Search results for: operations sequence
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 2816

Search results for: operations sequence

836 Virtual Process Hazard Analysis (Pha) Of a Nuclear Power Plant (Npp) Using Failure Mode and Effects Analysis (Fmea) Technique

Authors: Lormaine Anne A. Branzuela, Elysa V. Largo, Monet Concepcion M. Detras, Neil C. Concibido

Abstract:

The electricity demand is still increasing, and currently, the Philippine government is investigating the feasibility of operating the Bataan Nuclear Power Plant (BNPP) to address the country’s energy problem. However, the lack of process safety studies on BNPP focused on the effects of hazardous substances on the integrity of the structure, equipment, and other components, have made the plant operationalization questionable to the public. The three major nuclear power plant incidents – TMI-2, Chernobyl, and Fukushima – have made many people hesitant to include nuclear energy in the energy matrix. This study focused on the safety evaluation of possible operations of a nuclear power plant installed with a Pressurized Water Reactor (PWR), which is similar to BNPP. Failure Mode and Effects Analysis (FMEA) is one of the Process Hazard Analysis (PHA) techniques used for the identification of equipment failure modes and minimizing its consequences. Using the FMEA technique, this study was able to recognize 116 different failure modes in total. Upon computation and ranking of the risk priority number (RPN) and criticality rating (CR), it showed that failure of the reactor coolant pump due to earthquakes is the most critical failure mode. This hazard scenario could lead to a nuclear meltdown and radioactive release, as identified by the FMEA team. Safeguards and recommended risk reduction strategies to lower the RPN and CR were identified such that the effects are minimized, the likelihood of occurrence is reduced, and failure detection is improved.

Keywords: PHA, FMEA, nuclear power plant, bataan nuclear power plant

Procedia PDF Downloads 124
835 The Mashishing Marking Memories Project: A Culture-Centered Approach to Participation

Authors: Nongcebo Ngcobo

Abstract:

This research explores the importance of including a multitude of voices in the cultural heritage narrative, particularly in South Africa. The Mashishing project is an extension of and builds on the existing ‘Biesje Poort project’ which is a rock art project that was funded by the National Heritage Council in 2010 - 2013. Hence, the Mashishing marking memories project applies comparable Biesje Poort project objectives, though in a different geographical area. The wider project objectives are to transfer skills, promote social cohesion and empowerment, and lastly to add to the knowledge base of the Mashishing region and the repository of the local museum in the Lydenburg museum. This study is located in the Mashishing area, in Mpumalanga, South Africa. In this area, there were no present multi-vocal heritage projects. This research assesses the Mashishing marking memories project through the culture-centered approach for communication for social change, which examines the impact that the diverse participants have on the operations of the Mashishing project and also investigates whether the culturally diverse participants facilitates or hinders effective participation within the project. Key findings of this research uncovered the significance of participation and diverse voices in the cultural heritage field. Furthermore, this study highlights how unequal power relations affect effective participation. As a result, this study encourages the importance of bringing the researcher and the participant in a safe space to facilitate mutual learning. It also encourages an exchange of roles, where the researcher shifts from being an authoritarian figure to being in the role of a listener.

Keywords: culture, heritage, participation, social change

Procedia PDF Downloads 118
834 Mechanical Properties of Hybrid Ti6Al4V Part with Wrought Alloy to Powder-Bed Additive Manufactured Interface

Authors: Amnon Shirizly, Ohad Dolev

Abstract:

In recent years, the implementation and use of Metal Additive Manufacturing (AM) parts increase. As a result, the demand for bigger parts rises along with the desire to reduce it’s the production cost. Generally, in powder bed Additive Manufacturing technology the part size is limited by the machine build volume. In order to overcome this limitation, the parts can be built in one or more machine operations and mechanically joint or weld them together. An alternative option could be a production of wrought part and built on it the AM structure (mainly to reduce costs). In both cases, the mechanical properties of the interface have to be defined and recognized. In the current study, the authors introduce guidelines on how to examine the interface between wrought alloy and powder-bed AM. The mechanical and metallurgical properties of the Ti6Al4V materials (wrought alloy and powder-bed AM) and their hybrid interface were examined. The mechanical properties gain from tensile test bars in the built direction and fracture toughness samples in various orientations. The hybrid specimens were built onto a wrought Ti6Al4V start-plate. The standard fracture toughness (CT25 samples) and hybrid tensile specimens' were heat treated and milled as a post process to final diminutions. In this Study, the mechanical tensile tests and fracture toughness properties supported by metallurgical observation will be introduced and discussed. It will show that the hybrid approach of utilizing powder bed AM onto wrought material expanding the current limitation of the future manufacturing technology.

Keywords: additive manufacturing, hybrid, fracture-toughness, powder bed

Procedia PDF Downloads 101
833 Sustainable Agriculture Practices Using Bacterial-mediated Alleviation of Salinity Stress in Crop Plants

Authors: Mohamed Trigui, Fatma Masmoudi, Imen Zouari

Abstract:

Massive utilizations of chemical fertilizer and chemical pesticides in agriculture sector to improve the farming productivity have created increasing environmental damages. Then, agriculture must become sustainable, focusing on production systems that respect the environment and help to reduce climate change. Isolation and microbial identification of new bacterial strains from naturally saline habitats and compost extracts could be a prominent way in pest management and crop production under saline conditions. In this study, potential mechanisms involved in plant growth promotion and suppressive activity against fungal diseases of a compost extract produced from poultry manure/olive husk compost and halotolerant and halophilic bacterial strains under saline stress were investigated. On the basis of the antimicrobial tests, different strains isolated from Sfax solar saltern (Tunisia) and from compost extracts were selected and tested for their plant growth promoting traits, such as siderophores production, nitrogen fixation, phosphate solubilization and the production of extracellular hydrolytic enzymes (protease and lipase) under in-vitro conditions. Among 450 isolated bacterial strains, 16 isolates showed potent antifungal activity against the tested plant pathogenic fungi. Their identification based on 16S rRNA gene sequence revealed they belonged to different species. Some of these strains were also characterized for their plant growth promoting capacities. Obtained results showed the ability of four strains belonging to Bacillus genesis to ameliorate germination rate and root elongation compared to the untreated positive controls. Combinatorial capacity of halotolerant bacteria with antimicrobial activity and plant growth promoting traits could be promising sources of interesting bioactive substances under saline stress.

