Search results for: gene transfer

Authors: Eun-Young Kwon, Myung-Sook Choi, Su-Jung Cho, Ji-Young Choi, So Young Kim, Youngji Han

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Overweight and obesity have been linked to a low-grade chronic inflammatory response and an increased risk of developing metabolic syndrome including insulin resistance, type 2 diabetes mellitus and certain types of cancers. Luteolin is a dietary flavonoid with anti-inflammatory, anti-oxidant, anti-cancer and anti-diabetic properties. However, little is known about the detailed mechanism associated with the effect of luteolin on inflammation-related obesity and its complications. The aim of the present study was to reveal the anti-diabetic effect of luteolin in diet-induced obesity mice using “transcriptomics” tool. Thirty-nine male C57BL/6J mice (4-week-old) were randomly divided into 3 groups and were fed normal diet, high-fat diet (HFD, 20% fat) and HFD+0.005% (w/w) luteolin for 16 weeks. Luteolin improved insulin resistance, as measured by HOMA-IR and glucose tolerance, along with preservation action of pancreatic β-cells, compared to the HFD group. Luteoiln was significantly decreased the levels of leptin and ghrelin that play a pivotal role in energy balance, and the macrophage low-grade inflammation marker sCD163 (soluble Cd antigen 163) in plasma. Activities of hepatic anti-oxidant enzymes (catalase and glutathione peroxidase) were increased, while the levels of plasma transaminase (GOT and GPT) and oxidative damage markers (hepatic mitochondria H2O2 and TBARS) were markedly decreased by luteolin supplementation. In addition, luteolin increased oxidative capacity and fatty acid utilization by presenting decrease in enzyme activities of citrate synthase, cytochrome C oxidase and β-hydroxyacyl CoA dehydrogenase and UCP3 gene expression compared to high-fat diet. Moreover, our microarray results of muscle also revealed down-regulated gene expressions associated with TCA cycle by HFD were reversed to normal level by luteolin treatment. Taken together, our results indicate that luteolin is one of bioactive components for improving insulin resistance by increasing oxidative capacity, modulating anti-oxidant metabolism and suppressing inflammatory signaling cascades in diet-induced obese mice. These results provide possible therapeutic targets for prevention and treatment of diet-induced obesity and its complications.

Keywords: anti-oxidant metabolism, diabetes, luteolin, oxidative capacity

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Authors: Xi Liu, Fan Yuan

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In the evolving landscape of physics-based machine learning (PBML), particularly within fluid dynamics and its applications in electromechanical engineering, robot vision, and robot learning, achieving precision and alignment with researchers' specific needs presents a formidable challenge. In response, this work proposes a methodology that integrates neural transformation with a modified smoothed particle hydrodynamics model for generating transformed 3D fluid simulations. This approach is useful for nanoscale science, where the unique and complex behaviors of viscoelastic medium demand accurate neurally-transformed simulations for materials understanding and manipulation. In electromechanical engineering, the method enhances the design and functionality of fluid-operated systems, particularly microfluidic devices, contributing to advancements in nanomaterial design, drug delivery systems, and more. The proposed approach also aligns with the principles of PBML, offering advantages such as multi-fluid stylization and consistent particle attribute transfer. This capability is valuable in various fields where the interaction of multiple fluid components is significant. Moreover, the application of neurally-transformed hydrodynamical models extends to manufacturing processes, such as the production of microelectromechanical systems, enhancing efficiency and cost-effectiveness. The system's ability to perform neural transfer on 3D fluid scenes using a deep learning algorithm alongside physical models further adds a layer of flexibility, allowing researchers to tailor simulations to specific needs across scientific and engineering disciplines.

Keywords: physics-based machine learning, robot vision, robot learning, hydrodynamics

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Authors: Cleyton S. Stampa

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This paper addresses the perspectives of using low melting point metals (LMPMs) as phase change materials (PCMs) in latent thermal energy storage (LTES) units, through a numerical approach. This is a new class of PCMs that has been one of the most prospective alternatives to be considered in LTES, due to these materials present high thermal conductivity and elevated heat of fusion, per unit volume. The chosen type of LTES consists of several horizontal parallel slabs filled with PCM. The heat transfer fluid (HTF) circulates through the channel formed between each two consecutive slabs on a laminar regime through forced convection. The study deals with the LTES charging process (heat-storing) by using pure gallium as PCM, and it considers heat conduction in the solid phase during melting driven by natural convection in the melt. The transient heat transfer problem is analyzed in one arbitrary slab under the influence of the HTF. The mathematical model to simulate the isothermal phase change is based on a volume-averaged enthalpy method, which is successfully verified by comparing its predictions with experimental data from works available in the pertinent literature. Regarding the convective heat transfer problem in the HTF, it is assumed that the flow is thermally developing, whereas the velocity profile is already fully developed. The study aims to learn about the effect of the solid subcooling in the melting rate through comparisons with the melting process of the solid in which it starts to melt from its fusion temperature. In order to best understand this effect in a metallic compound, as it is the case of pure gallium, the study also evaluates under the same conditions established for the gallium, the melting process of commercial paraffin wax (organic compound) and of the calcium chloride hexahydrate (CaCl₂ 6H₂O-inorganic compound). In the present work, it is adopted the best options that have been established by several researchers in their parametric studies with respect to this type of LTES, which lead to high values of thermal efficiency. To do so, concerning with the geometric aspects, one considers a gap of the channel formed by two consecutive slabs, thickness and length of the slab. About the HTF, one considers the type of fluid, the mass flow rate, and inlet temperature.

Keywords: flat slab, heat storing, pure metal, solid subcooling

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Authors: Mouhamadou Diop, Mohamed I. Hassan

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Molten metallic flow in metallurgical plant is highly turbulent and presents a complex coupling with heat transfer, phase transfer, chemical reaction, momentum transport, etc. Molten silicon flow has significant effect in directional solidification of multicrystalline silicon by affecting the temperature field and the emerging crystallization interface as well as the transport of species and impurities during casting process. Owing to the complexity and limits of reliable measuring techniques, computational models of fluid flow are useful tools to study and quantify these problems. The overall objective of this study is to investigate the potential of a traveling magnetic field for an efficient operating control of the molten metal flow. A multidimensional numerical model will be developed for the calculations of Lorentz force, molten metal flow, and the related phenomenon. The numerical model is implemented in a laboratory-scale silicon crystallization furnace. This study presents the potential of traveling magnetic field approach for an efficient operating control of the molten flow. A numerical model will be used to study the effects of magnetic force applied on the molten flow, and their interdependencies. In this paper, coupled and decoupled, steady and unsteady models of molten flow and crystallization interface will be compared. This study will allow us to retrieve the optimal traveling magnetic field parameter range for crystallization furnaces and the optimal numerical simulations strategy for industrial application.

