Search results for: bloodstream expression site
Commenced in January 2007
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Paper Count: 4437

Search results for: bloodstream expression site

1287 Adaptation Mechanisms of the Polyextremophile Natranaerobius Thermophilus to Saline-Alkaline-Hermal Environments

Authors: Qinghua Xing, Xinyi Tao, Haisheng Wang, Baisuo Zhao

Abstract:

The first true anaerobic, halophilic alkali thermophile, Natranaerobius thermophilus DSM 18059T, serves as a valuable model for studying cellular adaptations to saline, alkaline and thermal extremes. To uncover the adaptive strategies employed by N. thermophilus in coping with these challenges, we conducted a comprehensive iTRAQ-based quantitative proteomic analysis under different conditions of salinity (3.5 M vs. 2.5 M Na+), pH (pH 9.6 vs. pH 8.6), and temperature (52°C vs. 42°C). The increased intracellular accumulation of glycine betaine, through both synthesis and transport, plays a critical role in N. thermophilus' adaptation to these combined stresses. Under all three stress conditions, the up-regulation of Trk family proteins responsible for K+ transport is observed. Intracellular K+ concentration rises in response to salt and pH levels. Multiple types of Na+/H+ antiporter (NhaC family, Mrp family and CPA family) and a diverse range of FOF1-ATP synthase are identified as vital components for maintaining ionic balance under different stress conditions. Importantly, proteins involved in amino acid metabolism, carbohydrate metabolism, ABC transporters, signaling and chemotaxis, as well as biological macromolecule repair and protection, exhibited significant up-regulation in response to these extreme conditions. These metabolic pathways emerge as critical factors in N. thermophilus' adaptation mechanisms under extreme environmental stress. To validate the proteomic data, ddPCR analysis confirmed changes in mRNA expression, thereby corroborating the up-regulation and down-regulation patterns of 19 co-up-regulated and 36 key proteins under saline, alkaline and thermal stresses. This research enriches our understanding of the complex regulatory systems that enable polyextremophiles to survive in combined extreme conditions.

Keywords: polyextremophiles, natranaerobius thermophilus, saline- alkaline- thermal stresses, combined extremes

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1286 Investigating the Feasibility of Promoting Safety in Civil Projects by BIM System Using Fuzzy Logic

Authors: Mohammad Reza Zamanian

Abstract:

The construction industry has always been recognized as one of the most dangerous available industries, and the statistics of accidents and injuries resulting from it say that the safety category needs more attention and the arrival of up-to-date technologies in this field. Building information modeling (BIM) is one of the relatively new and applicable technologies in Iran, that the necessity of using it is increasingly evident. The main purposes of this research are to evaluate the feasibility of using this technology in the safety sector of construction projects and to evaluate the effectiveness and operationality of its various applications in this sector. These applications were collected and categorized after reviewing past studies and researches then a questionnaire based on Delphi method criteria was presented to 30 experts who were thoroughly familiar with modeling software and safety guidelines. After receiving and exporting the answers to SPSS software, the validity and reliability of the questionnaire were assessed to evaluate the measuring tools. Fuzzy logic is a good way to analyze data because of its flexibility in dealing with ambiguity and uncertainty issues, and the implementation of the Delphi method in the fuzzy environment overcomes the uncertainties in decision making. Therefore, this method was used for data analysis, and the results indicate the usefulness and effectiveness of BIM in projects and improvement of safety status at different stages of construction. Finally, the applications and the sections discussed were ranked in order of priority for efficiency and effectiveness. Safety planning is considered as the most influential part of the safety of BIM among the four sectors discussed, and planning for the installation of protective fences and barriers to prevent falls and site layout planning with a safety approach based on a 3D model are the most important applications of BIM among the 18 applications to improve the safety of construction projects.

Keywords: building information modeling, safety of construction projects, Delphi method, fuzzy logic

Procedia PDF Downloads 169
1285 Indian Art Education and Career Opportunities: A Critical Analysis on Commercial Art

Authors: Pooja Jain

Abstract:

Art education is often ignored in syllabus of developing countries like India and in educational planning for development but now days Indian Art with a global recognition is becoming an integral part of the education at all levels. The term art, widely used in all parts of the modern world, carried varied significance in India as its meaning was continuously being extended, covering the many varieties of creative expression such as painting, sculpture, commercial art, design, poetry, music, dance, and architecture. Over the last 100 years Indian artists of all forms have evolved a wide variety of expressive styles. With the recommendations and initiatives by Government of India, Art Education has subsequently gained pace at the school level as a mandatory subject for all making a path way for students with a creative bend of mind. This paper investigates curriculum in various schools of the country at secondary and senior secondary levels along with some eminent institutions running the program. Findings depicted the role of art education and justified its importance primarily with commercial art being perceived to be essential for students learning skills for economic gain in their career ahead. With so many art colleges spread across India, emerging artists and designers are being trained and are creating art of infinite variety and style and have opened up many career avenues. Commercial Art being a plethora of artistic expressions has confidently come of age wherein a creative perception is mixed with an introspective imagination to bring out multi faceted career options with a significant future enveloped in art. Visual arts in education thus is an expanding field of result assured research.

Keywords: modern art, commercial art, introspective imagination, career

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1284 Double-Spear 1-H2-1 Oncolytic-Immunotherapy for Refractory and Relapsing High-Risk Human Neuroblastoma and Glioma

Authors: Lian Zeng

Abstract:

Double-Spear 1-H2-1 (DS1-H2-1) is an oncolytic virus and an innovative biological drug candidate. The chemical composition of the drug product is a live attenuated West Nile virus (WNV) containing the human T cell costimulator (CD86) gene. After intratumoral injection, the virus can rapidly self-replicate in the injected site and lyse/kill the tumor by repeated infection among tumor cells. We also established xenograft tumor models in mice to evaluate the drug candidate's efficacy on those tumors. The results from preclinical studies on transplanted tumors in immunodeficient mice showed that DS1-H2-1 had significant oncolytic effects on human-origin cancers: it completely (100%) shrieked human glioma; limited human neuroblastoma growth reached as high as 95% growth inhibition rate (%TGITW). The safety data of preclinical animal experiments confirmed that DS1-H2-1 is safe as a biological drug for clinical use. In the preclinical drug efficacy experiment, virus-drug administration with different doses did not show abnormal signs and disease symptoms in more than 300 tested mice, and no side effects or death occurred through various administration routes. Intravenous administration did not cause acute infectious disease or other side effects. However, the replication capacity of the virus in tumor tissue via intravenous administration is only 1% of that of direct intratumoral administration. The direct intratumoral administration of DS1-H2-1 had a higher rate of viral replication. Therefore, choosing direct intratumoral injection can ensure both efficacy and safety.