Keywords: abiotic stress, biofertilizer, biotic stress, compost extract, halobacteria, plant growth promoting (PGP), soil fertility

Procedia PDF Downloads 85
832 Smart Campus Digital Twin: Basic Framework - Current State, Trends and Challenges

Authors: Enido Fabiano de Ramos, Ieda Kanashiro Makiya, Francisco I. Giocondo Cesar

Abstract:

This study presents an analysis of the Digital Twin concept applied to the academic environment, focusing on the development of a Digital Twin Smart Campus Framework. Using bibliometric analysis methodologies and literature review, the research investigates the evolution and applications of the Digital Twin in educational contexts, comparing these findings with the advances of Industry 4.0. It was identified gaps in the existing literature and highlighted the need to adapt Digital Twin principles to meet the specific demands of a smart campus. By integrating Industry 4.0 concepts such as automation, Internet of Things, and real-time data analytics, we propose an innovative framework for the successful implementation of the Digital Twin in academic settings. The results of this study provide valuable insights for university campus managers, allowing for a better understanding of the potential applications of the Digital Twin for operations, security, and user experience optimization. In addition, our framework offers practical guidance for transitioning from a digital campus to a digital twin smart campus, promoting innovation and efficiency in the educational environment. This work contributes to the growing literature on Digital Twins and Industry 4.0, while offering a specific and tailored approach to transforming university campuses into smart and connected spaces, high demanded by Society 5.0 trends. It is hoped that this framework will serve as a basis for future research and practical implementations in the field of higher education and educational technology.

Keywords: smart campus, digital twin, industry 4.0, education trends, society 5.0

Procedia PDF Downloads 49
831 Comparison of Low Velocity Impact Test on Coir Fiber Reinforced Polyester Composites

Authors: Ricardo Mendoza, Jason Briceño, Juan F. Santa, Gabriel Peluffo, Mauricio Márquez, Beatriz Cardozo, Carlos Gutiérrez

Abstract:

The most common controlled method to obtain impact strength of composites materials is performing a Charpy Impact Test which consists of a pendulum with calibrated mass and length released from a known height. In fact, composites components experience impact events in normal operations such as when a tool drops or a foreign object strikes it. These events are categorized into low velocity impact (LVI) which typically occurs at velocities below 10m/s. In this study, the major aim was to calculate the absorbed energy during the impact. Tests were performed on three types of composite panels: fiberglass laminated panels, coir fiber reinforced polyester and coir fiber reinforced polyester subjected to water immersion for 48 hours. Coir fibers were obtained in local plantations of the Caribbean coast of Colombia. They were alkali treated in 5% aqueous NaOH solution for 2h periods. Three type of shape impactors were used on drop-weight impact test including hemispherical, ogive and pointed. Failure mechanisms and failure modes of specimens were examined using an optical microscope. Results demonstrate a reduction in absorbed energy correlated with the increment of water absorption of the panels. For each level of absorbed energy, it was possible to associate a different fracture state. This study compares results of energy absorbed obtained from two impact test methods.

Keywords: coir fiber, polyester composites, low velocity impact, Charpy impact test, drop-weight impact test

Procedia PDF Downloads 449
830 A Genre-Based Approach to the Teaching of Pronunciation

Authors: Marden Silva, Danielle Guerra

Abstract:

Some studies have indicated that pronunciation teaching hasn’t been paid enough attention by teachers regarding EFL contexts. In particular, segmental and suprasegmental features through genre-based approach may be an opportunity on how to integrate pronunciation into a more meaningful learning practice. Therefore, the aim of this project was to carry out a survey on some aspects related to English pronunciation that Brazilian students consider more difficult to learn, thus enabling the discussion of strategies that can facilitate the development of oral skills in English classes by integrating the teaching of phonetic-phonological aspects into the genre-based approach. Notions of intelligibility, fluency and accuracy were proposed by some authors as an ideal didactic sequence. According to their proposals, basic learners should be exposed to activities focused on the notion of intelligibility as well as intermediate students to the notion of fluency, and finally more advanced ones to accuracy practices. In order to test this hypothesis, data collection was conducted during three high school English classes at Federal Center for Technological Education of Minas Gerais (CEFET-MG), in Brazil, through questionnaires and didactic activities, which were recorded and transcribed for further analysis. The genre debate was chosen to facilitate the oral expression of the participants in a freer way, making them answering questions and giving their opinion about a previously selected topic. The findings indicated that basic students demonstrated more difficulty with aspects of English pronunciation than the others. Many of the intelligibility aspects analyzed had to be listened more than once for a better understanding. For intermediate students, the speeches recorded were considerably easier to understand, but nevertheless they found it more difficult to pronounce the words fluently, often interrupting their speech to think about what they were going to say and how they would talk. Lastly, more advanced learners seemed to express their ideas more fluently, but still subtle errors related to accuracy were perceptible in speech, thereby confirming the proposed hypothesis. It was also seen that using genre-based approach to promote oral communication in English classes might be a relevant method, considering the socio-communicative function inherent in the suggested approach.

Keywords: EFL, genre-based approach, oral skills, pronunciation

Procedia PDF Downloads 126
829 Extracellular Production of the Oncolytic Enzyme, Glutaminase Free L-Asparaginase, from Newly Isolated Streptomyces Olivaceus NEAE-119: Optimization of Culture Conditions Using Response Surface Methodology

Authors: Noura El-Ahmady El-Naggar

Abstract:

Among the antitumour drugs, bacterial enzyme L-asparaginase has been employed as the most effective chemotherapeutic agent in pediatric oncotherapy especially for acute lymphoblastic leukemia. Glutaminase free L-asparaginase producing actinomycetes were isolated from soil samples collected from Egypt. Among them, a potential culture, strain NEAE-119, was selected and identified on the basis of morphological, cultural, physiological and biochemical properties, together with 16S rDNA sequence as Streptomyces olivaceus NEAE-119 and sequencing product(1509 bp) was deposited in the GenBank database under accession number KJ200342. The optimization of different process parameters for L-asparaginase production by Streptomyces olivaceus NEAE-119 using Plackett–Burman experimental design and response surface methodology was carried out. Fifteen nutritional variables (temperature, pH, incubation time, inoculum size, inoculum age, agitation speed, dextrose, starch, L-asparagine, KNO3, yeast extract, K2HPO4, MgSO4.7H2O, NaCl and FeSO4. 7H2O) were screened using Plackett–Burman experimental design. The most positive significant independent variables affecting enzyme production (temperature, inoculum age and agitation speed) were further optimized by the central composite face-centered design -response surface methodology. As a result, a medium of the following formula is the optimum for producing an extracellular L-asparaginase in the culture filtrate of Streptomyces olivaceus NEAE-119: Dextrose 3g, starch 20g, L-asparagine 10g, KNO3 1g, K2HPO4 1g, MgSO4.7H2O 0.1g, NaCl 0.1g, pH 7, temperature 37°C, agitation speed 200 rpm/min, inoculum size 4%, v/v, inoculum age 72 h and fermentation period 5 days.

