Search results for: down regulated

Authors: Paula Costa, Ana Picado, Filomena Pinto, Justina Catarino

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Environmental impact associated with large scale shale gas development is of major concern to the public, policy makers and other stakeholders. To assess this impact on the atmosphere, it is important to monitoring ambient air quality prior to and during all shale gas operation stages. Baseline observations can provide a standard of the pre-shale gas development state of the environment. The lack of baseline concentrations was identified as an important knowledge gap to assess the impact of emissions to the air due to shale gas operations. In fact baseline monitoring of air quality are missing in several regions, where there is a strong possibility of future shale gas exploration. This makes it difficult to properly identify, quantify and characterize environmental impacts that may be associated with shale gas development. The implementation of a baseline air monitoring program is imperative to be able to assess the total emissions related with shale gas operations. In fact, any monitoring programme should be designed to provide indicative information on background levels. A baseline air monitoring program should identify and characterize targeted air pollutants, most frequently described from monitoring and emission measurements, as well as those expected from hydraulic fracturing activities, and establish ambient air conditions prior to start-up of potential emission sources from shale gas operations. This program has to be planned for at least one year accounting for ambient variations. In the literature, in addition to GHG emissions of CH4, CO2 and nitrogen oxides (NOx), fugitive emissions from shale gas production can release volatile organic compounds (VOCs), aldehydes (formaldehyde, acetaldehyde) and hazardous air pollutants (HAPs). The VOCs include a.o., benzene, toluene, ethyl benzene, xylenes, hexanes, 2,2,4-trimethylpentane, styrene. The concentrations of six air pollutants (ozone, particulate matter (PM), carbon monoxide (CO), nitrogen oxides (NOx), sulphur oxides (SOx), and lead) whose regional ambient air levels are regulated by the Environmental Protection Agency (EPA), are often discussed. However, the main concern in the emissions to air associated to shale gas operations, seems to be the leakage of methane. Methane is identified as a compound of major concern due to its strong global warming potential. The identification of methane leakage from shale gas activities is complex due to the existence of several other CH4 sources (e.g. landfill, agricultural activity or gas pipeline/compressor station). An integrated monitoring study of methane emissions may be a suitable mean of distinguishing the contribution of different sources of methane to ambient levels. All data analysis needs to be carefully interpreted taking, also, into account the meteorological conditions of the site. This may require the implementation of a more intensive monitoring programme. So, it is essential the development of a low-cost sampling strategy, suitable for establishing pre-operations baseline data as well as an integrated monitoring program to assess the emissions from shale gas operation sites. This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 640715.

Keywords: air emissions, baseline, green house gases, shale gas

Procedia PDF Downloads 335

Authors: Cynthia Adlerstein

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Physical learning environment (PLE) has been considered, after family and educators, as the third teacher. There have been conflicting and converging viewpoints on the role of the physical dimensions of places to learn, in facilitating educational innovation and quality. Despite the different approaches, PLE has been widely recognized as a key factor in the quality of the learning experience , and in the levels of learning achievement in ECE . The conceptual frameworks of the field assume that PLE consists of a complex web of factors that shape the overall conditions for learning, and that much more interdisciplinary and complementary methodologies of research and development are required. Although the relevance of PLE attracts a broad international consensus, in Chile it remains under-researched and weakly regulated by public policy. Gaining deeper contextual understanding and more thoughtfully-designed recommendations require the use of innovative assessment tools that cross cultural and disciplinary boundaries to produce new hybrid approaches and improvements. When considering a PLE-based change process for ECE improvement, a central question is what dimensions, variables and indicators could allow a comprehensive assessment of PLE in Chilean kindergartens? Based on a grounded theory social justice inquiry, we adopted a mixed method design, that enabled a multivocal and interdisciplinary construction of data. By using in-depth interviews, discussion groups, questionnaires, and documental analysis, we elicited the PLE discourses of politicians, early childhood practitioners, experts in architectural design and ergonomics, ECE stakeholders, and 3 to 5 year olds. A constant comparison method enabled the construction of the dimensions, variables and indicators through which PLE assessment is possible. Subsequently, the instrument was applied in a sample of 125 early childhood classrooms, to test reliability (internal consistency) and validity (content and construct). As a result, an interdisciplinary and multivocal tool for assessing physical learning environments was constructed and validated, for Chilean kindergartens. The tool is structured upon 7 dimensions (wellbeing, flexible, empowerment, inclusiveness, symbolically meaningful, pedagogically intentioned, institutional management) 19 variables and 105 indicators that are assessed through observation and registration on a mobile app. The overall reliability of the instrument is .938 while the consistency of each dimension varies between .773 (inclusive) and .946 (symbolically meaningful). The validation process through expert opinion and factorial analysis (chi-square test) has shown that the dimensions of the assessment tool reflect the factors of physical learning environments. The constructed assessment tool for kindergartens highlights the significance of the physical environment in early childhood educational settings. The relevance of the instrument relies in its interdisciplinary approach to PLE and in its capability to guide innovative learning environments, based on educational habitability. Though further analysis are required for concurrent validation and standardization, the tool has been considered by practitioners and ECE stakeholders as an intuitive, accessible and remarkable instrument to arise awareness on PLE and on equitable distribution of learning opportunities.

Keywords: Chilean kindergartens, early childhood education, physical learning environment, third teacher

Procedia PDF Downloads 362

Authors: Beihai Xiong, Dengke Hua, Wouter Hendriks, Wilbert Pellikaan

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To improve the energy status of dairy cows in the early lactation, lots of jobs have been done on adjusting the starch to fiber ratio in the diet. As a complex ecosystem, the rumen contains a large population of microorganisms which plays a crucial role in feed degradation. Further study on the microbiota alterations and metabolic changes under different dietary energy sources is essential and valuable to better understand the function of the ruminal microorganisms and thereby to optimize the rumen function and enlarge feed efficiency. The present study will focus on the effects of two glucogenic diets (G: ground corn and corn silage; S: steam-flaked corn and corn silage) and a lipogenic diet (L: sugar beet pulp and alfalfa silage) on rumen fermentation, gas production, the ruminal microbiota and metabolome, and also their correlations in vitro. The gas production was recorded consistently, and the gas volume and producing rate at times 6, 12, 24, 48 h were calculated separately. The fermentation end-products were measured after fermenting for 48 h. The ruminal bacteria and archaea communities were determined by 16S RNA sequencing technique, the metabolome profile was tested through LC-MS methods. Compared to the diet G and S, the L diet had a lower dry matter digestibility, propionate production, and ammonia-nitrogen concentration. The two glucogenic diets performed worse in controlling methane and lactic acid production compared to the L diet. The S diet produced the greatest cumulative gas volume at any time points during incubation compared to the G and L diet. The metabolic analysis revealed that the lipid digestion was up-regulated by the diet L than other diets. On the subclass level, most metabolites belonging to the fatty acids and conjugates were higher, but most metabolites belonging to the amino acid, peptides, and analogs were lower in diet L than others. Differences in rumen fermentation characteristics were associated with (or resulting from) changes in the relative abundance of bacterial and archaeal genera. Most highly abundant bacteria were stable or slightly influenced by diets, while several amylolytic and cellulolytic bacteria were sensitive to the dietary changes. The L diet had a significantly higher number of cellulolytic bacteria, including the genera of Ruminococcus, Butyrivibrio, Eubacterium, Lachnospira, unclassified Lachnospiraceae, and unclassified Ruminococcaceae. The relative abundances of amylolytic bacteria genera including Selenomonas_1, Ruminobacter, and Succinivibrionaceae_UCG-002 were higher in diet G and S. These affected bacteria was also proved to have high associations with certain metabolites. The Selenomonas_1 and Succinivibrionaceae_UCG-002 may contribute to the higher propionate production in the diet G and S through enhancing the succinate pathway. The results indicated that the two glucogenic diets had a greater extent of gas production, a higher dry matter digestibility, and produced more propionate than diet L. The steam-flaked corn did not show a better performance on fermentation end-products than ground corn. This study has offered a deeper understanding of ruminal microbial functions which could assistant the improvement in rumen functions and thereby in the ruminant production.

Keywords: gas production, metabolome, microbiota, rumen fermentation

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Authors: G. Kiran Kumar, K. Padmaja

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The rise of urban and peri-urban agriculture (UPA) is an important urban phenomenon that needs to be well understood before we pronounce a verdict whether it is beneficial or not. The challenge of supply of safe and nutritious food is faced by urban inhabitants. The definition of urban and peri-urban varies from city to city depending on the local policies framed with a view to bring regulated urban habitations as part of governance. Expansion of cities and the blurring of boundaries between urban and rural areas make it difficult to define peri-urban agriculture. The problem is further exacerbated by the fact that definition adopted in one region may not fit in the other. On the other hand the proportion of urban population is on the rise vis-à-vis rural. The rise of UPA does not promise that the food requirements of cities can be entirely met from this practice, since availability of enormous amounts of spaces on rooftops and vacant plots is impossible for raising crops. However, UPA reduces impact of price volatility, particularly for vegetables, which relatively have a longer shelf life. UPA improves access to fresh, nutritious and safe food for the urban poor. UPA provides employment to food handlers and traders in the supply chain. UPA can pose environmental and health risks from inappropriate agricultural practices; increased competition for land, water and energy; alter the ecological landscape and make it vulnerable to increased pollution. The present work is based on case studies in peri-urban agriculture in Hyderabad, India and relies on secondary data. This paper tries to analyze the need for more intensive production technologies without affecting the environment. An optimal solution in terms of urban-rural linkages has to be devised. There is a need to develop a spatial vision and integrate UPA in urban planning in a harmonious manner. Zoning of peri-urban areas for agriculture, milk and poultry production is an essential step to preserve the traditional nurturing character of these areas. Urban local bodies in conjunction with Departments of Agriculture and Horticulture can provide uplift to existing UPA models, without which the UPA can develop into a haphazard phenomenon and add to the increasing list of urban challenges. Land to be diverted for peri-urban agriculture may render the concept of urban and peri-urban forestry ineffective. This paper suggests that UPA may be practiced for high value vegetables which can be cultivated under protected conditions and are better resilient to climate change. UPA can provide models for climate resilient agriculture in urban areas which can be replicated in rural areas. Production of organic farm produce is another option for promote UPA owing to the proximity to informed consumers and access to markets within close range. Waste lands in peri-urban areas can be allotted to unemployed rural youth with the support of Urban Local Bodies (ULBs) and used for UPA. This can serve the purposes of putting wastelands to food production, enhancing employment opportunities and enhancing access to fresh produce for urban consumers.

