Search results for: small scale LNG

Authors: Elif Cakir, Görkem Özülkü, Hatice Bekiroğlu, Muhammet Arici, Osman Sağdic

Abstract:

It is important to be able to formulate cakes with a wide consumption mass with gluten-free and high nutritional value ingredients to increase the consumption possibilities of people with limited nutrition opportunities. Although people do not prefer Prunus spinosa (PS)because of its sour taste and its use in the food industry is limited on a local scale, the potential of using PS, which is a naturally rich source of many micronutrients and bioactive compounds, in glutenfree cake production has been investigated. In this study, the potential of using PS, a natural wild fruit, in the production of functional gluten-free cakes was investigated. It was aimed to evaluate the effects of freeze-dried and powdered PS-enriched rice flour cakes on tech functionality, nutrition and eating quality. In terms of physicochemical properties, PS raises increased the ash, protein, and moisture values of the cakes. PS with high phenolic content, phenolic component content, and radical reducing power made by ABTS, FRAP, and DPPH techniques were higher in all samples than control, and the highest 4% PS was determined in cakes. In terms of the glycemic index (GI), which is an important feature of diet products, it was determined that the GI in cakes decreased by 86.30±1.04.75.05±1.16 and 69.38±1.21, respectively, with the increase in PS ratio. Except for the 1%, PS added sample, the increase in PS caused a decrease in specific volume, % porosity and increase in hardness, including 4 days of storage. PS increase decreased the L* and b* values and increased a* value and redness of the cake. Sensory liking of the cake samples containing PS was scored significantly (p<0.05) higher of control.

Keywords: Prunus spinosa, gluten-free cake, antioxidant, phenolic, glycemic index

Procedia PDF Downloads 134

Authors: M. Bagheri Varzaneh, H. R. Rahmani, R. Jahanian

Abstract:

The present study aimed to investigate the effects of copper-methionine on ascites incidence and hematological, morphological and enzymatic responses in broiler chickens. A total of 480 one-day-old Ross 308 broiler chicks were used in a completely randomized design in a 2×3 factorial arrangement of treatments including two ambient temperatures (thermoneutral and cold stress) and three copper levels (0, 100, and 200 mg/kg as copper-methionine) with 4 replicates (20 birds in each replicate). Broilers were kept in an environmentally-controlled room from 1 to 28 days; then, half of them exposed to cold temperature from 28 to 45 days of age. The birds were sacrificed at days 38 and 45 of age. Heparinized blood samples were collected to measure hematocrit, hemoglobin concentration, red blood cell (RBC) count, alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Heart, lungs, liver, and spleen were collected and weighed separately on a sensitive digital scale. At d 38 of age, none of hematological variables, enzymatic parameters, and relative weights of organs were affected by treatments. Ascitic broilers were observed in group subjected to cold temperature and control diet (without supplemental copper) at d 45 of age. Relative weight of lungs and relative weight of heart in broilers fed on copper-methionine supplemented diets in cold temperature were lower compared with other groups. Relative liver weight, ALT, AST activities, and hematological parameters such as hematocrit, hemoglobin concentration, red blood cell count in ascitic broilers were significantly increased. In contrast, a significant decrease of the relative weight of spleen was shown in these chickens. The results showed that dietary supplementation with copper–methionine can decrease probability of ascites incidence in broilers chicks, especially under cold condition.

Keywords: ascites, cold temperature, copper-methionine, cold-stressed broiler

Procedia PDF Downloads 632

Authors: Axel Mancebo, Ana M. Bada, Angel Casacó, Bárbara González, Avelina León, María E. Arteaga, Consuelo González, Belinda Sánchez, Adriana Carr, Nuris Ledón, Arianna Iglesias

Abstract:

Despite the many preventive and therapeutic modalities aimed at curing cancer, it remains as a serious world health problem. Promising recent developments suggest that cancer immunotherapy may be the next great hope for cancer treatment. EGFRs are receptor tyrosine kinases and it is considered an important therapeutic target related with tumor progression, and several types of molecular therapies, including monoclonal antibodies, small molecules, and vaccines, have been developed to target the HER family of receptors. On the other hand, gangliosides are membrane glycosphingolipids that contain two variants of sialic acid, the N-acetylated (NeuAc) and the N-glycolylated (NeuGc) variant. The high expression of this antigen-specific molecule has been associated with malignant tumor progression and immunosuppressive mechanisms, so ganglioside could be considered as the target for cancer immunotherapy. We have been working for several years in the safety evaluation of cancer vaccines targeting these two systems, the EGF receptor and ganglioside. We presented in this work results of repeated dose toxicity studies performed in Sprague Dawley rats and Cynomolgus monkeys, including clinical observations, body weight and rectal temperature measuring, clinical pathology analysis, gross necropsy and histological examination in rodent studies, and immunological evaluation. Immunizations were capable of inducing mainly inflammatory effects at the injection site, with findings largely attributable to the adjuvants used and probably enhanced by the immunological properties of the antigens. In general, these vaccines were shown to be well tolerated, and these studies in relevant species allow treating cancer patients with tumors during long periods with relative weight safety margin.

Keywords: cancer vaccines, safety, toxicology, rats, non human primates

Procedia PDF Downloads 448

Authors: Lauren C. Porter, Andrew Curtis, Eric Jefferis, Susanne Mitchell

Abstract:

A wealth of research has been generated examining the variation in crime across neighborhoods. However, there is also a striking degree of crime concentration within neighborhoods. A number of studies show that a small percentage of street segments, intersections, or addresses account for a large portion of crime. Not surprisingly, a focus on these crime hot spots can be an effective strategy for reducing community level crime and related ills, such as health problems. However, research is also limited in an important respect. Studies tend to use official data to identify hot spots, such as 911 calls or calls for service. While the use of call data may be more representative of the actual level and distribution of crime than some other official measures (e.g. arrest data), call data still suffer from the 'dark figure of crime.' That is, there is most certainly a degree of error between crimes that occur versus crimes that are reported to the police. In this study, we present an alternative method of identifying crime hot spots, that does not rely on official data. In doing so, we highlight the potential utility of neighborhood-insiders to identify and understand crime dynamics within geographic spaces. Specifically, we use spatial video and geo-narratives to record the crime insights of 36 police, ex-offenders, and residents of a high crime neighborhood in northeast Ohio. Spatial mentions of crime are mapped to identify participant-identified hot spots, and these are juxtaposed with calls for service (CFS) data. While there are bound to be differences between these two sources of data, we find that one location, in particular, a corner store, emerges as a hot spot for all three groups of participants. Yet it does not emerge when we examine CFS data. A closer examination of the space around this corner store and a qualitative analysis of narrative data reveal important clues as to why this store may indeed be a hot spot, but not generate disproportionate calls to the police. In short, our results suggest that researchers who rely solely on official data to study crime hot spots may risk missing some of the most dangerous places.

