Search results for: hetero-junction solar cell
1375 Identifying Metabolic Pathways Associated with Neuroprotection Mediated by Tibolone in Human Astrocytes under an Induced Inflammatory Model
Authors: Daniel Osorio, Janneth Gonzalez, Andres Pinzon
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In this work, proteins and metabolic pathways associated with the neuroprotective response mediated by the synthetic neurosteroid tibolone under a palmitate-induced inflammatory model were identified by flux balance analysis (FBA). Three different metabolic scenarios (‘healthy’, ‘inflamed’ and ‘medicated’) were modeled over a gene expression data-driven constructed tissue-specific metabolic reconstruction of mature astrocytes. Astrocyte reconstruction was built, validated and constrained using three open source software packages (‘minval’, ‘g2f’ and ‘exp2flux’) released through the Comprehensive R Archive Network repositories during the development of this work. From our analysis, we predict that tibolone executes their neuroprotective effects through a reduction of neurotoxicity mediated by L-glutamate in astrocytes, inducing the activation several metabolic pathways with neuroprotective actions associated such as taurine metabolism, gluconeogenesis, calcium and the Peroxisome Proliferator Activated Receptor signaling pathways. Also, we found a tibolone associated increase in growth rate probably in concordance with previously reported side effects of steroid compounds in other human cell types.Keywords: astrocytes, flux balance analysis, genome scale metabolic reconstruction, inflammation, neuroprotection, tibolone
Procedia PDF Downloads 2231374 Biogenic Synthesis of ZnO Nanoparticles Using Annona muricata Plant Leaf Extract and Its Anti-Cancer Efficacy
Authors: Siva Chander Chabattula, Piyush Kumar Gupta, Debashis Chakraborty, Rama Shanker Verma
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Green nanoparticles have gotten a lot of attention because of their potential applications in tissue regeneration, bioimaging, wound healing, and cancer therapy. The physical and chemical methods to synthesize metal oxide nanoparticles have an environmental impact, necessitating the development of an environmentally friendly green strategy for nanoparticle synthesis. In this study, we used Annona muricata plant leaf extract to synthesize Zinc Oxide nanoparticles (Am-ZnO NPs), which were evaluated using UV/Visible spectroscopy, FTIR spectroscopy, X-Ray Diffraction, DLS, and Zeta potential. Nanoparticles had an optical absorbance of 355 nm and a net negative surface charge of ~ - 2.59 mV. Transmission Electron Microscope characterizes the Shape and size of the nanoparticles. The obtained Am-ZnO NPs are biocompatible and hemocompatible in nature. These nanoparticles caused an anti-cancer therapeutic effect in MIA PaCa2 and MOLT4 cancer cells by inducing oxidative stress, and a change in mitochondrial membrane potential leads to programmed cell death. Further, we observed a reduction in the size of lung cancer spheroids (act as tumor micro-environment) with doxorubicin as a positive control.Keywords: Biomaterials, nanoparticle, anticancer activity, ZnO nanoparticles
Procedia PDF Downloads 2041373 Network Based Molecular Profiling of Intracranial Ependymoma over Spinal Ependymoma
Authors: Hyeon Su Kim, Sungjin Park, Hae Ryung Chang, Hae Rim Jung, Young Zoo Ahn, Yon Hui Kim, Seungyoon Nam
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Ependymoma, one of the most common parenchymal spinal cord tumor, represents 3-6% of all CNS tumor. Especially intracranial ependymomas, which are more frequent in childhood, have a more poor prognosis and more malignant than spinal ependymomas. Although there are growing needs to understand pathogenesis, detailed molecular understanding of pathogenesis remains to be explored. A cancer cell is composed of complex signaling pathway networks, and identifying interaction between genes and/or proteins are crucial for understanding these pathways. Therefore, we explored each ependymoma in terms of differential expressed genes and signaling networks. We used Microsoft Excel™ to manipulate microarray data gathered from NCBI’s GEO Database. To analyze and visualize signaling network, we used web-based PATHOME algorithm and Cytoscape. We show HOX family and NEFL are down-regulated but SCL family is up-regulated in cerebrum and posterior fossa cancers over a spinal cancer, and JAK/STAT signaling pathway and Chemokine signaling pathway are significantly different in the both intracranial ependymoma comparing to spinal ependymoma. We are considering there may be an age-dependent mechanism under different histological pathogenesis. We annotated mutation data of each gene subsequently in order to find potential target genes.Keywords: systems biology, ependymoma, deg, network analysis