Keywords: environment, food security, urban and peri-urban agriculture, zoning

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Authors: Aleksander Ejsmont, Aleksandra Galarda, Joanna Goscianska

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Smart porous carriers with defined structure and physicochemical properties are required for releasing the therapeutic drug with precise control of delivery time and location in the body. Due to their non-toxicity, ordered structure, chemical, and thermal stability, mesoporous carbons can be considered as modern carriers for active pharmaceutical ingredients (APIs) whose effectiveness needs frequent dosing algorithms. Such an API-carrier system, if programmed precisely, may stabilize the pharmaceutical and increase its dissolution leading to enhanced bioavailability. The substance conjugated with the material, through its prior adsorption, can later be successfully applied internally to the organism, as well as externally if the API release is feasible under these conditions. In the present study, ordered mesoporous carbons of different morphologies and structures, prepared by hard template method, were applied as carriers in the adsorption and controlled release of active pharmaceutical ingredients. In the first stage, the carbon materials were synthesized and functionalized with carboxylic groups by chemical oxidation using ammonium persulfate solution and then with amine groups. Materials obtained were thoroughly characterized with respect to morphology (scanning electron microscopy), structure (X-ray diffraction, transmission electron microscopy), characteristic functional groups (FT-IR spectroscopy), acid-base nature of surface groups (Boehm titration), parameters of the porous structure (low-temperature nitrogen adsorption) and thermal stability (TG analysis). This was followed by a series of tests of adsorption and release of paracetamol, benzocaine, and losartan potassium. Drug release experiments were performed in the simulated gastric fluid of pH 1.2 and phosphate buffer of pH 7.2 or 6.8 at 37.0 °C. The XRD patterns in the small-angle range and TEM images revealed that functionalization of mesoporous carbons with carboxylic or amine groups leads to the decreased ordering of their structure. Moreover, the modification caused a considerable reduction of the carbon-specific surface area and pore volume, but it simultaneously resulted in changing their acid-base properties. Mesoporous carbon materials exhibit different morphologies, which affect the host-guest interactions during the adsorption process of active pharmaceutical ingredients. All mesoporous carbons show high adsorption capacity towards drugs. The sorption capacity of materials is mainly affected by BET surface area and the structure/size matching between adsorbent and adsorbate. Selected APIs are linked to the surface of carbon materials mainly by hydrogen bonds, van der Waals forces, and electrostatic interactions. The release behavior of API is highly dependent on the physicochemical properties of mesoporous carbons. The release rate of APIs could be regulated by the introduction of functional groups and by changing the pH of the receptor medium. Acknowledgments—This research was supported by the National Science Centre, Poland (project SONATA-12 no: 2016/23/D/NZ7/01347).

Keywords: ordered mesoporous carbons, sorption capacity, drug delivery, carbon nanocarriers

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Authors: Begona del Pino, Beatriz Prieto, Alberto Prieto

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Two opposite approaches to teaching can be considered: in-class learning (teacher-oriented) versus virtual learning (student-oriented). The most known example of the latter is Massive Online Open Courses (MOOCs). Both methodologies have pros and cons. Nowadays there is an increasing trend towards combining both of them. Blending learning is considered a valuable tool for improving learning since it combines student-centred interactive e-learning and face to face instruction. The aim of this contribution is to exchange and share the experience and research results of a blended-learning project that took place in the University of Granada (Spain). The research objective was to prove how combining didactic resources of a MOOC with in-class teaching, interacting directly with students, can substantially improve academic results, as well as student acceptance. The proposed methodology is based on the use of flipped learning technics applied to the subject ‘Fundamentals of Computer Science’ of the first course of two degrees: Telecommunications Engineering, and Industrial Electronics. In this proposal, students acquire the theoretical knowledges at home through a MOOC platform, where they watch video-lectures, do self-evaluation tests, and use other academic multimedia online resources. Afterwards, they have to attend to in-class teaching where they do other activities in order to interact with teachers and the rest of students (discussing of the videos, solving of doubts and practical exercises, etc.), trying to overcome the disadvantages of self-regulated learning. The results are obtained through the grades of the students and their assessment of the blended experience, based on an opinion survey conducted at the end of the course. The major findings of the study are the following: The percentage of students passing the subject has grown from 53% (average from 2011 to 2014 using traditional learning methodology) to 76% (average from 2015 to 2018 using blended methodology). The average grade has improved from 5.20±1.99 to 6.38±1.66. The results of the opinion survey indicate that most students preferred blended methodology to traditional approaches, and positively valued both courses. In fact, 69% of students felt ‘quite’ or ‘very’ satisfied with the classroom activities; 65% of students preferred the flipped classroom methodology to traditional in-class lectures, and finally, 79% said they were ‘quite’ or ‘very’ satisfied with the course in general. The main conclusions of the experience are the improvement in academic results, as well as the highly satisfactory assessments obtained in the opinion surveys. The results confirm the huge potential of combining MOOCs in formal undergraduate studies with on-campus learning activities. Nevertheless, the results in terms of students’ participation and follow-up have a wide margin for improvement. The method is highly demanding for both students and teachers. As a recommendation, students must perform the assigned tasks with perseverance, every week, in order to take advantage of the face-to-face classes. This perseverance is precisely what needs to be promoted among students because it clearly brings about an improvement in learning.

Keywords: blended learning, educational paradigm, flipped classroom, flipped learning technologies, lessons learned, massive online open course, MOOC, teacher roles through technology

Procedia PDF Downloads 183

Authors: Catherine McWhorter

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Robotics is a fast-evolving field lacking comprehensive and harm-mitigating regulation; it also lacks critical data on how human-robot interaction (HRI) may affect human psychology. As most anthropomorphic robots are intended as substitutes for humans, this paper asserts that the commercial robotics industry should be preemptively regulated at the federal level such that robots capable of embodying a victim role in criminal scenarios (“vicbots”) are prohibited until clinical studies determine their effects on the user and society. The results of these studies should then inform more permanent legislation that strives to mitigate risks of harm without infringing upon fundamental rights or stifling innovation. This paper explores these concepts through the lens of the sex robot industry. The sexbot industry offers some of the most realistic, interactive, and customizable robots for sale today. From approximately 2010 until 2017, some sex robot producers, such as True Companion, actively promoted ‘vicbot’ culture with personalities like “Frigid Farrah” and “Young Yoko” but received significant public backlash for fetishizing rape and pedophilia. Today, “Frigid Farrah” and “Young Yoko” appear to have vanished. Sexbot producers have replaced preprogrammed vicbot personalities in favor of one generic, customizable personality. According to the manufacturer ainidoll.com, when asked, there is only one thing the user won’t be able to program the sexbot to do – “…give you drama”. The ability to customize vicbot personas is possible with today’s generic personality sexbots and may undermine the intent of some current legislative efforts. Current debate on the effects of vicbots indicates a lack of consensus. Some scholars suggest vicbots may reduce the rate of actual sex crimes, and some suggest that vicbots will, in fact, create sex criminals, while others cite their potential for rehabilitation. Vicbots may have value in some instances when prescribed by medical professionals, but the overall uncertainty and lack of data further underscore the need for preemptive regulation and clinical research. Existing literature on exposure to media violence and its effects on prosocial behavior, human aggression, and addiction may serve as launch points for specific studies into the hyperrealism of vicbots. Of course, the customization, anthropomorphism and artificial intelligence of sexbots, and therefore more mainstream robots, will continue to evolve. The existing sexbot industry offers an opportunity to preemptively regulate and to research answers to these and many more questions before this type of technology becomes even more advanced and mainstream. Robots pose complicated moral, ethical, and legal challenges, most of which are beyond the scope of this paper. By examining the possibility for custom vicbots via the sexbots industry, reviewing existing literature on regulation, media violence, and vicbot user effects, this paper strives to underscore the need for preemptive federal regulation prohibiting vicbot capabilities in robots while advocating for further research into the potential for the user and societal harm by the same.

Keywords: human-robot interaction effects, regulation, research, robots

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Authors: Clemens Bulitta, Sasan Sadrizadeh, Sebastian Buhl

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Introduction: Ventilation technology in operating theatres (OT)is internationally regulated by dif-ferent standards, which define basic specifications for technical equipment and many times also the necessary operating and performance parameters. This confronts the operators of healthcare facilities with the question of finding the best ventilation and air conditioning system for the OT in order to achieve the goal of a large and robust surgicalworkzone with appropriate air quality and climate for patient safety and occupational health. Additionally, energy consumption and the potential need for clothing that limits transmission of bacteria must be considered as well as the total life cycle cost. However, the evaluation methodology of ventilation systems regarding these matters are still a topic of discussion. To date, there are neither any uniform standardized specifications nor any common validation criteria established. Thus, this study aimed to review data in the literature and add ourown research results to compare and assess the performance of different ventilations systems regarding infection preventive effects, energy efficiency, and staff comfort. Methods: We have conducted a comprehensive literature review on OT ventilation-related topics to understand the strengths and limitations of different ventilation systems. Furthermore, data from experimental assessments on OT ventilation systems at the University of Amberg-Weidenin Germany were in-cluded to comparatively assess the performance of Laminar Airflow (LAF), Turbulent Mixing Air-flow(TMA), and Temperature-controlled Airflow (TcAF) with regards to patient and occupational safety as well as staff comfort including indoor climate.CFD simulations from the Royal Institute of Technology in Sweden (KTH) were also studied to visualize the differences between these three kinds of ventilation systems in terms of the size of the surgical workzone, resilience to obstacles in the airflow, and energy use. Results: A variety of ventilation concepts are in use in the OT today. Each has its advantages and disadvantages, and thus one may be better suited than another depend-ing on the built environment and clinical workflow. Moreover, the proper functioning of OT venti-lation is also affected by multiple external and internal interfering factors. Based on the available data TcAF and LAF seem to provide the greatest effects regarding infection control and minimizing airborne risks for surgical site infections without the need for very tight surgical clothing systems. Resilience to obstacles, staff comfort, and energy efficiency seem to be favourable with TcAF. Conclusion: Based on literature data in current publications and our studies at the Technical Uni-versity of Applied Sciences Amberg-Weidenand the Royal Institute of Technoclogy, LAF and TcAF are more suitable for minimizing the risk for surgical site infections leading to improved clin-ical outcomes. Nevertheless, regarding the best management of thermal loads, atmosphere, energy efficiency, and occupational safety, overall results and data suggest that TcAF systems could pro-vide the economically most efficient and clinically most effective solution under routine clinical conditions.

