Search results for: synthetic gene network

Authors: Syed Jawad Hussain, Abir Touati, Farid Touati

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Free-Space Optics (FSO) is a wireless technology that enables the optical transmission of data though the air. FSO is emerging as a promising alternative or complementary technology to fiber optic and wireless radio-frequency (RF) links due to its high-bandwidth, robustness to EMI, and operation in unregulated spectrum. These systems are envisioned to be an essential part of future generation heterogeneous communication networks. Despite the vibrant advantages of FSO technology and the variety of its applications, its widespread adoption has been hampered by rather disappointing link reliability for long-range links due to atmospheric turbulence-induced fading and sensitivity to detrimental climate conditions. Qatar, with modest cloud coverage, high concentrations of airborne dust and high relative humidity particularly lies in virtually rainless sunny belt with a typical daily average solar radiation exceeding 6 kWh/m2 and 80-90% clear skies throughout the year. The specific objective of this work is to study for the first time in Qatar the effect of solar irradiation on the deliverability of the FSO Link. In order to analyze the transport media, we have ported Embedded Linux kernel on Field Programmable Gate Array (FPGA) and designed a network sniffer application that can run into FPGA. We installed new FSO terminals and configure and align them successively. In the reporting period, we carry out measurement and relate them to weather conditions.

Keywords: free space optics, solar irradiation, field programmable gate array, FSO outage

Procedia PDF Downloads 361

Authors: P. J. Sweeney, T. Ahtoniemi, J. Puoliväli, T. Laitinen, K. Lehtimäki, A. Nurmi, D. Wells

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Duchenne muscular dystrophy (DMD) is caused by an X linked mutation in the dystrophin gene; lack of dystrophin causes a progressive muscle necrosis which leads to a progressive decrease in mobility in those suffering from the disease. The MDX mouse, a mutant mouse model which displays a frank dystrophinopathy, is currently widely employed in pre clinical efficacy models for treatments and therapies aimed at DMD. In general the end-points examined within this model have been based on invasive histopathology of muscles and serum biochemical measures like measurement of serum creatine kinase (sCK). It is established that a “critical period” between 4 and 6 weeks exists in the MDX mouse when there is extensive muscle damage that is largely sub clinical but evident with sCK measurements and histopathological staining. However, a full characterization of the MDX model remains largely incomplete especially with respect to the ability to aggravate of the muscle damage beyond the critical period. The purpose of this study was to attempt to aggravate the muscle damage in the MDX mouse and to create a wider, more readily translatable and discernible, therapeutic window for the testing of potential therapies for DMD. The study consisted of subjecting 15 male mutant MDX mice and 15 male wild-type mice to an intense chronic exercise regime that consisted of bi-weekly (two times per week) treadmill sessions over a 12 month period. Each session was 30 minutes in duration and the treadmill speed was gradually built up to 14m/min for the entire session. Baseline plasma creatine kinase (pCK), treadmill training performance and locomotor activity were measured after the “critical period” at around 10 weeks of age and again at 14 weeks of age, 6 months, 9 months and 12 months of age. In addition, kinematic gait analysis was employed using a novel analysis algorithm in order to compare changes in gait and fine motor skills in diseased exercised MDX mice compared to exercised wild type mice and non exercised MDX mice. In addition, a morphological and metabolic profile (including lipid profile), from the muscles most severely affected, the gastrocnemius muscle and the tibialis anterior muscle, was also measured at the same time intervals. Results indicate that by aggravating or exacerbating the underlying muscle damage in the MDX mouse by exercise a more pronounced and severe phenotype in comes to light and this can be picked up earlier by kinematic gait analysis. A reduction in mobility as measured by open field is not apparent at younger ages nor during the critical period, but changes in gait are apparent in the mutant MDX mice. These gait changes coincide with pronounced morphological and metabolic changes by non-invasive anatomical MRI and proton spectroscopy (1H-MRS) we have reported elsewhere. Evidence of a progressive asymmetric pathology in imaging parameters as well as in the kinematic gait analysis was found. Taken together, the data show that chronic exercise regime exacerbates the muscle damage beyond the critical period and the ability to measure through non-invasive means are important factors to consider when performing preclinical efficacy studies in the MDX mouse.

Keywords: Gait, muscular dystrophy, Kinematic analysis, neuromuscular disease

Procedia PDF Downloads 276

Authors: Mohd Iz'aan Paiz Bin Zamri, Anis Salwa Mohd Khairuddin, Norrima Mokhtar, Rubiyah Yusof

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Effective statistical feature extraction and classification are important in image-based automatic inspection and analysis. An automatic wood species recognition system is designed to perform wood inspection at custom checkpoints to avoid mislabeling of timber which will results to loss of income to the timber industry. The system focuses on analyzing the statistical pores properties of the wood images. This paper proposed a fuzzy-based feature extractor which mimics the experts’ knowledge on wood texture to extract the properties of pores distribution from the wood surface texture. The proposed feature extractor consists of two steps namely pores extraction and fuzzy pores management. The total number of statistical features extracted from each wood image is 38 features. Then, a backpropagation neural network is used to classify the wood species based on the statistical features. A comprehensive set of experiments on a database composed of 5200 macroscopic images from 52 tropical wood species was used to evaluate the performance of the proposed feature extractor. The advantage of the proposed feature extraction technique is that it mimics the experts’ interpretation on wood texture which allows human involvement when analyzing the wood texture. Experimental results show the efficiency of the proposed method.

Keywords: classification, feature extraction, fuzzy, inspection system, image analysis, macroscopic images

Procedia PDF Downloads 426

Authors: Pankhudi Khandelwal

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The revenue models of digital giants such as Facebook and Google, use targeted advertising for revenues. Such a model requires huge amounts of consumer data. While the data protection law deals with the protection of personal data, however, this data is acquired by the companies on the basis of consent, performance of a contract, or legitimate interests. This paper analyses the role that competition law can play in evading these loopholes for the protection of data and privacy of online consumers. Digital markets have certain distinctive features such as network effects and feedback loop, which gives incumbents of these markets a first-mover advantage. This creates a situation where the winner takes it all, thus creating entry barriers and concentration in the market. It has been also seen that this dominant position is then used by the undertakings for leveraging in other markets. This can be harmful to the consumers in form of less privacy, less choice, and stifling innovation, as seen in the cases of Facebook Cambridge Analytica, Google Shopping, and Google Android. Therefore, the article aims to provide a legal framework wherein the data protection law and competition law can come together to provide a balance in regulating digital markets. The issue has become more relevant in light of the Facebook decision by German competition authority, where it was held that Facebook had abused its dominant position by not complying with data protection rules, which constituted an exploitative practice. The paper looks into the jurisdictional boundaries that the data protection and competition authorities can work from and suggests ex ante regulation through data protection law and ex post regulation through competition law. It further suggests a change in the consumer welfare standard where harm to privacy should be considered as an indicator of low quality.

