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Background: Maternal depression is a serious health concern impacting between 10-16% of birthing persons. It is associated with difficulty in emotional interaction and the formation of attachment bonds between parent and infant. Longitudinally, maternal depression can have severe, lasting impacts on both parent and child, increasing the risk for mental, social, and physical health issues. Rates of prenatal depression have been higher among individuals who were pregnant during the first year of the COVID-19 pandemic. Pregnant persons are considered a high-risk group for poor clinical outcomes from COVID-19 infection and may also have faced or continue to face additional stressors such as financial burdens, loss of income or employment, and the benefits accompanying employment, especially among those in the United States (U.S.). It is less clear whether individuals who gave birth during the pandemic continue to experience high levels of depressive symptoms or whether symptoms have been reduced as a pandemic response has shifted. The current study examined longitudinal reports of depressive symptoms among individuals in the U.S. who gave birth between March 2020 and September 2021. Methods: This mixed-method study involved surveys and interviews with birthing persons (18-45 years old) in their third trimester of pregnancy and at 8 weeks postpartum. Participants also completed a follow-up survey at 12-18 months postpartum. Participants were recruited using convenience methods via an online survey. Survey participants included 242 U.S. women who self-reported depressive symptoms (10-item Edinburgh Postnatal Depression Scale) at each data collection wave. A subset of 23 women participated in semi-structured prenatal and 8-week postpartum qualitative interviews. Follow-up interviews are currently underway and will be integrated into the presentation. Preliminary Results: Prenatal depressive symptoms were significantly positively correlated to 8-week and 12-18-month postpartum depressive symptoms. Participants who reported clinical levels of depression prenatally were 3.29 times (SE = .32, p < .001) more likely to report clinical levels of depression at 18 months postpartum. Those who reported clinical depression at 8-weeks postpartum were 6.52 times (SE = .41, p < .001) more likely to report clinical levels of depression at 18 months postpartum. Participants who gave birth earlier in the pandemic reported significantly higher prenatal (t(103) = 2.84, p < .01) and 8-week postpartum depressive symptoms (t(126) = 3.31, p < .001). Data from qualitative interviews contextualize the findings. Participants reported negative emotions during pregnancy, including sadness, grief, and anxiety. They attributed this in part to their experiences of pregnancy during the pandemic and uncertainty related to the birth experience and postpartum period. Postpartum interviews revealed some stressors specific to childbirth during the COVID-19 pandemic; however, most women reflected on positive experiences of birth and postpartum. Conclusions: Taken together, findings reveal a pattern of persistent depressive symptoms among U.S. parents who gave birth during the pandemic. Depressive symptoms are of significant concern for the health of parents and children, and the findings of this study suggest a need for continued mental health intervention for parents who gave birth during the pandemic. Policy and practice implications will be discussed.Keywords: maternal mental health, perinatal depression, postpartum depression, covid-19 pandemic
Procedia PDF Downloads 77180 CD97 and Its Role in Glioblastoma Stem Cell Self-Renewal
Authors: Niklas Ravn-Boess, Nainita Bhowmick, Takamitsu Hattori, Shohei Koide, Christopher Park, Dimitris Placantonakis
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Background: Glioblastoma (GBM) is the most common and deadly primary brain malignancy in adults. Tumor propagation, brain invasion, and resistance to therapy critically depend on GBM stem-like cells (GSCs); however, the mechanisms that regulate GSC self-renewal are incompletely understood. Given the aggressiveness and poor prognosis of GBM, it is imperative to find biomarkers that could also translate into novel drug targets. Along these lines, we have identified a cell surface antigen, CD97 (ADGRE5), an adhesion G protein-coupled receptor (GPCR), that is expressed on GBM cells but is absent from non-neoplastic brain tissue. CD97 has been shown to promote invasiveness, angiogenesis, and migration in several human cancers, but its frequency of expression and functional role in regulating GBM growth and