Keywords: ventilation systems, infection control, energy efficiency, operating theatre, airborne infection risks

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Authors: L. Kashyap, S. Jha, D. Shende, V. K. Mohan, P. Khanna, A. Aravindan, S. Kashyap, L. Singh, S. Aggarwal

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Obesity is associated with a chronic inflammatory state. During surgery, there is an interplay between anaesthetic and surgical stress vis-a-vis the already present complex immune state. Moreover, the postoperative period is dictated by inflammation, which is crucial for wound healing and regeneration. An excess of inflammatory response might hamper recovery besides increasing the risk for infection and complications. There is definite evidence of the immunosuppressive role of inhaled anaesthetic agents. This immune modulation may be brought into effect directly by influencing the innate and adaptive immunity cells. The effects of propofol on immune mechanisms in has been widely elucidated because of its popularity. It reduces superoxide generation, elastase release, and chemotaxis. However, there is no unequivocal proof of one’s superiority over the other. Hence, an anaesthetic regimen with lesser inflammatory potential and specific to the obese patient is needed. OBESITA trial protocol (2019) by Sousa and co-workers in progress aims to test the hypothesis that anaesthesia with sevoflurane results in a weaker proinflammatory response compared to propofol, as evidenced by lower IL-6 and other biomarkers and an increased macrophage differentiation into M2 phenotype in adipose tissue. IL-6 was used as the objective parameter to evaluate inflammation as it is regulated by both surgery and anesthesia. It is the most sensitive marker of the inflammatory response to tissue damage since it is released within minutes by blood leukocytes. We hypothesized that maintenance of anaesthesia with propofol would lead to less inflammation than that with desflurane. Aims: The effect of two anaesthetic techniques, total intravenous anaesthesia (TIVA) with propofol and desflurane, on surgical stress response was evaluated. The primary objective was to compare serum interleukin-6 (IL-6) levels before and after surgery. Methods: In this prospective single-blinded randomized controlled trial undertaken, 30 obese patients (BMI>30 kg/m2) undergoing laparoscopic bariatric surgery under general anaesthesia were recruited. Patients were randomized to receive desflurane or TIVA using a target-controlled infusion for maintenance of anaesthesia. As a marker of inflammation, pre-and post-surgery IL-6 levels were compared. Results: After surgery, IL-6 levels increased significantly in both groups. The rise in IL-6 was less with TIVA than with desflurane; however, it did not reach significance. IL-6 rise post-surgery correlated positively with the complexity of procedure and duration of surgery and anaesthesia, rather than anaesthetic technique. Both groups did not differ in terms of intra-operative hemodynamic and respiratory variables, time to awakening, postoperative pulmonary complications, and duration of hospital stay. The incidence of nausea was significantly higher with desflurane than with TIVA. Conclusion: Inflammatory response did not differ as a function of anaesthetic technique when propofol and desflurane were compared. Also, patient and surgical variables dictated post-operative inflammation more than the anaesthetic factors. Further, larger sample size is needed to confirm or refute these findings.

Keywords: bariatric, biomarkers, inflammation, laparoscopy

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Authors: Sandra Regina Cavalcante, Rodolfo A. G. Vilela

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Introduction: Work accidents and occupational diseases are a big problem for public health around the world and the main health problem of workers with high social and economic costs. Brazil has shown progress over the last years, with the development of the regulatory system to improve safety and quality of life in the workplace. However, the situation is far from acceptable, because the occurrences remain high and there is a great gap between legislation and reality, generated by the low level of voluntary compliance with the law. Brazilian laws provide procedural legal instruments for both, to compensate the damage caused to the worker's health and to prevent future injuries. In the Judiciary, the prevention idea is in the collective action, effected through Brazilian Class Actions. Inhibitory guardianships may impose both, improvements to the working environment, as well as determine the interruption of activity or a ban on the machine that put workers at risk. Both the Labor Prosecution and trade unions have to stand to promote this type of action, providing payment of compensation for collective moral damage. Objectives: To verify how class actions (known as ‘public civil actions’), regulated in Brazilian legal system to protect diffuse, collective and homogeneous rights, are being used to protect workers' health and safety. Methods: The author identified and evaluated decisions of Brazilian Superior Court of Labor involving collective actions and work accidents. The timeframe chosen was December 2015. The online jurisprudence database was consulted in page available for public consultation on the court website. The categorization of the data was made considering the result (court application was rejected or accepted), the request type, the amount of compensation and the author of the cause, besides knowing the reasoning used by the judges. Results: The High Court issued 21,948 decisions in December 2015, with 1448 judgments (6.6%) about work accidents and only 20 (0.09%) on collective action. After analyzing these 20 decisions, it was found that the judgments granted compensation for collective moral damage (85%) and/or obligation to make, that is, changes to improve prevention and safety (71%). The processes have been filed mainly by the Labor Prosecutor (83%), and also appeared lawsuits filed by unions (17%). The compensation for collective moral damage had average of 250,000 reais (about US$65,000), but it should be noted that there is a great range of values found, also are several situations repaired by this compensation. This is the last instance resource for this kind of lawsuit and all decisions were well founded and received partially the request made for working environment protection. Conclusions: When triggered, the labor court system provides the requested collective protection in class action. The values of convictions arbitrated in collective actions are significant and indicate that it creates social and economic repercussions, stimulating employers to improve the working environment conditions of their companies. It is necessary to intensify the use of collective actions, however, because they are more efficient for prevention than reparatory individual lawsuits, but it has been underutilized, mainly by Unions.

Keywords: Brazilian Class Action, collective action, work accident penalization, workplace accident prevention, workplace protection law

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Authors: Faheema Khan

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To investigate the ability of sensitive and tolerant genotype of Glycine max to adapt to a saline environment in a field, we examined the growth performance, water relation and activities of antioxidant enzymes in relation to photosynthetic rate, chlorophyll a fluorescence, photosynthetic pigment concentration, protein and proline in plants exposed to salt stress. Ten soybean genotypes (Pusa-20, Pusa-40, Pusa-37, Pusa-16, Pusa-24, Pusa-22, BRAGG, PK-416, PK-1042, and DS-9712) were selected and grown hydroponically. After 3 days of proper germination, the seedlings were transferred to Hoagland’s solution (Hoagland and Arnon 1950). The growth chamber was maintained at a photosynthetic photon flux density of 430 μmol m−2 s−1, 14 h of light, 10 h of dark and a relative humidity of 60%. The nutrient solution was bubbled with sterile air and changed on alternate days. Ten-day-old seedlings were given seven levels of salt in the form of NaCl viz., T1 = 0 mM NaCl, T2=25 mM NaCl, T3=50 mM NaCl, T4=75 mM NaCl, T5=100 mM NaCl, T6=125 mM NaCl, T7=150 mM NaCl. The investigation showed that genotype Pusa-24, PK-416 and Pusa-20 appeared to be the most salt-sensitive. genotypes as inferred from their significantly reduced length, fresh weight and dry weight in response to the NaCl exposure. Pusa-37 appeared to be the most tolerant genotype since no significant effect of NaCl treatment on growth was found. We observed a greater decline in the photosynthetic variables like photosynthetic rate, chlorophyll fluorescence and chlorophyll content, in salt-sensitive (Pusa-24) genotype than in salt-tolerant Pusa-37 under high salinity. Numerous primers were verified on ten soybean genotypes obtained from Operon technologies among which 30 RAPD primers shown high polymorphism and genetic variation. The Jaccard’s similarity coefficient values for each pairwise comparison between cultivars were calculated and similarity coefficient matrix was constructed. The closer varieties in the cluster behaved similar in their response to salinity tolerance. Intra-clustering within the two clusters precisely grouped the 10 genotypes in sub-cluster as expected from their physiological findings.Salt tolerant genotype Pusa-37, was further analysed by 2-Dimensional gel electrophoresis to analyse the differential expression of proteins at high salt stress. In the Present study, 173 protein spots were identified. Of these, 40 proteins responsive to salinity were either up- or down-regulated in Pusa-37. Proteomic analysis in salt-tolerant genotype (Pusa-37) led to the detection of proteins involved in a variety of biological processes, such as protein synthesis (12 %), redox regulation (19 %), primary and secondary metabolism (25 %), or disease- and defence-related processes (32 %). In conclusion, the soybean plants in our study responded to salt stress by changing their protein expression pattern. The photosynthetic, biochemical and molecular study showed that there is variability in salt tolerance behaviour in soybean genotypes. Pusa-24 is the salt-sensitive and Pusa-37 is the salt-tolerant genotype. Moreover this study gives new insights into the salt-stress response in soybean and demonstrates the power of genomic and proteomic approach in plant biology studies which finally could help us in identifying the possible regulatory switches (gene/s) controlling the salt tolerant genotype of the crop plants and their possible role in defence mechanism.

Keywords: glycine max, salt stress, RAPD, genomic and proteomic variability

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Authors: Lalit Ahuja, Nancy Das, Yashas Shetty

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LED lighting has been increasingly adopted for vehicles in both domestic and foreign automotive markets. Although this miniaturized technology gives the best light output, low energy consumption, and cost-efficient solutions for driving, the same is the need of the hour. In this paper, we present a methodology for driving the highest class two-wheeler headlamp with regulator and rectifier (RR) output. Unlike usual LED headlamps, which are driven by a battery, regulator, and rectifier (RR) driven, a low-cost and highly efficient LED Driver Module (LDM) is proposed. The positive half of magneto output is regulated and used to charge batteries used for various peripherals. While conventionally, the negative half was used for operating bulb-based exterior lamps. But with advancements in LED-based headlamps, which are driven by a battery, this negative half pulse remained unused in most of the vehicles. Our system uses negative half-wave rectified DC output from RR to provide constant light output at all RPMs of the vehicle. With the negative rectified DC output of RR, we have the advantage of pulsating DC input which periodically goes to zero, thus helping us to generate a constant DC output equivalent to the required LED load, and with a change in RPM, additional active thermal bypass circuit help us to maintain the efficiency and thermal rise. The methodology uses the negative half wave output of the RR along with a linear constant current driver with significantly higher efficiency. Although RR output has varied frequency and duty cycles at different engine RPMs, the driver is designed such that it provides constant current to LEDs with minimal ripple. In LED Headlamps, a DC-DC switching regulator is usually used, which is usually bulky. But with linear regulators, we’re eliminating bulky components and improving the form factor. Hence, this is both cost-efficient and compact. Presently, output ripple-free amplitude drivers with fewer components and less complexity are limited to lower-power LED Lamps. The focus of current high-efficiency research is often on high LED power applications. This paper presents a method of driving LED load at both High Beam and Low Beam using the negative half wave rectified pulsating DC from RR with minimum components, maintaining high efficiency within the thermal limitations. Linear regulators are significantly inefficient, with efficiencies typically about 40% and reaching as low as 14%. This leads to poor thermal performance. Although they don’t require complex and bulky circuitry, powering high-power devices is difficult to realise with the same. But with the input being negative half wave rectified pulsating DC, this efficiency can be improved as this helps us to generate constant DC output equivalent to LED load minimising the voltage drop on the linear regulator. Hence, losses are significantly reduced, and efficiency as high as 75% is achieved. With a change in RPM, DC voltage increases, which can be managed by active thermal bypass circuitry, thus resulting in better thermal performance. Hence, the use of bulky and expensive heat sinks can be avoided. Hence, the methodology to utilize the unused negative pulsating DC output of RR to optimize the utilization of RR output power and provide a cost-efficient solution as compared to costly DC-DC drivers.