Keywords: oncolytic virus, WNV-CD86, immunotherapy drugs, glioma, neuroblastoma

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1283 Comparing Field Displacement History with Numerical Results to Estimate Geotechnical Parameters: Case Study of Arash-Esfandiar-Niayesh under Passing Tunnel, 2.5 Traffic Lane Tunnel, Tehran, Iran

Authors: A. Golshani, M. Gharizade Varnusefaderani, S. Majidian

Abstract:

Underground structures are of those structures that have uncertainty in design procedures. That is due to the complexity of soil condition around. Under passing tunnels are also such affected structures. Despite geotechnical site investigations, lots of uncertainties exist in soil properties due to unknown events. As results, it possibly causes conflicting settlements in numerical analysis with recorded values in the project. This paper aims to report a case study on a specific under passing tunnel constructed by New Austrian Tunnelling Method in Iran. The intended tunnel has an overburden of about 11.3m, the height of 12.2m and, the width of 14.4m with 2.5 traffic lane. The numerical modeling was developed by a 2D finite element program (PLAXIS Version 8). Comparing displacement histories at the ground surface during the entire installation of initial lining, the estimated surface settlement was about four times the field recorded one, which indicates that some local unknown events affect that value. Also, the displacement ratios were in a big difference between the numerical and field data. Consequently, running several numerical back analyses using laboratory and field tests data, the geotechnical parameters were accurately revised to match with the obtained monitoring data. Finally, it was found that usually the values of soil parameters are conservatively low-estimated up to 40 percent by typical engineering judgment. Additionally, it could be attributed to inappropriate constitutive models applied for the specific soil condition.

Keywords: NATM, surface displacement history, numerical back-analysis, geotechnical parameters

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1282 Preparation of Ternary Metal Oxide Aerogel Catalysts for Carbon Dioxide and Propylene Oxide Cycloaddition Reaction

Authors: Y. J. Lin, Y. F. Lin

Abstract:

CO2 is the primary greenhouse gas which causes global warming in recent years. As the carbon capture and storage (CCS) getting maturing, the reuse of carbon dioxide which made from CCS is the important issue. In this way, the most common method is the synthesis of cyclic carbonate chemicals from the cycloaddition reaction of carbon dioxide and epoxide. The catalyst plays an important role in the CO2/epoxide cycloaddition reactions. The Lewis acid and base sites are both needed on the catalyst surface for the help of epoxide ring opening, leading to the synthesis of cyclic carbonate. Furthermore, the larger specific surface area and more active site of the catalyst are also needed to enhance the efficiency of the CO2/epoxide cycloaddition reactions. Aerogel is a mesoporous nanomaterial (pore size between 2~50 nm) with high specific surface area and porosity (at least 90%) and low density. In this study, the ternary metal oxide aerogels, Mg-doped Al2O3 aerogels, with higher specific surface area and Lewis acid and base sites on the aerogel surface are successfully prepared by using a facile sol-gel reaction. The as-prepared Mg-doped Al2O3 aerogels are also served as heterogenous catalyst for the CO2/propylene- oxide cycloaddition reaction. Compared to the pristine Al2O3 aerogels, the Mg-doped Al2O3 aerogels possessed both Lewis acid and base sites on the surface are able to enhance the efficiency of the CO2/propylene oxide cycloaddition reactions. As a result, the as-prepared Mg-doped Al2O3 aerogels are a promising and novel catalyst for the CO2/epoxide cycloaddition reactions.

Keywords: ternary, metal oxide aerogel, CO2 reuse, cycloaddition, propylene oxide

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1281 Crossing Multi-Source Climate Data to Estimate the Effects of Climate Change on Evapotranspiration Data: Application to the French Central Region

Authors: Bensaid A., Mostephaoui T., Nedjai R.

Abstract:

Climatic factors are the subject of considerable research, both methodologically and instrumentally. Under the effect of climate change, the approach to climate parameters with precision remains one of the main objectives of the scientific community. This is from the perspective of assessing climate change and its repercussions on humans and the environment. However, many regions of the world suffer from a severe lack of reliable instruments that can make up for this deficit. Alternatively, the use of empirical methods becomes the only way to assess certain parameters that can act as climate indicators. Several scientific methods are used for the evaluation of evapotranspiration which leads to its evaluation either directly at the level of the climatic stations or by empirical methods. All these methods make a point approach and, in no case, allow the spatial variation of this parameter. We, therefore, propose in this paper the use of three sources of information (network of weather stations of Meteo France, World Databases, and Moodis satellite images) to evaluate spatial evapotranspiration (ETP) using the Turc method. This first step will reflect the degree of relevance of the indirect (satellite) methods and their generalization to sites without stations. The spatial variation representation of this parameter using the geographical information system (GIS) accounts for the heterogeneity of the behaviour of this parameter. This heterogeneity is due to the influence of site morphological factors and will make it possible to appreciate the role of certain topographic and hydrological parameters. A phase of predicting the evolution over the medium and long term of evapotranspiration under the effect of climate change by the application of the Intergovernmental Panel on Climate Change (IPCC) scenarios gives a realistic overview as to the contribution of aquatic systems to the scale of the region.

Keywords: climate change, ETP, MODIS, GIEC scenarios

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1280 Performance of the Photovoltaic Module under Different Shading Patterns

Authors: E. T. El Shenawy, O. N. A. Esmail, Adel A. Elbaset, Hesham F. A. Hamed

Abstract:

Generation of the electrical energy based on photovoltaic (PV) technology has been increased over the world due to either the continuous reduction in the traditional energy sources in addition to the pollution problems related to their usage, or the clean nature and safe usage of the PV technology. Also, PV systems can generate clean electricity in the site of use without any transmission, which can be considered cost effective than other generation systems. The performance of the PV system is highly affected by the amount of solar radiation incident on it. Completely or partially shaded PV systems can affect its output. The PV system can be shaded by trees, buildings, dust, incorrect system configuration, or other obstacles. The present paper studies the effect of the partial shading on the performance of a thin film PV module under climatic conditions of Cairo, Egypt. This effect was measured and evaluated according to practical measurement of the characteristic curves such as current-voltage and power-voltage for two identical PV modules (with and without shading) placed at the same time on one mechanical structure for comparison. The measurements have been carried out for the following shading patterns; half cell (bottom, middle, and top of the PV module); complete cell; and two adjacent cells. The results showed that partially shading the PV module changes the shapes of the I-V and P-V curves and produces more than one maximum power point, that can disturb the traditional maximum power point trackers. Also, the output power from the module decreased according to the incomplete solar radiation reaching the PV module due to shadow patterns. The power loss due shading was 7%, 22%, and 41% for shading of half-cell, one cell, and two adjacent cells of the PV module, respectively.