Keywords: crime, narrative, video, neighborhood

Procedia PDF Downloads 236

Authors: Saeid Gharechelou, Stuart Green, Fiona Cawkwell

Abstract:

Hedgerow has an important role for a wide range of ecological habitats, landscape, agriculture management, carbon sequestration, wood production. Hedgerow detection accurately using satellite imagery is a challenging problem in remote sensing techniques, because in the special approach it is very similar to line object like a road, from a spectral viewpoint, a hedge is very similar to a forest. Remote sensors with very high spatial resolution (VHR) recently enable the automatic detection of hedges by the acquisition of images with enough spectral and spatial resolution. Indeed, recently VHR remote sensing data provided the opportunity to detect the hedgerow as line feature but still remain difficulties in monitoring the characterization in landscape scale. In this research is used the TerraSAR-x Spotlight and Staring mode with 3-5 m resolution in wet and dry season in the test site of Fermoy County, Ireland to detect the hedgerow by acquisition time of 2014-2015. Both dual polarization of Spotlight data in HH/VV is using for detection of hedgerow. The varied method of SAR image technique with try and error way by integration of classification algorithm like texture analysis, support vector machine, k-means and random forest are using to detect hedgerow and its characterization. We are applying the Shannon entropy (ShE) and backscattering analysis in single and double bounce in polarimetric analysis for processing the object-oriented classification and finally extracting the hedgerow network. The result still is in progress and need to apply the other method as well to find the best method in study area. Finally, this research is under way to ahead to get the best result and here just present the preliminary work that polarimetric image of TSX potentially can detect the hedgerow.

Keywords: TerraSAR-X, hedgerow detection, high resolution SAR image, dual polarization, polarimetric analysis

Procedia PDF Downloads 228

Authors: Y. S. Lin, H. L. Lin

Abstract:

Climate change and land-use change caused by urban expansion increase the frequency of urban flooding. To mitigate the increase in runoff volume, low-impact development (LID) is a green approach for reducing the area of impervious surface and managing stormwater at the source with decentralized micro-scale control measures. However, the current benefit assessment and practical application of LID in Taiwan is still tending to be development plan in the community and building site scales. As for urban design, site-based moisture-holding capacity has been common index for evaluating LID’s effectiveness of urban design, which ignore the diversity, and complexity of the urban built environments, such as different densities, positive and negative spaces, volumes of building and so on. Such inflexible regulations not only probably make difficulty for most of the developed areas to implement, but also not suitable for every different types of built environments, make little benefits to some types of built environments. Looking toward to enable LID to strength the link with urban design to reduce the runoff in coping urban flooding, the research consider different characteristics of different types of built environments in developing LID strategy. Classify the built environments by doing the cluster analysis based on density measures, such as Ground Space Index (GSI), Floor Space Index (FSI), Floors (L), and Open Space Ratio (OSR), and analyze their impervious surface rates and runoff volumes. Simulate flood situations by using quasi-two-dimensional flood plain flow model, and evaluate the flood mitigation effectiveness of different types of built environments in different low-impact development strategies. The information from the results of the assessment can be more precisely implement in urban design. In addition, it helps to enact regulations of low-Impact development strategies in urban design more suitable for every different type of built environments.

Keywords: low-impact development, urban design, flooding, density measures

Procedia PDF Downloads 330

Authors: Devesh Motwani, Ranjana S. Baruah

Abstract:

The prime incentive behind up gradation of heavy oil is to increase its API gravity for ease of transportation to refineries, thus expanding the market access of bitumen-based crude to the refineries. There has always been a demand for an integrated approach that aims at simplifying the upgrading scheme, making it adaptable to the production site in terms of economics, environment, and personnel safety. Recent advances in nanotechnology have facilitated the development of two lines of heavy oil upgrading processes that make use of nano-catalysts for producing upgraded oil: In Situ Upgrading and Field Upgrading. The In-Situ upgrading scheme makes use of Hot Fluid Injection (HFI) technique where heavy fractions separated from produced oil are injected into the formations to reintroduce heat into the reservoir along with suspended nano-catalysts and hydrogen. In the presence of hydrogen, catalytic exothermic hydro-processing reactions occur that produce light gases and volatile hydrocarbons which contribute to increased oil detachment from the rock resulting in enhanced recovery. In this way the process is a combination of enhanced heavy oil recovery along with up gradation that effectively handles the heat load within the reservoirs, reduces hydrocarbon waste generation and minimizes the need for diluents. By eliminating most of the residual oil, the Synthetic Crude Oil (SCO) is much easier to transport and more amenable for processing in refineries. For heavy oil reservoirs seriously impacted by the presence of aquifers, the nano-catalytic technology can still be implemented on field though with some additional investments and reduced synergies; however still significantly serving the purpose of production of transportable oil with substantial benefits with respect to both large scale upgrading, and known commercial field upgrading technologies currently on the market. The paper aims to delve deeper into the technology discussed, and the future compatibility.

Keywords: upgrading, synthetic crude oil, nano-catalytic technology, compatibility

Procedia PDF Downloads 400

Authors: Doua AlSaad, Ahmed Awaisu, Samah Elsalem, Palli Valapila Abdulrouf, Binny Thomas, Moza AlHail

Abstract:

Background: It has been suggested that pyridoxine has an anti-lactogenic effect. Studies of the efficacy of pyridoxine in suppressing lactation have reported conflicting results. The aim of this review is to evaluate the effectiveness and safety of high-dose pyridoxine in postpartum lactation inhibition. Methods: This systematic review included published trials that compared the efficacy and/or safety of pyridoxine to placebo or to other pharmacological agents for the inhibition of postpartum lactation. We searched PubMed, Embase, ScienceDirect, CINAHL, AMED, the Cochrane library, and the clinical trials registry to identify relevant literature. No limit was imposed on the year of publication of the studies, and the review included studies published until 15 January 2016. Two reviewers independently extracted data and assessed the risk of bias. Results: Seven studies were included, with a total of 1155 women, of which 471 women received pyridoxine. Three studies were randomized controlled trials, while the remaining four studies were non-randomized controlled trials. All of the included studies were relatively small (n = 18 – 482). The studies compared pyridoxine with placebo, bromocriptine, and/or stilboestrol. Pyridoxine was given orally, with a total daily dose of 450 – 600 mg for 5 to 7 days. Two trials (n = 349 participants) indicated that pyridoxine was effective in inhibiting lactation in approximately 95% of the enrolled patients. All other studies failed to demonstrate pyridoxine efficacy through either clinical assessment or prolactin level measurements. Pyridoxine safety was assessed by two trials in which no serious untoward side-effects were reported. Overall, the risk of bias for most of the studies was low to moderate. Conclusion: Current evidence supporting the effectiveness of high dose pyridoxine in the inhibition of postpartum lactation is inconsistent and insufficient. Larger randomized trials are needed to confirm the efficacy of pyridoxine in postpartum lactation inhibition. Acknowledgment: This review received a grant from the Medical Research Center of Hamad Medical Corporation in Qatar (grant number: 15100/15).

Keywords: pyridoxine, safety, effectiveness, lactation inhibition

Procedia PDF Downloads 128

Authors: Nahid Hassanshahi, Ayoub Karimi-Jashni, Nasser Talebbeydokhti

Abstract:

Due to the economic and environmental benefits of producing less waste, the US Environmental Protection Agency (EPA) introduces source reduction as one of the most important means to deal with the problems caused by increased landfills and pollution. Waste reduction involves all waste management methods, including source reduction, recycling, and composting, which reduce waste flow to landfills or other disposal facilities. Source reduction of waste can be studied from two perspectives: avoiding waste production, or reducing per capita waste production, and waste deviation that indicates the reduction of waste transfer to landfills. The present paper has investigated home composting as a managerial solution for reduction of waste transfer to landfills. Home composting has many benefits. The use of household waste for the production of compost will result in a much smaller amount of waste being sent to landfills, which in turn will reduce the costs of waste collection, transportation and burial. Reducing the volume of waste for disposal and using them for the production of compost and plant fertilizer might help to recycle the material in a shorter time and to use them effectively in order to preserve the environment and reduce contamination. Producing compost in a home-based manner requires very small piece of land for preparation and recycling compared with other methods. The final product of home-made compost is valuable and helps to grow crops and garden plants. It is also used for modifying the soil structure and maintaining its moisture. The food that is transferred to landfills will spoil and produce leachate after a while. It will also release methane and greenhouse gases. But, composting these materials at home is the best way to manage degradable materials, use them efficiently and reduce environmental pollution. Studies have shown that the benefits of the sale of produced compost and the reduced costs of collecting, transporting, and burying waste can well be responsive to the costs of purchasing home compost machine and the cost of related trainings. Moreover, the process of producing home compost may be profitable within 4 to 5 years and as a result, it will have a major role in reducing waste management.

Keywords: compost, home compost, reducing waste, waste management

Procedia PDF Downloads 422

Authors: Matthew P. Mancini, Vincent Ribiere

Abstract:

Today’s workers face more numerous and complex challenges and are required to be increasingly interdependent and faster learners. Knowledge sharing activities between people have been understood as a significant element affecting organizational innovation performance. While they do have the potential to spark cognitive conflict, disagreement is important from an organizational perspective because it can stimulate the development of new ideas and perhaps pave the way for creativity, innovation, and competitive advantage. How teams cope with the cognitive conflict dimension of knowledge sharing and the associated interpersonal risk is what captures our attention. Specifically, assertive conflict management strategies have a positive influence on knowledge sharing behaviors, and team psychological safety has a positive influence on knowledge sharing intention. This paper focuses on explaining the impact that these factors have on the shaping of an individual’s decision to engage or not in knowledge sharing activities. To accomplish this, we performed an empirical analysis on the results of our questionnaire about knowledge-sharing related conflict management and team psychological safety in pharmaceutical enterprises located in North America, Europe, and Asia. First, univariate analysis is used to characterize behavior regarding conflict management strategy into two groups. Group 1 presents assertive conflict management strategies and group 2 shows unassertive ones. Then, by using SEM methodology, we evaluated the relationships between them and the team psychological safety construct with the knowledge sharing process. The results of the SEM analysis show that assertive conflict management strategies affect the knowledge sharing process the most with a small, but significant effect from team psychological safety. The findings suggest that assertive conflict management strategies are just as important as knowledge sharing intentions for encouraging knowledge sharing behavior. This paper provides clear insights into how employees manage the sharing of their knowledge in the face of conflict and interpersonal risk and the relative importance of these factors in sustaining productive knowledge sharing activities.

Keywords: cognitive dissonance, conflict management, knowledge sharing, organizational behavior, psychological safety

Procedia PDF Downloads 313

Authors: Hyelim Park, Juan Martin Zorrilla

Abstract:

Climate change influences very widely and in various ways ocean ecosystem functioning. The consequences of climate change on marine ecosystems are an increase in temperature and irregular behavior of some solute concentrations. These changes would affect fisheries catches in several ways. Our aim is to assess the quantitative contribution change of fishery catches along the time and express them through four environment variables: Sea Surface Temperature (SST4) and the concentrations of Chlorophyll (CHL), Particulate Inorganic Carbon (PIC) and Particulate Organic Carbon (POC) at two spatial scales: Global and the nineteen FAO Major Fishing Areas divisions. Data collection was based on the FAO FishStatJ 2014 database as well as MODIS Aqua satellite observations from 2002 to 2012. Some data had to be corrected and interpolated using some existing methods. As the results, a multivariable regression model for average Global fisheries captures contained temporal mean of SST4, standard deviation of SST4, standard deviation of CHL and standard deviation of PIC. Global vector auto-regressive (VAR) model showed that SST4 was a statistical cause of global fishery capture. To accommodate varying conditions in fishery condition and influence of climate change variables, a model was constructed for each FAO major fishing area. From the management perspective it should be recognized some limitations of the FAO marine areas division that opens to possibility to the discussion of the subdivision of the areas into smaller units. Furthermore, it should be treated that the contribution changes of fishery species and the possible environment factor for specific species at various scale levels.