Procedia PDF Downloads 2981372 Detection of PCD-Related Transcription Factors for Improving Salt Tolerance in Plant
Authors: A. Bahieldin, A. Atef, S. Edris, N. O. Gadalla, S. M. Hassan, M. A. Al-Kordy, A. M. Ramadan, A. S. M. Al- Hajar, F. M. El-Domyati
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The idea of this work is based on a natural exciting phenomenon suggesting that suppression of genes related to the program cell death (or PCD) mechanism might help the plant cells to efficiently tolerate abiotic stresses. The scope of this work was the detection of PCD-related transcription factors (TFs) that might also be related to salt stress tolerance in plant. Two model plants, e.g., tobacco and Arabidopsis, were utilized in order to investigate this phenomenon. Occurrence of PCD was first proven by Evans blue staining and DNA laddering after tobacco leaf discs were treated with oxalic acid (OA) treatment (20 mM) for 24 h. A number of 31 TFs up regulated after 2 h and co-expressed with genes harboring PCD-related domains were detected via RNA-Seq analysis and annotation. These TFs were knocked down via virus induced gene silencing (VIGS), an RNA interference (RNAi) approach, and tested for their influence on triggering PCD machinery. Then, Arabidopsis SALK knocked out T-DNA insertion mutants in selected TFs analogs to those in tobacco were tested under salt stress (up to 250 mM NaCl) in order to detect the influence of different TFs on conferring salt tolerance in Arabidopsis. Involvement of a number of candidate abiotic-stress related TFs was investigated.Keywords: VIGS, PCD, RNA-Seq, transcription factors
Procedia PDF Downloads 2741371 Curcumin Attenuates Angiogenesis in Liver Fibrosis and Inhibits Angiogenic Properties of Hepatic Stellate Cells
Authors: Feng Zhang, Li Chen, Desong Kong, Xiaoping Zhang, Xiaojing Zhu, Yin Lu, Shizhong Zheng
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Sinusoidal pathological angiogenesis is a novel therapeutic target for liver fibrosis. We demonstrated that curcumin ameliorated fibrotic injury and sinusoidal angiogenesis in rat liver with fibrosis caused by carbon tetrachloride. Curcumin reduced the expression of angiogenic markers in fibrotic liver. Experiments in vitro showed that the viability and vascularization of rat liver sinusoidal endothelial cells (LSECs) were not impaired by curcumin. Further investigations showed that curcumin inhibited VEGF expression in hepatic stellate cells (HSCs) by disrupting PDGF-βR/ERK and mTOR pathways. HSC motility and vascularization were also suppressed by curcumin via blocking PDGF-βR/FAK/RhoA cascade. Gain- or loss-of-function analyses revealed that activation of PPARγ was required for curcumin to inhibit angiogenic properties of HSCs. We concluded that curcumin attenuated sinusoidal angiogenesis in liver fibrosis possibly by targeting HSCs via a PPARγ activation-dependent mechanism. PPARγ could be a target molecule for reducing pathological angiogenesis during liver fibrosis.Keywords: angiogenesis, hepatic stellate cell, curcumin, peroxisome proliferator-activated receptor-γ
Procedia PDF Downloads 5121370 High Density Polyethylene Biocomposites Reinforced with Hydroxyapatite Nanorods and Carbon Nanofibers for Joint Replacements
Authors: Chengzhu Liao, Jianbo Zhang, Haiou Wang, Jing Ming, Huili Li, Yanyan Li, Hua Cheng, Sie Chin Tjong
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Since Bonfield’s group’s pioneer work, there has been growing interest amongst the materials scientists, biomedical engineers and surgeons in the use of novel biomaterials for the treatment of bone defects and injuries. This study focuses on the fabrication, mechanical characterization and biocompatibility evaluation of high density polyethylene (HDPE) reinforced with hydroxyapatite nanorods (HANR) and carbon nanofibers (CNF). HANRs of 20 wt% and CNFs of 0.5-2 wt% were incorporated into HDPE to form biocomposites using traditional melt-compounding and injection molding techniques. The mechanical measurements show that CNF additions greatly improve the tensile strength and Young’s modulus of HDPE and HDPE-20% nHA composites. Meanwhile, the nHA and CNF fillers were found to be effective to improve dimensional and thermal stability of HDPE. The results of osteoblast cell cultivation and dimethyl thiazolyl diphenyl thiazolyl tetrazolium (MTT) tests showed that the HDPE/ CNF-nHA nanocomposites are biocompatible. Such HDPE/ CNF-nHA hybrids are found to be potential biomaterials for making orthopedic joint/bone replacements.Keywords: biocompatibility, biocomposite, carbon nanofiber, high density polyethylene, hydroxyapatite
Procedia PDF Downloads 3031369 Studying the Photodegradation Behavior of Microplastics Released from Agricultural Plastic Products to the Farmland