Keywords: multidimensional, numerical simulation, solidification, multicrystalline, traveling magnetic field

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Authors: Susan Lee

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Situated learning principles are adopted in the design of the module, professional communication, in its iteration of tasks and assignments to create a learning environment that simulates workplace reality. The success of situated learning is met when students are able to transfer and apply their skills beyond the classroom, in their personal life, and workplace. The learning process should help students recognize the relevance and opportunities for application. In the module’s learning component on negotiation, cases are created based on scenarios inspired by industry practices. The cases simulate scenarios that students on the course may encounter when they enter the workforce when they take on executive roles in the real estate sector. Engaging in the cases has enhanced students’ learning experience as they apply interpersonal communication skills in negotiation contexts of executives. Through the process of case analysis, role-playing, and peer feedback, students are placed in an experiential learning space to think and act in a deliberate manner not only as students but as professionals they will graduate to be. The immersive skills practices enable students to continuously apply a range of verbal and non-verbal communication skills purposefully as they stage their negotiations. The theme in students' feedback resonates with their awareness of the authentic and workplace experiences offered through visceral role-playing. Students also note relevant opportunities for the future transfer of the skills acquired. This indicates that students recognize the possibility of encountering similar negotiation episodes in the real world and realize they possess the negotiation tools and communication skills to deliberately apply them when these opportunities arise outside the classroom.

Keywords: deliberate practice, interpersonal communication skills, role-play, situated learning

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Authors: Talha A. Al-Dubai, Rashad A. Bantan, Ramadan H. Abu-Zied, Brian G. Jones, Aaid G. Al-Zubieri

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Contemporary foraminiferal samples sediments were collected from the intertidal sabkha of Al-Kharrar Lagoon, Saudi Arabia, to study the vertical distribution of Foraminifera and, based on a modern training set, their potential to develop a predictor of former sea-level changes in the area. Based on hierarchical cluster analysis, the intertidal sabkha is divided into three vertical zones (A, B & C) represented by three foraminiferal assemblages, where agglutinated species occupied Zone A and calcareous species occupied the other two zones. In Zone A (high intertidal), Agglutinella compressa, Clavulina angularis and C. multicamerata are dominant species with a minor presence of Peneroplis planatus, Coscinospira hemprichii, Sorites orbiculus, Quinqueloculina lamarckiana, Q. seminula, Ammonia convexa and A. tepida. In contrast, in Zone B (middle intertidal) the most abundant species are P. planatus, C. hemprichii, S. orbiculus, Q. lamarckiana, Q. seminula and Q. laevigata, while Zone C (low intertidal) is characterised by C. hemprichii, Q. costata, S. orbiculus, P. planatus, A. convexa, A. tepida, Spiroloculina communis and S. costigera. A transfer function for sea-level reconstruction was developed using a modern dataset of 75 contemporary sediment samples and 99 species collected from several transects across the sabkha. The model provided an error of 0.12m, suggesting that intertidal foraminifers are able to predict the past sea-level changes with high precision in Al-Kharrar Lagoon, and thus the future prediction of those changes in the area.

Keywords: Lagoonal foraminifers, intertidal sabkha, vertical zonation, transfer function, sea level

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Authors: Yayan Harry Yadi, L. Meily Kurniawidjaja

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Work activities for MMH (Manual Material Handling) in the storage of liquid catalyst raw material workstations in chemical industries identify high-risk MSDs (Musculoskeletal Disorders). Their work is often performed frequently requires an awkward body posture, twisting, bending because of physical space limited, cold, slippery, and limited tools for transfer container and weighing the liquid chemistry of the catalyst into the container. This study aims to develop an ergonomic work system design on the transfer and weighing process of liquid catalyst raw materials at the storage warehouse. A triangulation method through an interview, observation, and detail study team with assessing the level of risk work posture and complaints. Work postures were analyzed using the RULA method, through the support of CATIA software. The study concludes that ergonomic design can make reduce 3 levels of risk scores awkward posture. CATIA Software simulation provided a comprehensive solution for a better posture of manual material handling at task weigh. An addition of manual material handling tools such as adjustable conveyors, trolley and modification tools semi-mechanical weighing with techniques based on rule ergonomic design can reduce the hazard of chemical fluid spills.

Keywords: ergonomic design, MSDs, CATIA software, RULA, chemical industry

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Authors: Fahad Abbasi

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Flow of electrically conducting nanofluids is of pivotal importance in countless industrial and medical appliances. Fluctuations in thermophysical properties of such fluids due to variations in temperature have not received due attention in the available literature. Present investigation aims to fill this void by analyzing the flow of copper-water nanofluid with temperature dependent viscosity past a Riga plate. Strong wall suction and viscous dissipation have also been taken into account. Numerical solutions for the resulting nonlinear system have been obtained. Results are presented in the graphical and tabular format in order to facilitate the physical analysis. An estimated expression for skin friction coefficient and Nusselt number are obtained by performing linear regression on numerical data for embedded parameters. Results indicate that the temperature dependent viscosity alters the velocity, as well as the temperature of the nanofluid and, is of considerable importance in the processes where high accuracy is desired. Addition of copper nanoparticles makes the momentum boundary layer thinner whereas viscosity parameter does not affect the boundary layer thickness. Moreover, the regression expressions indicate that magnitude of rate of change in effective skin friction coefficient and Nusselt number with respect to nanoparticles volume fraction is prominent when compared with the rate of change with variable viscosity parameter and modified Hartmann number.

Keywords: heat transfer, peristaltic flows, radially varying magnetic field, curved channel

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Authors: Debbarma Asis, Guha Chandan

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Tumor Protein-53 (P53) is one of the tumor suppressor proteins. P53 regulates the cell cycle that conserves stability by preventing genome mutation. It is named so as it runs as 53-kilodalton (kDa) protein on Polyacrylamide gel electrophoresis although the actual mass is 43.7 kDa. Experimental evidence has indicated that P53 cancer mutants loses tumor suppression activity and subsequently gain oncogenic activities to promote tumourigenesis. Tumor-specific DNA has recently been detected in the plasma of breast cancer patients. Detection of tumor-specific genetic materials in cancer patients may provide a unique and valuable tumor marker for diagnosis and prognosis. Commercially available MDA-468 breast cancer cell line was used for the proposed study.