Keywords: data protection, dominance, ex ante regulation, ex post regulation

Procedia PDF Downloads 183

Authors: D. Malouch, M. Berchel, C. Dreanno, S. Stachowski-Haberkorn, P-A. Jaffres

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Biofilm is a predominant lifestyle chosen by bacteria. Whether it is developed on an immerged surface or a mobile biofilm known as flocs, the bacteria within this form of life show properties different from its planktonic ones. Within the biofilm, the self-formed matrix of Extracellular Polymeric Substances (EPS) offers hydration, resources capture, enhanced resistance to antimicrobial agents, and allows cell-communication. Biofouling is a complex natural phenomenon that involves biological, physical and chemical properties related to the environment, the submerged surface and the living organisms involved. Bio-colonization of artificial structures can cause various economic and environmental impacts. The increase in costs associated with the over-consumption of fuel from biocolonized vessels has been widely studied. Measurement drifts from submerged sensors, as well as obstructions in heat exchangers, and deterioration of offshore structures are major difficulties that industries are dealing with. Therefore, surfaces that inhibit biocolonization are required in different areas (water treatment, marine paints, etc.) and many efforts have been devoted to produce efficient and eco-compatible antifouling agents. The different steps of surface fouling are widely described in literature. Studying the biofilm and its stages provides a better understanding of how to elaborate more efficient antifouling strategies. Several approaches are currently applied, such as the use of biocide anti-fouling paint6 (mainly with copper derivatives) and super-hydrophobic coatings. While these two processes are proving to be the most effective, they are not entirely satisfactory, especially in a context of a changing legislation. Nowadays, the challenge is to prevent biofouling with non-biocide compounds, offering a cost effective solution, but with no toxic effects on marine organisms. Since the micro-fouling phase plays an important role in the regulation of the following steps of biofilm formation7, it is desired to reduce or delate biofouling of a given surface by inhibiting the micro fouling at its early stages. In our recent works, we reported that some amphiphilic compounds exhibited bacteriostatic or bactericidal properties at a concentration that did not affect eukaryotic cells. These remarkable properties invited us to assess this type of bio-inspired phospholipids9 to prevent the colonization of surfaces by marine bacteria. Of note, other studies reported that amphiphilic compounds interacted with bacteria leading to a reduction of their development. An amphiphilic compound is a molecule consisting of a hydrophobic domain and a polar head (ionic or non-ionic). These compounds appear to have interesting antifouling properties: some ionic compounds have shown antimicrobial activity, and zwitterions can reduce nonspecific adsorption of proteins. Herein, we investigate the potential of amphiphilic compounds as inhibitors of bacterial growth and marine biofilm formation. The aim of this study is to compare the efficacy of four synthetic phospholipids that features a cationic charge (BSV36, KLN47) or a zwitterionic polar-head group (SL386, MB2871) to prevent microfouling with marine bacteria. We also study the toxicity of these compounds in order to identify the most promising compound that must feature high anti-adhesive properties and a low cytotoxicity on two links representative of coastal marine food webs: phytoplankton and oyster larvae.

Keywords: amphiphilic phospholipids, bacterial biofilm, marine microfouling, non-toxic antifouling

Procedia PDF Downloads 147

Authors: Jamaiah H. Yahaya, Aziz Deraman, Abdul Razak Hamdan, Yusmadi Yah Jusoh

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One of the most essential issues in software products is to maintain it relevancy to the dynamics of the user’s requirements and expectation. Many studies have been carried out in quality aspect of software products to overcome these problems. Previous software quality assessment models and metrics have been introduced with strengths and limitations. In order to enhance the assurance and buoyancy of the software products, certification models have been introduced and developed. From our previous experiences in certification exercises and case studies collaborating with several agencies in Malaysia, the requirements for user based software certification approach is identified and demanded. The emergence of social network applications, the new development approach such as agile method and other varieties of software in the market have led to the domination of users over the software. As software become more accessible to the public through internet applications, users are becoming more critical in the quality of the services provided by the software. There are several categories of users in web-based systems with different interests and perspectives. The classifications and metrics are identified through brain storming approach with includes researchers, users and experts in this area. The new paradigm in software quality assessment is the main focus in our research. This paper discusses the classifications of users in web-based software system assessment and their associated factors and metrics for quality measurement. The quality model is derived based on IEEE structure and FCM model. The developments are beneficial and valuable to overcome the constraints and improve the application of software certification model in future.

Keywords: software certification model, user centric approach, software quality factors, metrics and measurements, web-based system

Procedia PDF Downloads 405

Authors: Sanjivrao Katakam, Thanumoorthi I., Antony Gerald, Ratan Kulkarni, Shaju Nair

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With increasing energy costs and its impact on the business, sustainability today has evolved from a social expectation to an economic imperative. Therefore, finding methods to reduce cost has become a critical directive for Industry leaders. Effective energy management is the only way to cut costs. However, Energy Management has been a challenge because it requires a change in old habits and legacy systems followed for decades. Today exorbitant levels of energy and operational data is being captured and stored by Industries, but they are unable to convert these structured and unstructured data sets into meaningful business intelligence. It must be noted that for quick decisions, organizations must learn to cope with large volumes of operational data in different formats. Energy analytics not only helps in extracting inferences from these data sets, but also is instrumental in transformation from old approaches of energy management to new. This in turn assists in effective decision making for implementation. It is the requirement of organizations to have an established corporate strategy for reducing operational costs through visibility and optimization of energy usage. Energy analytics play a key role in optimization of operations. The paper describes how today energy data analytics is extensively used in different scenarios like reducing operational costs, predicting energy demands, optimizing network efficiency, asset maintenance, improving customer insights and device data insights. The paper also highlights how analytics helps transform insights obtained from energy data into sustainable solutions. The paper utilizes data from an array of segments such as retail, transportation, and water sectors.