Authors: Maryam Salehi, Gholamreza Bonyadinejad
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The application of agricultural plastic products like mulch, greenhouse covers, and silage films is increasing due to their economic benefits in providing an early and better-quality harvest. In 2015, the 4 million tons (valued a 10.6 million USD) global market for agricultural plastic films was estimated to grow by 5.6% per year through 2030. Despite the short-term benefits provided by plastic products, their long-term sustainability issues and negative impacts on soil health are not well understood. After their removal from the field, some plastic residuals remain in the soil. Plastic residuals in farmlands may fragment to small particles called microplastics (d<5mm). The microplastics' exposure to solar radiation could alter their surface chemistry and make them susceptible to fragmentation. Thus, this study examined the photodegradation of low density polyethylene as the model microplastics that are released to the agriculture farmland. The variation of plastic’s surface chemistry, morphology, and bulk characteristics were studied after accelerated UV-A radiation experiments and sampling from an agricultural field. The Attenuated Total Reflectance Fourier Transform Spectroscopy (ATR-FTIR) and X-ray Photoelectron Spectroscopy (XPS) demonstrated the formation of oxidized surface functional groups onto the microplastics surface due to the photodegradation. The Differential Scanning Calorimetry (DSC) analysis revealed an increased crystallinity for the photodegraded microplastics compared to the new samples. The gel permeation chromatography (GPC) demonstrated the reduced molecular weight for the polymer due to the photodegradation. This study provides an important opportunity to advance understanding of soil pollution. Understanding the plastic residuals’ variations as they are left in the soil is providing a critical piece of information to better estimate the microplastics' impacts on environmental biodiversity, ecosystem sustainability, and food safety.Keywords: soil health, plastic pollution, sustainability, photodegradation
Procedia PDF Downloads 2201368 In-silico Analysis of Plumbagin against Cancer Receptors
Authors: Arpita Roy, Navneeta Bharadvaja
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Cancer is an uncontrolled growth of abnormal cells in the body. It is one of the most serious diseases on which extensive research work has been going on all over the world. Structure-based drug designing is a computational approach which helps in the identification of potential leads that can be used for the development of a drug. Plumbagin is a naphthoquinone derivative from Plumbago zeylanica roots and belongs to one of the largest and diverse groups of plant metabolites. Anticancer and antiproliferative activities of plumbagin have been observed in animal models as well as in cell cultures. Plumbagin shows inhibitory effects on multiple cancer-signaling proteins; however, the binding mode and the molecular interactions have not yet been elucidated for most of these protein targets. In this investigation, an attempt to provide structural insights into the binding mode of plumbagin against four cancer receptors using molecular docking was performed. Plumbagin showed minimal energy against targeted cancer receptors, therefore suggested its stability and potential towards different cancers. The least binding energies of plumbagin with COX-2, TACE, and CDK6 are -5.39, -4.93, -and 4.81 kcal/mol, respectively. Comparison studies of plumbagin with different receptors showed that it is a promising compound for cancer treatment. It was also found that plumbagin obeys the Lipinski’s Rule of 5 and computed ADMET properties which showed drug likeliness and improved bioavailability. Since plumbagin is from a natural source, it has reduced side effects, and these results would be useful for cancer treatment.Keywords: cancer, receptor, plumbagin, docking
Procedia PDF Downloads 1431367 Optimal Design of a PV/Diesel Hybrid System for Decentralized Areas through Economic Criteria
Authors: David B. Tsuanyo, Didier Aussel, Yao Azoumah, Pierre Neveu