Keywords: class D LED headlamp, regulator and rectifier, pulsating DC, low cost and highly efficient, LED driver module

Procedia PDF Downloads 71

Authors: Nabamita Nath, Sanghamitra Sarkar

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Urban development in traditional neighbourhoods of cities is undergoing a sea change due to imposition of irregular development patterns on a predominantly inclusive urban fabric. In recent times, traditional neighbourhoods of Kolkata have experienced irregular urban development which has resulted in transformation of its immediate urban character. The goal is to study and analyse impact of new urban developments within traditional neighbourhoods of Kolkata and establish development guidelines to balance the old with the new. Various cities predominantly in third world countries are also experiencing similar development patterns in their traditional neighbourhoods. Existing literature surveys of development patterns in such neighbourhoods have established 9 major parameters viz. edge, movement, node, landmark, size-density, pattern-grain-texture, open spaces, urban spaces, urban form and views-vistas of the neighbourhood. To evaluate impact of urban development in traditional neighbourhoods of Kolkata, 3 different areas have been chronologically selected based on their settlement patterns. Parameters established through literature surveys have been applied to the selected areas to study and analyse the existing patterns of development. The main sources of this study included extensive on-site surveys, academic archive, census data, organisational records and informational websites. Applying the established parameters, 5 major conclusions were derived. Firstly, it was found that pedestrian friendly neighbourhoods of the city were becoming more car-centric. This has resulted in loss of interactive and social spaces which defined the cultural heritage of Kolkata. Secondly, the urban pattern which was composed of dense and compact fabric is gradually losing its character due to incorporation of new building typologies. Thirdly, the new building typologies include gated communities with private open spaces which is a stark departure from the existing built typology. However, these open spaces have not contributed in creation of inclusive public places for the community which are a significant part of such heritage neighbourhood precincts. Fourthly, commercial zones that primarily developed along major access routes have now infiltrated within these neighbourhoods. Gated communities do not favour formation of on-street commercial activities generating haphazard development patterns. Lastly, individual residential buildings that reflected Indo-saracenic and Neo-gothic architectural styles are converting into multi-storeyed residential apartments. As a result, the axis that created a definite visual identity for a neighbourhood is progressively following an irregular pattern. Thus, uniformity of the old skyline is gradually becoming inconsistent. The major issue currently is threat caused by irregular urban development to heritage zones and buildings of traditional neighbourhoods. Streets, lanes, courtyards, open spaces and buildings of old neighbourhoods imparted a unique cultural identity to the city that is disappearing with emerging urban development patterns. It has been concluded that specific guidelines for urban development should be regulated primarily based on existing urban form of traditional neighbourhoods. Such neighbourhood development strategies should be formulated for various cities of third world countries to control irregular developments thereby balancing heritage and development.

Keywords: heritage, Kolkata, traditional neighbourhood, urban development

Procedia PDF Downloads 184

Authors: Wen-Yang Hu, Ranli Lu, Mark Maienschein-Cline, Danping Hu, Larisa Nonn, Toshi Shioda, Gail S. Prins

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Background: Genetic mutations are highly associated with increased prostate cancer risk. In addition to whole genome sequencing, somatic mutations can be identified by aligning transcriptome sequences to the human genome. Here we analyzed bulk RNAseq and single cell RNAseq data of human prostate cancer cells and their matched non-cancer cells in benign regions from 4 individual patients. Methods: Sequencing raw reads were aligned to the reference genome hg38 using STAR. Variants were annotated using Annovar with respect to overlap gene annotation information, effect on gene and protein sequence, and SIFT annotation of nonsynonymous variant effect. We determined cancer-specific novel alleles by comparing variant calls in cancer cells to matched benign cells from the same individual by selecting unique alleles that were only detected in the cancer samples. Results: In bulk RNAseq data from 3 patients, the most common variants were the noncoding mutations at UTR3/UTR5, and the major variant types were single-nucleotide polymorphisms (SNP) including frameshift mutations. C>T transversion is the most frequently presented substitution of SNP. A total of 222 genes carrying unique exonic or UTR variants were revealed in cancer cells across 3 patients but not in benign cells. Among them, transcriptome levels of 7 genes (CITED2, YOD1, MCM4, HNRNPA2B1, KIF20B, DPYSL2, NR4A1) were significantly up or down regulated in cancer stem cells. Out of the 222 commonly mutated genes in cancer, 19 have nonsynonymous variants and 11 are damaged genes with variants including SIFT, frameshifts, stop gain/loss, and insertions/deletions (indels). Two damaged genes, activating transcription factor 6 (ATF6) and histone demethylase KDM3A are of particular interest; the former is a survival factor for certain cancer cells while the later positively activates androgen receptor target genes in prostate cancer. Further, single cell RNAseq data of cancer cells and their matched non-cancer benign cells from both primary 2D and 3D tumoroid cultures were analyzed. Similar to the bulk RNAseq data, single cell RNAseq in cancer demonstrated that the exonic mutations are less common than noncoding variants, with SNPs including frameshift mutations the most frequently presented types in cancer. Compared to cancer stem cell enriched-3D tumoroids, 2D cancer cells carried 3-times higher variants, 8-times more coding mutations and 10-times more nonsynonymous SNP. Finally, in both 2D primary and 3D tumoroid cultures, cancer stem cells exhibited fewer coding mutations and noncoding SNP or insertions/deletions than non-stem cancer cells. Summary: Our study demonstrates the usefulness of bulk and single cell RNAseaq data in identifying somatic mutations in prostate cancer, providing an alternative method in screening candidate genes for prostate cancer diagnosis and potential therapeutic targets. Cancer stem cells carry fewer somatic mutations than non-stem cancer cells due to their inherited immortal stand DNA from parental stem cells that explains their long-lived characteristics.

Keywords: prostate cancer, stem cell, genomic mutation, RNAseq

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Authors: X. Simon, D. Copena, M. Montero

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The last decades have witnessed a significant increase in renewable energy, especially wind energy, to achieve sustainable development. Specialized literature in this field has carried out interesting case studies to extensively analyze both the environmental benefits of this energy and its social acceptance. However, to the best of our knowledge, work to date makes no analysis of the role of private owners of lands with wind potential within a broader territory of strong wind implantation, nor does it estimate their economic incomes relating them to social acceptance. This work fills this gap by focusing on Galicia, territory housing over 4,000 wind turbines and almost 3,400 MW of power. The main difficulty in getting this financial information is that it is classified, not public. We develop methodological techniques (semi- structured interviews and work groups), inserted within the Participatory Research, to overcome this important obstacle. In this manner, the work directly compiles qualitative and quantitative information on the processes as well as the economic results derived from implementing wind energy in Galicia. During the field work, we held 106 semi-structured interviews and 32 workshops with owners of lands occupied by wind farms. The compiled information made it possible to create the socioeconomic database on wind energy in Galicia (SDWEG). This database collects a diversity of quantitative and qualitative information and contains economic information on the income received by the owners of lands occupied by wind farms. In the Galician case, regulatory framework prevented local participation under the community wind farm formula. The possibility of local participation in the new energy model narrowed down to companies wanting to install a wind farm and demanding land occupation. The economic mechanism of local participation begins here, thus explaining the level of acceptance of wind farms. Land owners can receive significant income given that these payments constitute an important source of economic resources, favor local economic activity, allow rural areas to develop productive dynamism projects and improve the standard of living of rural inhabitants. This work estimates that land owners in Galicia perceive about 10 million euros per year in total wind revenues. This represents between 1% and 2% of total wind farm invoicing. On the other hand, relative revenues (Euros per MW), far from the amounts reached in other spaces, show enormous payment variability. This signals the absence of a regulated market, the predominance of partial agreements, and the existence of asymmetric positions between owners and developers. Sustainable development requires the replacement of conventional technologies by low environmental impact technologies, especially those that emit less CO₂. However, this new paradigm also requires rural owners to participate in the income derived from the structural transformation processes linked to sustainable development. This paper demonstrates that regulatory framework may contribute to increasing sustainable technologies with high social acceptance without relevant local economic participation.

Keywords: regulatory framework, social acceptance, sustainable development, wind energy, wind income for landowners

Procedia PDF Downloads 148

Authors: Rijnbout-St.James Willem, Lindner Volkhard, Scholand Mary Beth, Ashton M. Tillett, Di Gennaro Michael Jude, Smith Silvia Enrica

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Introduction: Fibrosing lung diseases are characterized by changes in the lung interstitium and are classified based on etiology: 1) environmental/exposure-related, 2) autoimmune-related, 3) sarcoidosis, 4) interstitial pneumonia, and 4) idiopathic. Among interstitial lung diseases (ILD) idiopathic forms, idiopathic pulmonary fibrosis (IPF) is the most severe. Pathogenesis of IPF is characterized by an increased presence of proinflammatory mediators, resulting in alveolar injury, where injury to alveolar epithelium precipitates an increase in collagen deposition, subsequently thickening the alveolar septum and decreasing gas exchange. Identifying biomarkers implicated in the pathogenesis of lung fibrosis is key to developing new therapies and improving the efficacy of existing therapies. The transforming growth factor-beta (TGF-B1), a mediator of tissue repair associated with WNT5A signaling, is partially responsible for fibroblast proliferation in ILD and is the target of Pirfenidone, one of the antifibrotic therapies used for patients with IPF. Canonical TGF-B signaling is mediated by the proteins SMAD 2/3, which are, in turn, indirectly regulated by Collagen Triple Helix Repeat Containing 1 (CTHRC1). In this study, we tested the following hypotheses: 1) CTHRC1 is more elevated in the ILD cohort compared to unaffected controls, and 2) CTHRC1 is differently expressed among ILD types. Material and Methods: CTHRC1 levels were measured by ELISA in 171 plasma samples from the deidentified University of Utah ILD cohort. Data represent a cohort of 131 ILD-affected participants and 40 unaffected controls. CTHRC1 samples were categorized by a pulmonologist based on affectation status and disease subtypes: IPF (n = 45), sarcoidosis (4), nonspecific interstitial pneumonia (16), hypersensitivity pneumonitis (n = 7), interstitial pneumonia (n=13), autoimmune (n = 15), other ILD - a category that includes undifferentiated ILD diagnoses (n = 31), and unaffected controls (n = 40). We conducted a single-factor ANOVA of plasma CTHRC1 levels to test whether CTHRC1 variance among affected and non-affected participants is statistically significantly different. In-silico analysis was performed with Ingenuity Pathway Analysis® to characterize the role of CTHRC1 in the pathway of lung fibrosis. Results: Statistical analyses of CTHRC1 in plasma samples indicate that the average CTHRC1 level is significantly higher in ILD-affected participants than controls, with the autoimmune ILD being higher than other ILD types, thus supporting our hypotheses. In-silico analyses show that CTHRC1 indirectly activates and phosphorylates SMAD3, which in turn cross-regulates TGF-B1. CTHRC1 also may regulate the expression and transcription of TGFB-1 via WNT5A and its regulatory relationship with CTNNB1. Conclusion: In-silico pathway analyses demonstrate that CTHRC1 may be an important biomarker in ILD. Analysis of plasma samples indicates that CTHRC1 expression is positively associated with ILD affectation, with autoimmune ILD having the highest average CTHRC1 values. While characterizing CTHRC1 levels in plasma can help to differentiate among ILD types and predict response to Pirfenidone, the extent to which plasma CTHRC1 level is a function of ILD severity or chronicity is unknown.