Keywords: energy analytics, energy management, operational data, business intelligence, optimization

Procedia PDF Downloads 364

Authors: Rao Fu, Jie Chen, Shutian Zeng, Yiping Zhuang, Agus Sudjianto

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Generative Adversarial Net (GAN) has proved to be a powerful machine learning tool in image data analysis and generation. In this paper, we propose to use Conditional Generative Adversarial Net (CGAN) to learn and simulate time series data. The conditions include both categorical and continuous variables with different auxiliary information. Our simulation studies show that CGAN has the capability to learn different types of normal and heavy-tailed distributions, as well as dependent structures of different time series. It also has the capability to generate conditional predictive distributions consistent with training data distributions. We also provide an in-depth discussion on the rationale behind GAN and the neural networks as hierarchical splines to establish a clear connection with existing statistical methods of distribution generation. In practice, CGAN has a wide range of applications in market risk and counterparty risk analysis: it can be applied to learn historical data and generate scenarios for the calculation of Value-at-Risk (VaR) and Expected Shortfall (ES), and it can also predict the movement of the market risk factors. We present a real data analysis including a backtesting to demonstrate that CGAN can outperform Historical Simulation (HS), a popular method in market risk analysis to calculate VaR. CGAN can also be applied in economic time series modeling and forecasting. In this regard, we have included an example of hypothetical shock analysis for economic models and the generation of potential CCAR scenarios by CGAN at the end of the paper.

Keywords: conditional generative adversarial net, market and credit risk management, neural network, time series

Procedia PDF Downloads 143

Authors: Penrug Pengsombut, Worawut Hamarn, Teerawuth Suwannasri, Kittiphong Songrukkiat, Kanatip Ratanachoo

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PTT Public Company Limited or simply PTT has played an important role in strengthening national energy security of the Kingdom of Thailand by transporting natural gas to customers in power, industrial and commercial sectors since 1981. PTT has been constructing and operating natural gas pipeline system of over 4,500-km network length both onshore and offshore laid through different area classifications i.e., marine, forest, agriculture, rural, urban, and city areas. During project development phase, an Environmental Impact Assessment (EIA) is conducted and submitted to the Office of Natural Resources and Environmental Policy and Planning (ONEP) for approval before project construction commencement. Knowledge and experiences gained and revealed from EIA in the past projects definitely are developed to further advance EIA study process for newly 5th Transmission Natural Gas Pipeline Project (5TP) with approximately 415 kilometers length. The preferred pipeline route is selected and justified by SMARTi map, an advance digital one-map platform with consists of multiple layers geographic and environmental information. Sensitive area impact focus (SAIF) is a practicable impact assessment methodology which appropriate for a particular long distance infrastructure project such as 5TP. An environmental modeling simulation is adopted into SAIF methodology for impact quantified in all sensitive areas whereas other area along pipeline right-of-ways is typically assessed as an impact representative. Resulting time and cost deduction is beneficial to project for early start.

Keywords: environmental impact assessment, EIA, natural gas pipeline, sensitive area impact focus, SAIF

Procedia PDF Downloads 408

Authors: V. Jagadeesh, K. Venkata Subbaiah, P. Govinda Rao

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This paper explaining about the significance of information technology tools and software packages in supply chain management (SCM) in order to manage the entire supply chain. Managing materials flow and financial flow and information flow effectively and efficiently with the aid of information technology tools and packages in order to deliver right quantity with right quality of goods at right time by using right methods and technology. Information technology plays a vital role in streamlining the sales forecasting and demand planning and Inventory control and transportation in supply networks and finally deals with production planning and scheduling. It achieves the objectives by streamlining the business process and integrates within the enterprise and its extended enterprise. SCM starts with customer and it involves sequence of activities from customer, retailer, distributor, manufacturer and supplier within the supply chain framework. It is the process of integrating demand planning and supply network planning and production planning and control. Forecasting indicates the direction for planning raw materials in order to meet the production planning requirements. Inventory control and transportation planning allocate the optimal or economic order quantity by utilizing shortest possible routes to deliver the goods to the customer. Production planning and control utilize the optimal resources mix in order to meet the capacity requirement planning. The above operations can be achieved by using appropriate information technology tools and software packages for the supply chain management.

Keywords: supply chain management, information technology, business process, extended enterprise

Procedia PDF Downloads 377

Authors: M. Zayoud, S. Oueida, S. Ionescu, P. AbiChar

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Background: Wireless sensor network is encompassed of diversified tools of information technology, which is widely applied in a range of domains, including military surveillance, weather forecasting, and earthquake forecasting. Strengthened grounds are always developed for wireless sensor networks, which usually emerges security issues during professional application. Thus, essential technological tools are necessary to be assessed for secure aggregation of data. Moreover, such practices have to be incorporated in the healthcare practices that shall be serving in the best of the mutual interest Objective: Aggregation of encrypted data has been assessed through homomorphic stream cipher to assure its effectiveness along with providing the optimum solutions to the field of healthcare. Methods: An experimental design has been incorporated, which utilized newly developed cipher along with CPU-constrained devices. Modular additions have also been employed to evaluate the nature of aggregated data. The processes of homomorphic stream cipher have been highlighted through different sensors and modular additions. Results: Homomorphic stream cipher has been recognized as simple and secure process, which has allowed efficient aggregation of encrypted data. In addition, the application has led its way to the improvisation of the healthcare practices. Statistical values can be easily computed through the aggregation on the basis of selected cipher. Sensed data in accordance with variance, mean, and standard deviation has also been computed through the selected tool. Conclusion: It can be concluded that homomorphic stream cipher can be an ideal tool for appropriate aggregation of data. Alongside, it shall also provide the best solutions to the healthcare sector.

Keywords: aggregation, cipher, homomorphic stream, encryption

Procedia PDF Downloads 261

Authors: Ebrahim Panah, Muhammad Yasir Babar

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Thanks to the development of online technology and social networks, people are able to communicate as well as learn. WhatsApp is a popular social network which is growingly gaining popularity. This app can be used for communication as well as education. It can be used for instructor-learner, learner-learner, and learner-content interactions; however, very little knowledge is available on these potentials of WhatsApp. The current study was undertaken to investigate university students’ perceptions of WhatsApp used as a tool for instructor-learner dialogue, learner-content dialogue, and learner-learner dialogue. The study adopted a survey approach and distributed the questionnaire developed by Google Forms to 54 (11 males and 43 females) university students. The obtained data were analyzed using SPSS version 20. The result of data analysis indicates that students have positive attitudes towards WhatsApp as a tool for Instructor-Learner Dialogue: it easy to reach the lecturer (4.07), the instructor gives me valuable feedback on my assignment (4.02), the instructor is supportive during course discussion and offers continuous support with the class (4.00). Learner-Content Dialogue: WhatsApp allows me to academically engage with lecturers anytime, anywhere (4.00), it helps to send graphics such as pictures or charts directly to the students (3.98), it also provides out of class, extra learning materials and homework (3.96), and Learner-Learner Dialogue: WhatsApp is a good tool for sharing knowledge with others (4.09), WhatsApp allows me to academically engage with peers anytime, anywhere (4.07), and we can interact with others through the use of group discussion (4.02). It was also found that there are significant positive correlations between students’ perceptions of Instructor-Learner Dialogue (ILD), Learner-Content Dialogue (LCD), Learner-Learner Dialogue (LLD) and WhatsApp Application in classroom. The findings of the study have implications for lectures, policy makers and curriculum developers.