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An innovative concept called “Flexy-Energy”is developing at 2iE. This concept aims to produce electricity at lower cost by smartly mix different available energies sources in accordance to the load profile of the region. With a higher solar irradiation and due to the fact that Diesel generator are massively used in sub-Saharan rural areas, PV/Diesel hybrid systems could be a good application of this concept and a good solution to electrify this region, provided they are reliable, cost effective and economically attractive to investors. Presentation of the developed approach is the aims of this paper. The PV/Diesel hybrid system designed consists to produce electricity and/or heat from a coupling between Diesel gensets and PV panels without batteries storage, while ensuring the substitution of gasoil by bio-fuels available in the area where the system will be installed. The optimal design of this system is based on his technical performances; the Life Cycle Cost (LCC) and Levelized Cost of Energy are developed and use as economic criteria. The Net Present Value (NPV), the internal rate of return (IRR) and the discounted payback (DPB) are also evaluated according to dual electricity pricing (in sunny and unsunny hours). The PV/Diesel hybrid system obtained is compared to the standalone Diesel gensets. The approach carried out in this paper has been applied to Siby village in Mali (Latitude 12 ° 23'N 8 ° 20'W) with 295 kWh as daily demand. This approach provides optimal physical characteristics (size of the components, number of component) and dynamical characteristics in real time (number of Diesel generator on, their load rate, fuel specific consumptions, and PV penetration rate) of the system. The system obtained is slightly cost effective; but could be improved with optimized tariffing strategies.Keywords: investments criteria, optimization, PV hybrid, sizing, rural electrification
Procedia PDF Downloads 4411366 Autophagy Suppresses Tumorigenesis through Upregulation of MiR-449a in Colorectal Cancer
Authors: Sheng-Hui Lan, Shan-Ying Wu, Shu-Ching Lin, Wei-Chen Wang, Hsiao-Sheng Liu
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Autophagy is an essential mechanism to maintain cellular homeostasis through its degradation function, and the autophagy deficiency is related various diseases including tumorigenesis in several cancers. MicroRNAs (miRNAs) are small none coding RNAs, which regulate gene expression through degradation of mRNA or inhibition of translation. However, the relationship between autophagy deficiency and dysregulated miRNAs is still unclear. We revealed a mechanism that autophagy up-regulates miR-449a expression at the transcriptional level through activation of forkhead transcription factor family member FoxO1 and then suppresses tumorigenesis in CRC. Our data showed that the autophagic activity and miR-449a expression were lower in colorectal cancer (CRC) and has a positive correlation. We further reveal that autophagy degrades p300 expression and then suppresses acetylation of FoxO1. Under autophagic induction conditions, FoxO1 is transported from the cytoplasm to the nucleus and binds to the miR-449a promoter and then promotes miR-449a expression. In addition, either miR-449a overexpression or amiodarone-induced autophagy inhibits cell cycle progression, proliferation, colony formation migration, invasion, and tumor formation of SW480 cells. Our findings indicate that autophagy inducers may have the potential to be used for prevention and treatment of CRC through upregulation of miR-449a expression.Keywords: autophagy, MiR-449a, FoxO1, colorectal cancer
Procedia PDF Downloads 3201365 Analysis and Modeling of the Building’s Facades in Terms of Different Convection Coefficients
Authors: Enes Yasa, Guven Fidan
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Building Simulation tools need to better evaluate convective heat exchanges between external air and wall surfaces. Previous analysis demonstrated the significant effects of convective heat transfer coefficient values on the room energy balance. Some authors have pointed out that large discrepancies observed between widely used building thermal models can be attributed to the different correlations used to calculate or impose the value of the convective heat transfer coefficients. Moreover, numerous researchers have made sensitivity calculations and proved that the choice of Convective Heat Transfer Coefficient values can lead to differences from 20% to 40% of energy demands. The thermal losses to the ambient from a building surface or a roof mounted solar collector represent an important portion of the overall energy balance and depend heavily on the wind induced convection. In an effort to help designers make better use of the available correlations in the literature for the external convection coefficients due to the wind, a critical discussion and a suitable tabulation is presented, on the basis of algebraic form of the coefficients and their dependence upon characteristic length and wind direction, in addition to wind speed. Many research works have been conducted since early eighties focused on the convection heat transfer problems inside buildings. In this context, a Computational Fluid Dynamics (CFD) program has been used to predict external convective heat transfer coefficients at external building surfaces. For the building facades model, effects of wind speed and temperature differences between the surfaces and the external air have been analyzed, showing different heat transfer conditions and coefficients. In order to provide further information on external convective heat transfer coefficients, a numerical work is presented in this paper, using a Computational Fluid Dynamics (CFD) commercial package (CFX) to predict convective heat transfer coefficients at external building surface.Keywords: CFD in buildings, external convective heat transfer coefficients, building facades, thermal modelling