Keywords: I-V measurements, PV module characteristics, PV module power loss, PV module shading

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1279 Reduction of Transient Receptor Potential Vanilloid 1 for Chronic Pain and Depression Co-Morbidity through Electroacupuncture and Gene Deletion in Mice Brain

Authors: Bernice Lottering, Yi-Wen Lin

Abstract:

Chronic pain and depression have an estimated 80% rate of comorbidity with unsatisfactory treatment interventions signifying the importance of developing effective therapeutic interventions for a serious chronic condition affecting a large majority of the global population. Chronic pain is defined as persistent pain presenting for over 3 months. This disease state increases the risk of developing depression in comparison to healthy individuals. In the current study, complete Freund’s adjuvant (CFA) was used to induce cell-mediated chronic inflammatory pain in a murine model. Significant mechanical and thermal hyperalgesia was induced, alongside observable depression-like behaviors. These conditions were attenuated through the use of electroacupuncture (EA). Similarly, these effects were also investigated with respect to the transient receptor potential vanilloid 1 (TRPV1), by analyzing the effects of TRPV1 gene deletion on the comorbidity of chronic pain and depression. The expression of the TRPV1 inflammatory response, and related downstream molecules, including protein kinases (PKs), mitogen-activated protein kinase (MAPKs), and transcriptional factors, were significantly reduced in the thalamus, prefrontal cortex (PFC), hippocampus, and periaqueductal gray (PAG) of CFA-treated mice. In addition, phosphorylated N-methyl-D-aspartate (NMDA) receptor 1 was also found to be reduced in the aforementioned areas, suggesting potential application and validity in a clinical setting. Our study determined the prospective therapeutic effects of EA in the treatment of chronic inflammatory pain and depression comorbidity and provides a novel and detailed mechanism underlying EA-mediated analgesia. These findings may be relevant in the utilization of clinical intervention approaches related to chronic pain and depression comorbidity.

Keywords: chronic pain, depression, NMDA, prefrontal cortex, TRPV1

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1278 Pattern the Location and Area of Earth-Dumping Stations from Vehicle GPS Data in Taiwan

Authors: Chun-Yuan Chen, Ming-Chang Li, Xiu-Hui Wen, Yi-Ching Tu

Abstract:

The objective of this study explores GPS (Global Positioning System) applied to trace construction vehicles such as trucks or cranes, help to pattern the earth-dumping stations of traffic construction in Taiwan. Traffic construction in this research is defined as the engineering of high-speed railways, expressways, and which that distance more than kilometers. Audit the location and check the compliance with regulations of earth-dumping stations is one of important tasks in Taiwan EPA. Basically, the earth-dumping station was known as one source of particulate matter from air pollution during construction process. Due to GPS data can be analyzed quickly and be used conveniently, this study tried to find out dumping stations by modeling vehicles tracks from GPS data during work cycle of construction. The GPS data updated from 13 vehicles related to an expressway construction in central Taiwan. The GPS footprints were retrieved to Keyhole Markup Language (KML) files so that can pattern the tracks of trucks by computer applications, the data was collected about eight months- from Feb. to Oct. in 2017. The results of GPS footprints identified dumping station and outlined the areas of earthwork had been passed to the Taiwan EPA for on-site inspection. Taiwan EPA had issued advice comments to the agency which was in charge of the construction to prevent the air pollution. According to the result of this study compared to the commonly methods in inspecting environment by manual collection, the GPS with KML patterning and modeling method can consumes less time. On the other hand, through monitoring the GPS data from construction vehicles could be useful for administration to development and implementation of strategies in environmental management.

Keywords: automatic management, earth-dumping station, environmental management, Global Positioning System (GPS), particulate matter, traffic construction

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1277 Effects of Environmental Parameters on Salmonella Contaminated in Harvested Oysters (Crassostrea lugubris and Crassostrea belcheri)

Authors: Varangkana Thaotumpitak, Jarukorn Sripradite, Saharuetai Jeamsripong

Abstract:

Environmental contamination from wastewater discharges originated from anthropogenic activities introduces the accumulation of enteropathogenic bacteria in aquatic animals, especially in oysters, and in shellfish harvesting areas. The consumption of raw or partially cooked oysters can be a risk for seafood-borne diseases in human. This study aimed to evaluate the relationship between the presence of Salmonella in oyster meat samples, and environmental factors (ambient air temperature, relative humidity, gust wind speed, average wind speed, tidal condition, precipitation and season) by using the principal component analysis (PCA). One hundred and forty-four oyster meat samples were collected from four oyster harvesting areas in Phang Nga province, Thailand from March 2016 to February 2017. The prevalence of Salmonella of each site was ranged from 25.0-36.11% in oyster meat. The results of PCA showed that ambient air temperature, relative humidity, and precipitation were main factors correlated with Salmonella detection in these oysters. Positive relationship was observed between positive Salmonella in the oysters and relative humidity (PC1=0.413) and precipitation (PC1=0.607), while the negative association was found between ambient air temperature (PC1=0.338) and the presence of Salmonella in oyster samples. These results suggested that lower temperature and higher precipitation and higher relative humidity will possibly effect on Salmonella contamination of oyster meat. During the high risk period, harvesting of oysters should be prohibited to reduce pathogenic bacteria contamination and to minimize a hazard of humans from Salmonellosis.

Keywords: oyster, Phang Nga Bay, principal component analysis, Salmonella

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1276 Impact of Anthropogenic Activities on Soil Quality Using the Land Snail Cantareus apertus as Bioindicator of Heavy Metals Accumulation in The Bejaia Region (Northeastern Algeria)

Authors: Benbelil-Tafoughalt Saida, Tababouchet Meriem

Abstract:

The main goal of this study was to investigate the impact of anthropogenic activities on soil quality using the land snail Cantareusapertus as a bioindicator of heavy metal accumulation. Concentrations of cadmium, copper, and zinc were measured in various body organs, viz: viscera and foot of the land snail Cantareusapertus. The snails were collected from two different sites in the Bejaia region (Northeastern Algeria), exposed to different sources of contamination by trace metals. The first sampling site is an urban areas, and the second is characterized by heavy industry, a potential source of soil pollution via heavy metal contamination. The concentrations of heavy metal in all viscera and foot samples were measured using an atomic absorption spectrophotometer. Bioconcentration of the trace metals Cu, Zn, and Cd varied between the viscera and the foot with the viscera having the highest concentration (µgg-1) of all metals than the foots; Cu, 2.03 – 5.8 (Viscera), 0.05 – 3.30 (Foot), Zn, 23.64 – 45.02 (Viscera), 1.87 – 15.15 (Foot) and Cd, 0.36 – 15.26 (Viscera), 0.18 – 13.73 (Foot), which suggest that ingestion may be the main uptake route of these essential metals. On the other hand, the levels of heavy metals varied significantly among the sampling area (P<0.001). in fact, in the foots as well as in the viscera, the concentrations of all studied metals is significantly higher in the snails sampled from sites closest to potential sources of pollution compared to those collected from urban areas characterized by moderate pollution.