Keywords: tumor protein (P53), cancer mutants, MDA-468, tumor suppressor gene

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Authors: A. A. Abid

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Wave-particle interactions are considered to be the paramount in the transmission of energy in collisionless space plasmas, where electromagnetic fields confined the charged particles movement. One of the distinct features of energy transfer in collisionless plasma is wave-particle interaction which is ubiquitous in space plasmas. The three essential populations of the inner magnetosphere are cold plasmaspheric plasmas, ring-currents, and radiation belts high energy particles. The transition region amid such populations initiates wave-particle interactions among distinct plasmas and the wave mode perceived in the magnetosphere is the electromagnetic ion cyclotron (EMIC) wave. These waves can interact with numerous particle species resonantly, accompanied by plasma particle heating is still in debate. In this work we paid particular attention to how EMIC waves impact plasma species, specifically how they affect the heating of electrons and ions during storm and substorm in the Magnetosphere. Using Magnetospheric Multiscale (MMS) mission and electromagnetic hybrid simulation, this project will investigate the energy transfer mechanism (e.g., Landau interactions, bounce resonance interaction, cyclotron resonance interaction, etc.) between EMIC waves and cold-warm plasma populations. Other features such as the production of EMIC waves and the importance of cold plasma particles in EMIC wave-particle interactions will also be worth exploring. Wave particle interactions, electromagnetic hybrid simulation, electromagnetic ion cyclotron (EMIC) waves, Magnetospheric Multiscale (MMS) mission, space plasmas, inner magnetosphere

Keywords: MMS, magnetosphere, wave particle interraction, non-maxwellian distribution

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Authors: Keigo Ide, Toru Maruyama, Michihiro Ito, Hiroyuki Fujimura, Yoshikatu Nakano, Shoichiro Suda, Sachiyo Aburatani, Haruko Takeyama

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Understanding environmental system is one of the important tasks. In recent years, conservation of coral environments has been focused for biodiversity issues. The damage of coral reef under environmental impacts has been observed worldwide. However, the casual relationship between damage of coral and environmental impacts has not been clearly understood. On the other hand, structure/diversity of marine bacterial community may be relatively robust under the certain strength of environmental impact. To evaluate the coral environment conditions, it is necessary to investigate relationship between marine bacterial composition in coral reef and environmental factors. In this study, the Time Scale Network Analysis was developed and applied to analyze the marine environmental data for investigating the relationship among coral, bacterial community compositions and environmental factors. Seawater samples were collected fifteen times from November 2014 to May 2016 at two locations, Ishikawabaru and South of Sesoko in Sesoko Island, Okinawa. The physicochemical factors such as temperature, photosynthetic active radiation, dissolved oxygen, turbidity, pH, salinity, chlorophyll, dissolved organic matter and depth were measured at the coral reef area. Metagenome and metatranscriptome in seawater of coral reef were analyzed as the biological factors. Metagenome data was used to clarify marine bacterial community composition. In addition, functional gene composition was estimated from metatranscriptome. For speculating the relationships between physicochemical and biological factors, cross-correlation analysis was applied to time scale data. Even though cross-correlation coefficients usually include the time precedence information, it also included indirect interactions between the variables. To elucidate the direct regulations between both factors, partial correlation coefficients were combined with cross correlation. This analysis was performed against all parameters such as the bacterial composition, the functional gene composition and the physicochemical factors. As the results, time scale network analysis revealed the direct regulation of seawater temperature by photosynthetic active radiation. In addition, concentration of dissolved oxygen regulated the value of chlorophyll. Some reasonable regulatory relationships between environmental factors indicate some part of mechanisms in coral reef area.

Keywords: coral environment, marine microbiology, network analysis, omics data analysis

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Authors: Jonghyuk Yoon, Hyoungwoon Song, Youngbae Kim, Eunju Kim

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Recently, with the rapid growth of semiconductor industry, lots of interests have been focused on after treatment system that remove the polluted gas produced from semiconductor manufacturing process, and a wet scrubber is the one of the widely used system. When it comes to mechanism of removing the gas, the polluted gas is removed firstly by chemical reaction in a reactor part. After that, the polluted gas stream is brought into contact with the scrubbing liquid, by spraying it with the liquid. Effective design of the reactor part inside the wet scrubber is highly important since removal performance of the polluted gas in the reactor plays an important role in overall performance and stability. In the present study, a CFD (Computational Fluid Dynamics) analysis was performed to figure out the thermal and flow characteristics inside unit a reactor of wet scrubber. In order to verify the numerical result, temperature distribution of the numerical result at various monitoring points was compared to the experimental result. The average error rates (12~15%) between them was shown and the numerical result of temperature distribution was in good agreement with the experimental data. By using validated numerical method, the effect of the reactor geometry on heat transfer rate was also taken into consideration. Uniformity of temperature distribution was improved about 15%. Overall, the result of present study could be useful information to identify the fluid behavior and thermal performance for various scrubber systems. This project is supported by the ‘R&D Center for the reduction of Non-CO₂ Greenhouse gases (RE201706054)’ funded by the Korea Ministry of Environment (MOE) as the Global Top Environment R&D Program.

Keywords: semiconductor, polluted gas, CFD (Computational Fluid Dynamics), wet scrubber, reactor

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Authors: Veerle Van Hoeck, Ingrid Somers, Dany Morisset

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Anti-nutritional factors such as non-starch polysaccharides (NSP) are present in viscous cereals used to feed poultry. Therefore, exogenous carbohydrases are commonly added to monogastric feed to degrade these NSP. Our hypothesis is that xylanase not only improves laying hen performance and digestibility but also induces a significant shift in microbial composition within the intestinal tract and, thereby, can cause a prebiotic effect. In this context, a better understanding of whether and how the chicken gut flora can be modulated by xylanase is needed. To do so, in the herein laying hen study, the effects of dietary supplementation of xylanase on performance, digestibility, and cecal microbiome were evaluated. A total of 96 HiSex laying hens was used in this experiment (3 diets and 16 replicates of 2 hens). Xylanase was added to the diets at concentrations of 0, 45,000 (15 g/t XygestTM HT) and 90,000 U/kg (30 g/t Xygest HT). The diets were based on wheat (~55 %), soybean, and sunflower meal. The lowest dosage, 45,000 U/kg, significantly increased average egg weight and improved feed efficiency compared to the control treatment (p < 0.05). Egg quality parameters were significantly improved in the experiment in response to the xylanase addition. For example, during the last 28 days of the trial, the 45,000 U/kg and the 90,000 U/kg treatments exhibited an increase in Haugh units and albumin heights (p < 0.05). Compared with the control, organic matter digestibility and N retention were drastically improved in the 45,000 U/kg treatment group, which implies better nutrient digestibility at this lowest recommended dosage compared to the control (p < 0.05). Furthermore, gross energy and crude fat digestibility were improved significantly for birds fed 90,000 U/kg group compared to the control. Importantly, 16S rRNA gene analysis revealed that xylanase at 45,000 U/kg dosages can exert a prebiotic effect. This conclusion was drawn based on studying the sequence variation in the 16S rRNA gene in order to characterize diverse microbial communities of the cecal content. A significant increase in beneficial bacteria (Lactobacilli spp and Enterococcus casseliflavus) was documented when adding 45,000 U/kg xylanase to the diet of laying hens. In conclusion, dietary supplementation of xylanase, even at the lowest dose of (45,000 U/kg), significantly improved laying hen performance and digestibility. Furthermore, it is generally accepted that a proper bacterial balance between the number of beneficial bacteria and pathogenic bacteria in the intestine is vital for the host. It seems that the xylanase enzyme is able to modulate the laying hen microbiome beneficially and thus exerts a prebiotic effect. This microbiome plasticity in response to the xylanase provides an attractive target for stimulating intestinal health.