Keywords: interstitial lung disease, CTHRC1, idiopathic pulmonary fibrosis, pathway analyses

Procedia PDF Downloads 195

Authors: Mingqian Zhang

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Tip-enhanced Raman spectroscopy (TERS) is a scanning probe technique for individual objects and structured surfaces investigation that provides a wealth of enhanced spectral information with nanoscale spatial resolution and high detection sensitivity. It has become a powerful and promising chemical and physical information detection method in the nanometer scale. The TERS technique uses a sharp metallic tip regulated in the near-field of a sample surface, which is illuminated with a certain incident beam meeting the excitation conditions of the wave-vector matching. The local electric field, and, consequently, the Raman scattering, from the sample in the vicinity of the tip apex are both greatly tip-enhanced owning to the excitation of localized surface plasmons and the lightning-rod effect. Typically, a TERS setup is composed of a scanning probe microscope, excitation and collection optical configurations, and a Raman spectroscope. In the illumination configuration, an objective lens or a parabolic mirror is always used as the most important component, in order to focus the incident beam on the tip apex for excitation. In this research, a novel TERS setup was built up by introducing a plasmonic lens to the excitation optics as a focusing device. A plasmonic lens with symmetry breaking semi-annular slits corrugated on gold film was designed for the purpose of generating concentrated sub-wavelength light spots with strong longitudinal electric field. Compared to conventional far-field optical components, the designed plasmonic lens not only focuses an incident beam to a sub-wavelength light spot, but also realizes a strong z-component that dominants the electric field illumination, which is ideal for the excitation of tip-enhancement. Therefore, using a PL in the illumination configuration of TERS contributes to improve the detection sensitivity by both reducing the far-field background and effectively exciting the localized electric field enhancement. The FDTD method was employed to investigate the optical near-field distribution resulting from the light-nanostructure interaction. And the optical field distribution was characterized using an scattering-type scanning near-field optical microscope to demonstrate the focusing performance of the lens. The experimental result is in agreement with the theoretically calculated one. It verifies the focusing performance of the plasmonic lens. The optical field distribution shows a bright elliptic spot in the lens center and several arc-like side-lobes on both sides. After the focusing performance was experimentally verified, the designed plasmonic lens was used as a focusing component in the excitation configuration of TERS setup to concentrate incident energy and generate a longitudinal optical field. A collimated linearly polarized laser beam, with along x-axis polarization, was incident from the bottom glass side on the plasmonic lens. The incident light focused by the plasmonic lens interacted with the silver-coated tip apex and enhanced the Raman signal of the sample locally. The scattered Raman signal was gathered by a parabolic mirror and detected with a Raman spectroscopy. Then, the plasmonic lens based setup was employed to investigate carbon nanotubes and TERS experiment was performed. Experimental results indicate that the Raman signal is considerably enhanced which proves that the novel TERS configuration is feasible and promising.

Keywords: longitudinal electric field, plasmonics, raman spectroscopy, tip-enhancement

Procedia PDF Downloads 378

Authors: Muhammad Alhada Fuadilah Habib, Ayla Karina Budita, Cut Rizka Al Usrah, Mukhammad Fatkhullah, Kanita Khoirun Nisa, Siti Muslihatul Mukaromah

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In this contemporary era, the term of development often emphasised merely on the economic growth aspect. Development of a program often considered as superior by the government, in fact, it often raises various problems. The problems occur because the development policies determined by the government tend to favor private entrepreneurs and impose on the oppression toward the community. The development promised to prosper the community's life, turn out in fact of harming the community, threatening the survival of the community and damaging the ecosystem of nature where the community hangs their life to it. Nowadays many natural resources should be used for the community’s life prosperity. However, the prosperity is conquered by the private entrepreneurs that are regulated through the free market mechanism and wrapped in democratization. This condition actually is a form of neoliberalism that builds new administration order system which is far from the meaning of the word democracy. The government should play more role in protecting community's life and prosperity, but in fact, the government sides with the private entrepreneurs for the sake of the economic benefits regardless of other aspects of the community’s life. This unjustified condition presents a wide range of social movements from the community in response to the neoliberalis policy that actually eliminates the doctrine of community sovereignty. Social movements performed by Yogyakarta south coastal area community, as the focus of the discussion in this paper, is one of the community’s response toward the government policies related to the construction of the ferruginous sand quarry which is tend to favor on private entrepreneurs and highly prejudicing or even threatening the survival of Yogyakarta south coastal area community. The data collection in this study uses qualitative research methods with in-depth interview data collection techniques and purposive informant determination techniques. This method was chosen in order to obtain the insightful data and detailed information to uncover the injustice policies committed by the government-private entrepreneurs toward Yogyakarta south coastal area community. The brief results of this study show that the conflicts between the community and government-private entrepreneurs occurred because of the differences of interests and paradigm of natural resource management. The resistance movements done by the community to fight back the government-private entrepreneurs was conducted by forming an organization called Paguyupan Petani Lahan Pantai Kulon Progo (PPLP-KP). This organization do the resistances through two ways; firstly, quiet action done through various actions such as; refusing against the socialization, performing discussion to deliberate their argument with the government-private entrepreneurs, complaining the problems to the central government, creating banners or billboards which contain the writing of rejection, performing pray rituals to invoke the justice from the God, as well as instill the resistance ideology to their young generation. Secondly, the rough action also is done through various actions such as; doing roadblocks, conducting rallies, as well as doing clash with the government apparatus. In case the resistances done by the community are seen from the pattern. Actually, the resistances are reaction toward the aggression carried out by the government-private entrepreneurs.

Keywords: community resistance, conflict, ferruginous sand quarry construction, social movement

Procedia PDF Downloads 284

Authors: Irina Mizeva, Elena Potapova, Viktor Dremin, Mikhail Mezentsev, Valeri Shupletsov

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The local tissue perfusion is regulated by the microvascular tone which is under the control of a number of physiological mechanisms. Laser Doppler flowmetry (LDF) together with wavelet analyses is the most commonly used technique to study the regulatory mechanisms of cutaneous microcirculation. External factors such as temperature, local pressure of the probe on the skin, etc. influence on the blood flow characteristics and are used as physiological tests to evaluate microvascular regulatory mechanisms. Local probe pressure influences on the microcirculation parameters measured by optical methods: diffuse reflectance spectroscopy, fluorescence spectroscopy, and LDF. Therefore, further study of probe pressure effects can be useful to improve the reliability of optical measurement. During pressure tests variation of the mean perfusion measured by means of LDF usually is estimated. An additional information concerning the physiological mechanisms of the vascular tone regulation system in response to local pressure can be obtained using spectral analyses of LDF samples. The aim of the present work was to develop protocol and algorithm of data processing appropriate for study physiological response to the local pressure test. Involving 6 subjects (20±2 years) and providing 5 measurements for every subject we estimated intersubject and-inter group variability of response of both averaged and oscillating parts of the LDF sample on external surface pressure. The final purpose of the work was to find special features which further can be used in wider clinic studies. The cutaneous perfusion measurements were carried out by LAKK-02 (SPE LAZMA Ltd., Russia), the skin loading was provided by the originally designed device which allows one to distribute the pressure around the LDF probe. The probe was installed on the dorsal part of the distal finger of the index figure. We collected measurements continuously for one hour and varied loading from 0 to 180mmHg stepwise with a step duration of 10 minutes. Further, we post-processed the samples using the wavelet transform and traced the energy of oscillations in five frequency bands over time. Weak loading leads to pressure-induced vasodilation, so one should take into account that the perfusion measured under pressure conditions will be overestimated. On the other hand, we revealed a decrease in endothelial associated fluctuations. Further loading (88 mmHg) induces amplification of pulsations in all frequency bands. We assume that such loading leads to a higher number of closed capillaries, higher input of arterioles in the LDF signal and as a consequence more vivid oscillations which mainly are formed in arterioles. External pressure higher than 144 mmHg leads to the decrease of oscillating components, after removing the loading very rapid restore of the tissue perfusion takes place. In this work, we have demonstrated that local skin loading influence on the microcirculation parameters measured by optic technique; this should be taken into account while developing portable electronic devices. The proposed protocol of local loading allows one to evaluate PIV as far as to trace dynamic of blood flow oscillations. This study was supported by the Russian Science Foundation under project N 18-15-00201.

Keywords: blood microcirculation, laser Doppler flowmetry, pressure-induced vasodilation, wavelet analyses blood

Procedia PDF Downloads 154

Authors: Erica Cochran Hameen, Bobuchi Ken-Opurum, Mounica Guturu

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The United Stated (U.S.) populous spends the majority of their time indoors in spaces where building codes and voluntary sustainability standards provide clear Indoor Environmental Quality (IEQ) metrics. The existing sustainable building standards and codes are aimed towards improving IEQ, health of occupants, and reducing the negative impacts of buildings on the environment. While they address the post-occupancy stage of buildings, there are fewer standards on the pre-occupancy stage thereby placing a large labor population in environments much less regulated. Construction personnel are often exposed to a variety of uncomfortable and unhealthy elements while on construction sites, primarily thermal, visual, acoustic, and air quality related. Construction site power generators, equipment, and machinery generate on average 9 decibels (dBA) above the U.S. OSHA regulations, creating uncomfortable noise levels. Research has shown that frequent exposure to high noise levels leads to chronic physiological issues and increases noise induced stress, yet beyond OSHA no other metric focuses directly on the impacts of noise on contractors’ well-being. Research has also associated natural light with higher productivity and attention span, and lower cases of fatigue in construction workers. However, daylight is not always available as construction workers often perform tasks in cramped spaces, dark areas, or at nighttime. In these instances, the use of artificial light is necessary, yet lighting standards for use during lengthy tasks and arduous activities is not specified. Additionally, ambient air, contaminants, and material off-gassing expelled at construction sites are one of the causes of serious health effects in construction workers. Coupled with extreme hot and cold temperatures for different climate zones, health and productivity can be seriously compromised. This research evaluates the impact of existing green building metrics on construction and risk management, by analyzing two codes and nine standards including LEED, WELL, and BREAM. These metrics were chosen based on the relevance to the U.S. construction industry. This research determined that less than 20% of the sustainability context within the standards and codes (texts) are related to the pre-occupancy building sector. The research also investigated the impact of construction personnel’s health and well-being on construction management through two surveys of project managers and on-site contractors’ perception of their work environment on productivity. To fully understand the risks of limited Environmental and Health Quality metrics for contractors (EHQ) this research evaluated the connection between EHQ factors such as inefficient lighting, on construction workers and investigated the correlation between various site coping strategies for comfort and productivity. Outcomes from this research are three-pronged. The first includes fostering a discussion about the existing conditions of EQH elements, i.e. thermal, lighting, ergonomic, acoustic, and air quality on the construction labor force. The second identifies gaps in sustainability standards and codes during the pre-occupancy stage of building construction from ground-breaking to substantial completion. The third identifies opportunities for improvements and mitigation strategies to improve EQH such as increased monitoring of effects on productivity and health of contractors and increased inclusion of the pre-occupancy stage in green building standards.