Keywords: fisheries-catch, FAO FishStatJ, MODIS Aqua, sea surface temperature (SST), chlorophyll, particulate inorganic carbon (PIC), particulate organic carbon (POC), VAR, granger causality

Procedia PDF Downloads 480

Authors: Luciano Tarantino, Emanuele Balzano, Aurelio Nasto

Abstract:

S.R. 53 years. January 2009: HCV-related cirrhosis, Child-Pugh A5 class, EGDS no aesophageal Varices. No important comorbidities. Treated with PEG-IFN+Ribavirin (march-november 2009) with subsequent sustained virologic response. HCVRNA absent overtime. October 2016 :CT detected small HCC nodule in the VIII segment (diam.=12 mm). Treated with US guided RF-ablation. November 2016 CT: complete necrosis. Unfortunately, the patient dropped out US and CT follow-up controls.September 2018: asthenia and weight loss. CT showed a large tumor infiltrating V-VII-VI segments and complete PVTT of right portal vein and its branches . Surgical Consultation excluded indication to Liver resection and OLT . 23 october 2018: ECT of a large peri-hilar area of the tumor including the PVTT. 1 and 3 months post-treatment CT showed complete necrosis and retraction of the thrombus and residual viable tumor in the peripheral portion of the right lobe . Therefor, the patient was reevaluated for OLT and considered eligible in waiting list . March 2019: CT showed no perihilar or portal vein recurrence and distant progression in the right lobe . March 2019 : Trans-arterial-Radio-therapy (TARE) of the right lobe. Post-treatment CT demonstrated no perihilar or portal vein recurrence and extensive necrosis of the residual tumor . December 2019: CT demonstrated several recurrences of HCC infiltrating the VI and VII segment . Howewer no recurrence was observed at hepatic hilum and in portal vessels . Therefore, on February 2020 the patient received OLT. At 44 months follow-up, no complication or recurrence or liver disfunction have been observed.

Keywords: hepatocellular carcinoma, portal vein tumor thrombosis, interventional ultrasound, liver tumor ablation, liver transplantation

Procedia PDF Downloads 63

Authors: Getaneh Berie Tarekegn

Abstract:

A precise localization system is crucial for many artificial intelligence Internet of Things (AI-IoT) applications in the era of smart cities. Their applications include traffic monitoring, emergency alarming, environmental monitoring, location-based advertising, intelligent transportation, and smart health care. The most common method for providing continuous positioning services in outdoor environments is by using a global navigation satellite system (GNSS). Due to nonline-of-sight, multipath, and weather conditions, GNSS systems do not perform well in dense urban, urban, and suburban areas.This paper proposes a generative AI-based positioning scheme for large-scale wireless settings using fingerprinting techniques. In this article, we presented a semi-supervised deep convolutional generative adversarial network (S-DCGAN)-based radio map construction method for real-time device localization. It also employed a reliable signal fingerprint feature extraction method with t-distributed stochastic neighbor embedding (t-SNE), which extracts dominant features while eliminating noise from hybrid WLAN and long-term evolution (LTE) fingerprints. The proposed scheme reduced the workload of site surveying required to build the fingerprint database by up to 78.5% and significantly improved positioning accuracy. The results show that the average positioning error of GAILoc is less than 0.39 m, and more than 90% of the errors are less than 0.82 m. According to numerical results, SRCLoc improves positioning performance and reduces radio map construction costs significantly compared to traditional methods.

Keywords: location-aware services, feature extraction technique, generative adversarial network, long short-term memory, support vector machine

Procedia PDF Downloads 55

Authors: Maha Bakakri, Rachid Tadili, Fatiha Lemmini

Abstract:

Morocco is one of the few countries that have kept their traditional crafts, despite the competition of modern industry and its impact on manual labor. Therefore the optimization of energy consumption becomes an obligation and this is the purpose of this document. In this work we present some characteristics of the furnace studied, its operating principle and the experimental measurements of the evolutions of the temperatures inside and outside the walls of the furnace, values which will be used later in the calculation of its thermal losses. In order to determine the major source of the thermal losses of the furnace we have established the heat balance of the furnace. The energy consumed, the useful energy and the thermal losses through the walls and the chimney of the furnace are calculated thanks to the experimental measurements which we realized for several firings. The results show that the energy consumption of this type of furnace is very high and that the main source of energy loss is mainly due to the heat losses of the combustion gases that escape from the furnace by the chimney while the losses through the walls are relatively small. it have opted for energy recovery as a solution where we can recover some of the heat lost through the use of a heat exchanger system using a double tube introduced into the flue gas exhaust stack compartment. The study on the heat recovery system is presented and the heat balance inside the exchanger is established. In this paper we also present the numerical modeling of heat transfer by conduction through the walls of the furnace. A numerical model has been established based on the finite volume method and the double scan method. It makes it possible to determine the temperature profile of the furnace and thus to calculate the thermal losses of its walls and to deduce the thermal losses due to the combustion gases. Validation of the model is done using the experimental measurements carried out on the furnace. The results obtained in this work, relating to the energy consumed during the operation of the furnace are important and are part of the energy efficiency framework that has become a key element in global energy policies. It is the fastest and cheapest way to solve energy, environmental and economic security problems.

Keywords: energy cunsumption, energy recovery, modeling, energy eficiency

Procedia PDF Downloads 68

Authors: Mulusew G. Jebena, David Lindstrom, Tefera Belachew, Craig Hadley, Carl Lachat, Patrick Kolsteren

Abstract:

Background: The biological and psychosocial consequence of food insecurity on physical health and nutritional status has been reported. But, its effect on mental health during adolescence remains unexplored. Thus, the main aim of this analysis is to examine the mechanism by which food insecurity is linked to mental health among adolescents living in Jimma, Southwest Ethiopia. Methods: We used data from third round observation of Jimma Longitudinal Family and Youth Survey (JLFSY). A total of 1,521 adolescents included for the main analysis. Food insecurity was measured using 5-items scale and The Self Reporting Questionnaire (SRQ-20) was used to measure mental distress. Structural equation modeling analysis was done using maximum likelihood estimation method. Model diagnostics test was reported. All p values were two tailed and P value ≤ 0.05 was used to determine statistical significance. Results: The prevalence of mental distress was 20.8%, 95% CI: (18.8, 22.9). After adjusted for covariates, the final model depicts food insecurity was associated with adolescent mental distress (β=.324). This analysis showed 94.1% of the effect of food insecurity on mental distress is direct. By contrast, 5.9% of the food insecurity effect is mediated by physical health. In addition, Self-rated health (β=.356), socioeconomic status (β=-.078) parental educational (β= .170), living in urban (β= .193) and female headed household (β=.205) were associated with adolescent mental distress. Conclusions: This finding highlights the direct effect of food insecurity on adolescent mental distress. Therefore, any intervention aimed to improve mental distress of adolescents should consider strategies to improve access to sufficient, safe, and nutritious food. Beside this, prevention of underlying factors such as psychosomatic health illness and improving socio economic status is also very critical. Furthermore longitudinal relationship of the long term effect of food insecurity on mental health should be investigated.