Keywords: laying hen, prebiotic, XygestTM HT, xylanase

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Authors: Katarzyna Lubecka, Kirsty Flower, Megan Beetch, Lucinda Kurzava, Hannah Buvala, Samer Gawrieh, Suthat Liangpunsakul, Tracy Gonzalez, George McCabe, Naga Chalasani, James M. Flanagan, Barbara Stefanska

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Hepatocellular carcinoma (HCC), the most prevalent type of primary liver cancer, is the second leading cause of cancer death worldwide. Late onset of clinical symptoms in HCC results in late diagnosis and poor disease outcome. Approximately 85% of individuals with HCC have underlying liver cirrhosis. However, not all cirrhotic patients develop cancer. Reliable early detection biomarkers that can distinguish cirrhotic patients who will develop cancer from those who will not are urgently needed and could increase the cure rate from 5% to 80%. We used Illumina-450K microarray to test whether blood DNA, an easily accessible source of DNA, bear site-specific changes in DNA methylation in response to HCC before diagnosis with conventional tools (pre-diagnostic). Top 11 differentially methylated sites were selected for validation by pyrosequencing. The diagnostic potential of the 11 pyrosequenced probes was tested in blood samples from a prospective cohort of cirrhotic patients. We identified 971 differentially methylated CpG sites in pre-diagnostic HCC cases as compared with healthy controls (P < 0.05, paired Wilcoxon test, ICC ≥ 0.5). Nearly 76% of differentially methylated CpG sites showed lower levels of methylation in cases vs. controls (P = 2.973E-11, Wilcoxon test). Classification of the CpG sites according to their location relative to CpG islands and transcription start site revealed that those hypomethylated loci are located in regulatory regions important for gene transcription such as CpG island shores, promoters, and 5’UTR at higher frequency than hypermethylated sites. Among 735 CpG sites hypomethylated in cases vs. controls, 482 sites were assigned to gene coding regions whereas 236 hypermethylated sites corresponded to 160 genes. Bioinformatics analysis using GO, KEGG and DAVID knowledgebase indicate that differentially methylated CpG sites are located in genes associated with functions that are essential for gene transcription, cell adhesion, cell migration, and regulation of signal transduction pathways. Taking into account the magnitude of the difference, statistical significance, location, and consistency across the majority of matched pairs case-control, we selected 11 CpG loci corresponding to 10 genes for further validation by pyrosequencing. We established that methylation of CpG sites within 5 out of those 10 genes distinguish cirrhotic patients who subsequently developed HCC from those who stayed cancer free (cirrhotic controls), demonstrating potential as biomarkers of early detection in populations at risk. The best predictive value was detected for CpGs located within BARD1 (AUC=0.70, asymptotic significance ˂0.01). Using an additive logistic regression model, we further showed that 9 CpG loci within those 5 genes, that were covered in pyrosequenced probes, constitute a panel with high diagnostic accuracy (AUC=0.887; 95% CI:0.80-0.98). The panel was able to distinguish pre-diagnostic cases from cirrhotic controls free of cancer with 88% sensitivity at 70% specificity. Using blood as a minimally invasive material and pyrosequencing as a straightforward quantitative method, the established biomarker panel has high potential to be developed into a routine clinical test after validation in larger cohorts. This study was supported by Showalter Trust, American Cancer Society (IRG#14-190-56), and Purdue Center for Cancer Research (P30 CA023168) granted to BS.

Keywords: biomarker, DNA methylation, early detection, hepatocellular carcinoma

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Authors: Sonia Bedhiaf-Romdhani

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The sheep (Ovis aries) was domesticated, approximately 11,000 years ago (YBP), in the Fertile Crescent from Asian Mouflon (Ovis Orientalis). The Northern African (NA) sheep is 7,000 years old, represents a remarkable diversity of sheep populations reared under traditional and low input farming systems (LIFS) over millennia. The majority of small ruminants in developing countries are encountered in low input production systems and the resilience of local communities in rural areas is often linked to the wellbeing of small ruminants. Regardless of the rich biodiversity encountered in sheep ecotypes there are four main sheep breeds in the country with 61,6 and 35.4 percents of Barbarine (fat tail breed) and Queue Fine de l’Ouest (thin tail breed), respectively. Phoenicians introduced the Barbarine sheep from the steppes of Central Asia in the Carthaginian period, 3000 years ago. The Queue Fine de l’Ouest is a thin-tailed meat breed heavily concentrated in the Western and the central semi-arid regions. The Noire de Thibar breed, involving mutton-fine wool producing animals, has been on the verge of extinction, it’s a composite black coated sheep breed found in the northern sub-humid region because of its higher nutritional requirements and non-tolerance of the prevailing harsher condition. The D'Man breed, originated from Morocco, is mainly located in the southern oases of the extreme arid ecosystem. A genetic investigation of Tunisian sheep breeds using a genome-wide scan of approximately 50,000 SNPs was performed. Genetic analysis of relationship between breeds highlighted the genetic differentiation of Noire de Thibar breed from the other local breeds, reflecting the effect of past events of introgression of European gene pool. The Queue Fine de l’Ouest breed showed a genetic heterogeneity and was close to Barbarine. The D'Man breed shared a considerable gene flow with the thin-tailed Queue Fine de l'Ouest breed. Native small ruminants breeds, are capable to be efficiently productive if essential ingredients and coherent breeding schemes are implemented and followed. Assessing the status of genetic variability of native sheep breeds could provide important clues for research and policy makers to devise better strategies for the conservation and management of genetic resources.

Keywords: sheep, farming systems, diversity, SNPs.