Procedia PDF Downloads 4211364 The Effect of Iron Deficiency on the Magnetic Properties of Ca₀.₅La₀.₅Fe₁₂₋yO₁₉₋δ M-Type Hexaferrites
Authors: Kang-Hyuk Lee, Wei Yan, Sang-Im Yoo
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Recently, Ca₁₋ₓLaₓFe₁₂O₁₉ (Ca-La M-type) hexaferrites have been reported to possess higher crystalline anisotropy compared with SrFe₁₂O₁₉ (Sr M-type) hexaferrite without reducing its saturation magnetization (Ms), resulting in higher coercivity (Hc). While iron deficiency is known to be helpful for the growth and the formation of NiZn spinel ferrites, the effect of iron deficiency in Ca-La M-type hexaferrites has never been reported yet. In this study, therefore, we tried to investigate the effect of iron deficiency on the magnetic properties of Ca₀.₅La₀.₅Fe₁₂₋yO₁₉₋δ hexaferrites prepared by solid state reaction. As-calcined powder was pressed into pellets and sintered at 1275~1325℃ for 4 h in air. Samples were characterized by powder X-ray diffraction (XRD), vibrating sample magnetometer (VSM), and scanning electron microscope (SEM). Powder XRD analyses revealed that Ca₀.₅La₀.₅Fe₁₂₋yO₁₉₋δ (0.75 ≦ y ≦ 2.15) ferrites calcined at 1250-1300℃ for 12 h in air were composed of single phase without the second phases. With increasing the iron deficiency, y, the lattice parameters a, c and unite cell volumes were decreased first up to y=10.25 and then increased again. The highest Ms value of 77.5 emu/g was obtainable from the sample of Ca₀.₅La₀.₅Fe₁₂₋yO₁₉₋δ sintered at 1300℃ for 4 h in air. Detailed microstructures and magnetic properties of Ca-La M-type hexagonal ferrites will be presented for a discussionKeywords: Ca-La M-type hexaferrite, magnetic properties, iron deficiency, hexaferrite
Procedia PDF Downloads 4601363 Selection of Green Fluorescent Protein and mCherry Nanobodies Using the Yeast Surface Display Method
Authors: Lavinia Ruta, Ileana Farcasanu
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The yeast surface display (YSD) technique enables the expression of proteins on yeast cell surfaces, facilitating the identification and isolation of proteins with targeted binding properties, such as nanobodies. Nanobodies, derived from camelid species, are single-domain antibody fragments renowned for their high affinity and specificity towards target proteins, making them valuable in research and potentially in therapeutics. Their advantages include a compact size (~15 kDa), robust stability, and the ability to target challenging epitopes. The project endeavors to establish and validate a platform for producing Green Fluorescent Protein (GFP) and mCherry nanobodies using the yeast surface display method. mCherry, a prevalent red fluorescent protein sourced from coral species, is commonly utilized as a genetic marker in biological studies due to its vibrant red fluorescence. The GFP-nanobody, a single variable domain of heavy-chain antibodies (VHH), exhibits specific binding to GFP, offering a potent means for isolating and engineering fluorescent protein fusions across various biological research domains. Both GFP and mCherry nanobodies find specific utility in cellular imaging and protein analysis applications.Keywords: YSD, nanobodies, GFP, Saccharomyces cerevisiae
Procedia PDF Downloads 611362 A Review on the Mechanism Removal of Pesticides and Heavy Metal from Agricultural Runoff in Treatment Train
Authors: N. A. Ahmad Zubairi, H. Takaijudin, K. W. Yusof
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Pesticides have been used widely over the world in agriculture to protect from pests and reduce crop losses. However, it affects the environment with toxic chemicals. Exceed of toxic constituents in the ecosystem will result in bad side effects. The hydrological cycle is related to the existence of pesticides and heavy metal which it can penetrate through varieties of sources into the soil or water bodies, especially runoff. Therefore, proper mechanisms of pesticide and heavy metal removal should be studied to improve the quality of ecosystem free or reduce from unwanted substances. This paper reviews the use of treatment train and its mechanisms to minimize pesticides and heavy metal from agricultural runoff. Organochlorine (OCL) is a common pesticide that was found in the agricultural runoff. OCL is one of the toxic chemicals that can disturb the ecosystem such as inhibiting plants' growth and harm human health by having symptoms as asthma, active cancer cell, vomit, diarrhea, etc. Thus, this unwanted contaminant gives disadvantages to the environment and needs treatment system. Hence, treatment train by bioretention system is suitable because removal efficiency achieves until 90% of pesticide removal with selected vegetated plant and additive.Keywords: pesticides, heavy metal, agricultural runoff, bioretention, mechanism removal, treatment train