Keywords: instructor-learner dialogue, learners-contents dialogue, learner-learner dialogue, whatsapp application

Procedia PDF Downloads 158

Authors: Abdul Rahmat

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Community-based education in the economic empowerment of the family is an attempt to accelerate human development index (HDI) Dumbo Kingdom District of Gorontalo economics (purchasing power) program developed in this activity is the manufacture of functional skills shredded fish, fish balls, fish nuggets, chips anchovies, and corn sticks fish. The target audience of this activity is fishing se mothers subdistrict Dumbo Kingdom include Talumolo Village, Village Botu, Kampung Bugis Village, Village North and Sub Leato South Leato that each village is represented by 20 participants so totaling 100 participants. Time activities beginning in October s/d November 2014 held once a week on every Saturday at 9.00 s/d 13:00/14:00. From the results of the learning process of testing the skills of functional skills of making shredded fish, fish balls, fish nuggets, chips anchovies, fish and corn sticks residents have additional knowledge and experience are: 1) Order the concept include: nutrient content, processing food with fish raw materials , variations in taste, packaging, pricing and marketing sales. 2) Products made: in accordance with the wishes of the residents learned that estimated Eligible selling, product packaging logo creation, preparation and realization of the establishment of Business Study Group (KBU) and pioneered the marketing network with restaurant, store / shop staple food vendors that are around CLC.

Keywords: community development, functional skills, gender, HDI

Procedia PDF Downloads 313

Authors: Raheel Shakoor Siddiqui, Sanjay Narayana Murthy, Manikandar Srinivas Cheruvu, Kash Akhtar

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Major trauma is a dynamic public health epidemic that is continuously evolving. Major trauma care services rely on multi-disciplinary team input involving highly trained pre and in-hospital critical care teams. Pre-hospital critical care teams (PHCCTs), major trauma centres (MTCs), trauma units, and rehabilitation facilities all form an efficient and organised trauma system. England comprises 27 MTCs funded by the National Health Service (NHS). Major trauma care entails enhanced resuscitation protocols coupled with the expertise of dedicated trauma teams and rapid radiological imaging to improve trauma outcomes. Literature reports a change in the demographic of major trauma as elderly patients (silver trauma) with injuries sustained from a fall of 2 metres or less commonly present to services. Evidence of an increasing population age with multiple comorbidities necessitates treatment within the first hour of injury (golden hour) to improve trauma survival outcomes. Staffing and funding pressures within the NHS have subsequently led to a shortfall of available physician-led PHCCTs. Thus, there is a strong emphasis on targeted research and funding to appropriately deploy resources to deprived areas. This review article will discuss the current English trauma system whilst critically appraising present challenges, identifying insufficiencies, and recommending aims for an improved future trauma system in England.

Keywords: trauma, orthopaedics, major trauma, trauma system, trauma network

Procedia PDF Downloads 187

Authors: Dorit Olenik-Shemesh, Tali Heiman

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The rapid increase in the massive use of the internet in recent yearshas led to an increase in the prevalence of a phenomenon called 'Problematic Internet use' (PIU), an emerging, growing health problem, especially during adolescents, that poses a challenge for mental health research and practitioners. Problematic Internet use (PIU) is defined as an excessive overuse of the internet, including an inability to control time spent on the internet, cognitivepreoccupation with the Internet, and continued use in spite of the adverse consequences, which may lead to psychological, social, and academic difficulties in one's life and daily functioning. However, little is known about the nature of the nexusbetween PIU and subjective well-being among adolescents. The main purpose of the current study was to explore in depth the network of connections between PIU, sense of well-being, and fourpersonal-emotional factors (resilience, self-control, depressive mood, and loneliness) that may mediate these relationships. A total sample of 433 adolescents, 214 (49.4%) girls and 219 (50.6%) boys between the ages of 12–17 (mean = 14.9, SD = 2.16), completed self-reportquestionnaires relating to the study variables. In line with the hypothesis, analysis of a Structural Equation modeling (SEM) revealed the main following results: high levels of PIU predicted low levels of well-being among adolescents. In addition, low levels of resilience and high levels of depressivemood (together), as well as low levels of self control and high levels of depressivemood (together), as well as low levels of resilience and high levels of loneliness, mediated the relationships between PIU and well-being. In general, girls were found to be higher in PIU and inresilience than boys. The study results revealed specific implications for developing intervention programs for adolescents in the context of PIU; aiming at more balanced adjusted use of the Internet along withpreventingthe decrease in well being.

Keywords: probelmatic inetrent Use, well-being, adolescents, SEM model

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

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

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

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Authors: Mohammadjavad Sotoudeheian

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Heart failure (HF) prevalence, as a global cardiovascular problem, is increasing gradually. A variety of molecular mechanisms contribute to HF. Proteins involved in cardiac contractility regulation, such as ion channels and calcium handling proteins, are altered. Additionally, epigenetic modifications and gene expression can lead to altered cardiac function. Moreover, inflammation and oxidative stress contribute to HF. The progression of HF can be attributed to mitochondrial dysfunction that impairs energy production and increases apoptosis. Molecular mechanisms such as these contribute to the development of cardiomyocyte defects and HF and can be therapeutically targeted. The heart's contractile function is controlled by cardiomyocytes. Calpain, and its related molecules, including Bax, VEGF, and AMPK, are among the proteins involved in regulating cardiomyocyte function. Apoptosis is facilitated by Bax. Cardiomyocyte apoptosis is regulated by this protein. Furthermore, cardiomyocyte survival, contractility, wound healing, and proliferation are all regulated by VEGF, which is produced by cardiomyocytes during inflammation and cytokine stress. Cardiomyocyte proliferation and survival are also influenced by AMPK, an enzyme that plays an active role in energy metabolism. They all play key roles in apoptosis, angiogenesis, hypertrophy, and metabolism during myocardial inflammation. The role of calpains has been linked to several molecular pathways. The calpain pathway plays an important role in signal transduction and apoptosis, as well as autophagy, endocytosis, and exocytosis. Cell death and survival are regulated by these calcium-dependent cysteine proteases that cleave proteins. As a result, protein fragments can be used for various cellular functions. By cleaving adhesion and motility proteins, calcium proteins also contribute to cell migration. HF may be brought about by calpain-mediated pathways. Many physiological processes are mediated by the calpain molecular pathways. Signal transduction, cell death, and cell migration are all regulated by these molecular pathways. Calpain is activated by calcium binding to calmodulin. In the presence of calcium, calmodulin activates calpain. Calpains are stimulated by calcium, which increases matrix metalloproteinases (MMPs). In order to develop novel treatments for these diseases, we must understand how this pathway works. A variety of myocardial remodeling processes involve calpains, including remodeling of the extracellular matrix and hypertrophy of cardiomyocytes. Calpains also play a role in maintaining cardiac homeostasis through apoptosis and autophagy. The development of HF may be in part due to calpain-mediated pathways promoting cardiomyocyte death. Numerous studies have suggested the importance of the Ca2+ -dependent protease calpain in cardiac physiology and pathology. Therefore, it is important to consider this pathway to develop and test therapeutic options in humans that targets calpain in HF. Apoptosis, autophagy, endocytosis, exocytosis, signal transduction, and disease progression all involve calpain molecular pathways. Therefore, it is conceivable that calpain inhibitors might have therapeutic potential as they have been investigated in preclinical models of several conditions in which the enzyme has been implicated that might be treated with them. Ca 2+ - dependent proteases and calpains contribute to adverse ventricular remodeling and HF in multiple experimental models. In this manuscript, we will discuss the calpain molecular pathway's important roles in HF development.