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Authors: Saeed Asiri, Yousuf Z. AL-Zahrani

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A new class of support structures, called periodic structures, is introduced in this paper as a viable means for isolating the vibration transmitted from the sea waves to offshore platform structures through its legs. A passive approach to reduce transmitted vibration generated by waves is presented. The approach utilizes the property of periodic structural components that creates stop and pass bands. The stop band regions can be tailored to correspond to regions of the frequency spectra that contain harmonics of the wave frequency, attenuating the response in those regions. A periodic structural component is comprised of a repeating array of cells, which are themselves an assembly of elements. The elements may have differing material properties as well as geometric variations. For the purpose of this research, only geometric and material variations are considered and each cell is assumed to be identical. A periodic leg is designed in order to reduce transmitted vibration of sea waves. The effectiveness of the periodicity on the vibration levels of platform will be demonstrated theoretically. The theory governing the operation of this class of periodic structures is introduced using the transfer matrix method. The unique filtering characteristics of periodic structures are demonstrated as functions of their design parameters for structures with geometrical and material discontinuities; and determine the propagation factor by using the spectral finite element analysis and the effectiveness of design on the leg structure by changing the ratio of step length and area interface between the materials is demonstrated in order to find the propagation factor and frequency response.

Keywords: vibrations, periodic structures, offshore, platforms, transfer matrix method

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Authors: Lillian Musila, Valerie Oundo, Daniel Erwin, Willie Sang

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Staphylococcus aureus infections are a major cause of nosocomial infections in Kenya. Methicillin resistant S. aureus (MRSA) infections are a significant burden to public health and are associated with considerable morbidity and mortality. At a hospital in Western Kenya two clusters of MRSA cases emerged within short periods of time. In this study we explored whether these clusters represented a nosocomial outbreak by characterizing the isolates using phenotypic and molecular assays and examining epidemiological data to identify possible transmission patterns. Specimens from the site of infection of the subjects were collected, cultured and S. aureus isolates identified phenotypically and confirmed by APIStaph™. MRSA were identified by cefoxitin disk screening per CLSI guidelines. MRSA were further characterized based on their antibiotic susceptibility patterns and spa gene typing. Characteristics of cases with MRSA isolates were compared with those with MSSA isolated around the same time period. Two cases of MRSA infection were identified in the two week period between 21 April and 4 May 2015. A further 2 MRSA isolates were identified on the same day on 7 September 2015. The antibiotic resistance patterns of the two MRSA isolates in the 1st cluster of cases were different suggesting that these were distinct isolates. One isolate had spa type t2029 and the other had a novel spa type. The 2 isolates were obtained from urine and an open skin wound. In the 2nd cluster of MRSA isolates, the antibiotic susceptibility patterns were similar but isolates had different spa types: one was t037 and the other a novel spa type different from the novel MRSA spa type in the first cluster. Both cases in the second cluster were admitted into the hospital but one infection was community- and the other hospital-acquired. Only one of the four MRSA cases was classified as an HAI from an infection acquired post-operatively. When compared to other S. aureus strains isolated within the same time period from the same hospital only one spa type t2029 was found in both MRSA and non-MRSA strains. None of the cases infected with MRSA in the two clusters shared any common epidemiological characteristic such as age, sex or known risk factors for MRSA such as prolonged hospitalization or institutionalization. These data suggest that the observed MRSA clusters were multi strain clusters and not an outbreak of a single strain. There was no clear relationship between the isolates by spa type suggesting that no transmission was occurring within the hospital between these cluster cases but rather that the majority of the MRSA strains were circulating in the community. There was high diversity of spa types among the MRSA strains with none of the isolates sharing spa types. Identification of disease clusters in space and time is critical for immediate infection control action and patient management. Spa gene typing is a rapid way of confirming or ruling out MRSA outbreaks so that costly interventions are applied only when necessary.

Keywords: cluster, Kenya, MRSA, spa typing

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Authors: Lei Zhang, Jean-Michel Ghidaglia, Anela Kumbaro

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This work focuses on numerical simulation of two-phase flows based on the bi-fluid six-equation model widely used in many industrial areas, such as nuclear power plant safety analysis. A pressure-based numerical method is adopted in our studies due to the fact that in two-phase flows, it is common to have a large range of Mach numbers because of the mixture of liquid and gas, and density-based solvers experience stiffness problems as well as a loss of accuracy when approaching the low Mach number limit. This work extends the semi-implicit pressure solver in the nuclear component CUPID code, where the governing equations are solved on unstructured grids with co-located variables to accommodate complicated geometries. A conservative version of the solver is developed in order to capture exactly the shock in one-phase flows, and is extended to two-phase situations. An inter-facial pressure term is added to the bi-fluid model to make the system hyperbolic and to establish a well-posed mathematical problem that will allow us to obtain convergent solutions with refined meshes. The ability of the numerical method to treat phase appearance and disappearance as well as the behavior of the scheme at low Mach numbers will be demonstrated through several numerical results. Finally, inter-facial mass and heat transfer models are included to deal with situations when mass and energy transfer between phases is important, and associated industrial numerical benchmarks with tabulated EOS (equations of state) for fluids are performed.

Keywords: two-phase flows, numerical simulation, bi-fluid model, unstructured grids, phase appearance and disappearance

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Authors: M. Acin-Albiac, P. Filannino, R. Coda, Carlo G. Rizzello, M. Gobbetti, R. Di Cagno

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Demand for smart management of large amounts of agro-food by-products has become an area of major environmental and economic importance worldwide. Brewers' spent grain (BSG), the most abundant by-product generated in the beer-brewing process, represents an example of valuable raw material and source of health-promoting compounds. To the date, the valorization of BSG as a food ingredient has been limited due to poor technological and sensory properties. Tailored bioprocessing through lactic acid bacteria (LAB) fermentation is a versatile and sustainable means for the exploitation of food industry by-products. Indigestible carbohydrates (e.g., hemicelluloses and celluloses), high phenolic content, and mostly lignin make of BSG a hostile environment for microbial survival. Hence, the selection of tailored starters is required for successful fermentation. Our study investigated the metabolic strategies of Leuconostoc pseudomesenteroides and Lactobacillus plantarum strains to exploit BSG as a food ingredient. Two distinctive BSG samples from different breweries (Italian IT- and Finish FL-BSG) were microbially and chemically characterized. Growth kinetics, organic acid profiles, and the evolution of phenolic profiles during the fermentation in two BSG model media were determined. The results were further complemented with gene expression targeting genes involved in the degradation cellulose, hemicelluloses building blocks, and the metabolism of anti-nutritional factors. Overall, the results were LAB genus dependent showing distinctive metabolic capabilities. Leuc. pseudomesenteroides DSM 20193 may degrade BSG xylans while sucrose metabolism could be furtherly exploited for extracellular polymeric substances (EPS) production to enhance BSG pro-technological properties. Although L. plantarum strains may follow the same metabolic strategies during BSG fermentation, the mode of action to pursue such strategies was strain-dependent. L. plantarum PU1 showed a great preference for β-galactans compared to strain WCFS1, while the preference for arabinose occurred at different metabolic phases. Phenolic compounds profiling highlighted a novel metabolic route for lignin metabolism. These findings will allow an improvement of understanding of how lactic acid bacteria transform BSG into economically valuable food ingredients.