survival, and its potential as a therapeutic target has not been investigated. Design: We assessed CD97 mRNA and protein expression in patient derived GBM samples and cell lines using publicly available RNA-sequencing datasets and flow cytometry, respectively. To assess CD97 function, we generated shRNA lentiviral constructs that target a sequence in the CD97 extracellular domain (ECD). A scrambled shRNA (scr) with no predicted targets in the genome was used as a control. We evaluated CD97 shRNA lentivirally transduced GBM cells for Ki67, Annexin V, and DAPI. We also tested CD97 KD cells for their ability to self-renew using clonogenic tumorsphere formation assays. Further, we utilized synthetic Abs (sAbs) generated against the ECD of CD97 to test for potential antitumor effects using patient-derived GBM cell lines. Results: CD97 mRNA expression was expressed at high levels in all GBM samples available in the TCGA cohort. We found high levels of surface CD97 protein expression in 6/6 patient-derived GBM cell cultures, but not human neural stem cells. Flow cytometry confirmed downregulation of CD97 in CD97 shRNA lentivirally transduced cells. CD97 KD induced a significant reduction in cell growth in 3 independent GBM cell lines representing mesenchymal and proneural subtypes, which was accompanied by reduced (~20%) Ki67 staining and increased (~30%) apoptosis. Incubation of GBM cells with sAbs (20 ug/ ml) against the ECD of CD97 for 3 days induced GSC differentiation, as determined by the expression of GFAP and Tubulin. Using three unique GBM patient derived cultures, we found that CD97 KD attenuated the ability of GBM cells to initiate sphere formation by over 300 fold, consistent with an impairment in GSC self-renewal. Conclusion: Loss of CD97 expression in patient-derived GBM cells markedly decreases proliferation, induces cell death, and reduces tumorsphere formation. sAbs against the ECD of CD97 reduce tumorsphere formation, recapitulating the phenotype of CD97 KD, suggesting that sAbs that inhibit CD97 function exhibit anti-tumor activity. Collectively, these findings indicate that CD97 is necessary for the proliferation and survival of human GBM cells and identify CD97 as a promising therapeutically targetable vulnerability in GBM.Keywords: adhesion GPCR, CD97, GBM stem cell, glioblastoma
Procedia PDF Downloads 137179 Optimization of Metal Pile Foundations for Solar Power Stations Using Cone Penetration Test Data
Authors: Adrian Priceputu, Elena Mihaela Stan
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Our research addresses a critical challenge in renewable energy: improving efficiency and reducing the costs associated with the installation of ground-mounted photovoltaic (PV) panels. The most commonly used foundation solution is metal piles - with various sections adapted to soil conditions and the structural model of the panels. However, direct foundation systems are also sometimes used, especially in brownfield sites. Although metal micropiles are generally the first design option, understanding and predicting their bearing capacity, particularly under varied soil conditions, remains an open research topic. CPT Method and Current Challenges: Metal piles are favored for PV panel foundations due to their adaptability, but existing design methods rely heavily on costly and time-consuming in situ tests. The Cone Penetration Test (CPT) offers a more efficient alternative by providing valuable data on soil strength, stratification, and other key characteristics with reduced resources. During the test, a cone-shaped probe is pushed into the ground at a constant rate. Sensors within the probe measure the resistance of the soil to penetration, divided into cone penetration resistance and shaft friction resistance. Despite some existing CPT-based design approaches for metal piles, these methods are often cumbersome and difficult to apply. They vary significantly due to soil type and foundation method, and traditional approaches like the LCPC method involve complex calculations and extensive empirical data. The method was developed by testing 197 piles on a wide range of ground conditions, but the tested piles were very different from the ones used for PV pile foundations, making the method less accurate and practical for steel micropiles. Project Objectives and Methodology: Our research aims to develop a calculation method for metal micropile foundations using CPT data, simplifying the complex relationships involved. The goal is to estimate the pullout bearing capacity of piles without additional laboratory tests, streamlining the design process. To achieve this, a case study was selected which will serve for