Keywords: calpain, heart failure, autophagy, apoptosis, cardiomyocyte

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Authors: Hariyadi, Rili Windiasih

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Halal tourism is a recent global phenomenon that emerged out of the needs of Muslim tourists. However, works on halal tourism rarely discuss the connection of it to the rising religiosity in Indonesia since halal tourism has been mostly studied in the sphere of tourism, business, and management studies. A few works on the increase of Islamic expressions in Indonesia do mention the recent booming of non-mandatory pilgrimage to Mecca and the emergence of sharia compliant accommodation, yet they do not go into details on the issue. To our best knowledge, there is a lack of more critical, cultural political studies on halal tourism in which the paper attempts to fill in. The paper is a result of fieldwork research in Central Java, Indonesia. The study focuses on sacred sites for pilgrimage and sharia-compliant hotels. It combines in-depth interviews and participatory observation methods to gather the data. It is important for us to take a look at the network of halal tourism actors (businessperson, local government, clerics, etc.) in Central Java, how they conceive halal tourism, and how their networking shape halal tourism discourses, policies, and practices. Despite having numerous Islamic pilgrimage places and being designated by the Ministry of Tourism as one of 12 Muslim friendly tourist destinations, the province is not yet widely recognised as the main destination for halal tourism as it is known as the place for more secular, nationalist groups rather than for more Islamic oriented ones. However, in some of its municipalities, there is increasingly more attention to develop halal tourism. In this study, we found out that the development of halal tourism in Central Java connected to dynamics of Islamisation and ideological competition as well as the influence of the more pragmatist businesspersons in a 'nationalist province' in Indonesia.

Keywords: actor networking, halal tourism, Islamisation, Indonesia

Procedia PDF Downloads 169

Authors: Hui Luo, Zhenhong Li, Zhen Dong

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The analysis of multi-temporal InSAR (MTInSAR) such as persistent scatterer (PS) and small baseline subset (SBAS) techniques usually relies on temporal/spatial phase unwrapping (PU). Unfortunately, it always fails to unwrap the phase for two reasons: 1) spatial phase jump between adjacent pixels larger than π, such as layover and high discontinuous terrain; 2) temporal phase discontinuities such as time varied atmospheric delay. To overcome these limitations, a least-square based PU method is introduced in this paper, which incorporates baseline-combination interferograms and adjacent phase gradient network. Firstly, permanent scatterers (PS) are selected for study. Starting with the linear baseline-combination method, we obtain equivalent 'small baseline inteferograms' to limit the spatial phase difference. Then, phase different has been conducted between connected PSs (connected by a specific networking rule) to suppress the spatial correlated phase errors such as atmospheric artifact. After that, interval phase difference along arcs can be computed by least square method and followed by an outlier detector to remove the arcs with phase ambiguities. Then, the unwrapped phase can be obtained by spatial integration. The proposed method is tested on real data of TerraSAR-X, and the results are also compared with the ones obtained by StaMPS(a software package with 3D PU capabilities). By comparison, it shows that the proposed method can successfully unwrap the interferograms in urban areas even when high discontinuities exist, while StaMPS fails. At last, precise DEM errors can be got according to the unwrapped interferograms.

Keywords: phase unwrapping, time series, InSAR, urban areas

Procedia PDF Downloads 151

Authors: Meenu Kaushik, Ayon K. Bandhoyadhayay, Lalit M. Joshi

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Inductive output tubes (IOTs) are widely used as microwave power amplifiers for broadcast and scientific applications. It is capable of amplifying radio frequency (RF) power with very good efficiency. Its compactness, reliability, high efficiency, high linearity and low operating cost make this device suitable for various applications. The device consists of an integrated structure of electron gun and RF cavity, collector and focusing structure. The working principle of IOT is a combination of triode and klystron. The cathode lies in the electron gun produces a stream of electrons. A control grid is placed in close proximity to the cathode. Basically, the input part of IOT is the integrated structure of gridded electron gun which acts as an input cavity thereby providing the interaction gap where the input RF signal is applied to make it interact with the produced electron beam for supporting the amplification phenomena. The paper presents the design, fabrication and testing of a radial re-entrant cavity for implementing in the input structure of IOT at 350 MHz operating frequency. The model’s suitability has been discussed and a generalized mathematical relation has been introduced for getting the proper transverse magnetic (TM) resonating mode in the radial narrow gap RF cavities. The structural modeling has been carried out in CST and SUPERFISH codes. The cavity is fabricated with the Aluminum material and the RF characterization is done using vector network analyzer (VNA) and the results are presented for the resonant frequency peaks obtained in VNA.

Keywords: inductive output tubes, IOT, radial cavity, coaxial cavity, particle accelerators

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Authors: Arvind Srivastav, Tarun Kanti Bhattacharyya

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The north-eastern, Himalayan, and Eastern Ghats Belt of India comprise of earthquake-prone, remote, and hilly terrains. Earthquakes have caused enormous damages in these regions in the past. A wireless sensor network based earthquake early warning system (EEWS) is being developed to mitigate the damages caused by earthquakes. It consists of sensor nodes, distributed over the region, that perform majority voting of the output of the seismic sensors in the vicinity, and relay a message to a base station to alert the residents when an earthquake is detected. At the heart of the EEWS is a low-power two-stage seismic sensor that continuously tracks seismic events from incoming three-axis accelerometer signal at the first-stage, and, in the presence of a seismic event, triggers the second-stage P-wave detector that detects the onset of P-wave in an earthquake event. The parameters of the P-wave detector have been optimized for minimizing detection time and maximizing the accuracy of detection.Working of the sensor scheme has been verified with seven earthquakes data retrieved from IRIS. In all test cases, the scheme detected the onset of P-wave accurately. Also, it has been established that the P-wave onset detection time reduces linearly with the sampling rate. It has been verified with test data; the detection time for data sampled at 10Hz was around 2 seconds which reduced to 0.3 second for the data sampled at 100Hz.