Keywords: anthropogenic activities, Bioconcentration, Cantareus apertus, trace metals

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1275 Analysis of Rockfall Hazard along Himalayan Road Cut Slopes

Authors: Sarada Prasad Pradhan, Vikram Vishal, Tariq Siddique

Abstract:

With a vast area of India comprising of hilly terrain and road cut slopes, landslides and rockfalls are a common phenomenon. However, while landslide studies have received much attention in the past in India, very little literature and analysis is available regarding rockfall hazard of many rockfall prone areas, specifically in Uttarakhand Himalaya, India. The subsequent lack of knowledge and understanding of the rockfall phenomenon as well as frequent incidences of rockfall led fatalities urge the necessity of conducting site-specific rockfall studies to highlight the importance of addressing this issue as well as to provide data for safe design of preventive structures. The present study has been conducted across 10 rockfall prone road cut slopes for a distance of 15 km starting from Devprayag, India along National Highway 58 (NH-58). In order to make a qualitative assessment of Rockfall Hazard posed by these slopes, Rockfall Hazard Rating using standards for Indian Rockmass has been conducted at 10 locations under different slope conditions. Moreover, to accurately predict the characteristics of the possible rockfall phenomenon, numerical simulation was carried out to calculate the maximum bounce heights, total kinetic energies, translational velocities and trajectories of the falling rockmass blocks when simulated on each of these slopes according to real-life conditions. As it was observed that varying slope geometry had more fatal impacts on Rockfall hazard than size of rock masses, several optimizations have been suggested for each slope regarding location of barriers and modification of slope geometries in order to minimize damage by falling rocks. This study can be extremely useful in emphasizing the significance of rockfall studies and construction of mitigative barriers and structures along NH-58 around Devprayag.

Keywords: rockfall, slope stability, rockmass, hazard

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1274 Silymarin Reverses Scopolamine-Induced Memory Deficit in Object Recognition Test in Rats: A Behavioral, Biochemical, Histopathological and Immunohistochemical Study

Authors: Salma A. El-Marasy, Reham M. Abd-Elsalam, Omar A. Ahmed-Farid

Abstract:

Dementia is characterized by impairments in memory and other cognitive abilities. This study aims to elucidate the possible ameliorative effect of silymarin on scopolamine-induced dementia using the object recognition test (ORT). The study was extended to demonstrate the role of cholinergic activity, oxidative stress, neuroinflammation, brain neurotransmitters and histopathological changes in the anti-amnestic effect of silymarin in demented rats. Wistar rats were pretreated with silymarin (200, 400, 800 mg/kg) or donepezil (10 mg/kg) orally for 14 consecutive days. Dementia was induced after the last drug administration by a single intraperitoneal dose of scopolamine (16 mg/kg). Then behavioral, biochemical, histopathological, and immunohistochemical analyses were then performed. Rats pretreated with silymarin counteracted scopolamine-induced non-spatial working memory impairment in the ORT and decreased acetylcholinesterase (AChE) activity, reduced malondialdehyde (MDA), elevated reduced glutathione (GSH), restored gamma-aminobutyric acid (GABA) and dopamine (DA) contents in the cortical and hippocampal brain homogenates. Silymarin dose-dependently reversed scopolamine-induced histopathological changes. Immunohistochemical analysis showed that silymarin dose-dependently mitigated protein expression of a glial fibrillary acidic protein (GFAP) and nuclear factor kappa-B (NF-κB) in the brain cortex and hippocampus. All these effects of silymarin were similar to that of the standard anti-amnestic drug, donepezil. This study reveals that the ameliorative effect of silymarin on scopolamine-induced dementia in rats using the ORT maybe in part mediated by, enhancement of cholinergic activity, anti-oxidant and anti-inflammatory activities as well as mitigation in brain neurotransmitters and histopathological changes.

Keywords: dementia, donepezil, object recognition test, rats, silymarin, scopolamine

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1273 Design and Characterization of Ecological Materials Based on Demolition and Concrete Waste, Casablanca (Morocco)

Authors: Mourad Morsli, Mohamed Tahiri, Azzedine Samdi

Abstract:

The Cities are the urbanized territories most favorable to the consumption of resources (materials, energy). In Morocco, the economic capital Casablanca is one of them, with its 4M inhabitants and its 60% share in the economic and industrial activity of the kingdom. In the absence of legal status in force, urban development has favored the generation of millions of tons of demolition and construction waste scattered in open spaces causing a significant nuisance to the environment and citizens. Hence the main objective of our work is to valorize concrete waste. The representative wastes are mainly concrete, concrete, and fired clay bricks, ceramic tiles, marble panels, gypsum, and scrap metal. The work carried out includes: geolocation with a combination of artificial intelligence, GIS, and Google Earth, which allowed the estimation of the quantity of these wastes per site; then the sorting, crushing, grinding, and physicochemical characterization of the collected samples allowed the definition of the exploitation ways for each extracted fraction for integrated management of the said wastes. In the present work, we proceeded to the exploitation of the fractions obtained after sieving the representative samples to incorporate them in the manufacture of new ecological materials for construction. These formulations prepared studies have been tested and characterized: physical criteria (specific surface, resistance to flexion and compression) and appearance (cracks, deformation). We will present in detail the main results of our research work and also describe the specific properties of each material developed.