the development of an 80ha solar power station. Four testing locations were chosen spread throughout the site. At each location, two types of steel profiles (H160 and C100) were embedded into the ground at various depths (1.5m and 2.0m). The piles were tested for pullout capacity under natural and inundated soil conditions. CPT tests conducted nearby served as calibration points. The results served for the development of a preliminary equation for estimating pullout capacity. Future Work: The next phase involves validating and refining the proposed equation on additional sites by comparing CPT-based forecasts with in situ pullout tests. This validation will enhance the accuracy and reliability of the method, potentially transforming the foundation design process for PV panels.Keywords: cone penetration test, foundation optimization, solar power stations, steel pile foundations
Procedia PDF Downloads 54178 Evaluation of Toxicity of Cerium Oxide on Zebrafish Developmental Stages
Authors: Roberta Pecoraro, Elena Maria Scalisi
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Engineered Nanoparticles (ENPs) and Nanomaterials (ENMs) concern an active research area and a sector in full expansion. They have physical-chemical characteristics and small size that improve their performance compared to common materials. Due to the increase in their production and their subsequent release into the environment, new strategies are emerging to assess risk of nanomaterials. NPs can be released into the environment through aquatic systems by human activities and exert toxicity on living organisms. We evaluated the potential toxic effect of cerium oxide (CeO2) nanoparticles because it’s used in different fields due to its peculiar properties. In order to assess nanoparticles toxicity, Fish Embryo Toxicity (FET) test was performed. Powders of CeO2 NPs supplied by the CNR-IMM of Catania are indicated as CeO2 type 1 (as-prepared) and CeO2 type 2 (modified), while CeO2 type 3 (commercial) is supplied by Sigma-Aldrich. Starting from a stock solution (0.001g/10 ml dilution water) of each type of CeO2 NPs, the other concentration solutions were obtained adding 1 ml of the stock solution to 9 ml of dilution water, leading to three different solutions of concentration (10-4, 10-5, 10-6 g/ml). All the solutions have been sonicated to avoid natural tendency of NPs to aggregate and sediment. FET test was performed according to the OECD guidelines for testing chemicals using our internal protocol procedure. A number of eight selected fertilized eggs were placed in each becher filled with 5 ml of each concentration of the three types of CeO2 NPs; control samples were incubated only with dilution water. Replication was performed for each concentration. During the exposure period, we observed four endpoints (embryo coagulation, lack of formation of somites, failure to lift the yolk bag, no heartbeat) by a stereomicroscope every 24 hours. Immunohistochemical analysis on treated larvae was performed to evaluate the expression of metallothioneins (MTs), Heat Shock Proteins 70 (HSP70) and 7-ethoxyresorufin-O-diethylase (EROD). Our results have not shown evident alterations on embryonic development because all embryos completed the development and the hatching of the eggs, started around the 48th hour after exposure, took place within the last observation at 72 hours. A good reactivity, both in the embryos and in the newly hatched larvae, was found. The presence of heartbeat has also been observed in embryos with reduced mobility confirming their viability. A higher expression of EROD biomarker was observed in the larvae exposed to the three types of CeO2, showing a clear difference with the control. A weak positivity was found for MTs biomarker in treated larvae as well as in the control. HSP70 are expressed homogeneously in all the type of nanoparticles tested but not too much greater than control. Our results are in agreement with other studies in the literature, in which the exposure of Danio rerio larvae to other metal oxide nanoparticles does not show adverse effects on survival and hatching time. Further studies are necessary to clarify the role of these NPs and also to solve conflicting opinions.Keywords: Danio rerio, endpoints, fish embryo toxicity test, metallic nanoparticles
Procedia PDF Downloads 132177 Investigating the Association between Escherichia Coli Infection and Breast Cancer Incidence: A Retrospective Analysis and Literature Review
Authors: Nadia Obaed, Lexi Frankel, Amalia Ardeljan, Denis Nigel, Anniki Witter, Omar Rashid