Keywords: Streptomyces olivaceus NEAE-119, glutaminase free L-asparaginase, production, Plackett-Burman design, central composite face-centered design, 16S rRNA, scanning electron microscope

Procedia PDF Downloads 358
828 Toehold Mediated Shape Transition of Nucleic Acid Nanoparticles

Authors: Emil F. Khisamutdinov

Abstract:

Development of functional materials undergoing structural transformations in response to an external stimulus such as environmental changes (pH, temperature, etc.), the presence of particular proteins, or short oligonucleotides are of great interest for a variety of applications ranging from medicine to electronics. The dynamic operations of most nucleic acid (NA) devices, including circuits, nano-machines, and biosensors, rely on networks of NA strand displacement processes in which an external or stimulus strand displaces a target strand from a DNA or RNA duplex. The rate of strand displacement can be greatly increased by the use of “toeholds,” single-stranded regions of the target complex to which the invading strand can bind to initiate the reaction, forming additional base pairs that provide a thermodynamic driving force for transformation. Herein, we developed a highly robust nanoparticle shape transition, sequentially transforming DNA polygons from one shape to another using the toehold-mediated DNA strand displacement technique. The shape transformation was confirmed by agarose gel electrophoresis and atomic force microscopy. Furthermore, we demonstrate that our approach is applicable for RNA shape transformation from triangle to square, which can be detected by fluorescence emission from malachite green binding RNA aptamer. Using gel-shift and fluorescence assays, we demonstrated efficient transformation occurs at isothermal conditions (37°C) that can be implemented within living cells as reporter molecules. This work is intended to provide a simple, cost-effective, and straightforward model for the development of biosensors and regulatory devices in nucleic acid nanotechnology.

Keywords: RNA nanotechnology, bionanotechnology, toehold mediated DNA switch, RNA split fluorogenic aptamers

Procedia PDF Downloads 70
827 A Nucleic Acid Extraction Method for High-Viscosity Floricultural Samples

Authors: Harunori Kawabe, Hideyuki Aoshima, Koji Murakami, Minoru Kawakami, Yuka Nakano, David D. Ordinario, C. W. Crawford, Iri Sato-Baran

Abstract:

With the recent advances in gene editing technologies allowing the rewriting of genetic sequences, additional market growth in the global floriculture market beyond previous trends is anticipated through increasingly sophisticated plant breeding techniques. As a prerequisite for gene editing, the gene sequence of the target plant must first be identified. This necessitates the genetic analysis of plants with unknown gene sequences, the extraction of RNA, and comprehensive expression analysis. Consequently, a technology capable of consistently and effectively extracting high-purity DNA and RNA from plants is of paramount importance. Although model plants, such as Arabidopsis and tobacco, have established methods for DNA and RNA extraction, floricultural species such as roses present unique challenges. Different techniques to extract DNA and RNA from various floricultural species were investigated. Upon sampling and grinding the petals of several floricultural species, it was observed that nucleic acid extraction from the ground petal solutions of low viscosity was straightforward; solutions of high viscosity presented a significant challenge. It is postulated that the presence of substantial quantities of polysaccharides and polyphenols in the plant tissue was responsible for the inhibition of nucleic acid extraction. Consequently, attempts were made to extract high-purity DNA and RNA by improving the CTAB method and combining it with commercially available nucleic acid extraction kits. The quality of the total extracted DNA and RNA was evaluated using standard methods. Finally, the effectiveness of the extraction method was assessed by determining whether it was possible to create a library that could be applied as a suitable template for a next-generation sequencer. In conclusion, a method was developed for consistent and accurate nucleic acid extraction from high-viscosity floricultural samples. These results demonstrate improved techniques for DNA and RNA extraction from flowers, help facilitate gene editing of floricultural species and expand the boundaries of research and commercial opportunities.

Keywords: floriculture, gene editing, next-generation sequencing, nucleic acid extraction

Procedia PDF Downloads 10
826 Examination of Public Hospital Unions Technical Efficiencies Using Data Envelopment Analysis and Machine Learning Techniques

Authors: Songul Cinaroglu

Abstract:

Regional planning in health has gained speed for developing countries in recent years. In Turkey, 89 different Public Hospital Unions (PHUs) were conducted based on provincial levels. In this study technical efficiencies of 89 PHUs were examined by using Data Envelopment Analysis (DEA) and machine learning techniques by dividing them into two clusters in terms of similarities of input and output indicators. Number of beds, physicians and nurses determined as input variables and number of outpatients, inpatients and surgical operations determined as output indicators. Before performing DEA, PHUs were grouped into two clusters. It is seen that the first cluster represents PHUs which have higher population, demand and service density than the others. The difference between clusters was statistically significant in terms of all study variables (p ˂ 0.001). After clustering, DEA was performed for general and for two clusters separately. It was found that 11% of PHUs were efficient in general, additionally 21% and 17% of them were efficient for the first and second clusters respectively. It is seen that PHUs, which are representing urban parts of the country and have higher population and service density, are more efficient than others. Random forest decision tree graph shows that number of inpatients is a determinative factor of efficiency of PHUs, which is a measure of service density. It is advisable for public health policy makers to use statistical learning methods in resource planning decisions to improve efficiency in health care.

Keywords: public hospital unions, efficiency, data envelopment analysis, random forest

Procedia PDF Downloads 121
825 Rheumatoid Arthritis, Periodontitis and the Subgingival Microbiome: A Circular Relationship

Authors: Isabel Lopez-Oliva, Akshay Paropkari, Shweta Saraswat, Stefan Serban, Paola de Pablo, Karim Raza, Andrew Filer, Iain Chapple, Thomas Dietrich, Melissa Grant, Purnima Kumar

Abstract:

Objective: We aimed to explicate the role of the subgingival microbiome in the causal link between rheumatoid arthritis (RA) and periodontitis (PD). Methods: Subjects with/without RA and with/without PD were randomized for treatment with scaling and root planing (SRP) or oral hygiene instructions. Subgingival biofilm, gingival crevicular fluid, and serum were collected at baseline and at 3- and 6-months post-operatively. Correlations were generated between 72 million 16S rDNA sequences, immuno-inflammatory mediators, circulating antibodies to oral microbial antigens, serum inflammatory molecules, and clinical metrics of RA. The dynamics of inter-microbial and host-microbial interactions were modeled using differential network analysis. Results: RA superseded periodontitis as a determinant of microbial composition, and DAS28 score superseded the severity of periodontitis as a driver of microbial assemblages (p=0.001, ANOSIM). RA subjects evidenced higher serum anti-PPAD (p=0.0013), anti-Pg-enolase (p=0.0031), anti-RPP3, anti- Pg-OMP and anti- Pi-OMP (p=0.001) antibodies than non-RA controls (with and without periodontitis). Following SRP, bacterial networks anchored by IL-1b, IL-4, IL-6, IL-10, IL-13, MIP-1b, and PDGF-b underwent ≥5-fold higher rewiring; and serum antibodies to microbial antigens decreased significantly. Conclusions: Our data suggest a circular relationship between RA and PD, beginning with an RA-influenced dysbiosis within the healthy subgingival microbiome that leads to exaggerated local inflammation in periodontitis and circulating antibodies to periodontal pathogens and positive correlation between severity of periodontitis and RA activity. Periodontal therapy restores host-microbial homeostasis, reduces local inflammation, and decreases circulating microbial antigens. Our data highlights the importance of integrating periodontal care into the management of RA patients.

Keywords: rheumatoid arthritis, periodontal, subgingival, DNA sequence analysis, oral microbiome

Procedia PDF Downloads 102
824 Synergistic Anti-Proliferation Effect of PLK-1 Inhibitor and Livistona Chinensis Fruit Extracts on Lung Adenocarcinoma A549 Cells

Authors: Min-Chien Su, Tzu-Hsuan Hsu, Guan-Xuan Wu, Shyh-Ming Kuo

Abstract:

Lung cancer is one of the clinically challenging malignant diseases worldwide. For efficient therapeutics in cancer, combination therapy has developed to acquire a better outcome. PLK-1 was one of the major factors affecting cell mitosis in cancer cells, its inhibitor Bi6727 was proven effective in treating several different cancers namely oral cancer, colon cancer and lung cancer. Despite its low toxicity toward normal cells compared to traditional chemotherapy, it is still yet to be evaluated in detail. Livistona Chinensis (LC) is a Chinese herb that used as a traditional prescription to treat lung cancer. Due to the uncertainty of the efficacy of LC, we utilized a water extraction method to extract the Livistona Chinensis and then lyophilized into powder for further study. In this study we investigated the antiproliferation activities of Bi6727 and LC extracts (LCE) on A549 non-small lung cancer cells. The IC50 of Bi6727 and LCE on A549 are 60 nM and 0.8 mg/mL, respectively. The fluorescent staining images shown nucleolus damage in cells treated with Bi6727 and mitochondrial damage after treated with LCE. A549 cells treated with Bi6727 and LCE showed increased expression of Bax, Caspase-3 and Caspase-9 proteins from Western blot assay. LCE also inhibited A549 cells growth keeping cells at G2-M phase from cell cycle assay. Apoptosis assay results showed that LCE induced late apoptosis of A549 cells. JC-1 assay showed that the mitochondria damaged at the LCE concentration of 0.4 mg/mL. In our preliminary anti-proliferation test of combined LCE and Bi-6727 on A549 cells, we found a dramatically decrease in proliferation after treated with LCE first for 24-h and then Bi-6727 for extra 24-h. This was an important finding regarding synergistic anti-proliferation effect of these drugs, However, the usage, the application sequence of LCE and Bi-6727 on A549 cells and their related mechanisms still need to be evaluated. In summary, the drugs exerted anti-proliferation effect on A549 cells independently. We hopefully combine the usage of these two drugs will bring a different and potential outcome in treating lung cancer.

Keywords: anti-proliferation, A549, Livistona Chinensis fruit extracts, PLK-1 inhibitor

Procedia PDF Downloads 136
823 Maximizing Profit Using Optimal Control by Exploiting the Flexibility in Thermal Power Plants

Authors: Daud Mustafa Minhas, Raja Rehan Khalid, Georg Frey

Abstract:

The next generation power systems are equipped with abundantly available free renewable energy resources (RES). During their low-cost operations, the price of electricity significantly reduces to a lower value, and sometimes it becomes negative. Therefore, it is recommended not to operate the traditional power plants (e.g. coal power plants) and to reduce the losses. In fact, it is not a cost-effective solution, because these power plants exhibit some shutdown and startup costs. Moreover, they require certain time for shutdown and also need enough pause before starting up again, increasing inefficiency in the whole power network. Hence, there is always a trade-off between avoiding negative electricity prices, and the startup costs of power plants. To exploit this trade-off and to increase the profit of a power plant, two main contributions are made: 1) introducing retrofit technology for state of art coal power plant; 2) proposing optimal control strategy for a power plant by exploiting different flexibility features. These flexibility features include: improving ramp rate of power plant, reducing startup time and lowering minimum load. While, the control strategy is solved as mixed integer linear programming (MILP), ensuring optimal solution for the profit maximization problem. Extensive comparisons are made considering pre and post-retrofit coal power plant having the same efficiencies under different electricity price scenarios. It concludes that if the power plant must remain in the market (providing services), more flexibility reflects direct economic advantage to the plant operator.

Keywords: discrete optimization, power plant flexibility, profit maximization, unit commitment model

Procedia PDF Downloads 135
822 Epigenetic Modifying Potential of Dietary Spices: Link to Cure Complex Diseases

Authors: Jeena Gupta

Abstract:

In the today’s world of pharmaceutical products, one should not forget the healing properties of inexpensive food materials especially spices. They are known to possess hidden pharmaceutical ingredients, imparting them the qualities of being anti-microbial, anti-oxidant, anti-inflammatory and anti-carcinogenic. Further aberrant epigenetic regulatory mechanisms like DNA methylation, histone modifications or altered microRNA expression patterns, which regulates gene expression without changing DNA sequence, contribute significantly in the development of various diseases. Changing lifestyles and diets exert their effect by influencing these epigenetic mechanisms which are thus the target of dietary phytochemicals. Bioactive components of plants have been in use since ages but their potential to reverse epigenetic alterations and prevention against diseases is yet to be explored. Spices being rich repositories of many bioactive constituents are responsible for providing them unique aroma and taste. Some spices like curcuma and garlic have been well evaluated for their epigenetic regulatory potential, but for others, it is largely unknown. We have evaluated the biological activity of phyto-active components of Fennel, Cardamom and Fenugreek by in silico molecular modeling, in vitro and in vivo studies. Ligand-based similarity studies were conducted to identify structurally similar compounds to understand their biological phenomenon. The database searching has been done by using Fenchone from fennel, Sabinene from cardamom and protodioscin from fenugreek as a query molecule in the different small molecule databases. Moreover, the results of the database searching exhibited that these compounds are having potential binding with the different targets found in the Protein Data Bank. Further in addition to being epigenetic modifiers, in vitro study had demonstrated the antimicrobial, antifungal, antioxidant and cytotoxicity protective effects of Fenchone, Sabinene and Protodioscin. To best of our knowledge, such type of studies facilitate the target fishing as well as making the roadmap in drug design and discovery process for identification of novel therapeutics.