Keywords: construction contractors, health and well-being, environmental quality, risk management

Procedia PDF Downloads 135

Authors: Jyh-Ping Chen, Yu-Tin Lai

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Wound healing is a complicated process involving overlapping hemostasis, inflammation, proliferation, and maturation phases. Ideal wound dressings can replace native skin functions in full thickness skin wounds through faster healing rate and also by reducing scar formation. Poly(lactic-co-glycolic acid) (PLGA) is an U.S. FDA approved biodegradable polymer to be used as ideal wound dressing material. Several in vitro and in vivo studies have demonstrated the effectiveness of curcumin in decreasing the release of inflammatory cytokines, inhibiting enzymes associated with inflammations, and scavenging free radicals that are the major cause of inflammation during wound healing. Heparin has binding affinities to various growth factors. With the unique and beneficial features offered by those molecules toward the complex process of wound healing, we postulate a composite wound dressing constructed from PLGA, curcumin and heparin would be a good candidate to accelerate scarless wound healing. In this work, we use electrospinning to prepare curcumin-loaded aligned PLGA nanofibrous membranes (PC NFMs). PC NFMs were further subject to oxygen plasma modification and surfaced-grafted with heparin through carbodiimide-mediated covalent bond formation to prepare curcumin-loaded PLGA-g-heparin (PCH) NFMs. The nanofibrous membranes could act as three-dimensional scaffolds to attract fibroblast migration, reduce inflammation, and increase wound-healing related growth factors concentrations at wound sites. From scanning electron microscopy analysis, the nanofibers in each NFM are with diameters ranging from 456 to 479 nm and with alignment angles within  0.5°. The NFMs show high tensile strength and good water absorptivity and provide suitable pore size for nutrients/wastes transport. Exposure of human dermal fibroblasts to the extraction medium of PC or PCH NFM showed significant protective effects against hydrogen peroxide than PLGA NFM. In vitro wound healing assays also showed that the extraction medium of PCH NFM showed significantly better migration ability toward fibroblasts than PC NFM, which is further better than PLGA NFM. The in vivo healing efficiency of the NFMs was further evaluated by a full thickness excisional wound healing diabetic rat model. After 14 days, PCH NFMs exhibits 86% wound closure rate, which is significantly different from other groups (79% for PC and 73% for PLGA NFM). Real-time PCR analysis indicated PC and PCH NFMs down regulated anti-oxidative enzymes like glutathione peroxidase (GPx) and superoxide dismutase (SOD), which are well-known transcription factors involved in cellular inflammatory responses to stimuli. From histology, the wound area treated with PCH NFMs showed more vascular lumen formation from immunohistochemistry of α-smooth muscle actin. The wound site also had more collagen type III (65.8%) expression and less collagen type I (3.5%) expression, indicating scar-less wound healing. From Western blot analysis, the PCH NFM showed good affinity toward growth factors from increased concentration of transforming growth factor-β (TGF-β) and fibroblast growth factor-2 (FGF-2) at the wound site to accelerate wound healing. From the results, we suggest PCH NFM as a promising candidate for wound dressing applications.

Keywords: Curcumin, heparin, nanofibrous membrane, poly(lactic-co-glycolic acid) (PLGA), wound dressing

Procedia PDF Downloads 162

Authors: Karisma Karisma, Pardis Moslemzadeh Tehrani

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This study aims to conduct a high-level strategic dialogue on the lack of consensus, consistency, and legal certainty regarding blockchain-based energy prosumerism so that appropriate institutional and governance structures can be put in place to address the inadequacies and gaps in the legal and regulatory framework. The drive to achieve national and global decarbonization targets is a driving force behind climate goals and policies under the Paris Agreement. In recent years, efforts to ‘demonopolize’ and ‘decentralize’ energy generation and distribution have driven the energy transition toward decentralized systems, invoking concepts such as ownership, sovereignty, and autonomy of RE sources. The emergence of individual and collective forms of prosumerism and the rapid diffusion of blockchain is expected to play a critical role in the decarbonization and democratization of energy systems. However, there is a ‘regulatory void’ relating to individual and collective forms of prosumerism that could prevent the rapid deployment of blockchain systems and potentially stagnate the operationalization of blockchain-enabled energy sharing and trading activities. The application of broad and facile regulatory fixes may be insufficient to address the major regulatory gaps. First, to the authors’ best knowledge, the concepts and elements circumjacent to individual and collective forms of prosumerism have not been adequately described in the legal frameworks of many countries. Second, there is a lack of legal certainty regarding the creation and adaptation of business models in a highly regulated and centralized energy system, which inhibits the emergence of prosumer-driven niche markets. There are also current and prospective challenges relating to the legal status of blockchain-based platforms for facilitating energy transactions, anticipated with the diffusion of blockchain technology. With the rise of prosumerism in the energy sector, the areas of (a) network charges, (b) energy market access, (c) incentive schemes, (d) taxes and levies, and (e) licensing requirements are still uncharted territories in many countries. The uncertainties emanating from this area pose a significant hurdle to the widespread adoption of blockchain technology, a complementary technology that offers added value and competitive advantages for energy systems. The authors undertake a conceptual and theoretical investigation to elucidate the lack of consensus, consistency, and legal certainty in the study of blockchain-based prosumerism. In addition, the authors set an exploratory tone to the discussion by taking an analytically eclectic approach that builds on multiple sources and theories to delve deeper into this topic. As an interdisciplinary study, this research accounts for the convergence of regulation, technology, and the energy sector. The study primarily adopts desk research, which examines regulatory frameworks and conceptual models for crucial policies at the international level to foster an all-inclusive discussion. With their reflections and insights into the interaction of blockchain and prosumerism in the energy sector, the authors do not aim to develop definitive regulatory models or instrument designs, but to contribute to the theoretical dialogue to navigate seminal issues and explore different nuances and pathways. Given the emergence of blockchain-based energy prosumerism, identifying the challenges, gaps and fragmentation of governance regimes is key to facilitating global regulatory transitions.

Keywords: blockchain technology, energy sector, prosumer, legal and regulatory.

Procedia PDF Downloads 184

Authors: John E. Boberg, Steven J. Bourgeois

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The decline in student engagement and motivation through the middle years is well documented and clearly associated with a decline in mathematics achievement that persists through high school. To combat this trend and, very often, to meet high-stakes accountability standards, a growing number of parents, teachers, and schools have implemented various methods to incentivize learning. However, according to Self-Determination Theory, forms of incentivized learning such as public praise, tangible rewards, or threats of punishment tend to undermine intrinsic motivation and learning. By focusing on external forms of motivation that thwart autonomy in children, adults also potentially threaten relatedness measures such as trust and emotional engagement. Furthermore, these controlling motivational techniques tend to promote shallow forms of cognitive engagement at the expense of more effective deep processing strategies. Therefore, any short-term gains in apparent engagement or test scores are overshadowed by long-term diminished motivation, resulting in inauthentic approaches to learning and lower achievement. The current study focuses on the relationships between student trust, engagement, and motivation during these crucial years as students transition from elementary to middle school. In order to test the effects of controlled motivational techniques on achievement in mathematics, this quantitative study was conducted on a convenience sample of 22 elementary and middle schools from a single public charter school district in the south-central United States. The study employed multi-source data from students (N = 1,054), parents (N = 7,166), and teachers (N = 356), along with student achievement data and contextual campus variables. Cross-sectional questionnaires were used to measure the students’ self-regulated learning, emotional and cognitive engagement, and trust in teachers. Parents responded to a single item on incentivizing the academic performance of their child, and teachers responded to a series of questions about their acceptance of various incentive strategies. Structural equation modeling (SEM) was used to evaluate model fit and analyze the direct and indirect effects of the predictor variables on achievement. Although a student’s trust in teacher positively predicted both emotional and cognitive engagement, none of these three predictors accounted for any variance in achievement in mathematics. The parents’ use of incentives, on the other hand, predicted a student’s perception of his or her controlled motivation, and these two variables had significant negative effects on achievement. While controlled motivation had the greatest effects on achievement, parental incentives demonstrated both direct and indirect effects on achievement through the students’ self-reported controlled motivation. Comparing upper elementary student data with middle-school student data revealed that controlling forms of motivation may be taking their toll on student trust and engagement over time. While parental incentives positively predicted both cognitive and emotional engagement in the younger sub-group, such forms of controlling motivation negatively predicted both trust in teachers and emotional engagement in the middle-school sub-group. These findings support the claims, posited by Self-Determination Theory, about the dangers of incentivizing learning. Short-term gains belie the underlying damage to motivational processes that lead to decreased intrinsic motivation and achievement. Such practices also appear to thwart basic human needs such as relatedness.