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Breast cancer is the most common cancer among women, with a lifetime risk of one in eight of all women in the United States. Although breast cancer is prevalent throughout the world, the uneven distribution in incidence and mortality rates is shaped by the variation in population structure, environment, genetics and known lifestyle risk factors. Furthermore, the bacterial profile in healthy and cancerous breast tissue differs with a higher relative abundance of bacteria capable of causing DNA damage in breast cancer patients. Previous bacterial infections may change the composition of the microbiome and partially account for the environmental factors promoting breast cancer. One study found that higher amounts of Staphylococcus, Bacillus, and Enterobacteriaceae, of which Escherichia coli (E. coli) is a part, were present in breast tumor tissue. Based on E. coli’s ability to damage DNA, it is hypothesized that there is an increased risk of breast cancer associated with previous E. coli infection. Therefore, the purpose of this study was to evaluate the correlation between E. coli infection and the incidence of breast cancer. Holy Cross Health, Fort Lauderdale, provided access to the Health Insurance Portability and Accountability (HIPAA) compliant national database for the purpose of academic research. International Classification of Disease 9th and 10th Codes (ICD-9, ICD-10) was then used to conduct a retrospective analysis using data from January 2010 to December 2019. All breast cancer diagnoses and all patients infected versus not infected with E. coli that underwent typical E. coli treatment were investigated. The obtained data were matched for age, Charlson Comorbidity Score (CCI score), and antibiotic treatment. Standard statistical methods were applied to determine statistical significance and an odds ratio was used to estimate the relative risk. A total of 81286 patients were identified and analyzed from the initial query and then reduced to 31894 antibiotic-specific treated patients in both the infected and control group, respectively. The incidence of breast cancer was 2.51% and present in 2043 patients in the E. coli group compared to 5.996% and present in 4874 patients in the control group. The incidence of breast cancer was 3.84% and present in 1223 patients in the treated E. coli group compared to 6.38% and present in 2034 patients in the treated control group. The decreased incidence of breast cancer in the E. coli and treated E. coli groups was statistically significant with a p-value of 2.2x10-16 and 2.264x10-16, respectively. The odds ratio in the E. coli and treated E. coli groups was 0.784 and 0.787 with a 95% confidence interval, respectively (0.756-0.813; 0.743-0.833). The current study shows a statistically significant decrease in breast cancer incidence in association with previous Escherichia coli infection. Researching the relationship between single bacterial species is important as only up to 10% of breast cancer risk is attributable to genetics, while the contribution of environmental factors including previous infections potentially accounts for a majority of the preventable risk. Further evaluation is recommended to assess the potential and mechanism of E. coli in decreasing the risk of breast cancer.Keywords: breast cancer, escherichia coli, incidence, infection, microbiome, risk
Procedia PDF Downloads 253176 Anti-tuberculosis, Resistance Modulatory, Anti-pulmonary Fibrosis and Anti-silicosis Effects of Crinum Asiaticum Bulbs and Its Active Metabolite, Betulin
Authors: Theophilus Asante, Comfort Nyarko, Daniel Antwi
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Drug-resistant tuberculosis, together with the associated comorbidities like pulmonary fibrosis and silicosis, has been one of the most serious global public health threats that requires immediate action to curb or mitigate it. This prolongs hospital stays, increases the cost of medication, and increases the death toll recorded annually. Crinum asiaticum bulb (CAE) and betulin (BET) are known for their biological and pharmacological effects. Pharmacological effects reported on CAE include antimicrobial, anti-inflammatory, anti-pyretic, anti-analgesic, and anti-cancer effects. Betulin has exhibited a multitude of powerful pharmacological properties ranging from antitumor, anti-inflammatory, anti-parasitic, anti-microbial, and anti-viral activities. This work sought to investigate the anti-tuberculosis and resistant modulatory effects and also assess their effects on mitigating pulmonary fibrosis and silicosis. In the anti-tuberculosis and resistant modulatory effects, both CAE and BET showed strong antimicrobial activities (31.25 ≤ MIC ≤ 500) µg/ml against the studied