Keywords: epigenetics, spices, phytochemicals, fenchone

Procedia PDF Downloads 151
821 Integrating a Security Operations Centre with an Organization’s Existing Procedures, Policies and Information Technology Systems

Authors: M. Mutemwa

Abstract:

A Cybersecurity Operation Centre (SOC) is a centralized hub for network event monitoring and incident response. SOCs are critical when determining an organization’s cybersecurity posture because they can be used to detect, analyze and report on various malicious activities. For most organizations, a SOC is not part of the initial design and implementation of the Information Technology (IT) environment but rather an afterthought. As a result, it is not natively a plug and play component; therefore, there are integration challenges when a SOC is introduced into an organization. A SOC is an independent hub that needs to be integrated with existing procedures, policies and IT systems of an organization such as the service desk, ticket logging system, reporting, etc. This paper discussed the challenges of integrating a newly developed SOC to an organization’s existing IT environment. Firstly, the paper begins by looking at what data sources should be incorporated into the Security Information and Event Management (SIEM) such as which host machines, servers, network end points, software, applications, web servers, etc. for security posture monitoring. That is which systems need to be monitored first and the order by which the rest of the systems follow. Secondly, the paper also describes how to integrate the organization’s ticket logging system with the SOC SIEM. That is how the cybersecurity related incidents should be logged by both analysts and non-technical employees of an organization. Also the priority matrix for incident types and notifications of incidents. Thirdly, the paper looks at how to communicate awareness campaigns from the SOC and also how to report on incidents that are found inside the SOC. Lastly, the paper looks at how to show value for the large investments that are poured into designing, building and running a SOC.

Keywords: cybersecurity operation centre, incident response, priority matrix, procedures and policies

Procedia PDF Downloads 149
820 Loss of Function of Only One of Two CPR5 Paralogs Causes Resistance Against Rice Yellow Mottle Virus

Authors: Yugander Arra, Florence Auguy, Melissa Stiebner, Sophie Chéron, Michael M. Wudick, Van Schepler-Luu, Sébastien Cunnac, Wolf B. Frommer, Laurence Albar

Abstract:

Rice yellow mottle virus (RYMV) is one of the most important diseases affecting rice in Africa. The most promising strategy to reduce yield losses is the use of highly resistant varieties. The resistance gene RYMV2 is homolog of the Arabidopsis constitutive expression of pathogenesis related protein-5 (AtCPR5) nucleoporin gene. Resistance alleles are originating from African cultivated rice Oryza glaberrima, rarely cultivated, and are characterized by frameshifts or early stop codons, leading to a non-functional or truncated protein. Rice possesses two paralogs of CPR5 and function of these genes are unclear. Here, we evaluated the role of the two rice candidate nucleoporin paralogs OsCPR5.1 (pathogenesis-related gene 5; RYMV2) and OsCPR5.2 by CRISPR/Cas9 genome editing. Despite striking sequence and structural similarity, only loss-of-function of OsCPR5.1 led to full resistance, while loss-of-function oscpr5.2 mutants remained susceptible. Short N-terminal deletions in OsCPR5.1 also did not lead to resistance. In contrast to Atcpr5 mutants, neither OsCPR5.1 nor OsCPR5.2 knock out mutants showed substantial growth defects. Taken together, the candidate nucleoporin OsCPR5.1, but not its close homolog OsCPR5.2, plays a specific role for the susceptibility to RYMV, possibly by impairing the import of viral RNA or protein into the nucleus. Whereas gene introgression from O. glaberrima to high yielding O. sativa varieties is impaired by strong sterility barriers and the negative impact of linkage drag, genome editing of OsCPR5.1, while maintaining OsCPR5.2 activity, thus provides a promising strategy to generate O. sativa elite lines that are resistant to RYMV.

Keywords: CRISPR Cas9, genome editing, knock out mutant, recessive resistance, rice yellow mottle virus

Procedia PDF Downloads 111
819 Reactivity of Clay Minerals of the Hydrocarbon Reservoir Rocks and the Effect of Zeolites on Operation and Production Costs That the Oil Industry in the World Assumes

Authors: Carlos Alberto Ríos Reyes

Abstract:

Traditionally, clays have been considered as one of the main problems in the flow of fluids in hydrocarbon reservoirs. However, there is not known the significance of zeolites formed from the reactivity of clays and their effect not only on the costs of operations carried out by the oil industry in the world but also on production. The present work focused on understanding the interaction between clay minerals with brines and alkaline solutions used in the oil industry. For this, a comparative study was conducted where the reaction of sedimentary rocks under laboratory conditions was examined. Original and treated rocks were examined by X-ray powder diffraction (XRPD) and Scanning Electron Microscopy (SEM) to determine the changes that these rocks underwent upon contact with fluids of variable chemical composition. As a result, zeolite Linde Type A (LTA), sodalite (SOD), and cancrinite (CAN) can be formed after experimental work, which coincided with the dissolution of kaolinite and smectite. Results reveal that the Oil Industry should invest efforts and focus its gaze to understand at the pore scale the problem that could arise as a consequence of the clay-fluid interaction in hydrocarbon reservoir rocks due to the presence of clays in their porous system, as well as the formation of zeolites, which are better hydrocarbon absorbents. These issues could be generating losses in world production. We conclude that there is a critical situation that may be occurring in the stimulation of hydrocarbon reservoirs, where real solutions are necessary not only for the formulation of more efficient and effective injection fluids but also to contribute to the improvement of production and avoid considerable losses in operating costs.

Keywords: clay minerals, zeolites, rock-fluid interaction, experimental work, reactivity

Procedia PDF Downloads 77
818 Implementation of Lean Tools (Value Stream Mapping and ECRS) in an Oil Refinery

Authors: Ronita Singh, Yaman Pattanaik, Soham Lalwala

Abstract:

In today’s highly competitive business environment, every organization is striving towards lean manufacturing systems to achieve lower Production Lead Times, lower costs, less inventory and overall improvement in supply chains efficiency. Based on the similar idea, this paper presents the practical application of Value Stream Mapping (VSM) tool and ECRS (Eliminate, Combine, Reduce, and Simplify) technique in the receipt section of the material management center of an oil refinery. A value stream is an assortment of all actions (value added as well as non-value added) that are required to bring a product through the essential flows, starting with raw material and ending with the customer. For drawing current state value stream mapping, all relevant data of the receipt cycle has been collected and analyzed. Then analysis of current state map has been done for determining the type and quantum of waste at every stage which helped in ascertaining as to how far the warehouse is from the concept of lean manufacturing. From the results achieved by current VSM, it was observed that the two processes- Preparation of GRN (Goods Receipt Number) and Preparation of UD (Usage Decision) are both bottle neck operations and have higher cycle time. This root cause analysis of various types of waste helped in designing a strategy for step-wise implementation of lean tools. The future state thus created a lean flow of materials at the warehouse center, reducing the lead time of the receipt cycle from 11 days to 7 days and increasing overall efficiency by 27.27%.