Keywords: demolition and construction waste, GIS combination software, inert waste recovery, ecological materials, Casablanca, Morocco

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1272 External Vacuum Dressing: Optimising Non-Operative Management of Flail Sternum Post CPR

Authors: Nicholas Bayfield, Mark Newman

Abstract:

Case Presentation: A 48-year-old male was brought in by ambulance after an out-of-hospital cardiac arrest, with 20 minutes of good-quality cardiopulmonary resuscitation in the community. Return of spontaneous circulation was achieved with defibrillation, revealing an inferior ST-elevation myocardial infarction. He was revascularized emergently in the cath lab and stabilised. Following the procedure, he was noted to have paradoxical respiratory movements of the sternum and high oxygen requirements. CT imaging demonstrated a flail chest with bilateral anterior rib 1-7 fractures as well as a large left-sided extra-pleural haematoma and small haemopneumothorax, secondary to CPR. The patient’s ventilation was stabilised with oxygen via a high-flow humidifier. Pain relief was provided. The anatomy of his rib fractures was not easily amenable to operative fixation. In addition, he was considered to be a high-risk operative candidate due to his recent arrest. He was managed thus non-operatively with an external vacuum dressing applied to the anterior chest wall to minimise respiratory compromise and minimise pain from the motion around the rib fracture sites. Non-operative management was successful, and the patient was reviewed one month later. The paradoxical sternal movement had abated. Discussion: External vacuum dressing has been trialled for non-operative management of rib fractures with varying success. It provides an external brace to minimise fracture site movement during respiration and coughing, thus minimising pain. This modality should be considered a low-cost, high-reward adjunct to non-operative management of bony thoracic trauma.

Keywords: thoracic surgery, thoracic trauma, rib fractures, negative pressure dressing

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1271 Human Metabolism of the Drug Candidate PBTZ169

Authors: Vadim Makarov, Stewart T.Cole

Abstract:

PBTZ169 is novel drug candidate with high efficacy in animals models, and its combination treatment of PBTZ169 with BDQ and pyrazinamide was shown to be more efficacious than the standard treatment for tuberculosis in a mouse model. The target of PBTZ169 is famous DprE1, an essential enzyme in cell wall biosynthesis. The crystal structure of the DprE1-PBTZ169 complex reveals formation of a semimercaptal adduct with Cys387 in the active site and explains the irreversible inactivation of the enzyme. Furthermore, this drug candidate demonstrated during preclinical research ‘drug like’ properties what made it an attractive drug candidate to treat tuberculosis in humans. During first clinical trials several cohorts of the healthy volunteers were treated by the single doses of PBTZ169 as well as two weeks repeated treatment was chosen for two maximal doses. As expected PBTZ169 was well tolerated, and no significant toxicity effects were observed during the trials. The study of the metabolism shown that human metabolism of PBTZ169 is very different from microbial or animals compound transformation. So main pathway of microbial, mice and less rats metabolism connected with reduction processes, but human metabolism mainly connected with oxidation processes. Due to this difference we observed several metabolites of PBTZ169 in humans with antitubercular activity, and now we can conclude that animal antituberculosis activity of PBTZ169 is a result not only activity of the drug itself, but it is a result of the sum activity of the drug and its metabolites. Direct antimicrobial plasma activity was studied, and such activity was observed for 24 hours after human treatment for some doses. This data gets high chance for good efficacy of PBTZ169 in human for treatment TB infection. Second phase of clinical trials was started summer of 2017 and continues to the present day. Available data will be presented.

Keywords: clinical trials, DprE1, PBTZ169, metabolism

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1270 Relationship between Mental Health and Food Access among Healthcare College Students in a Snowy Area in Japan

Authors: Yuki Irie, Shota Ogawa, Hitomi Kosugi, Hiromitsu Shinozaki

Abstract:

Background: Dropout from higher educational institutions is a major problem both for students and institutions, and poor mental health is one of the risk factors. Medical college students are at higher risk of poor mental health than general students because of their hard academic schedules. On the other hand, food insecurity has negative impacts on mental health. The healthcare college of the project site is located heavily snowy area. The students without own vehicles may be at higher risk of food insecurity, especially in the winter season. Therefore, they have many risks to mental health. The aim of the study is to clarify the relationship between mental health and its risk factors to promote students’ mental well-being. Method: A cross-sectional design was used to investigate the relationship between mental health status and lifestyle, including diet and food security among the students (n=421, 147 male, 274 females; 20.7 ± 2.8 years old). Participants were required to answer 3 questionnaires which consisted of diet, lifestyle, food security, and mental health. The survey was conducted during the snowy season from Dec. 2022 to Jan. 2023. Results: Mean mental score was 6.7±4.6 (max. score 27, a higher score means worse mental health). Significant risk factors in mental health were breakfast habit (p=0.02), subjective dietary habit (p=0.00), subjective health (p=0.00), exercise habit (p=0.02), food insecurity in the winter season (p=0.01), and vitamin A intakes (p=0.03). Conclusions: Nutrients intakes are not associated with mental health except vitamin A; however, some other lifestyle factors are significantly associated with mental health. Nutrition doesn’t lead to poor mental health directly; however, the promotion of a healthy lifestyle and improved food security in winter may be effective in better mental health.

Keywords: mental health, winter, lifestyle, students

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1269 Analyzing the Water Quality of Settling Pond after Revegetation at Ex-Mining Area

Authors: Iis Diatin, Yani Hadiroseyani, Muhammad Mujahid, Ahmad Teduh, Juang R. Matangaran

Abstract:

One of silica quarry managed by a mining company is located at Sukabumi District of West Java Province Indonesia with an area of approximately 70 hectares. Since 2013 this company stopped the mining activities. The company tries to restore the ecosystem post-mining with rehabilitation activities such as reclamation and revegetation of their ex-mining area. After three years planting the area the trees grown well. Not only planting some tree species but also some cover crop has covered the soil surface. There are two settling ponds located in the middle of the ex-mining area. Those settling pond were built in order to prevent the effect of acid mine drainage. Acid mine drainage (AMD) or the acidic water is created when sulphide minerals are exposed to air and water and through a natural chemical reaction produce sulphuric acid. AMD is the main pollutant at the open pit mining. The objective of the research was to analyze the effect of revegetation on water quality change at the settling pond. The physical and chemical of water quality parameter were measured and analysed at site and at the laboratory. Physical parameter such as temperature, turbidity and total organic matter were analyse. Also heavy metal and some other chemical parameter such as dissolved oxygen, alkalinity, pH, total ammonia nitrogen, nitrate and nitrite were analysed. The result showed that the acidity of first settling pond was higher than that of the second settling pond. Both settling pond water’s contained heavy metal. The turbidity and total organic matter were the parameter of water quality which become better after revegetation.