Keywords: controlled motivation, student engagement, incentivized learning, mathematics achievement, self-determination theory, student trust

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Authors: Emanuela Chiarella, Annamaria Aloisio, Nisticò Clelia, Maria Mesuraca

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ZNF521 is a stem cell-associated transcription co-factor, that plays a crucial role in the homeostatic regulation of the stem cell compartment in the hematopoietic, osteo-adipogenic, and neural system. In normal hematopoiesis, primary human CD34+ hematopoietic stem cells display typically a high expression of ZNF521, while its mRNA levels rapidly decrease when these progenitors progress towards erythroid, granulocytic, or B-lymphoid differentiation. However, most acute myeloid leukemias (AMLs) and leukemia-initiating cells keep high ZNF521 expression. In particular, AMLs are often characterized by chromosomal translocations involving the Mixed Lineage Leukemia (MLL) gene, which MLL gene includes a variety of fusion oncogenes arisen from genes normally required during hematopoietic development; once they are fused, they promote epigenetic and transcription factor dysregulation. The chromosomal translocation t(9;11)(p21-22;q23), fusing the MLL gene with AF9 gene, results in a monocytic immune phenotype with an aggressive course, frequent relapses, and a short survival time. To better understand the dysfunctional transcriptional networks related to genetic aberrations, AML gene expression profile datasets were queried for ZNF521 expression and its correlations with specific gene rearrangements and mutations. The results showed that ZNF521 mRNA levels are associated with specific genetic aberrations: the highest expression levels were observed in AMLs involving t(11q23) MLL rearrangements in two distinct datasets (MILE and den Boer); elevated ZNF521 mRNA expression levels were also revealed in AMLs with t(7;12) or with internal rearrangements of chromosome 16. On the contrary, relatively low ZNF521 expression levels seemed to be associated with the t(8;21) translocation, that in turn is correlated with the AML1-ETO fusion gene or the t(15;17) translocation and in AMLs with FLT3-ITD, NPM1, or CEBPα double mutations. Invitro, we found that the enforced co-expression of ZNF521 in cord blood-derived CD34+ cells induced a significant proliferative advantage, improving MLL-AF9 effects on the induction of proliferation and the expansion of leukemic progenitor cells. Transcriptome profiling of CD34+ cells transduced with either MLL-AF9, ZNF521, or a combination of the two transgenes highlighted specific sets of up- or down-regulated genes that are involved in the leukemic phenotype, including those encoding transcription factors, epigenetic modulators, and cell cycle regulators as well as those engaged in the transport or uptake of nutrients. These data enhance the functional cooperation between ZNF521 and MA9, resulting in the development, maintenance, and clonal expansion of leukemic cells. Finally, silencing of ZNF521 in MLL-AF9-transformed primary CD34+ cells inhibited their proliferation and led to their extinction, as well as ZNF521 silencing in the MLL-AF9+ THP-1 cell line resulted in an impairment of their growth and clonogenicity. Taken together, our data highlight ZNF521 role in the control of self-renewal and in the immature compartment of malignant hematopoiesis, which, by altering the gene expression landscape, contributes to the development and/or maintenance of AML acting in concert with the MLL-AF9 fusion oncogene.

Keywords: AML, human zinc finger protein 521 (hZNF521), mixed lineage leukemia gene (MLL) AF9 (MLLT3 or LTG9), cord blood-derived hematopoietic stem cells (CB-CD34+)

Procedia PDF Downloads 115

Authors: Kbrom Mearg Haile

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Introduction: Membrane fouling is the bottleneck for the anaerobic membrane bioreactor (AnMBR) robust continuous operation, primarily caused by the mixed liquor suspended solids (MLSS) characteristics formed by aggregated flocs and a scaffold of microbial self-produced extracellular polymeric substances (EPS), which dictates the flocs integrity. Accordingly, the adhesion of EPS to the membrane surface versus their role in forming firm, elastic, and mechanically stable flocs under the reactor’s hydraulic shear is critical for minimizing interactions between EPS and colloids originating from the MLSS flocs with the membrane. This study aims to gain insight and investigate the effect of MLSS flocs properties, EPS adhesion and viscoelasticity, viscoelastic properties of the sludge, and membrane fouling propensity. Experimental: As a working hypothesis, to alter the aforementioned flocs’ and EPS’s properties, the addition of either coagulant or surfactant was carried out during the AnMBR operation. In the AnMBR, two flat-sheet 300 kDa pore size polyether sulfone (PES) membranes with a total filtration area of 352 cm2 were immersed in the AnMBR system treating municipal wastewater of Midreshet Ben-Gurion village at the Negev highlands, Israel. The system temperature, pH, biogas recirculation, and hydraulic retention time were regulated. TMP fluctuations during a 30-day experiment were recorded under three operating conditions: Baseline (without the addition of coagulating or dispersing agent), coagulant addition (FeCl3), and surfactant addition (sodium dodecyl sulfate). At the end of each experiment, EPS were extracted from the MLSS and from the fouled membrane, characterized for their protein, polysaccharides, and DOC contents, and correlated with the fouling tendency of the submerged UF membrane. The EPS adherence and viscoelastic properties were revealed using QCM-D via the PES-coated gold sensor used as a membrane-mimicking surface providing a detailed real-time EPS adhesion. The associated shifts in the resonance frequency and dissipation at different overtones were further modeled using the Voigt-based viscoelastic model (using Dfind software, Q-Sense Biolin Scientific) in which the thickness, shear modulus, and shear viscosity values of the adsorbed EPS layers on the PES coated sensor were calculated. Results and discussion: The observations obtained from the QCM-D analysis indicate a greater decrease in the frequency shift for the elevated membrane fouling scenarios, likely due to an observed decrease in the calculated shear viscosity and shear modulus of the EPS adsorbed layer, coupled with an increase in EPS layer hydrated thickness and fluidity (ΔD/Δf slopes). Further analysis is being conducted for the three major operating conditions-analyzing their effects on sludge rheology, dewaterability (capillary suction time-CST) and settle ability (SVI). The biofouling layer is further characterized microscopically using a confocal laser scanning microscope (CLSM) and scanning electron microscope (SEM), for analyzing the consistency of the development of the biofouling layer with sludge characteristics, i.e., thicker biofouling layer on the membrane surface when operated with surfactant addition, due to flocs with reduced integrity and availability of EPS/colloids to the membrane. Conversely, a thinner layer when operated with coagulant compared to the baseline experiment, due to elevation in flocs integrity.

Keywords: viscoelasticity, biofouling, viscoelastic, AnMBR, EPS, elocintegrity

Procedia PDF Downloads 29

Authors: Beth Vale

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Academic research has often neglected the city after dark. Surprisingly little consideration has been given to the every night life of cities: the spatial tactics and creative insurgencies of urban residents when night falls. The focus on ‘pleasure’ in the nocturnal city has often negated the subtle politics of night-time play, embedded in expressions of identity, attachment and resistance. This paper investigates Johannesburg nightclubs as sites of quotidian political labour, through which young people contest social space and their place in it, thereby contributing to the city’s effective and socio-political cartography. The tactical remodelling of the nocturnal city through nightclubbing traces lines of desire (material, emotional, sexual), affiliation, and fear. These in turn map onto young people’s expressions of their social and political identities, as well as their attempts at place-making in a ‘post-apartheid’ context. By examining the micro-politics of the cities' nightclubs, this paper speaks back to an earlier post-94 literature, which regularly characterised Johannesburg youth as superficial, individualist and idealistic. Similarly, some might position nightclubs as sites of frivolous consumption or liberatory permissiveness. Yet because nightclub spaces are racialised, classed and gendered, historically-signified and socially regulated, they are also profoundly political. Through ordinary encounters on the cities' dancefloors, young Jo’burgers are imagining, contesting and negotiating their socio-political identities and indeed their claims to the city. Meanwhile, the politics of this generation of youth, who are increasingly critical of the utopian post-apartheid city, are being increasingly inserted and coopted into night-time cultures. Data for this study was gathered through five months of ethnographic fieldwork in Johannesburg nightclubs, including over 120 hours of participant observation and in-depth interviews with organisers and partygoers. Interviewees recognised that parties, rather than being simple frivolity, are a cacophony of celebration, mourning, worship, rage, rebellion and attachment. Countering standard associations between partying and escapism, party planners, venue owners and nightclub audiences were infusing night-time infrastructures with the aesthetics of politics and protest. Not unlike parties, local political assemblies so often rely on music, dance, the occupation of space, and a heaving crowd. References to social movements, militancy and anti-establishment emerged in nightclub themes, dress codes and décor. Metaphors of fire crossed over between party and protest, both of which could be described as having ‘been lit’ or having ‘brought flames’. More so, young people’s articulations of the city’s night-time geography, and their place in it, reflected articulations of race, class and ideological affiliation. The location, entrance fees and stylistic choices of one’s chosen club destination demarcated who was welcome, while also signalling membership to a particular politics (whether progressive or materialistic, inclusive or elitist, mainstream or counter-culture). Because of their ability to divide and unite, aggravate and titillate, mask and reveal, club cultures might offer a mirror to the complex socialities of a generation of Jo’burg youth, as they inhabit, and bring into being, a contemporary South African city.

Keywords: affect, Johannesburg, nightclub, nocturnal city, politics

Procedia PDF Downloads 230

Authors: Dilek Ozturk, Narin Ozturk, Zeliha Pala Kara, Engin Kaptan, Serap Sancar Bas, Nurten Ozsoy, Alper Okyar

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Most physiological processes oscillate in a rhythmic manner in mammals including metabolism and energy homeostasis, locomotor activity, hormone secretion, immune and endocrine system functions. Endocrine body rhythms are tightly regulated by the circadian timing system. The hypothalamic-pituitary-thyroid (HPT) axis is under circadian control at multiple levels from hypothalamus to thyroid gland. Since circadian timing system controls a variety of biological functions in mammals, circadian rhythms of biological functions may modify the drug tolerability/toxicity depending on the dosing time. Selective mTOR (mammalian target of rapamycin) inhibitor everolimus is an immunosuppressant and anticancer agent that is active against many cancers. It was also found to be active in medullary thyroid cancer. The aim of this study was to investigate the dosing time-dependent toxicity of everolimus on the thyroid gland and hormones in mice. Healthy C57BL/6J mice were synchronized with 12h:12h Light-Dark cycle (LD12:12, with Zeitgeber Time 0 – ZT0 – corresponding to Light onset). Everolimus was administered to male (5 mg/kg/day) and female mice (15 mg/kg/day) orally at ZT1-rest period- and ZT13-activity period- for 4 weeks; body weight loss, clinical signs and possible changes in serum thyroid hormone levels (TSH and free T4) were examined. Histological alterations in the thyroid gland were evaluated according to the following criteria: follicular size, colloid density and viscidity, height of the follicular epithelium and the presence of necrotic cells. The statistical significance between differences was analyzed with ANOVA. Study findings included everolimus-related diarrhea, decreased activity, decreased body weight gains, alterations in serum TSH levels, and histopathological changes in thyroid gland. Decreases in mean body weight gains were more evident in mice treated at ZT1 as compared to ZT13 (p < 0.001, for both sexes). Control tissue sections of thyroid glands exhibited well-organized histoarchitecture when compared to everolimus-treated groups. Everolimus caused histopathological alterations in thyroid glands in male (5 mg/kg, slightly) and female mice (15 mg/kg; p < 0.01 for both ZT as compared to their controls) irrespective of dosing-time. TSH levels were slightly decreased upon everolimus treatment at ZT13 in both males and females. Conversely, increases in TSH levels were observed when everolimus treated at ZT1 in both males (5 mg/kg; p < 0.05) and females (15 mg/kg; slightly). No statistically significant alterations in serum free T4 levels were observed. TSH and free T4 is clinically important thyroid hormones since a number of disease states have been linked to alterations in these hormones. Serum free T4 levels within the normal ranges in the presence of abnormal serum TSH levels in everolimus treated mice may suggest subclinical thyroid disease which may have repercussions on the cardiovascular system, as well as on other organs and systems. Our study has revealed the histological damage on thyroid gland induced by subacute everolimus administration, this effect was irrespective of dosing time. However, based on the body weight changes and clinical signs upon everolimus treatment, tolerability for the drug was best following dosing at ZT13 in both male and females. Yet, effects of everolimus on thyroid functions may deserve further studies regarding their clinical importance and chronotoxicity.