microorganisms and also produced significant anti-efflux pump and biofilm inhibitory effects (ρ < 0.0001) as well as exhibiting resistance modulatory and synergistic effects when combined with standard antibiotics. Crinum asiaticum bulbs extract and betulin were shown to possess anti-pulmonary fibrosis effects. There was an increased survival rate in the CAE and BET treatment groups compared to the BLM-induced group. There was a marked decrease in the levels of hydroxyproline and collagen I and III in the CAE and BET treatment groups compared to the BLM-treated group. The treatment groups of CAE and BET significantly downregulated the levels of pro-fibrotic and pro-inflammatory cytokine concentrations such as TGF-β1, MMP9, IL-6, IL-1β and TNF-alpha compared to an increase in the BLM-treated groups. The histological findings of the lungs suggested the curative effects of CAE and BET following BLM-induced pulmonary fibrosis in mice. The study showed improved lung functions with a wide focal area of viable alveolar spaces and few collagen fibers deposition on the lungs of the treatment groups. In the anti-silicosis and pulmonoprotective effects of CAE and BET, the levels of NF-κB, TNF-α, IL-1β, IL-6 and hydroxyproline, collagen types I and III were significantly reduced by CAE and BET (ρ < 0.0001). Both CAE and BET significantly (ρ < 0.0001) inhibited the levels of hydroxyproline, collagen I and III when compared with the negative control group. On BALF biomarkers such as macrophages, lymphocytes, monocytes, and neutrophils, CAE and BET were able to reduce their levels significantly (ρ < 0.0001). The CAE and BET were examined for anti-oxidant activity and shown to raise the levels of catalase (CAT) and superoxide dismutase (SOD) while lowering the level of malondialdehyde (MDA). There was an improvement in lung function when lung tissues were examined histologically. Crinum asiaticum bulbs extract and betulin were discovered to exhibit anti-tubercular and resistance-modulatory properties, as well as the capacity to minimize TB comorbidities such as pulmonary fibrosis and silicosis. In addition, CAE and BET may act as protective mechanisms, facilitating the preservation of the lung's physiological integrity. The outcomes of this study might pave the way for the development of leads for producing single medications for the management of drug-resistant tuberculosis and its accompanying comorbidities.Keywords: fibrosis, crinum, tuberculosis, antiinflammation, drug resistant
Procedia PDF Downloads 83175 Defective Autophagy Disturbs Neural Migration and Network Activity in hiPSC-Derived Cockayne Syndrome B Disease Models
Authors: Julia Kapr, Andrea Rossi, Haribaskar Ramachandran, Marius Pollet, Ilka Egger, Selina Dangeleit, Katharina Koch, Jean Krutmann, Ellen Fritsche
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It is widely acknowledged that animal models do not always represent human disease. Especially human brain development is difficult to model in animals due to a variety of structural and functional species-specificities. This causes significant discrepancies between predicted and apparent drug efficacies in clinical trials and their subsequent failure. Emerging alternatives based on 3D in vitro approaches, such as human brain spheres or organoids, may in the future reduce and ultimately replace animal models. Here, we present a human induced pluripotent stem cell (hiPSC)-based 3D neural in a vitro disease model for the Cockayne Syndrome B (CSB). CSB is a rare hereditary disease and is accompanied by severe neurologic defects, such as microcephaly, ataxia and intellectual disability, with currently no treatment options. Therefore, the aim of this study is to investigate the molecular and cellular defects found in neural hiPSC-derived CSB models. Understanding the underlying pathology of CSB enables the development of treatment options. The two CSB models used in this study comprise a patient-derived hiPSC line and its isogenic control as well as a CSB-deficient cell line based on a healthy hiPSC line (IMR90-4) background thereby excluding genetic background-related effects. Neurally induced and differentiated brain sphere cultures were characterized via RNA Sequencing, western blot (WB), immunocytochemistry (ICC) and multielectrode arrays (MEAs). CSB-deficiency leads to an altered gene expression of markers for autophagy, focal adhesion and neural network formation. Cell migration was significantly reduced and electrical activity was significantly increased in the disease cell lines. These data hint that the cellular pathologies is possibly underlying CSB. By induction of autophagy, the migration phenotype