Keywords: brewery by-product valorization, metabolism of plant phenolics, metabolism of lactic acid bacteria, gene expression

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Authors: M. Khlifa, A. Youssef, A. F. Zaed, A. Kraft, V. Arrighi

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A series of PS-nanoparticles were prepared by grafting PS from both aggregated silica and colloidally silica using atom-transfer radical polymerisation (ATRP). The mechanical behaviour of the nanocomposites have been examined by differential scanning calorimetry (DSC)and dynamic mechanical thermal analysis (DMTA).

Keywords: ATRP, nanocomposites, polystyrene, reinforcement

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Authors: Muhammad Haroon, LI Xiangju

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C. communis L. is an important weed of many crop, but very little information about the adaptation strategies of C. communis L. biotypes under drought stress. We investigated five biotypes of C. communis L under drought stress to identify the adaptation mechanism. The expression of drought stress related genes (DRS1, EREB and HRB1) was up-regulated in biotypes, while in some biotypes their expression was down regulated. All five biotypes can thus regulate water balance to consume less water to maintain their status under drought stress condition. This result concluded that C. communis L. biotypes can survive longer under drought stress condition. Weed scientist should seek more effective management strategies to deal with C. communis L.

Keywords: C. communis, biotypes, drought stress, gene expression

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Authors: Ayesha Khatun

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In 21st century where markets are unstable, technologies rapidly proliferate, competitors multiply, products and services become obsolete almost overnight and customers demand low cost high value product, leveraging and harnessing knowledge is not just a potential source of competitive advantage rather a necessity in technology based and information intensive industries. Knowledge management focuses on leveraging the available knowledge and sharing the same among the individuals in the organization so that the employees can make best use of it towards achieving the organizational goals. Knowledge is not a discrete object. It is embedded in people and so difficult to transfer outside the immediate context that it becomes a major competitive advantage. However, internal transfer of knowledge among the employees is essential to maximize the use of knowledge available in the organization in an unstructured manner. But as knowledge is the source of competitive advantage for the organization it is also the source of competitive advantage for the individuals. People think that knowledge is power and sharing the same may lead to lose the competitive position. Moreover, the very nature of tacit knowledge poses many difficulties in sharing the same. But sharing tacit knowledge is the vital part of knowledge management process because it is the tacit knowledge which is inimitable. Knowledge management has been made synonymous with the use of software and technology leading to the management of explicit knowledge only ignoring personal interaction and forming of informal networks which are considered as the most successful means of sharing tacit knowledge. Factors responsible for effective sharing of tacit knowledge are grouped into –individual, organizational and technological factors. Different factors under each category have been identified. Creating a positive organizational culture, encouraging personal interaction, practicing reward system are some of the strategies that can help to overcome many of the barriers to effective sharing of tacit knowledge. Methodology applied here is completely secondary. Extensive review of relevant literature has been undertaken for the purpose.

Keywords: knowledge, tacit knowledge, knowledge management, sustainable competitive advantage, organization, knowledge sharing

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Authors: Kanika Taneja, V. K. Soni, Kafeel Ahmad, Shamshad Ahmad

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A severe dust storm generated from a western disturbance over north Pakistan and adjoining Afghanistan affected the north-west region of India between May 28 and 31, 2014, resulting in significant reductions in air quality and visibility. The air quality of the affected region degraded drastically. PM10 concentration peaked at a very high value of around 1018 μgm-3 during dust storm hours of May 30, 2014 at New Delhi. The present study depicts aerosol optical properties monitored during the dust days using ground based multi-wavelength Sky radiometer over the National Capital Region of India. High Aerosol Optical Depth (AOD) at 500 nm was observed as 1.356 ± 0.19 at New Delhi while Angstrom exponent (Alpha) dropped to 0.287 on May 30, 2014. The variation in the Single Scattering Albedo (SSA) and real n(λ) and imaginary k(λ) parts of the refractive index indicated that the dust event influences the optical state to be more absorbing. The single scattering albedo, refractive index, volume size distribution and asymmetry parameter (ASY) values suggested that dust aerosols were predominant over the anthropogenic aerosols in the urban environment of New Delhi. The large reduction in the radiative flux at the surface level caused significant cooling at the surface. Direct Aerosol Radiative Forcing (DARF) was calculated using a radiative transfer model during the dust period. A consistent increase in surface cooling was evident, ranging from -31 Wm-2 to -82 Wm-2 and an increase in heating of the atmosphere from 15 Wm-2 to 92 Wm-2 and -2 Wm-2 to 10 Wm-2 at top of the atmosphere.

Keywords: aerosol optical properties, dust storm, radiative transfer model, sky radiometer

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Authors: V. Santamarina Campos, M. de Miguel Molina, B. de Miguel Molina, M. Á. Carabal Montagud

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With this contribution, we want to show a successful example of the application of the Design Thinking methodology, in the European project 'Technology transfer of Remotely Piloted Aircraft Systems (RPAS) for the creative industry'. The use of this methodology has allowed us to design and build a drone, based on the real needs of prospective users. It has demonstrated that this is a powerful tool for generating innovative ideas in the field of robotics, by focusing its effectiveness on understanding and solving real user needs. In this way, with the support of an interdisciplinary team, comprised of creatives, engineers and economists, together with the collaboration of prospective users from three European countries, a non-linear work dynamic has been created. This teamwork has generated a sense of appreciation towards the creative industries, through continuously adaptive, inventive, and playful collaboration and communication, which has facilitated the development of prototypes. These have been designed to enable filming and photography in interior spaces, within 13 sectors of European creative industries: Advertising, Architecture, Fashion, Film, Antiques and Museums, Music, Photography, Televison, Performing Arts, Publishing, Arts and Crafts, Design and Software. Furthermore, it has married the real needs of the creative industries, with what is technologically and commercially viable. As a result, a product of great value has been obtained, which offers new business opportunities for small companies across this sector.