Keywords: adolescent, Ethiopia, food insecurity, mental health

Procedia PDF Downloads 588

Authors: K. S. Sivakumaran, T. Thanga, B. Halabieh

Abstract:

The end panels of a large rectangular industrial duct, which experience significant internal pressures, also experience considerable transverse shear due to transfer of gravity loads to the supports. The current design practice of such thin plate panels for shear load is based on methods used for the design of plate girder webs. The structural arrangements, the loadings and the resulting behavior associated with the industrial duct end panels are, however, significantly different than those of the web of a plate girder. The large aspect ratio of the end panels gives rise to multiple bands of tension fields, whereas the plate girder web design is based on one tension field. In addition to shear, the industrial end panels are subjected to internal pressure which in turn produces significant membrane action. This paper reports a study which was undertaken to review the current industrial analysis and design methods and to propose a comprehensive method of designing industrial duct end panels for shear resistance. In this investigation, a nonlinear finite element model was developed to simulate the behavior of industrial duct end panel subjected to transverse shear and internal pressures. The model considered the geometric imperfections and constitutive relations for steels. Six scale independent dimensionless parameters that govern the behavior of such end panel were identified and were then used in an extensive parametric study. It was concluded that the plate slenderness dominates the shear strength of stockier end panels, and whereas, the aspect ratio and plate slenderness influence the shear strength of slender end panels. Based on these studies, this paper proposes design aids for estimating the shear strength of rectangular duct end panels.

Keywords: thin plate, transverse shear, tension field, finite element analysis, parametric study, design

Procedia PDF Downloads 216

Authors: Anindita Banik, Anjali Kant, Aninda Duti Banik, Arun Banik

Abstract:

Speech is a complex, dynamic unique motor activity through which we express thoughts and emotions and respond to and control our environment. The aim was based to compare select Motor Speech parameters and their sub parameters across typical Marathi speaking adults and children. The subjects included a total of 300 divided into Group I, II, III including males and females. Subjects included were reported of no significant medical history and had a rating of 0-1 on GRBAS scale. The recordings were obtained utilizing three stimuli for the acoustic analysis of Diadochokinetic rate (DDK), Second Formant Transition, Voice and Tremor and its sub parameters. And these aforementioned parameters were acoustically analyzed in Motor Speech Profile software in VisiPitch IV. The statistical analyses were done by applying descriptive statistics and Two- Way ANOVA.The results obtained showed statistically significant difference across age groups and gender for the aforementioned parameters and its sub parameters.In DDK, for avp (ms) there was a significant difference only across age groups. However, for avr (/s) there was a significant difference across age groups and gender. It was observed that there was an increase in rate with an increase in age groups. The second formant transition sub parameter F2 magn (Hz) also showed a statistically significant difference across both age groups and gender. There was an increase in mean value with an increase in age. Females had a higher mean when compared to males. For F2 rate (/s) a statistically significant difference was observed across age groups. There was an increase in mean value with increase in age. It was observed for Voice and Tremor MFTR (%) that a statistically significant difference was present across age groups and gender. Also for RATR (Hz) there was statistically significant difference across both age groups and gender. In other words, the values of MFTR and RATR increased with an increase in age. Thus, this study highlights the variation of the motor speech parameters amongst the typical population which would be beneficial for comparison with the individuals with motor speech disorders for assessment and management.

Keywords: adult, children, diadochokinetic rate, second formant transition, tremor, voice

Procedia PDF Downloads 304

Authors: Geetika Richa, M. L. Sharma

Abstract:

Bamboo as an ancient herbal medicine has been used for thousands of years in Asia and goes by many names such as tabashir, banslochan etc. It is often used for its tonic and astringent properties. Modern analysis of bamboos show high amount of vitamins and minerals which makes them valuable as a curative. Bamboo leaf decoction and young shoots are known as remedy for intestinal worms, healing of ulcers and stomach disorders. Bamboos are known to be propagated by large scale plantations but propagation through seeds occurs very limited as they have very short viability of few months. Seeds loses viability over a period of time even under controlled conditions and important factors that affect seed viability is the decline in reserve food material, decrease in membrane integrity and fall in endogenous level of growth hormones. Invigoration treatments that include hydration, dehydration, incorporation of bioactive chemicals such as growth regulators, nutrients and antioxidants etc. improve the seed performance. Our studies were aimed to determine the most effective invigoration treatments to enhance vigour and viability of seeds by following invigoration treatments, i.e., hardening. Treated seeds were stored at controlled temperature and humidity (in desiccators at 4°C). In hardening, chemicals were applied in 3 different concentrations to three replicates of 10 seeds. Hardening was done withGA3, IAA, (each with concentrations of 10 ppm, 20 ppm and 50 ppm), calcium oxychloride, neem leaf powder and clay (each with concentrations of 2%, 5% and 10%). Statistically all the hardening materials were effective but GA3 50 ppm was the most effective one in maintaining germination percentage and vigour index. Hardening treatments increased the germination percentage of seeds, i.e. 86.2%, over control which showed germination percentage of 80.2%. It was concluded that in order to maintain seed viability during storage for longer period of time, invigoration treatments have been found to be very effective.