could be partially rescued, suggesting a crucial role of disturbed autophagy in defective neural migration of the disease lines. Altered autophagy may also lead to inefficient mitophagy. Accordingly, disease cell lines were shown to have a lower mitochondrial base activity and a higher susceptibility to mitochondrial stress induced by rotenone. Since mitochondria play an important role in neurotransmitter cycling, we suggest that defective mitochondria may lead to altered electrical activity in the disease cell lines. Failure to clear the defective mitochondria by mitophagy and thus missing initiation cues for new mitochondrial production could potentiate this problem. With our data, we aim at establishing a disease adverse outcome pathway (AOP), thereby adding to the in-depth understanding of this multi-faced disorder and subsequently contributing to alternative drug development.Keywords: autophagy, disease modeling, in vitro, pluripotent stem cells
Procedia PDF Downloads 120174 Feasibility of Applying a Hydrodynamic Cavitation Generator as a Method for Intensification of Methane Fermentation Process of Virginia Fanpetals (Sida hermaphrodita) Biomass
Authors: Marcin Zieliński, Marcin Dębowski, Mirosław Krzemieniewski
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The anaerobic degradation of substrates is limited especially by the rate and effectiveness of the first (hydrolytic) stage of fermentation. This stage may be intensified through pre-treatment of substrate aimed at disintegration of the solid phase and destruction of substrate tissues and cells. The most frequently applied criterion of disintegration outcomes evaluation is the increase in biogas recovery owing to the possibility of its use for energetic purposes and, simultaneously, recovery of input energy consumed for the pre-treatment of substrate before fermentation. Hydrodynamic cavitation is one of the methods for organic substrate disintegration that has a high implementation potential. Cavitation is explained as the phenomenon of the formation of discontinuity cavities filled with vapor or gas in a liquid induced by pressure drop to the critical value. It is induced by a varying field of pressures. A void needs to occur in the flow in which the pressure first drops to the value close to the pressure of saturated vapor and then increases. The process of cavitation conducted under controlled conditions was found to significantly improve the effectiveness of anaerobic conversion of organic substrates having various characteristics. This phenomenon allows effective damage and disintegration of cellular and tissue structures. Disintegration of structures and release of organic compounds to the dissolved phase has a direct effect on the intensification of biogas production in the process of anaerobic fermentation, on reduced dry matter content in the post-fermentation sludge as well as a high degree of its hygienization and its increased susceptibility to dehydration. A device the efficiency of which was confirmed both in laboratory conditions and in systems operating in the technical scale is a hydrodynamic generator of cavitation. Cavitators, agitators and emulsifiers constructed and tested worldwide so far have been characterized by low efficiency and high energy demand. Many of them proved effective under laboratory conditions but failed under industrial ones. The only task successfully realized by these appliances and utilized on a wider scale is the heating of liquids. For this reason, their usability was limited to the function of heating installations. Design of the presented cavitation generator allows achieving satisfactory energy efficiency and enables its use under industrial conditions in depolymerization processes of biomass with various characteristics. Investigations conducted on the laboratory and industrial scale confirmed the effectiveness of applying cavitation in the process of biomass destruction. The use of the cavitation generator in laboratory studies for disintegration of sewage sludge allowed increasing biogas production by ca. 30% and shortening the treatment process by ca. 20 - 25%. The shortening of the technological process and increase of wastewater treatment plant effectiveness may delay investments aimed at increasing system output. The use of a mechanical cavitator and application of repeated cavitation process (4-6 times) enables significant acceleration of the biogassing process. In addition, mechanical cavitation accelerates increases in COD and VFA levels.Keywords: hydrodynamic cavitation, pretreatment, biomass, methane fermentation, Virginia fanpetals
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