Keywords: circadian rhythm, chronotoxicity, everolimus, thyroid gland, thyroid hormones

Procedia PDF Downloads 351

Authors: Marcela Parra-Vargas, Ana Sandoval-Rodriguez, Roberto Rodriguez-Echevarria, Jose Dominguez-Rosales, Juan Armendariz-Borunda

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Non-alcoholic fatty liver disease (NAFLD) is characterized by an excess of hepatic lipids, and it is to author’s best knowledge, the most prevalent chronic liver disorder. Anthocyanin-rich food consumption is linked to health benefits in metabolic disorders associated with obesity and NAFLD, although the precise functional role of anthocyanidin delphinidin (Dp) has yet to be established. The aim of this study was to investigate the effect of the Dp in NAFLD metabolic alterations by evaluating prevention or amelioration of hepatic lipid accumulation, as well as molecular mechanisms in two experimental obesity-related models of NALFD. In vitro: HepG2 cells were incubated with sodium palmitate (PA, 1 mM) to induce lipotoxic damage, and concomitantly treated with Dp (180 uM) for 24 h. Subsequently, total lipid accumulation was measured by colorimetric staining with Oil Red O, and total intrahepatic triglycerides were determined by an enzymatic assay. To assess molecular mechanisms, cells were pre-treated with PA for 24 h and then exposed to Dp for 1 h. In vivo: four-week-old male C57BL/6Nhsd mice were allocated in two main groups. Mice were fed with standard diet (control) or high-fat and high-carbohydrate diet (45% fat, HFD) for 16 wk to induce NAFLD. Then HFD was divided into subgroups: one treated orally with Dp (15 mg/kg bw, HFD-Dp) every day for 4 wk, while HFD group treated with vehicle (DMSO). Weight and fasting glucose were recorded weekly, while dietary ingestion was measured daily. Insulin tolerance test was performed at the end of treatment. Liver histology was evaluated with H&E and Masson’s trichrome stain. RT-PCR was used to evaluate gene expression and Western Blot to determine levels of protein in both experimental models. Parametric data were analyzed with one-way ANOVA and Tukey’s post-hoc test. Kruskal-Wallis and Mann-Whitney U test for non-parametric data, and P < 0.5 were considered significant. Dp prevented hepatic lipid accumulation by PA in HepG2 hepatocytes. Furthermore, Dp down-regulated gene expression of SREBP1c, FAS, and CPT1a without modifying AMPK phosphorylation levels. In vivo, Dp oral administration did not ameliorate lipid metabolic alterations raised by HFD. Adiposity, dietary ingestion, fasting glucose, and insulin sensitivity after Dp treatment remained similar to HFD group. Histological analysis showed hepatic damage in HFD groups and no differences between HFD and HFD-Dp groups were found. Hepatic gene expression of ACC and FAS were not altered by HFD. SREBP1c was similar in both HFD and HFD-Dp groups. No significant changes were observed in SREBP1c, ACC, and FAS adipose tissue gene expression by HFD or Dp treatment. Additionally, immunoblotting analysis revealed no changes in pathway SIRT1-LKB-AMPK and PPAR alpha by both HFD groups compared to control. In conclusion, the antioxidant Dp may provoke beneficial effects in the prevention of hepatic lipid accumulation. Nevertheless, the oral dose administrated in mice that simulated the total intake of anthocyanins consumed daily by humans has no effect as a treatment on hepatic lipid metabolic alterations and histological abnormalities associated with exposure to chronic HFD. A healthy lifestyle with regular intake of antioxidants such as anthocyanins may prevent metabolic alterations in NAFLD.

Keywords: anthocyanins, antioxidants, delphinidin, non-alcoholic fatty liver disease, obesity

Procedia PDF Downloads 206

Authors: Amandeep Thakur, Yi-Hsuan Chu, Chun-Hsu Pan, Kunal Nepali

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The transfer of ADP-ribose residues onto target substrates from nicotinamide adenine dinucleotide (NAD) (PARylation) is catalyzed by Poly (ADP-ribose) polymerases (PARPs). Amongst the PARP family members, the DNA damage response in cancer is majorly regulated by PARP1 and PARP2. The blockade of DNA repair by PARP inhibitors leads to the progression of DNA single-strand breaks (induced by some triggering factors) to double-strand breaks. Notably, PARP inhibitors are remarkably effective in cancers with defective homologous recombination repair (HRR). In particular, cancer cells with BRCA mutations are responsive to therapy with PARP inhibitors. The aforementioned requirement for PARP inhibitors to be effective confers a narrow activity spectrum to PARP inhibitors, which hinders their clinical applicability. Thus, the quest to expand the application horizons of PARP inhibitors beyond BRCA mutations is the need of the hour. Literature precedents reveal that HDAC inhibition induces BRCAness in cancer cells and can broaden the therapeutic scope of PARP inhibitors. Driven by such disclosures, dual inhibitors targeting both PARP and HDAC enzymes were designed by our research group to extend the efficacy of PARP inhibitors beyond BRCA-mutated cancers to cancers with induced BRCAness. The design strategy involved the installation of Veliparib, an investigational PARP inhibitor, as a surface recognition part in the HDAC inhibitor pharmacophore model. The chemical architecture of veliparib was deemed appropriate as a starting point for the generation of dual inhibitors by virtue of its size and structural flexibility. A validatory docking study was conducted at the outset to predict the binding mode of the designed dual modulatory chemical architectures. Subsequently, the designed chemical architectures were synthesized via a multistep synthetic route and evaluated for antitumor efficacy. Delightfully, one compound manifested impressive anti-leukemic effects (HL-60 cell lines) mediated via dual inhibition of PARP and class I HDACs. The outcome of the western blot analysis revealed that the compound could downregulate the expression levels of PARP1 and PARP2 and the HDAC isoforms (HDAC1, 2, and 3). Also, the dual PARP-HDAC inhibitor upregulated the protein expression of the acetyl histone H3, confirming its abrogation potential for class I HDACs. In addition, the dual modulator could arrest the cell cycle at the G0/G1 phase and induce autophagy. Further, polymer-based nanoformulation of the dual inhibitor was furnished to afford targeted delivery of the dual inhibitor at the cancer site. Transmission electron microscopy (TEM) results indicate that the nanoparticles were monodispersed and spherical. Moreover, the polymeric nanoformulation exhibited an appropriate particle size. Delightfully, pH-sensitive behavior was manifested by the polymeric nanoformulation that led to selective antitumor effects towards the HL-60 cell lines. In light of the magnificent anti-leukemic profile of the identified dual PARP-HDAC inhibitor, in-vivo studies (pharmacokinetics and pharmacodynamics) are currently being conducted. Notably, the optimistic findings of the aforementioned study have spurred our research group to initiate several medicinal chemistry campaigns to create bifunctional small molecule inhibitors addressing PARP as the primary target.

Keywords: PARP inhibitors, HDAC inhibitors, BRCA mutations, leukemia

Procedia PDF Downloads 32

Authors: Ankur Chaudhuri, Sibani Sen Chakraborty

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In human, glutaminyl cyclase activity is highly abundant in neuronal and secretory tissues and is preferentially restricted to hypothalamus and pituitary. The N-terminal modification of β-amyloids (Aβs) peptides by the generation of a pyro-glutamyl (pGlu) modified Aβs (pE-Aβs) is an important process in the initiation of the formation of neurotoxic plaques in Alzheimer’s disease (AD). This process is catalyzed by glutaminyl cyclase (QC). The expression of QC is characteristically up-regulated in the early stage of AD, and the hallmark of the inhibition of QC is the prevention of the formation of pE-Aβs and plaques. A computer-aided drug design (CADD) process was employed to give an idea for the designing of potentially active compounds to understand the inhibitory potency against human glutaminyl cyclase (QC). This work elaborates the ligand-based and structure-based pharmacophore exploration of glutaminyl cyclase (QC) by using the known inhibitors. Three dimensional (3D) quantitative structure-activity relationship (QSAR) methods were applied to 154 compounds with known IC50 values. All the inhibitors were divided into two sets, training-set, and test-sets. Generally, training-set was used to build the quantitative pharmacophore model based on the principle of structural diversity, whereas the test-set was employed to evaluate the predictive ability of the pharmacophore hypotheses. A chemical feature-based pharmacophore model was generated from the known 92 training-set compounds by HypoGen module implemented in Discovery Studio 2017 R2 software package. The best hypothesis was selected (Hypo1) based upon the highest correlation coefficient (0.8906), lowest total cost (463.72), and the lowest root mean square deviation (2.24Å) values. The highest correlation coefficient value indicates greater predictive activity of the hypothesis, whereas the lower root mean square deviation signifies a small deviation of experimental activity from the predicted one. The best pharmacophore model (Hypo1) of the candidate inhibitors predicted comprised four features: two hydrogen bond acceptor, one hydrogen bond donor, and one hydrophobic feature. The Hypo1 was validated by several parameters such as test set activity prediction, cost analysis, Fischer's randomization test, leave-one-out method, and heat map of ligand profiler. The predicted features were then used for virtual screening of potential compounds from NCI, ASINEX, Maybridge and Chembridge databases. More than seven million compounds were used for this purpose. The hit compounds were filtered by drug-likeness and pharmacokinetics properties. The selective hits were docked to the high-resolution three-dimensional structure of the target protein glutaminyl cyclase (PDB ID: 2AFU/2AFW) to filter these hits further. To validate the molecular docking results, the most active compound from the dataset was selected as a reference molecule. From the density functional theory (DFT) study, ten molecules were selected based on their highest HOMO (highest occupied molecular orbitals) energy and the lowest bandgap values. Molecular dynamics simulations with explicit solvation systems of the final ten hit compounds revealed that a large number of non-covalent interactions were formed with the binding site of the human glutaminyl cyclase. It was suggested that the hit compounds reported in this study could help in future designing of potent inhibitors as leads against human glutaminyl cyclase.

Keywords: glutaminyl cyclase, hit lead, pharmacophore model, simulation

Procedia PDF Downloads 134