Keywords: current VSM, ECRS, future VSM, receipt cycle, supply chain, VSM

Procedia PDF Downloads 304
817 Study of Composite Materials for Aisha Containment Chamber

Authors: G. Costa, F. Noto, L. Celona, F. Chines, G. Ciavola, G. Cuttone, S. Gammino, O. Leonardi, S. Marletta, G. Torrisi

Abstract:

The ion sources for accelerators devoted to medical applications must provide intense ion beams, with high reproducibility, stability and brightness. AISHa (Advanced Ion Source for Hadron-therapy) is a compact ECRIS whose hybrid magnetic system consists of a permanent Halbach-type hexapole magnet and a set of independently energized superconducting coils. These coils will be enclosed in a compact cryostat with two cryocoolers for LHe-free operation. The AISHa ion source has been designed by taking into account the typical requirements of hospital-based facilities, where the minimization of the mean time between failures (MTBF) is a key point together with the maintenance operations which should be fast and easy. It is intended to be a multipurpose device, operating at 18 GHz, in order to achieve higher plasma densities. It should provide enough versatility for future needs of the hadron therapy, including the ability to run at larger microwave power to produce different species and highly charged ion beams. The source is potentially interesting for any hadrontherapy center using heavy ions. In the paper, we designed an innovative solution for the plasma containment chamber that allows us to solve our isolation and structural problems. We analyzed the materials chosen for our aim (glass fibers and carbon fibers) and we illustrated the all process (spinning, curing and machining) of the assembly of our chamber. The glass fibers and carbon fibers are used to reinforce polymer matrices and give rise to structural composites and composites by molding.

Keywords: hadron-therapy, carbon fiber, glass fiber, vacuum-bag, ECR, ion source

Procedia PDF Downloads 204
816 Identifying Issues of Corporate Governance and the Effect on Organizational Performance

Authors: Abiodun Oluwaseun Ibude

Abstract:

Every now and then we hear of companies closing down their operations due to unethical practices like an overstatement of company’s balance sheet, concealing company’s debt, embezzlement of company’s fund, declaring false profit and so on. This has led to the liquidation of companies and the loss of investments of shareholders as well as the interest of other stakeholders. As a result of these ugly trends, there is need to put in place a formidable mechanism that will ensure that business activities are conducted in a healthy manner. It should also promote good ethics as well as ensure that the interest of stakeholders and the objectives of any organization is achieved within the confines of the law; wherein law exists to provide criminal penalties for falsification of documents and for conducting other irregularities. Based on the foregoing, it becomes imperative to ensure that steps are taken to stop this menace and face the challenges ahead. This calls for the practice of good governance. The purpose of this study is to identify various components of corporate governance and determine the impact of it on the performance of established organizations. A survey method with the use of questionnaire was applied in collecting data useful for this study which were later analyzed using correlation co-efficiency statistical tools in generating finding, making a conclusion, and necessary recommendation. From the research conducted, it was discovered that there are systems within organizations apart from regulatory agencies that ensure effective control of activities, promote accountability, and operational efficiency. However, some members of organizations fail to explore the usage of corporate governance and impact negatively of an organization’s performance. In conclusion, good corporate governance will not be achieved unless there is openness, honesty, transparency, accountability, and fairness.

Keywords: corporate governance, formidable mechanism, company’s balance sheet, stakeholders

Procedia PDF Downloads 110
815 Managing Data from One Hundred Thousand Internet of Things Devices Globally for Mining Insights

Authors: Julian Wise

Abstract:

Newcrest Mining is one of the world’s top five gold and rare earth mining organizations by production, reserves and market capitalization in the world. This paper elaborates on the data acquisition processes employed by Newcrest in collaboration with Fortune 500 listed organization, Insight Enterprises, to standardize machine learning solutions which process data from over a hundred thousand distributed Internet of Things (IoT) devices located at mine sites globally. Through the utilization of software architecture cloud technologies and edge computing, the technological developments enable for standardized processes of machine learning applications to influence the strategic optimization of mineral processing. Target objectives of the machine learning optimizations include time savings on mineral processing, production efficiencies, risk identification, and increased production throughput. The data acquired and utilized for predictive modelling is processed through edge computing by resources collectively stored within a data lake. Being involved in the digital transformation has necessitated the standardization software architecture to manage the machine learning models submitted by vendors, to ensure effective automation and continuous improvements to the mineral process models. Operating at scale, the system processes hundreds of gigabytes of data per day from distributed mine sites across the globe, for the purposes of increased improved worker safety, and production efficiency through big data applications.

Keywords: mineral technology, big data, machine learning operations, data lake

Procedia PDF Downloads 106
814 Conjunctive Management of Surface and Groundwater Resources under Uncertainty: A Retrospective Optimization Approach

Authors: Julius M. Ndambuki, Gislar E. Kifanyi, Samuel N. Odai, Charles Gyamfi

Abstract:

Conjunctive management of surface and groundwater resources is a challenging task due to the spatial and temporal variability nature of hydrology as well as hydrogeology of the water storage systems. Surface water-groundwater hydrogeology is highly uncertain; thus it is imperative that this uncertainty is explicitly accounted for, when managing water resources. Various methodologies have been developed and applied by researchers in an attempt to account for the uncertainty. For example, simulation-optimization models are often used for conjunctive water resources management. However, direct application of such an approach in which all realizations are considered at each iteration of the optimization process leads to a very expensive optimization in terms of computational time, particularly when the number of realizations is large. The aim of this paper, therefore, is to introduce and apply an efficient approach referred to as Retrospective Optimization Approximation (ROA) that can be used for optimizing conjunctive use of surface water and groundwater over a multiple hydrogeological model simulations. This work is based on stochastic simulation-optimization framework using a recently emerged technique of sample average approximation (SAA) which is a sampling based method implemented within the Retrospective Optimization Approximation (ROA) approach. The ROA approach solves and evaluates a sequence of generated optimization sub-problems in an increasing number of realizations (sample size). Response matrix technique was used for linking simulation model with optimization procedure. The k-means clustering sampling technique was used to map the realizations. The methodology is demonstrated through the application to a hypothetical example. In the example, the optimization sub-problems generated were solved and analysed using “Active-Set” core optimizer implemented under MATLAB 2014a environment. Through k-means clustering sampling technique, the ROA – Active Set procedure was able to arrive at a (nearly) converged maximum expected total optimal conjunctive water use withdrawal rate within a relatively few number of iterations (6 to 7 iterations). Results indicate that the ROA approach is a promising technique for optimizing conjunctive water use of surface water and groundwater withdrawal rates under hydrogeological uncertainty.