Keywords: invigoration, seed quality, viability, hardening, membrane integrity, decoction

Procedia PDF Downloads 317

Authors: Lani Fraizer

Abstract:

Increasingly, individuals from diverse professional and academic backgrounds are making a conscious choice to pursue careers related to social change; a sophisticated understanding of social entrepreneur education is becoming ever more important. Social entrepreneurs are impassioned change makers who characteristically combine leadership and entrepreneurial spirits to problem solve social ills affecting our planet. Generating partnership opportunities and nurturing them is an important part of their change-making work. Faced with the complexities of these partnerships, social entrepreneurs and people who work with them need to be well prepared to tackle new and unforeseen challenges faced. As partnerships become even more critical to advance initiatives at scale, for example, understanding the partnership brokering role is even more important for educators who prepare these leaders to establish and sustain multi-stakeholder partnerships. This paper aims to provide practitioners in social entrepreneurship with enhanced knowledge of partnership brokering and identify directions for future research. A literature review search from January 1977 to May 2015 was conducted using the combined keywords ‘partnership brokering’ and ‘social entrepreneurship’ via WorldCat, one of the largest database catalogs in the world with collections of more than 10,000 worldwide. This query focused on literature written in the English language and analyzed solely the role of partnership brokering in social entrepreneurship. The synthesis of the literature review found three main themes emerging: the need for more professional awareness of partnership brokering and its value add in systems change-making work, the need for more knowledge on developing partnership brokering competencies, and the need for more applied research in the area of partnership brokering and how it is practiced by practitioners in social entrepreneurship. The results of the review serve to emphasize and reiterate the importance of partnership brokers in social entrepreneurship work, and act as a reminder of the need for further scholarly research in this area to bridge the gap between practice and research.

Keywords: partnership brokering, leadership, social entrepreneurship, systems changemaking

Procedia PDF Downloads 340

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

Procedia PDF Downloads 83

Authors: Afsaneh Mohammadnejad, Marianne Nygaard, Jan Baumbach, Shuxia Li, Weilong Li, Jesper Lund, Jacob v. B. Hjelmborg, Lene Christensen, Qihua Tan

Abstract:

Cognitive impairment in the elderly is a key issue affecting the quality of life. Despite a strong genetic background in cognition, only a limited number of single nucleotide polymorphisms (SNPs) have been found. These explain a small proportion of the genetic component of cognitive function, thus leaving a large proportion unaccounted for. We hypothesize that one reason for this missing heritability is the misspecified modeling in data analysis concerning phenotype distribution as well as the relationship between SNP dosage and the phenotype of interest. In an attempt to overcome these issues, we introduced a model-free method based on the generalized correlation coefficient (GCC) in a genome-wide association study (GWAS) of cognitive function in twin samples and compared its performance with two popular linear regression models. The GCC-based GWAS identified two genome-wide significant (P-value < 5e-8) SNPs; rs2904650 near ZDHHC2 on chromosome 8 and rs111256489 near CD6 on chromosome 11. The kinship model also detected two genome-wide significant SNPs, rs112169253 on chromosome 4 and rs17417920 on chromosome 7, whereas no genome-wide significant SNPs were found by the linear mixed model (LME). Compared to the linear models, more meaningful biological pathways like GABA receptor activation, ion channel transport, neuroactive ligand-receptor interaction, and the renin-angiotensin system were found to be enriched by SNPs from GCC. The GCC model outperformed the linear regression models by identifying more genome-wide significant genetic variants and more meaningful biological pathways related to cognitive function. Moreover, GCC-based GWAS was robust in handling genetically related twin samples, which is an important feature in handling genetic confounding in association studies.

Keywords: cognition, generalized correlation coefficient, GWAS, twins

Procedia PDF Downloads 117

Authors: Adam N. Bell, Sarina J. Ergas, Michael Nystrom, Nathan P. Brennan, Kevan L. Main

Abstract:

Integrated Multi-Trophic Aquaculture systems (IMTA) have the potential to improve the sustainability of seafood production, generate organic fertilizer and feed, remove waste discharges and reduce energy use. IMTA can include periphyton biofilters where algae and microbes grow on surfaces, along with caught detritus and amphipods. Periphyton biofilters provide many advantages: nitrification, denitrification, primary production and ecological diversity. The goal of this study was to determine how biofilter hydraulic residence time (τ) effects periphyton biomass production, dissolved oxygen (DO) and nutrient removal. A pilot scale recirculating aquaculture system (RAS) was designed, constructed and operated at different hydraulic residence times (τ= 1, 2, 4, 6, 8 hours per tank). For each τ, a conservative tracer study was conducted to investigate system hydrodynamics. Data on periphyton weights, pH, nitrogen species, phosphorus, temperature and DO were collected. The tracer study for τ =1 hour revealed that the normalized time < τ, indicating short-circuiting. Periphyton biomass production rate was relatively unaffected by τ (R_e<1 for all τ). Average ammonia nitrogen removal was > 75% for all trials. Nitrate and nitrite did not accumulate in the RAS for τ≥4 hours due to enhanced denitrification in anoxic zones. For τ≥4 hours DO concentration was at a maximum of 4 mg L-1 after 14:00, and decreased to 0 mg L-1 during nighttime. At τ=1 hour, the RAS stayed > 2 mg L-1 and DO was more evenly distributed. For the validation trial, the culture tank was stocked with Centropomus undecimalis (common snook) and the system was operated at τ= 1 hr. Preliminary results showed that a RAS with an integrated periphyton biofilter could support fish health with low nutrient concentrations DO > 6 mg L-1.

Keywords: sustainable aquaculture, resource recovery, nitrogen, microalgae, hydrodynamics, integrated multi-trophic aquaculture

Procedia PDF Downloads 127

Authors: Ali Akbar, Seungho Shin, Sukkee Um

Abstract:

The composition of catalyst layers (CLs) plays an important role in the overall performance and cost of the proton exchange membrane fuel cells (PEMFCs). Low platinum loading, high utilization, and more durable catalyst still remain as critical challenges for PEMFCs. In this study, a three-dimensional material network model is developed to visualize the nanostructure of carbon supported platinum Pt/C and Pt/VACNT catalysts in pursuance of maximizing the catalyst utilization. The quadruple-phase randomly generated CLs domain is formulated using quasi-random stochastic Monte Carlo-based method. This unique statistical approach of four-phase (i.e., pore, ionomer, carbon, and platinum) model is closely mimic of manufacturing process of CLs. Various CLs compositions are simulated to elucidate the effect of electrons, ions, and mass transport paths on the catalyst utilization factor. Based on simulation results, the effect of key factors such as porosity, ionomer contents and Pt weight percentage in Pt/C catalyst have been investigated at the represented elementary volume (REV) scale. The results show that the relationship between ionomer content and Pt utilization is in good agreement with existing experimental calculations. Furthermore, this model is implemented on the state-of-the-art Pt/VACNT CLs. The simulation results on Pt/VACNT based CLs show exceptionally high catalyst utilization as compared to Pt/C with different composition ratios. More importantly, this study reveals that the maximum catalyst utilization depends on the distance spacing between the carbon nanotubes for Pt/VACNT. The current simulation results are expected to be utilized in the optimization of nano-structural construction and composition of Pt/C and Pt/VACNT CLs.