Keywords: earthquake early warning system, EEWS, STA/LTA, polarization, wavelet, event detector, P-wave detector

Procedia PDF Downloads 176

Authors: Nahla Elsherbiny, Ahmed Ahmed, Hamada Mohammed, Mohamed Ali

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Background: The enterococci may be considered as opportunistic agents particularly in immunocompromised patients. It is one of the top three pathogens causing many healthcare associated infections (HAIs). Resistance to several commonly used antimicrobial agents is a remarkable characteristic of most species which may carry various genes contributing to virulence. Objectives: to determine the prevalence of enterococci species in different intensive care units (ICUs) causing health care-associated infections (HAIs), intestinal carriage and environmental contamination. Also, to study the antimicrobial susceptibility pattern of the isolates with special reference to vancomycin resistance. In addition to phenotypic and genotypic detection of gelatinase, cytolysin and biofilm formation among isolates. Patients and Methods: This study was carried out in the infection control laboratory at Assiut University Hospitals over a period of one year. Clinical samples were collected from 285 patients with various (HAIs) acquired after admission to different ICUs. Rectal swabs were taken from 14 cases for detection of enterococci carriage. In addition, 1377 environmental samples were collected from the surroundings of the patients. Identification was done by conventional bacteriological methods and confirmed by analytical profile index (API). Antimicrobial sensitivity testing was performed by Kirby Bauer disc diffusion method and detection of vancomycin resistance was done by agar screen method. For the isolates, phenotypic detection of cytolysin, gelatinase production and detection of biofilm by tube method, Congo red method and microtiter plate. We performed polymerase chain reaction (PCR) for detection of some virulence genes (gelE, cylA, vanA, vanB and esp). Results: Enterococci caused 10.5% of the HAIs. Respiratory tract infection was the predominant type (86.7%). The commonest species were E.gallinarum (36.7%), E.casseliflavus (30%), E.faecalis (30%), and E.durans (3.4 %). Vancomycin resistance was detected in a total of 40% (12/30) of those isolates. The risk factors associated with acquiring vancomycin resistant enterococci (VRE) were immune suppression (P= 0.031) and artificial feeding (P= 0.008). For the rectal swabs, enterococci species were detected in 71.4% of samples with the predominance of E. casseliflavus (50%). Most of the isolates were vancomycin resistant (70%). Out of a total 1377 environmental samples, 577 (42%) samples were contaminated with different microorganisms. Enterococci were detected in 1.7% (10/577) of total contaminated samples, 50% of which were vancomycin resistant. All isolates were resistant to penicillin, ampicillin, oxacillin, ciprofloxacin, amikacin, erythromycin, clindamycin and trimethoprim-sulfamethaxazole. For the remaining antibiotics, variable percentages of resistance were reported. Cytolysin and gelatinase were detected phenotypically in 16% and 48 % of the isolates respectively. The microtiter plate method showed the highest percentages of detection of biofilm among all isolated species (100%). The studied virulence genes gelE, esp, vanA and vanB were detected in 62%, 12%, 2% and 12% respectively, while cylA gene was not detected in any isolates. Conclusions: A significant percentage of enterococci was isolated from patients and environments in the ICUs. Many virulence factors were detected phenotypically and genotypically among isolates. The high percentage of resistance, coupled with the risk of cross transmission to other patients make enterococci infections a significant infection control issue in hospitals.

Keywords: antimicrobial resistance, enterococci, ICUs, virulence factors

Procedia PDF Downloads 285

Authors: Bianca Peterson, Tomasz J. Sańko, Carlos C. Bezuidenhout, Johnnie Van Den Berg

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Busseola fusca (Fuller) (Lepidoptera: Noctuidae), the maize stem borer, is a major pest in sub-Saharan Africa. It causes economic damage to maize and sorghum crops and has evolved non-recessive resistance to genetically modified (GM) maize expressing the Cry1Ab insecticidal toxin. Since B. fusca is a non-model organism, very little genomic information is publicly available, and is limited to some cytochrome c oxidase I, cytochrome b, and microsatellite data. The biology of B. fusca is well-described, but still poorly understood. This, in combination with its larval-specific behavior, may pose problems for limiting the spread of current resistant B. fusca populations or preventing resistance evolution in other susceptible populations. As part of on-going research into resistance evolution, B. fusca larvae were collected from Bt and non-Bt maize in South Africa, followed by RNA isolation (15 specimens) and sequencing on the Illumina HiSeq 2500 platform. Quality of reads was assessed with FastQC, after which Trimmomatic was used to trim adapters and remove low quality, short reads. Trinity was used for the de novo assembly, whereas TransRate was used for assembly quality assessment. Transcript identification employed BLAST (BLASTn, BLASTp, and tBLASTx comparisons), for which two libraries (nucleotide and protein) were created from 3.27 million lepidopteran sequences. Several transcripts that have previously been implicated in Cry toxin resistance was identified for B. fusca. These included aminopeptidase N, cadherin, alkaline phosphatase, ATP-binding cassette transporter proteins, and mitogen-activated protein kinase. MEGA7 was used to align these transcripts to reference sequences from Lepidoptera to detect mutations that might potentially be contributing to Cry toxin resistance in this pest. RSEM and Bioconductor were used to perform differential gene expression analysis on groups of B. fusca larvae challenged and unchallenged with the Cry1Ab toxin. Pairwise expression comparisons of transcripts that were at least 16-fold expressed at a false-discovery corrected statistical significance (p) ≤ 0.001 were extracted and visualized in a hierarchically clustered heatmap using R. A total of 329,194 transcripts with an N50 of 1,019 bp were generated from the over 167.5 million high-quality paired-end reads. Furthermore, 110 transcripts were over 10 kbp long, of which the largest one was 29,395 bp. BLAST comparisons resulted in identification of 157,099 (47.72%) transcripts, among which only 3,718 (2.37%) were identified as Cry toxin receptors from lepidopteran insects. According to transcript expression profiles, transcripts were grouped into three subclusters according to the similarity of their expression patterns. Several immune-related transcripts (pathogen recognition receptors, antimicrobial peptides, and inhibitors) were up-regulated in the larvae feeding on Bt maize, indicating an enhanced immune status in response to toxin exposure. Above all, extremely up-regulated arylphorin genes suggest that enhanced epithelial healing is one of the resistance mechanisms employed by B. fusca larvae against the Cry1Ab toxin. This study is the first to provide a resource base and some insights into a potential mechanism of Cry1Ab toxin resistance in B. fusca. Transcriptomic data generated in this study allows identification of genes that can be targeted by biotechnological improvements of GM crops.