Keywords: acid mine drainage, ex-mining area, revegetation, settling pond, water quality

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1268 The Dark Side of Tourism's Implications: A Structural Equation Modeling Study of the 2016 Earthquake in Central Italy

Authors: B. Kulaga, A. Cinti, F. J. Mazzocchini

Abstract:

Despite the fact that growing academic attention on dark tourism is a fairly recent phenomenon, among the various reasons for travelling death-related ones, are very ancient. Furthermore, the darker side of human nature has always been fascinated and curious regarding death, or at least, man has always tried to learn lessons from death. This study proposes to describe the phenomenon of dark tourism related to the 2016 earthquake in Central Italy, deadly for 302 people and highly destructive for the rural areas of Lazio, Marche, and Umbria Regions. The primary objective is to examine the motivation-experience relationship in a dark tourism site, using the structural equation model, applied for the first time to a dark tourism research in 2016, in a study conducted after the Beichuan earthquake. The findings of the current study are derived from the calculations conducted on primary data compiled from 350 tourists in the areas mostly affected by the 2016 earthquake, including the town of Amatrice, near the epicenter, Castelluccio, Norcia, Ussita and Visso, through conducting a Likert scale survey. Furthermore, we use the structural equation model to examine the motivation behind dark travel and how this experience can influence the motivation and emotional reaction of tourists. Expected findings are in line with the previous study mentioned above, indicating that: not all tourists visit the thanatourism sites for dark tourism purpose, tourists’ emotional reactions influence more heavily the emotional tourist experience than cognitive experiences do, and curious visitors are likely to engage cognitively by learning about the incident or related issues.

Keywords: dark tourism, emotional reaction, experience, motivation, structural equation model

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1267 Effects of Injectable Thermosensitive Hydrogel Containing Chitosan as a Barrier for Prevention of Post-operative Peritoneal Adhesion in Rats

Authors: Sara Javanmardi, Sepehr Aziziz, Baharak Divband, Masoumeh Firouzamandi

Abstract:

Post-operative adhesions are the most common cause of intestinal obstruction, female infertility and chronic abdominal pain. We developed a novel approach for preventing post-operative peritoneal adhesions using a biodegradable and thermosensitive curcumin hydrogel in rats. Thirteen male Sprague-Dawley rats were assigned randomly into five groups of six animals each: In SHAM group, the cecum was exteriorized, gently manipulated and sent back into the abdomen. In CONTROL group, the surgical abrasion was performed with no further treatment. In Hydrogel group, surgical abrasion was performed with local application of blank hydrogel (1 mL). In Curcumin group, surgical abrasion was performed with local application of curcumin (1 mL). In CUR/HGEL group, surgical abrasion was performed with local application of curcumin hydrogel (1 mL). On day 10, adhesions were assessed using a standardized scale (Evans model), and samples were collected for the Real-time PCR. Real-time PCR was performed to determine mRNA levels of VCAM-1, ICAM-1 and GAPDH. The macroscopic adhesion intensity showed statistically significant differences between the CUR/HGEL and other groups (P=0.0005). The findings of the present study revealed there were statistically significant differences between the groups regarding adhesion band length and numbers (P<0.0001). The protein and mRNA expression of VCAM-1 and ICAM-1 in secal tissues were significantly down regulated due to curcumin-hydrogel application in CUR/HGEL compared to other groups (p<0.05). The thermosensitive hydrogel could reduce the severity and even prevent formation of intra-abdominal adhesion. Curcumin hydrogel could serve as a potential barrier agent to prevent post-operative peritoneal adhesion in rats.

Keywords: peritoneal adhesion, hydrogel, curcumijn, ICAM-1, VCAM-1

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1266 Immunomodulatory Activity of Polysaccharide-Protein Complex Isolated from the Sclerotia of Polyporus Rhinocerus in Murine Macrophages

Authors: Chaoran Liu

Abstract:

Bioactive polysaccharides and polysaccharide-protein complex derived from mushrooms and fungi have a wide range of immunomodulatory activity with low side-effects and have therefore the potential to be developed as an adjuvant in cancer therapies. Mushrooms sclerotium is rich in polysaccharides and the polysaccharides isolated from the sclerotium of Polyporus rhinocerus have shown potent in vivo and in vitro immunomodulatory effects. Macrophages are considered to be an important component of the innate immune response against bacterial infection and cancer. To better understanding the immunomodulatory effects and its underlying mechanisms of sclerotial water-soluble polysaccharides extracted from P. rhinocerus on macrophages, the objectives of this study are to purify the water-soluble novel sclerotial polysaccharides and to characterize the structure and properties as well as to study the detailed molecular mechanisms of the in vitro immunomodulating effects in murine macrophages. The hot water-soluble fraction PRW from the sclerotium of P. rhinocerus was obtained using solvent extraction. PRW was further fractionated by membrane ultrafiltration to a give a fraction (PRW1) with molecular mass less than 50 kDa. PRW1 was characterized to be a polysaccharide-protein complex composed of 45.7% polysaccharide and 44.2% protein. The chemical structure of the carbohydrate moiety of PRW1 was elucidated by GC and FTIR to be mainly beta-D-glucan with trace amount of galactose and mannose. The immunomodulatory effects of PRW1 on murine RAW 264.7 macrophages were demonstrated in terms of the increase in nitric oxide production and cytokine production. Mechanistically, PRW1 initiates ERK phosphorylation to activate macrophages within 15 min and significantly improves the expression level of inducible NOS (iNOS) from 6 h after treatment. In summary, this study indicates that PRW1 is a potent immunomodulatory agent for macrophages and suggests that mushroom sclerotia from Polyporus rhinocerus requires for further investigation in cancer research.

Keywords: Polyporus rhinocerus, mushroom sclerotia, Polysaccharide-Protein Complex, macrophage activation

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1265 Enhanced Production of Endo-β-1,4-Xylanase from a Newly Isolated Thermophile Geobacillus stearothermophilus KIBGE-IB29 for Prospective Industrial Applications

Authors: Zainab Bibi, Afsheen Aman, Shah Ali Ul Qader

Abstract:

Endo-β-1,4-xylanases [EC 3.2.1.8] are one of the major groups of enzymes that are involved in degradation process of xylan and have several applications in food, textile and paper processing industries. Due to broad utility of endo-β-1,4-xylanase, researchers are focusing to increase the productivity of this hydrolase from various microbial species. Harsh industrial condition, faster reaction rate and efficient hydrolysis of xylan with low risk of contamination are critical requirements of industry that can be fulfilled by synthesizing the enzyme with efficient properties. In the current study, a newly isolated thermophile Geobacillus stearothermophilus KIBGE-IB29 was used in order to attain the maximum production of endo-1,4-β-xylanase. Bacterial culture was isolated from soil, collected around the blast furnace site of a steel processing mill, Karachi. Optimization of various nutritional and physical factors resulted the maximum synthesis of endo-1,4-β-xylanase from a thermophile. High production yield was achieved at 60°C and pH-6.0 after 24 hours of incubation period. Various nitrogen sources viz. peptone, yeast extract and meat extract improved the enzyme synthesis with 0.5%, 0.2% and 0.1% optimum concentrations. Dipotassium hydrogen phosphate (0.25%), potassium dihydrogen phosphate (0.05%), ammonium sulfate (0.05%) and calcium chloride (0.01%) were noticed as valuable salts to improve the production of enzyme. The thermophilic nature of isolate, with its broad pH stability profile and reduced fermentation time indicates its importance for effective xylan saccharification and for large scale production of endo-1,4-β-xylanase.