Keywords: design thinking, design for effectiveness, methodology, active toolkit, storyboards, PAR, focus group, innovation, RPAS, indoor drone, aerial film, creative industry, end users, stakeholder

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Authors: Sultan Z. Mahmud, Emily C. Graff, Adil Bashir

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Phosphoprotein enriched in astrocytes 15 kDa (PEA-15) is a multifunctional adapter protein which is associated with the regulation of apoptotic cell death. Recently it has been discovered that PEA-15 is crucial in normal neurodevelopment of domestic cats, a gyrencephalic animal model, although the exact function of PEA-15 in neurodevelopment is unknown. This study investigates how PEA-15 affects the blood-brain barrier (BBB) permeability in cat brain, which can cause abnormalities in tissue metabolite and energy supplies. Severe polymicrogyria and microcephaly have been observed in cats with a loss of function PEA-15 mutation, affecting the normal neurodevelopment of the cat. This suggests that the vital role of PEA-15 in neurodevelopment is associated with gyrification. Neurodevelopment is a highly energy demanding process. The mammalian brain depends on glucose as its main energy source. PEA-15 plays a very important role in glucose uptake and utilization by interacting with phospholipase D1 (PLD1). Mitochondria also plays a critical role in bioenergetics and essential to supply adequate energy needed for neurodevelopment. Cerebral blood flow regulates adequate metabolite supply and recent findings also showed that blood plasma contains mitochondria as well. So the BBB can play a very important role in regulating metabolite and energy supply in the brain. In this study the blood-brain permeability in cat brain was measured using MRI magnetization transfer (MT) effect on the perfusion signal. Perfusion is the tissue mass normalized supply of blood to the capillary bed. Perfusion also accommodates the supply of oxygen and other metabolites to the tissue. A fraction of the arterial blood can diffuse to the tissue, which depends on the BBB permeability. This fraction is known as water extraction fraction (EF). MT is a process of saturating the macromolecules, which has an effect on the blood that has been diffused into the tissue while having minimal effect on intravascular blood water that has not been exchanged with the tissue. Measurement of perfusion signal with and without MT enables to estimate the microvascular blood flow, EF and permeability surface area product (PS) in the brain. All the experiments were performed with Siemens 7T Magnetom with 32 channel head coil. Three control cats and three PEA-15 mutant cats were used for the study. Average EF in white and gray matter was 0.9±0.1 and 0.86±0.15 respectively, perfusion in white and gray matter was 85±15 mL/100g/min and 97±20 mL/100g/min respectively, PS in white and gray matter was 201±25 mL/100g/min and 225±35 mL/100g/min respectively for control cats. For PEA-15 mutant cats, average EF in white and gray matter was 0.81±0.15 and 0.77±0.2 respectively, perfusion in white and gray matter was 140±25 mL/100g/min and 165±18 mL/100g/min respectively, PS in white and gray matter was 240±30 mL/100g/min and 259±21 mL/100g/min respectively. This results show that BBB is compromised in PEA-15 mutant cat brain, where EF is decreased and perfusion as well as PS are increased in the mutant cats compared to the control cats. This findings might further explain the function of PEA-15 in neurodevelopment.

Keywords: BBB, cat brain, magnetization transfer, PEA-15

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Authors: Haseen Siddiqui, Sanjay M. Mahajani

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Various important reactions in chemical and metallurgical industries fall in the category of gas-solid reactions. These reactions can be categorized as catalytic and non-catalytic gas-solid reactions. In gas-solid reaction systems, heat and mass transfer limitations put an appreciable influence on the rate of the reaction. The consequences can be unavoidable for overlooking such effects while collecting the reaction rate data for the design of the reactor. Pyrolysis reaction comes in this category that involves the production of gases due to the interaction of heat and solid substance. Pyrolysis is also an important step in the gasification process and therefore, the gasification reactivity majorly influenced by the pyrolysis process that produces the char, as a feed for the gasification process. Therefore, in the present study, a non-isothermal transient 1-D model is developed for a single biomass pellet to investigate the effect of heat and mass transfer limitations on the rate of pyrolysis reaction. The obtained set of partial differential equations are firstly discretized using the concept of ‘method of lines’ to obtain a set of ordinary differential equation with respect to time. These equations are solved, then, using MATLAB ode solver ode15s. The model is capable of incorporating structural changes, porosity variation, variation in various thermal properties and various pellet shapes. The model is used to analyze the effectiveness factor for different values of Lewis number and heat of reaction (G factor). Lewis number includes the effect of thermal conductivity of the solid pellet. Higher the Lewis number, the higher will be the thermal conductivity of the solid. The effectiveness factor was found to be decreasing with decreasing Lewis number due to the fact that smaller Lewis numbers retard the rate of heat transfer inside the pellet owing to a lower rate of pyrolysis reaction. G factor includes the effect of the heat of reaction. Since the pyrolysis reaction is endothermic in nature, the G factor takes negative values. The more the negative value higher will be endothermic nature of the pyrolysis reaction. The effectiveness factor was found to be decreasing with more negative values of the G factor. This behavior can be attributed to the fact that more negative value of G factor would result in more energy consumption by the reaction owing to a larger temperature gradient inside the pellet. Further, the analytical expressions are also derived for gas and solid concentrations and effectiveness factor for two limiting cases of the general model developed. The two limiting cases of the model are categorized as the homogeneous model and unreacted shrinking core model.

Keywords: effectiveness factor, G-factor, homogeneous model, lewis number, non-catalytic, shrinking core model

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Authors: Angel Champion

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Chemotherapy and radiation use an acidified approach to induce apoptosis, which only kills mature cancer cells while resulting in gene and cell damage with significant levels of toxicity in tumor-affected tissues and organs. The acid approach, where the cells exterminated are not differentiated, induces the disappearance of white blood cells from the blood. This increases susceptibility to infection in severe forms of cancer spread. However, chemotherapy and radiation cannot kill cancer stem cells that metastasize, being the leading cause of 98% of cancer fatalities. With over 12 million new cancer cases symptomatic each year, including common malignancies such as Hepatocellular Carcinoma (HCC), this study aims to assess the bioactive constituents and phytochemical composition of Taraxacum Officinale (Dandelion). This analysis enables pharmaceutical quality and potency to be applied to studies on cancer cell proliferation and apoptosis. A phytochemical screening is carried out to identify the antioxidant components of Dandelion root, stem, and flower extract. The constituents tested for are phlorotannins, carbohydrates, glycosides, saponins, flavonoids, alkaloids, sterols, triterpenes, and anthraquinone glycosides. To conserve the existing phenolic compounds, a portion of the constituent tests will be examined with an acid, alcohol, or aqueous solvent. As a result, the qualitative and quantitative variations within the Dandelion extract that measure uniform effective potency are vital to the conformity for producing medicinal products. These medicines will be constructed with a consistent, uniform composition that physicians can use to control and effectively eradicate malignant diseases safely. Taraxacum Officinale's phytochemical composition comprises a highly-graded potency due to present bioactive contents that will essentially drive out malignant disease within the human body. Its high potency rate is powerful enough to eliminate both mature cancer cells and cancer stem cells without the cell and gene damage induced by chemotherapy and radiation. Correspondingly, the high margins of cancer mortality on a global scale are mitigated. This remarkable contribution to modern therapeutics will essentially optimize the margins of natural products and their derivatives, which account for 50% of pharmaceuticals in modern therapeutics, while preventing the adverse effects of radiation and chemotherapy drugs.