Keywords: epithelial healing, Lepidoptera, resistance, transcriptome

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Authors: L. Spitaleri, C. M. A. Gangemi, R. Purrello, G. Nicotra, G. Trusso Sfrazzetto, G. Casella, M. Casarin, A. Gulino

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Hybrid molecular–nanoparticle materials, obtained with a bottom-up approach, are suitable for the fabrication of functional nanostructures showing structural control and well-defined properties, i.e., optical, electronic or catalytic properties, in the perspective of applications in different fields of nanotechnology. Gold nanoparticles (Au NPs) exhibit important chemical, electronic and optical properties due to their size, shape and electronic structures. In fact, Au NPs containing no more than 30-40 atoms are only luminescent because they can be considered as large molecules with discrete energy levels, while nano-sized Au NPs only show the surface plasmon resonance. Hence, it appears that gold nanoparticles can alternatively be luminescent or plasmonic, and this represents a severe constraint for their use as an optical material. The aim of this work was the fabrication of nanoscale assembly of Au NPs covalently anchored to each other by means of novel bi-functional porphyrin molecules that work as bridges between different gold nanoparticles. This functional architecture shows a strong surface plasmon due to the Au nanoparticles and a strong luminescence signal coming from porphyrin molecules, thus, behaving like an artificial organized plasmonic and fluorescent network. The self-assembly geometry of this porphyrin on the Au NPs was studied by investigation of the conformational properties of the porphyrin derivative at the DFT level. The morphology, electronic structure and optical properties of the conjugated Au NPs – porphyrin system were investigated by TEM, XPS, UV–vis and Luminescence. The present nanostructures can be used for plasmon-enhanced fluorescence, photocatalysis, nonlinear optics, etc., under atmospheric conditions since our system is not reactive to air nor water and does not need to be stored in a vacuum or inert gas.

Keywords: gold nanoparticle, porphyrin, surface plasmon resonance, luminescence, nanostructures

Procedia PDF Downloads 155

Authors: Alaa Sheta

Abstract:

Economic Load Dispatch (ELD) is one of the vital optimization problems in power system planning. Solving the ELD problems mean finding the best mixture of power unit outputs of all members of the power system network such that the total fuel cost is minimized while sustaining operation requirements limits satisfied across the entire dispatch phases. Many optimization techniques were proposed to solve this problem. A famous one is the Quadratic Programming (QP). QP is a very simple and fast method but it still suffer many problem as gradient methods that might trapped at local minimum solutions and cannot handle complex nonlinear functions. Numbers of metaheuristic algorithms were used to solve this problem such as Genetic Algorithms (GAs) and Particle Swarm Optimization (PSO). In this paper, another meta-heuristic search algorithm named Differential Evolution (DE) is used to solve the ELD problem in power systems planning. The practicality of the proposed DE based algorithm is verified for three and six power generator system test cases. The gained results are compared to existing results based on QP, GAs and PSO. The developed results show that differential evolution is superior in obtaining a combination of power loads that fulfill the problem constraints and minimize the total fuel cost. DE found to be fast in converging to the optimal power generation loads and capable of handling the non-linearity of ELD problem. The proposed DE solution is able to minimize the cost of generated power, minimize the total power loss in the transmission and maximize the reliability of the power provided to the customers.

Keywords: economic load dispatch, power systems, optimization, differential evolution

Procedia PDF Downloads 282

Authors: Rani Danavath, V. B. Narsimha

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Cloud computing is emerging as a new paradigm of large scale distributed computing. Cloud computing is a model for enabling ubiquitous, convenient, on-demand network access to a shared pool of configurable computing resources (e.g., three service models, and four deployment networks, servers, storage, applications, and services) that can be rapidly provisioned and released with minimal management effort or service provider interaction. This cloud model is composed of five essential characteristics models. Load balancing is one of the main challenges in cloud computing, which is required to distribute the dynamic workload across multiple nodes, to ensure that no single node is overloaded. It helps in optimal utilization of resources, enhancing the performance of the system. The goal of the load balancing is to minimize the resource consumption and carbon emission rate, that is the direct need of cloud computing. This determined the need of new metrics energy consumption and carbon emission for energy-efficiency load balancing techniques in cloud computing. Existing load balancing techniques mainly focuses on reducing overhead, services, response time and improving performance etc. In this paper we introduced a Technique for energy-efficiency, but none of the techniques have considered the energy consumption and carbon emission. Therefore, our proposed work will go towards energy – efficiency. So this energy-efficiency load balancing technique can be used to improve the performance of cloud computing by balancing the workload across all the nodes in the cloud with the minimum resource utilization, in turn, reducing energy consumption, and carbon emission to an extent, which will help to achieve green computing.

Keywords: cloud computing, distributed computing, energy efficiency, green computing, load balancing, energy consumption, carbon emission

Procedia PDF Downloads 449

Authors: Maddalena Arigoni, Maria Luisa Ratto, Raffaele A. Calogero, Luca Alessandri