Keywords: geobacillus, optimization, production, xylanase

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1264 A Transformational Ecology Model of School Based Universal Mental Health Development

Authors: Cheryl M. Bowen

Abstract:

Understanding that children thrive in a multi-systems approach to mental health development, a growing number of schools often promote school-based positive youth development however, there is scant empirical evidence investigating effective school-based “wraparound” mental health services for low income, Latinx children and their families. This 10-month case study utilizes a sample of 281 low-income, Latinx parents and their children, and 23 K-5th grade teachers living in northern California to test the hypothesis that a school-based mental health program can strengthen students’ developmental asset attainment and positively impact the school environment. The study utilized triangulated data to ascertain the effects of two program levels - (a) mental health and (b) positive child development services. All services were site-based and meant to target a wide variety of families. Findings from the study report that the universal mental health program increased the developmental asset attainment in 5 out of 8 thriving indicators thus transforming the child within his/her environment. Data collected from the administrative referral report demonstrate that the project also positively impacted the school climate. Parents and teachers felt more connected to the school, and referrals were down for discipline (35%), academics (66%), and suspensions (51%). The study concludes that a transformational ecology model of positive child development is the most effective means to nurture connections to all socializing agencies in a child’s ecosystem.

Keywords: case study, child development, positive youth development, developmental assets, ecological systems theory

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1263 Optimum Dewatering Network Design Using Firefly Optimization Algorithm

Authors: S. M. Javad Davoodi, Mojtaba Shourian

Abstract:

Groundwater table close to the ground surface causes major problems in construction and mining operation. One of the methods to control groundwater in such cases is using pumping wells. These pumping wells remove excess water from the site project and lower the water table to a desirable value. Although the efficiency of this method is acceptable, it needs high expenses to apply. It means even small improvement in a design of pumping wells can lead to substantial cost savings. In order to minimize the total cost in the method of pumping wells, a simulation-optimization approach is applied. The proposed model integrates MODFLOW as the simulation model with Firefly as the optimization algorithm. In fact, MODFLOW computes the drawdown due to pumping in an aquifer and the Firefly algorithm defines the optimum value of design parameters which are numbers, pumping rates and layout of the designing wells. The developed Firefly-MODFLOW model is applied to minimize the cost of the dewatering project for the ancient mosque of Kerman city in Iran. Repetitive runs of the Firefly-MODFLOW model indicates that drilling two wells with the total rate of pumping 5503 m3/day is the result of the minimization problem. Results show that implementing the proposed solution leads to at least 1.5 m drawdown in the aquifer beneath mosque region. Also, the subsidence due to groundwater depletion is less than 80 mm. Sensitivity analyses indicate that desirable groundwater depletion has an enormous impact on total cost of the project. Besides, in a hypothetical aquifer decreasing the hydraulic conductivity contributes to decrease in total water extraction for dewatering.

Keywords: groundwater dewatering, pumping wells, simulation-optimization, MODFLOW, firefly algorithm

Procedia PDF Downloads 294
1262 Plant Mediated RNAi Approach to Knock Down Ecdysone Receptor Gene of Colorado Potato Beetle

Authors: Tahira Hussain, Ilhom Rahamkulov, Muhammad Aasim, Ugur Pirlak, Emre Aksoy, Mehmet Emin Caliskan, Allah Bakhsh

Abstract:

RNA interference (RNAi) has proved its usefulness in functional genomic research on insects recently and is considered potential strategy in crop improvement for the control of insect pests. The different insect pests incur significant losses to potato yield worldwide, Colorado Potato Beetle (CPB) being most notorious one. The present study focuses to knock down highly specific 20-hydroxyecdysone hormone-receptor complex interaction by using RNAi approach to silence Ecdysone receptor (EcR) gene of CPB in transgenic potato plants expressing dsRNA of EcR gene. The partial cDNA of Ecdysone receptor gene of CPB was amplified using specific primers in sense and anti-sense orientation and cloned in pRNAi-GG vector flanked by an intronic sequence (pdk). Leaf and internodal explants of Lady Olympia, Agria and Granola cultivars of potato were infected with Agrobacterium strain LBA4404 harboring plasmid pRNAi-CPB, pRNAi-GFP (used as control). Neomycin phosphotransferase (nptII) gene was used as a plant selectable marker at a concentration of 100 mg L⁻¹. The primary transformants obtained have shown proper integration of T-DNA in plant genome by standard molecular analysis like polymerase chain reaction (PCR), real-time PCR, Sothern blot. The transgenic plants developed out of these cultivars are being evaluated for their efficacy against larvae as well adults of CPB. The transgenic lines are expected to inhibit expression of EcR protein gene, hindering their molting process, hence leading to increased potato yield.

Keywords: plant mediated RNAi, molecular strategy, ecdysone receptor, insect metamorphosis

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1261 Genuine Domestic Change or Fake Compliance: Political Pervasiveness in the Serbian Media

Authors: Aleksandra Dragojlov

Abstract:

Since the election of Aleksandar Vučić and the Progressives, Serbia has witnessed a slow decline in media freedom, which has been worse than in the 1990s. Although the government adopted a package of three laws in August 2014 to bring the media landscape up to European standards, the implementation of the laws has been limited and marginal, with the progressives engaging in fake compliance. The adoption of the new media strategy for 2020-2025 in 2020 has not led to genuine domestic reform and compliance with EU conditionality. In fact, the EU Commission and journalists’ associations in Serbia have criticised the decline in Serbia’s media freedom citing continued attacks on journalists and indirect political and economic control through advertising and project co-financing, which continue to be features of the Serbian media landscape. In the absence of clear and credible EU conditionality, the decline of media freedom is in the eye of the beholder, where the gap between public engagements with Serbian politicians and the critical stance of progress reports regarding the degradation of the media have enabled Serbian elites to exploit this ambiguity to continue their strategy of fake compliance vis-a-vis rule of law. This study used a mixed methods approach combining both primary and secondary sources with those semi-structured interviews via Zoom, email, and in person with EU and Serbian officials and journalists. Our findings add to the studies where the lack of clear and credible conditionality has allowed Serbia politicians to exploit them in a manner that would suit their own interests, finding new means to retain their control over the media. We argued and concluded that it is this discrepancy between public engagements with Serbia and the progress reports in the area of freedom of expression that has not led to genuine domestic media reforms in Serbia and instead allowed Serbian elites to engage in a strategy of fake and even non-compliance towards media freedom conditionality.