Keywords: catalyst layer, platinum utilization, proton exchange membrane fuel cell, stochastic modeling

Procedia PDF Downloads 118

Authors: Abdallah Al-ZoubI, Mamoun Dmour

Abstract:

The spectrum of IoT devices is becoming widely diversified, entering almost all possible fields and finding applications in industry, health, finance, logistics, education, to name a few. The IoT active endpoint sensors and devices exceeded the 12 billion mark in 2021 and are expected to reach 27 billion in 2025, with over $34 billion in total market value. This sheer rise in numbers and use of IoT devices bring with it considerable concerns regarding data storage, analysis, manipulation and protection. IoT Blockchain-based systems have recently been proposed as a decentralized solution for large-scale data storage and protection. COVID-19 has actually accelerated the desire to utilize IoT devices as it impacted both demand and supply and significantly affected several regions due to logistic reasons such as supply chain interruptions, shortage of shipping containers and port congestion. An IoT-blockchain system is proposed to handle big data generated by a distributed network of sensors and controllers in an interactive manner. The system is designed using the Ethereum platform, which utilizes smart contracts, programmed in solidity to execute and manage data generated by IoT sensors and devices. such as Raspberry Pi 4, Rasbpian, and add-on hardware security modules. The proposed system will run a number of applications hosted by a local machine used to validate transactions. It then sends data to the rest of the network through InterPlanetary File System (IPFS) and Ethereum Swarm, forming a closed IoT ecosystem run by blockchain where a number of distributed IoT devices can communicate and interact, thus forming a closed, controlled environment. A prototype has been deployed with three IoT handling units distributed over a wide geographical space in order to examine its feasibility, performance and costs. Initial results indicated that big IoT data retrieval and storage is feasible and interactivity is possible, provided that certain conditions of cost, speed and thorough put are met.

Keywords: IoT devices, blockchain, Ethereum, big data

Procedia PDF Downloads 146

Authors: Najith Duminda Galmangoda Guruge, Nadeeka Rathnayake, Vinodani Wimalasena, Dinesha Wijesooriya

Abstract:

Investing in Early Learning can improve children’ interests for education and makes them ready for school. Children in economically disadvantaged communities may have reduced readiness for schools. Health Promotion approach enables communities including disadvantaged to control over their health. Mothers of children under the age five in ‘Alapathwewa’ community (n=40) were selected as the sample with the aim to promote early learning of children to improve their school readiness. Mothers in ‘Morakeewa’ community (n=40) were the control. Interventions were for a period of 2 years and children of these mothers were followed up to school entry. Importance of early learning and possibility of providing quality learning environments for children at a low cost was discussed with mothers in an experimental setting by facilitators. Mothers were enabled to make age-appropriate baby rooms which provide learning opportunities. Collective community playhouses and play areas were developed by mothers to provide opportunities for children to interact and learn with each other. Mothers started discussing with each other and sharing experiences. The progress was monitored by mothers at regular intervals. Data regarding school competencies of children were obtained from school teachers. School teachers measured thirteen competencies of children on a scale of ‘very good, good, moderate and weak’. All children in the experimental group were in ‘very good’ level in two competencies, ‘communicate friendly with others’ and ‘express ideas well’. Children in the experimental group reported a significantly higher achievement of all thirteen competencies (p < .05) than children in control. Providing quality early learning environments for children even in economically disadvantaged settings makes them ready for schools. Through a Health Promotion approach, early learning experiences for children can be provided at a low cost.

Keywords: disadvantaged, early learning, economically, health promotion

Procedia PDF Downloads 252

Authors: Kathryn Rooney, Kaitlyn Eddy, Evan Landers, Weihui Li

Abstract:

The international mortality rate for neonates and infants has been declining at a disproportionally low rate when compared to the overall decline in child mortality in recent decades. A significant portion of infant deaths could be prevented with the implementation of low-cost and easy to use physiological monitoring devices, by enabling early identification of symptoms before they progress into life-threatening illnesses. The oral diagnostic device discussed in this paper serves to continuously monitor the key vital signs of body temperature, respiratory rate, heart rate, and oxygen saturation. The device mimics an infant pacifier, designed to be easily tolerated by infants as well as orthodontically inert. The fundamental measurements are gathered via thermistors and a pulse oximeter, each encapsulated in medical-grade silicone and wired internally to a microcontroller chip. The chip then translates the raw measurements into physiological values via an internal algorithm, before outputting the data to a liquid crystal display screen and an Android application. Additionally, a biological sample collection chamber is incorporated into the internal portion of the device. The movement within the oral chamber created by sucking on the pacifier-like device pushes saliva through a small check valve in the distal end, where it is accumulated and stored. The collection chamber can be easily removed, making the sample readily available to be tested for various diseases and analytes. With the vital sign monitoring and sample collection offered by this device, abnormal fluctuations in physiological parameters can be identified and appropriate medical care can be sought. This device enables preventative diagnosis for infants who may otherwise have gone undiagnosed, due to the inaccessibility of healthcare that plagues vast numbers of underprivileged populations.

Keywords: neonate mortality, infant mortality, low-cost diagnostics, vital signs, saliva testing, preventative care

Procedia PDF Downloads 151

Authors: Zongyao Sha

Abstract:

Green vegetation plays a vital role in energy flows and matter cycles in terrestrial ecosystems, and vegetation phenology may not only be influenced by but also impose active feedback on climate changes. The phenological events of vegetation, such as the start of the season (SOS), end of the season (EOS), and length of the season (LOS), can respond to climate changes and affect gross primary productivity (GPP). Here we coupled satellite remote sensing imagery with FLUXNET observations to systematically map the shift of SOS, EOS, and LOS in global vegetated areas and explored their response to climate fluctuations and feedback on GPP during the last two decades. Results indicated that SOS advanced significantly, at an average rate of 0.19 days/year at a global scale, particularly in the northern hemisphere above the middle latitude (≥30°N) and that EOS was slightly delayed during the past two decades, resulting in prolonged LOS in 72.5% of the vegetated area. The climate factors, including seasonal temperature and precipitation, are attributed to the shifts in vegetation phenology but with a high spatial and temporal difference. The study revealed interactions between vegetation phenology and climate changes. Both temperature and precipitation affect vegetation phenology. Higher temperature as a direct consequence of global warming advanced vegetation green-up date. On the other hand, 75.9% and 20.2% of the vegetated area showed a positive correlation and significant positive correlation between annual GPP and length of vegetation growing season (LOS), likely indicating an enhancing effect on vegetation productivity and thus increased carbon uptake from the shifted vegetation phenology. Our study highlights a comprehensive view of the vegetation phenology changes of the global terrestrial ecosystems during the last two decades. The interactions between the shifted vegetation phenology and climate changes may provide useful information for better understanding the future trajectory of global climate changes. The feedback on GPP from the shifted vegetation phenology may serve as an adaptation mechanism for terrestrial ecosystems to mitigate global warming through improved carbon uptake from the atmosphere.