Keywords: conjunctive water management, retrospective optimization approximation approach, sample average approximation, uncertainty

Procedia PDF Downloads 228
813 Relationship between Wave Velocities and Geo-Pressures in Shallow Libyan Carbonate Reservoir

Authors: Tarek Sabri Duzan

Abstract:

Knowledge of the magnitude of Geo-pressures (Pore, Fracture & Over-burden pressures) is vital especially during drilling, completions, stimulations, Enhance Oil Recovery. Many times problems, like lost circulation could have been avoided if techniques for calculating Geo-pressures had been employed in the well planning, mud weight plan, and casing design. In this paper, we focused on the relationships between Geo-pressures and wave velocities (P-Wave (Vp) and S-wave (Vs)) in shallow Libyan carbonate reservoir in the western part of the Sirte Basin (Dahra F-Area). The data used in this report was collected from four new wells recently drilled. Those wells were scattered throughout the interested reservoir as shown in figure-1. The data used in this work are bulk density, Formation Mult -Tester (FMT) results and Acoustic wave velocities. Furthermore, Eaton Method is the most common equation used in the world, therefore this equation has been used to calculate Fracture pressure for all wells using dynamic Poisson ratio calculated by using acoustic wave velocities, FMT results for pore pressure, Overburden pressure estimated by using bulk density. Upon data analysis, it has been found that there is a linear relationship between Geo-pressures (Pore, Fracture & Over-Burden pressures) and wave velocities ratio (Vp/Vs). However, the relationship was not clear in the high-pressure area, as shown in figure-10. Therefore, it is recommended to use the output relationship utilizing the new seismic data for shallow carbonate reservoir to predict the Geo-pressures for future oil operations. More data can be collected from the high-pressure zone to investigate more about this area.

Keywords: bulk density, formation mult-tester (FMT) results, acoustic wave, carbonate shalow reservoir, d/jfield velocities

Procedia PDF Downloads 284
812 Shortening Distances: The Link between Logistics and International Trade

Authors: Felipe Bedoya Maya, Agustina Calatayud, Vileydy Gonzalez Mejia

Abstract:

Encompassing inventory, warehousing, and transportation management, logistics is a crucial predictor of firm performance. This has been extensively proven by extant literature in business and operations management. Logistics is also a fundamental determinant of a country's ability to access international markets. Available studies in international and transport economics have shown that limited transport infrastructure and underperforming transport services can severely affect international competitiveness. However, the evidence lacks the overall impact of logistics performance-encompassing all inventory, warehousing, and transport components- on global trade. In order to fill this knowledge gap, the paper uses a gravitational trade model with 155 countries from all geographical regions between 2007 and 2018. Data on logistics performance is obtained from the World Bank's Logistics Performance Index (LPI). First, the relationship between logistics performance and a country’s total trade is estimated, followed by a breakdown by the economic sector. Then, the analysis is disaggregated according to the level of technological intensity of traded goods. Finally, after evaluating the intensive margin of trade, the relevance of logistics infrastructure and services for the extensive trade margin is assessed. Results suggest that: (i) improvements in both logistics infrastructure and services are associated with export growth; (ii) manufactured goods can significantly benefit from these improvements, especially when both exporting and importing countries increase their logistics performance; (iii) the quality of logistics infrastructure and services becomes more important as traded goods are technology-intensive; and (iv) improving the exporting country's logistics performance is essential in the intensive margin of trade while enhancing the importing country's logistics performance is more relevant in the extensive margin.

Keywords: gravity models, infrastructure, international trade, logistics

Procedia PDF Downloads 201
811 Molecular Diversity of Forensically Relevant Insects from the Cadavers of Lahore

Authors: Sundus Mona, Atif Adnan, Babar Ali, Fareeha Arshad, Allah Rakha

Abstract:

Molecular diversity is the variation in the abundance of species. Forensic entomology is a neglected field in Pakistan. Insects collected from the crime scene should be handled by forensic entomologists who are currently virtually non-existent in Pakistan. Correct identification of insect specimen along with knowledge of their biodiversity can aid in solving many problems related to complicated forensic cases. Inadequate morphological identification and insufficient thermal biological studies limit the entomological utility in Forensic Medicine. Recently molecular identification of entomological evidence has gained attention globally. DNA barcoding is the latest and established method for species identification. Only proper identification can provide a precise estimation of postmortem intervals. Arthropods are known to be the first tourists scavenging on decomposing dead matter. The objective of the proposed study was to identify species by molecular techniques and analyze their phylogenetic importance with barcoded necrophagous insect species of early succession on human cadavers. Based upon this identification, the study outcomes will be the utilization of established DNA bar codes to identify carrion feeding insect species for concordant estimation of post mortem interval. A molecular identification method involving sequencing of a 658bp ‘barcode’ fragment of the mitochondrial cytochrome oxidase subunit 1 (CO1) gene from collected specimens of unknown dipteral species from cadavers of Lahore was evaluated. Nucleotide sequence divergences were calculated using MEGA 7 and Arlequin, and a neighbor-joining phylogenetic tree was generated. Three species were identified, Chrysomya megacephala, Chrysomya saffranea, and Chrysomya rufifacies with low genetic diversity. The fixation index was 0.83992 that suggests a need for further studies to identify and classify forensically relevant insects in Pakistan. There is an exigency demand for further research especially when immature forms of arthropods are recovered from the crime scene.