Keywords: media freedom, EU conditionality, Serbia, fake compliance, EU integration, Chapter 23, justice and fundamental rights

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1260 SIRT1 Gene Polymorphisms and Its Protein Level in Colorectal Cancer

Authors: Olfat Shaker, Miriam Wadie, Reham Ali, Ayman Yosry

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Colorectal cancer (CRC) is a major cause of mortality and morbidity and accounts for over 9% of cancer incidence worldwide. Silent information regulator 2 homolog 1 (SIRT1) gene is located in the nucleus and exert its effects via modulation of histone and non-histone targets. They function in the cell via histone deacetylase (HDAC) and/or adenosine diphosphate ribosyl transferase (ADPRT) enzymatic activity. The aim of this work was to study the relationship between SIRT1 polymorphism and its protein level in colorectal cancer patients in comparison to control cases. This study includes 2 groups: thirty healthy subjects (control group) & one hundred CRC patients. All subjects were subjected to: SIRT-1 serum level was measured by ELISA and gene polymorphisms of rs12778366, rs375891 and rs3740051 were detected by real time PCR. For CRC patients clinical data were collected (size, site of tumor as well as its grading, obesity) CRC patients showed high significant increase in the mean level of serum SIRT-1 compared to control group (P<0.001). Mean serum level of SIRT-1 showed high significant increase in patients with tumor size ≥5 compared to the size < 5 cm (P<0.05). In CRC patients, percentage of T allele of rs12778366 was significantly lower than controls, CC genotype and C allele C of rs 375891 were significantly higher than control group. In CRC patients, the CC genotype of rs12778366, was 75% in rectosigmoid and 25% in cecum & ascending colon. According to tumor size, the percentage of CC genotype was 87.5% in tumor size ≥5 cm. Conclusion: serum level of SIRT-1 and T allele, C allele of rs12778366 and rs 375891 respectively can be used as diagnostic markers for CRC patients.

Keywords: CRC, SIRT1, polymorphisms, ELISA

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1259 Multi-Criteria Optimal Management Strategy for in-situ Bioremediation of LNAPL Contaminated Aquifer Using Particle Swarm Optimization

Authors: Deepak Kumar, Jahangeer, Brijesh Kumar Yadav, Shashi Mathur

Abstract:

In-situ remediation is a technique which can remediate either surface or groundwater at the site of contamination. In the present study, simulation optimization approach has been used to develop management strategy for remediating LNAPL (Light Non-Aqueous Phase Liquid) contaminated aquifers. Benzene, toluene, ethyl benzene and xylene are the main component of LNAPL contaminant. Collectively, these contaminants are known as BTEX. In in-situ bioremediation process, a set of injection and extraction wells are installed. Injection wells supply oxygen and other nutrient which convert BTEX into carbon dioxide and water with the help of indigenous soil bacteria. On the other hand, extraction wells check the movement of plume along downstream. In this study, optimal design of the system has been done using PSO (Particle Swarm Optimization) algorithm. A comprehensive management strategy for pumping of injection and extraction wells has been done to attain a maximum allowable concentration of 5 ppm and 4.5 ppm. The management strategy comprises determination of pumping rates, the total pumping volume and the total running cost incurred for each potential injection and extraction well. The results indicate a high pumping rate for injection wells during the initial management period since it facilitates the availability of oxygen and other nutrients necessary for biodegradation, however it is low during the third year on account of sufficient oxygen availability. This is because the contaminant is assumed to have biodegraded by the end of the third year when the concentration drops to a permissible level.

Keywords: groundwater, in-situ bioremediation, light non-aqueous phase liquid, BTEX, particle swarm optimization

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1258 DNA Methylation 6mA and Histone Methylation Involved in Multi-/Trans-Generational Reproductive Effects in Caenorhabditis elegans Induced by Atrazine

Authors: Jiechen Yin, Xiang Hong, Ran Liu

Abstract:

Atrazine (ATR), a widely used triazine herbicide, is an environmental endocrine disruptor that can cause health problems. However, whether there are multi/trans-generational reproductive impacts of ATR have not been studied to our best knowledge. Therefore, in this study, Caenorhabditis elegans was used as a preferable model organism to identify the multi/trans-generational reproductive toxicity of ATR. L1 larvae were exposed to different concentrations (0.0004–40 mg/L) of ATR for 48 h. Successive generations (F1 to F5) were fed without ATR and consecutive exposure. The results showed that ATR exposure during P0 decreased fecundity, including a reduction in fertilized eggs, oocytes, and ovulation rate, delayed gonadal development, and decreased the relative area of the gonad arm and germ cell number. Furthermore, continuous ATR exposure (P0–F5) causes a significant increase in reproductive toxicity in subsequent generations, although no significant toxicity occurred in the P0 generation after exposure to environmental-related concentrations, suggesting that ATR exposure might have cumulative effects. Likewise, parental exposure to ATR caused transgenerational toxicity impairments. Interestingly, reproductive toxicity not development toxicity was transmitted to several generations (F1–F4), and the F2 generation showed the most notable changes. QRT-PCR results showed that genes related to DNA methylation 6mA (damt-1, nmad-1) and histone H3 methylation (mes-4, met-2, set-25, set-2, and utx-1) can also be passed on to offspring. The function of H3K4 and H3K9 methylation were explored by using loss-of-function mutants for set-2, set-25, and met-2. Transmissible reproductive toxicity was absent in met-2(n4256), set-2(ok952), and set-25(n5021) mutants, which suggests that the histone methyltransferases H3K4 and H3K9 activity are indispensable for the transgenerational effect of ATR. Finally, the downstream genes of DNA methylation and histone H3 methylation were determined. ATR upregulated the expression of ZC317.7, hsp-6, and hsp-60. Mitochondrial stress in parental generation dependent transcription 6mA modifiers may establish these epigenetic marks in progeny.

Keywords: ATR, Caenorhabditis elegans, multi-/trans-generation, reproductive toxicity

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