Keywords: antioxidant, apoptosis, metastasize, phytochemical, proliferation, potency

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Authors: M. Sakthivel, A. Devaki, D. Balasubramanyam, P. Kumarasamy, A. Raja, R. Anilkumar, H. Gopi

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The New Zealand White breed of rabbit is one of the most commonly used, well adapted exotic breeds in India. Earlier studies were limited only to analyze the environmental factors affecting the growth and reproductive performance. In the present study, the population of the New Zealand White rabbits in a closed herd was evaluated for its genetic structure. Data on pedigree information (n=2508) for 18 years (1995-2012) were utilized for the study. Pedigree analysis and the estimates of population genetic parameters based on gene origin probabilities were performed using the software program ENDOG (version 4.8). The analysis revealed that the mean values of generation interval, coefficients of inbreeding and equivalent inbreeding were 1.489 years, 13.233 percent and 17.585 percent, respectively. The proportion of population inbred was 100 percent. The estimated mean values of average relatedness and the individual increase in inbreeding were 22.727 and 3.004 percent, respectively. The percent increase in inbreeding over generations was 1.94, 3.06 and 3.98 estimated through maximum generations, equivalent generations, and complete generations, respectively. The number of ancestors contributing the most of 50% genes (fₐ₅₀) to the gene pool of reference population was 4 which might have led to the reduction in genetic variability and increased amount of inbreeding. The extent of genetic bottleneck assessed by calculating the effective number of founders (fₑ) and the effective number of ancestors (fₐ), as expressed by the fₑ/fₐ ratio was 1.1 which is indicative of the absence of stringent bottlenecks. Up to 5th generation, 71.29 percent pedigree was complete reflecting the well-maintained pedigree records. The maximum known generations were 15 with an average of 7.9 and the average equivalent generations traced were 5.6 indicating of a fairly good depth in pedigree. The realized effective population size was 14.93 which is very critical, and with the increasing trend of inbreeding, the situation has been assessed to be worse in future. The proportion of animals with the genetic conservation index (GCI) greater than 9 was 39.10 percent which can be used as a scale to use such animals with higher GCI to maintain balanced contribution from the founders. From the study, it was evident that the herd was completely inbred with very high inbreeding coefficient and the effective population size was critical. Recommendations were made to reduce the probability of deleterious effects of inbreeding and to improve the genetic variability in the herd. The present study can help in carrying out similar studies to meet the demand for animal protein in developing countries.

Keywords: effective population size, genetic structure, pedigree analysis, rabbit genetics

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Authors: Atsuko Okazaki, Jurg Ott

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Some genetic diseases (‘digenic traits’) are due to the interaction between two DNA variants. For example, certain forms of Retinitis Pigmentosa (a genetic form of blindness) occur in the presence of two mutant variants, one in the ROM1 gene and one in the RDS gene, while the occurrence of only one of these mutant variants leads to a completely normal phenotype. Detecting such digenic traits by genetic methods is difficult. A common approach to finding disease-causing variants is to compare 100,000s of variants between individuals with a trait (cases) and those without the trait (controls). Such genome-wide association studies (GWASs) have been very successful but hinge on genetic effects of single variants, that is, there should be a difference in allele or genotype frequencies between cases and controls at a disease-causing variant. Frequent pattern mining (FPM) methods offer an avenue at detecting digenic traits even in the absence of single-variant effects. The idea is to enumerate pairs of genotypes (genotype patterns) with each of the two genotypes originating from different variants that may be located at very different genomic positions. What is needed is for genotype patterns to be significantly more common in cases than in controls. Let Y = 2 refer to cases and Y = 1 to controls, with X denoting a specific genotype pattern. We are seeking association rules, ‘X → Y’, with high confidence, P(Y = 2|X), significantly higher than the proportion of cases, P(Y = 2) in the study. Clearly, generally available FPM methods are very suitable for detecting disease-associated genotype patterns. We use fpgrowth as the basic FPM algorithm and built a framework around it to enumerate high-frequency digenic genotype patterns and to evaluate their statistical significance by permutation analysis. Application to a published dataset on opioid dependence furnished results that could not be found with classical GWAS methodology. There were 143 cases and 153 healthy controls, each genotyped for 82 variants in eight genes of the opioid system. The aim was to find out whether any of these variants were disease-associated. The single-variant analysis did not lead to significant results. Application of our FPM implementation resulted in one significant (p < 0.01) genotype pattern with both genotypes in the pattern being heterozygous and originating from two variants on different chromosomes. This pattern occurred in 14 cases and none of the controls. Thus, the pattern seems quite specific to this form of substance abuse and is also rather predictive of disease. An algorithm called Multifactor Dimension Reduction (MDR) was developed some 20 years ago and has been in use in human genetics ever since. This and our algorithms share some similar properties, but they are also very different in other respects. The main difference seems to be that our algorithm focuses on patterns of genotypes while the main object of inference in MDR is the 3 × 3 table of genotypes at two variants.

Keywords: digenic traits, DNA variants, epistasis, statistical genetics

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Authors: Rebecca Richards Steed, James Van Derslice, Ken Smith, Richard Medina, Amanda Bakian

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Elucidating gene-environment interactions for heritable disease outcomes is an emerging area of disease research, with genetic studies informing hypotheses for environment and gene interactions underlying some of the most confounding diseases of our time, like autism spectrum disorder (ASD). Geography has thus far played a key role in identifying environmental factors contributing to disease, but its use can be broadened to include genetic and environmental factors that have a synergistic effect on disease. Through the use of family pedigrees and disease outcomes with life-course residential histories, space-time clustering of generations at critical developmental windows can provide further understanding of (1) environmental factors that contribute to disease patterns in families, (2) susceptible critical windows of development most impacted by environment, (3) and that are most likely to lead to an ASD diagnosis. This paper introduces a retrospective case-control study that utilizes pedigree data, health data, and residential life-course location points to find space-time clustering of ancestors with a grandchild/child with a clinical diagnosis of ASD. Finding space-time clusters of ancestors at critical developmental windows serves as a proxy for shared environmental exposures. The authors refer to geographic life-course exposures as geographic legacies. Identifying space-time clusters of ancestors creates a bridge for researching exposures of past generations that may impact modern-day progeny health. Results from the space-time cluster analysis show multiple clusters for the maternal and paternal pedigrees. The paternal grandparent pedigree resulted in the most space-time clustering for birth and childhood developmental windows. No statistically significant clustering was found for adolescent years. These results will be further studied to identify the specific share of space-time environmental exposures. In conclusion, this study has found significant space-time clusters of parents, and grandparents for both maternal and paternal lineage. These results will be used to identify what environmental exposures have been shared with family members at critical developmental windows of time, and additional analysis will be applied.

Keywords: family pedigree, environmental exposure, geographic legacy, medical geography, transgenerational inheritance

Procedia PDF Downloads 118