Keywords: vegetation phenology, growing season, NPP, correlation analysis

Procedia PDF Downloads 98

Authors: Chetna Khandelwal

Abstract:

This research aims to study the contentions that Farm Animal Sanctuaries pose to human-animal relationships in modernity, which have developed as a result of globalisation of the meat industry and advancements in technology. The sociological history of human-animal relationships in farming is contextualised in order to set a foundation for the follow-up examination of challenges to existing human-(farm)animal relationships by Farm Animal Sanctuaries. The methodology was influenced by relativism, and the method involved three semi-structured small-group interviews, conducted at locations of sanctuaries. The sample was chosen through purposive sampling and varied by location and size of the sanctuary. Data collected were transcribed and qualitatively coded to generate themes. Findings revealed that sanctuary contentions to established human-animal relationships by factory farming could be divided into 4 broad categories – Revealing horrors of factory farming (involving uncovering power relations in agribusiness); transforming relationships with animals (including letting them emotionally heal in accordance with their individual personalities and treating them as partial-pets); educating the public regarding welfare conditions in factory farms as well as animal sentience through practical experience or positive imagery of farm animals, and addressing retaliation made by agribusiness in the form of technologies or discursive strategies. Hence, this research concludes that The human-animal relationship in current times has been characterised by – (ideological and physical) distance from farm animals, commodification due to increased chasing of profits over welfare and exploitation using technological advancements, creating unequal power dynamics that rid animals of any agency. Challenges to this relationship can be influenced by local populations around the sanctuary but not so dependent upon the size of it. This research can benefit from further academic exploration into farm animal sanctuaries and their role in feminist animal rights activism to enrich the ongoing fight against intensive farming.

Keywords: animal rights, factory farming, farm animal sanctuaries, human-animal relationships

Procedia PDF Downloads 134

Authors: Vakhtang Charaia, Mariam Lashkhi

Abstract:

Foreign direct investment (FDI) plays a vital role in global business. It provides firms with new markets and advertising channels, cheaper production facilities, admission to new technology, products, skills and financing. FDI can provide a recipient country/company with a source of new technologies, capital, practice, products, management skills, and as such can be a powerful drive for economic development. It is one of the key elements of stable economic development in many countries, especially in developing ones. Therefore the size of FDI inflow is one of the most crustal factors for economic perfection in small economy countries (like, Georgia), while most of developed ones are net exporters of FDI. Since, FDI provides firms with new markets; admission to new technologies, products and management skills; marketing channels; cheaper production facilities, and financing opportunities. It plays a significant role in Georgian economic development. Increasing FDI inflows from all over the world to Georgia in last decade was achieved with the outstanding reforms managed by the Georgian government. However, such important phenomenon as world financial crisis and Georgian-Russian war put its consequence on the over amount of FDI inflow in Georgia in the last years. It is important to mention that the biggest investor region for Georgia is EU, which is interested in Georgia not only from the economic points of view but from political. The case studies from main EU investor countries show that Georgia has a big potential of investment in different areas, such as; financial sector, energy, construction, tourism industry, transport and communications. Moreover, signing of Association Agreement between Georgia and EU will further boost all the fields of economy in Georgia in both short and long terms. It will attract more investments from different countries and especially from EU. The last, but not least important issue is the calculation of annual FDI inflow to Georgia, which it is calculated differently by different organizations, based on different methodologies, but what is more important is that all of them show significant increase of FDI in last decade, which gives a positive signal to investors and underlines necessity of further improvement of investment climate in the same direction.

Keywords: foreign direct investment (FDI), Georgia, investment development path, investment climate

Procedia PDF Downloads 274

Authors: Adel Alblihy, Reem Ali, Mashael Algethami, Ahmed Shoqafi, Michael S. Toss, Juliette Brownlie, Natalie J. Tatum, Ian Hickson, Paloma Ordonez Moran, Anna Grabowska, Jennie N. Jeyapalan, Nigel P. Mongan, Emad A. Rakha, Srinivasan Madhusudan

Abstract:

Platinum resistance is a clinical challenge in ovarian cancer. Platinating agents induce DNA damage which activate Mre11 nuclease directed DNA damage signalling and response (DDR). Upregulation of DDR may promote chemotherapy resistance. Here we have comprehensively evaluated Mre11 in epithelial ovarian cancers. In clinical cohort that received platinum- based chemotherapy (n=331), Mre11 protein overexpression was associated with aggressive phenotype and poor progression free survival (PFS) (p=0.002). In the ovarian cancer genome atlas (TCGA) cohort (n=498), Mre11 gene amplification was observed in a subset of serous tumours (5%) which correlated highly with Mre11 mRNA levels (p<0.0001). Altered Mre11 levels was linked with genome wide alterations that can influence platinum sensitivity. At the transcriptomic level (n=1259), Mre11 overexpression was associated with poor PFS (p=0.003). ROC analysis showed an area under the curve (AUC) of 0.642 for response to platinum-based chemotherapy. Pre-clinically, Mre11 depletion by gene knock down or blockade by small molecule inhibitor (Mirin) reversed platinum resistance in ovarian cancer cells and in 3D spheroid models. Importantly, Mre11 inhibition was synthetically lethal in platinum sensitive XRCC1 deficient ovarian cancer cells and 3D-spheroids. Selective cytotoxicity was associated with DNA double strand break (DSB) accumulation, S-phase cell cycle arrest and increased apoptosis. We conclude that pharmaceutical development of Mre11 inhibitors is a viable clinical strategy for platinum sensitization and synthetic lethality in ovarian cancer.

Keywords: MRE11; XRCC1, ovarian cancer, platinum sensitization, synthetic lethality

Procedia PDF Downloads 126