Keywords: molecular diversity, DNA barcoding, species identification, forensically relevant

Procedia PDF Downloads 140
810 Role and Impact of Artificial Intelligence in Sales and Distribution Management

Authors: Kiran Nair, Jincy George, Suhaib Anagreh

Abstract:

Artificial intelligence (AI) in a marketing context is a form of a deterministic tool designed to optimize and enhance marketing tasks, research tools, and techniques. It is on the verge of transforming marketing roles and revolutionize the entire industry. This paper aims to explore the current dissemination of the application of artificial intelligence (AI) in the marketing mix, reviewing the scope and application of AI in various aspects of sales and distribution management. The paper also aims at identifying the areas of the strong impact of AI in factors of sales and distribution management such as distribution channel, purchase automation, customer service, merchandising automation, and shopping experiences. This is a qualitative research paper that aims to examine the impact of AI on sales and distribution management of 30 multinational brands in six different industries, namely: airline; automobile; banking and insurance; education; information technology; retail and telecom. Primary data is collected by means of interviews and questionnaires from a sample of 100 marketing managers that have been selected using convenient sampling method. The data is then analyzed using descriptive statistics, correlation analysis and multiple regression analysis. The study reveals that AI applications are extensively used in sales and distribution management, with a strong impact on various factors such as identifying new distribution channels, automation in merchandising, customer service, and purchase automation as well as sales processes. International brands have already integrated AI extensively in their day-to-day operations for better efficiency and improved market share while others are investing heavily in new AI applications for gaining competitive advantage.

Keywords: artificial intelligence, sales and distribution, marketing mix, distribution channel, customer service

Procedia PDF Downloads 151
809 Influencing Factors to Mandatory versus Non-Mandatory E-Government Services Adoption in India: An Empirical Study

Authors: Rajiv Kumar, Amit Sachan, Arindam Mukherjee

Abstract:

Government agencies around the world, including India, are incorporating digital technologies and processes into their day-to-day operations to become more efficient. Despite low internet penetration (around 34.8% of total population) in India, Government of India has made some public services mandatory to access online (e.g. passport, tax filing).This is insisting citizens to access mandatory public services online. However, due to digital divide, all citizens do not have equal access to internet. In light of this, it is an interesting topic to explore how citizens are able to access mandatory online public services. It is important to understand how citizens are adopting these mandatory e-government services and how the adoption behavior of these mandatory e-government services is different or similar to adoption behavior of non-mandatory e-government services. The purpose of this research is to investigate the factors that influence adoption of mandatory and non-mandatory e-government services in India. A quantitative technique is employed in this study. A conceptual model has been proposed by integrating the influencing factors to adopt e-government services from previous studies. The proposed conceptual model highlights a comprehensive set of potential factors influencing the adoption of e-government services. The proposed model has been validated by keeping in view the local context of Indian society. Online and paper based survey was administered, collected data was analyzed and results have been discussed. A total of 463 valid responses were received and further the responses were analyzed. The research reveals that the influencing factors to adopt e-government services are not same for both mandatory and non-mandatory e-government services. There are some factors that influence adoption of both mandatory and non-mandatory e-government services but there are some which are relevant for either of mandatory and non-mandatory e-government services. The research findings may help government or concerned agencies in successfully implementing e-government services.

Keywords: adoption, e-government, India, mandatory, non-mandatory

Procedia PDF Downloads 314
808 3D Geomechanical Model the Best Solution of the 21st Century for Perforation's Problems

Authors: Luis Guiliana, Andrea Osorio

Abstract:

The lack of comprehension of the reservoir geomechanics conditions may cause operational problems that cost to the industry billions of dollars per year. The drilling operations at the Ceuta Field, Area 2 South, Maracaibo Lake, have been very expensive due to problems associated with drilling. The principal objective of this investigation is to develop a 3D geomechanical model in this area, in order to optimize the future drillings in the field. For this purpose, a 1D geomechanical model was built at first instance, following the workflow of the MEM (Mechanical Earth Model), this consists of the following steps: 1) Data auditing, 2) Analysis of drilling events and structural model, 3) Mechanical stratigraphy, 4) Overburden stress, 5) Pore pressure, 6) Rock mechanical properties, 7) Horizontal stresses, 8) Direction of the horizontal stresses, 9) Wellbore stability. The 3D MEM was developed through the geostatistic model of the Eocene C-SUP VLG-3676 reservoir and the 1D MEM. With this data the geomechanical grid was embedded. The analysis of the results threw, that the problems occurred in the wells that were examined were mainly due to wellbore stability issues. It was determined that the stress field change as the stratigraphic column deepens, it is normal to strike-slip at the Middle Miocene and Lower Miocene, and strike-slipe to reverse at the Eocene. In agreement to this, at the level of the Eocene, the most advantageous direction to drill is parallel to the maximum horizontal stress (157º). The 3D MEM allowed having a tridimensional visualization of the rock mechanical properties, stresses and operational windows (mud weight and pressures) variations. This will facilitate the optimization of the future drillings in the area, including those zones without any geomechanics information.

Keywords: geomechanics, MEM, drilling, stress

Procedia PDF Downloads 270
807 Identification of New Familial Breast Cancer Susceptibility Genes: Are We There Yet?

Authors: Ian Campbell, Gillian Mitchell, Paul James, Na Li, Ella Thompson

Abstract:

The genetic cause of the majority of multiple-case breast cancer families remains unresolved. Next generation sequencing has emerged as an efficient strategy for identifying predisposing mutations in individuals with inherited cancer. We are conducting whole exome sequence analysis of germ line DNA from multiple affected relatives from breast cancer families, with the aim of identifying rare protein truncating and non-synonymous variants that are likely to include novel cancer predisposing mutations. Data from more than 200 exomes show that on average each individual carries 30-50 protein truncating mutations and 300-400 rare non-synonymous variants. Heterogeneity among our exome data strongly suggest that numerous moderate penetrance genes remain to be discovered, with each gene individually accounting for only a small fraction of families (~0.5%). This scenario marks validation of candidate breast cancer predisposing genes in large case-control studies as the rate-limiting step in resolving the missing heritability of breast cancer. The aim of this study is to screen genes that are recurrently mutated among our exome data in a larger cohort of cases and controls to assess the prevalence of inactivating mutations that may be associated with breast cancer risk. We are using the Agilent HaloPlex Target Enrichment System to screen the coding regions of 168 genes in 1,000 BRCA1/2 mutation-negative familial breast cancer cases and 1,000 cancer-naive controls. To date, our interim analysis has identified 21 genes which carry an excess of truncating mutations in multiple breast cancer families versus controls. Established breast cancer susceptibility gene PALB2 is the most frequently mutated gene (13/998 cases versus 0/1009 controls), but other interesting candidates include NPSR1, GSN, POLD2, and TOX3. These and other genes are being validated in a second cohort of 1,000 cases and controls. Our experience demonstrates that beyond PALB2, the prevalence of mutations in the remaining breast cancer predisposition genes is likely to be very low making definitive validation exceptionally challenging.

Keywords: predisposition, familial, exome sequencing, breast cancer

Procedia PDF Downloads 488