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The presence of tumor heterogeneity, where distinct cancer cells exhibit diverse morphological and phenotypic profiles, including gene expression, metabolism, and proliferation, poses challenges for molecular prognostic markers and patient classification for targeted therapies. Understanding the causes and progression of cancer requires research efforts aimed at characterizing heterogeneity, which can be facilitated by evolving single-cell sequencing technologies. However, analyzing single-cell data necessitates computational methods that often lack objective validation. Therefore, the establishment of benchmarking datasets is necessary to provide a controlled environment for validating bioinformatics tools in the field of single-cell oncology. Benchmarking bioinformatics tools for single-cell experiments can be costly due to the high expense involved. Therefore, datasets used for benchmarking are typically sourced from publicly available experiments, which often lack a comprehensive cell annotation. This limitation can affect the accuracy and effectiveness of such experiments as benchmarking tools. To address this issue, we introduce omics benchmark experiments designed to evaluate bioinformatics tools to depict the heterogeneity in single-cell tumor experiments. We conducted single-cell RNA sequencing on six lung cancer tumor cell lines that display resistant clones upon treatment of EGFR mutated tumors and are characterized by driver genes, namely ROS1, ALK, HER2, MET, KRAS, and BRAF. These driver genes are associated with downstream networks controlled by EGFR mutations, such as JAK-STAT, PI3K-AKT-mTOR, and MEK-ERK. The experiment also featured an EGFR-mutated cell line. Using 10XGenomics platform with cellplex technology, we analyzed the seven cell lines together with a pseudo-immunological microenvironment consisting of PBMC cells labeled with the Biolegend TotalSeq™-B Human Universal Cocktail (CITEseq). This technology allowed for independent labeling of each cell line and single-cell analysis of the pooled seven cell lines and the pseudo-microenvironment. The data generated from the aforementioned experiments are available as part of an online tool, which allows users to define cell heterogeneity and generates count tables as an output. The tool provides the cell line derivation for each cell and cell annotations for the pseudo-microenvironment based on CITEseq data by an experienced immunologist. Additionally, we created a range of pseudo-tumor tissues using different ratios of the aforementioned cells embedded in matrigel. These tissues were analyzed using 10XGenomics (FFPE samples) and Curio Bioscience (fresh frozen samples) platforms for spatial transcriptomics, further expanding the scope of our benchmark experiments. The benchmark experiments we conducted provide a unique opportunity to evaluate the performance of bioinformatics tools for detecting and characterizing tumor heterogeneity at the single-cell level. Overall, our experiments provide a controlled and standardized environment for assessing the accuracy and robustness of bioinformatics tools for studying tumor heterogeneity at the single-cell level, which can ultimately lead to more precise and effective cancer diagnosis and treatment.

Keywords: single cell omics, benchmark, spatial transcriptomics, CITEseq

Procedia PDF Downloads 117

Authors: Jaco Oosthuizen, Nerina C. Van Der Merwe

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The National Health Laboratory Services in Bloemfontien has been the diagnostic testing facility for 1830 patients for familial breast cancer since 1997. From the cohort, 540 were comprehensively screened using High-Resolution Melting Analysis or Next Generation Sequencing for the presence of point mutations and/or indels. Approximately 90% of these patients stil remain undiagnosed as they are BRCA1/2 negative. Multiplex ligation-dependent probe amplification was initially added to screen for copy number variation detection, but with the introduction of next generation sequencing in 2017, was substituted and is currently used as a confirmation assay. The aim was to investigate the viability of utilizing internationally designed copy number variation detection assays based on mostly European/Caucasian genomic data for use within a South African context. The multiplex ligation-dependent probe amplification technique is based on the hybridization and subsequent ligation of multiple probes to a targeted exon. The ligated probes are amplified using conventional polymerase chain reaction, followed by fragment analysis by means of capillary electrophoresis. The experimental design of the assay was performed according to the guidelines of MRC-Holland. For BRCA1 (P002-D1) and BRCA2 (P045-B3), both multiplex assays were validated, and results were confirmed using a secondary probe set for each gene. The next generation sequencing technique is based on target amplification via multiplex polymerase chain reaction, where after the amplicons are sequenced parallel on a semiconductor chip. Amplified read counts are visualized as relative copy numbers to determine the median of the absolute values of all pairwise differences. Various experimental parameters such as DNA quality, quantity, and signal intensity or read depth were verified using positive and negative patients previously tested internationally. DNA quality and quantity proved to be the critical factors during the verification of both assays. The quantity influenced the relative copy number frequency directly whereas the quality of the DNA and its salt concentration influenced denaturation consistency in both assays. Multiplex ligation-dependent probe amplification produced false positives due to ligation failure when ligation was inhibited due to a variant present within the ligation site. Next generation sequencing produced false positives due to read dropout when primer sequences did not meet optimal multiplex binding kinetics due to population variants in the primer binding site. The analytical sensitivity and specificity for the South African population have been proven. Verification resulted in repeatable reactions with regards to the detection of relative copy number differences. Both multiplex ligation-dependent probe amplification and next generation sequencing multiplex panels need to be optimized to accommodate South African polymorphisms present within the genetically diverse ethnic groups to reduce the false copy number variation positive rate and increase performance efficiency.

Keywords: familial breast cancer, multiplex ligation-dependent probe amplification, next generation sequencing, South Africa

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Authors: Leyla Noroozbabaee, David Nickerson

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We introduce a modular, consistent, reusable bond graph model of the renal nephron’s proximal convoluted tubule (PCT), which can reproduce biological behaviour. In this work, we focus on ion and volume transport in the proximal convoluted tubule of the renal nephron. Modelling complex systems requires complex modelling problems to be broken down into manageable pieces. This can be enabled by developing models of subsystems that are subsequently coupled hierarchically. Because they are based on a graph structure. In the current work, we define two modular subsystems: the resistive module representing the membrane and the capacitive module representing solution compartments. Each module is analyzed based on thermodynamic processes, and all the subsystems are reintegrated into circuit theory in network thermodynamics. The epithelial transport system we introduce in the current study consists of five transport membranes and four solution compartments. Coupled dissipations in the system occur in the membrane subsystems and coupled free-energy increasing, or decreasing processes appear in solution compartment subsystems. These structural subsystems also consist of elementary thermodynamic processes: dissipations, free-energy change, and power conversions. We provide free and open access to the Python implementation to ensure our model is accessible, enabling the reader to explore the model through setting their simulations and reproducibility tests.

Keywords: Bond Graph, Epithelial Transport, Water Transport, Mathematical Modeling

Procedia PDF Downloads 87

Authors: Hong Yu, Ion Matei

Abstract:

Carbon fiber reinforced composites (CFRP) used as aircraft structure are subject to lightning strike, putting structural integrity under risk. Indirect damage may occur after a lightning strike where the internal structure can be damaged due to excessive heat induced by lightning current, while the surface of the structures remains intact. Three damage modes may be observed after a lightning strike: fiber breakage, inter-ply delamination and intra-ply cracks. The assessment of internal damage states in composite is challenging due to complicated microstructure, inherent uncertainties, and existence of multiple damage modes. In this work, a model based approach is adopted to diagnose faults in carbon composites after lighting strikes. A resistor network model is implemented to relate the overall electrical and thermal conduction behavior under simulated lightning current waveform to the intrinsic temperature dependent material properties, microstructure and degradation of materials. A fault detection and identification (FDI) module utilizes the physics based model and a particle filtering algorithm to identify damage mode as well as calculate the probability of structural failure. Extensive simulation results are provided to substantiate the proposed fault diagnosis methodology with both single fault and multiple faults cases. The approach is also demonstrated on transient resistance data collected from a IM7/Epoxy laminate under simulated lightning strike.

Keywords: carbon composite, fault detection, fault identification, particle filter

Procedia PDF Downloads 195