Procedia PDF Downloads 1581361 Conductometric Methanol Microsensor Based on Electrospun PVC-Nickel Phthalocyanine Composite Nanofiber Technology
Authors: Ibrahim Musa, Guy Raffin, Marie Hangouet, Nadia Zine, Nicole Jaffrezic-Renault, Abdelhamid Errachid
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Due to its application in different domains, such as fuel cell configuration and adulteration of alcoholic beverages, a miniaturized sensor for methanol detection is urgently required. A conductometric microsensor for measuring volatile organic compounds (VOC) was conceived, based on electrospun composite nanofibers of polyvinyl chloride (PVC) doped with nickel phthalocyanine(NiPc) deposited on interdigitated electrodes (IDEs) used transducers. The nanofiber's shape, structure, percent atomic content and thermal properties were studied using analytical techniques, including scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), and thermogravimetric analysis (TGA), respectively. The methanol sensor showed good sensitivity (505µS/cm(v/v) ⁻¹), low LOD (15 ppm), short response time (13 s), and short recovery time (15 s). The sensor was 4 times more sensitive to methanol than to ethanol and 19 times more sensitive to methanol than to acetone. Furthermore, the sensor response was unaffected by the interfering water vapor, making it more suitable for VOC sensing in the presence of humidity. The sensor was applied for conductometric detection of methanol in rubbing alcohol.Keywords: composite, methanol, conductometric sensor, electrospun, nanofiber, nickel phthalocyanine, PVC
Procedia PDF Downloads 221360 Analysis of the Factors of Local Acceptance of Wind Power Generation Facilities
Authors: Hyunjoo Park, Taehyun Kim, Taehyun Kim
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The government that declared 'de-nuclearization' pushes up renewable energy policies such as solar power and wind power as an alternative to nuclear power generation. However, local residents who are concerned about the development and natural disasters have been hit by opposition, and related businesses around the country are experiencing difficulties. There is also a voice saying that installing a large wind power generator will cause landslides, low frequencies and noise, which will have a bad influence. Renewal is only a harmful and disgusting facility for the residents. In this way, it is expected that extreme social conflicts will occur in the decision making process related to the locally unwanted land-use (LULU). The government's efforts to solve this problem have been steadily progressing, but the systematic methodology for bringing in active participation and opinion gathering of the residents has not yet been established except for the simple opinion poll or referendum. Therefore, it is time to identify the factors that concern the local residents about the wind power generation facilities, and to find ways to make policy decision-making possible. In this study, we analyze the perception of people about offshore and onshore wind power facilities through questionnaires or interviews, and examine quantitative and qualitative precedent studies to analyze them. In addition, the study evaluates what factors affect the local acceptance of wind power facilities. As a result of the factor analysis of the questionnaire items, factors affecting the residents' acceptance of the wind power facility were extracted from four factors such as environmental, economic, risk, social, and management factor. The study also found that the influence of the determinants of local acceptance on the regional acceptability differs according to the demographic characteristics such as gender and income level. This study will contribute to minimizing the conflict on the installation of wind power facilities through communication among the local residents.Keywords: factor analysis, local acceptance, locally unwanted land-use, LULU, wind power generation facilities
Procedia PDF Downloads 1561359 Lipoic Acid Accelerates Wound Healing by Diminishing Pro-Inflammatory Markers and Chemokine Expression in Rheumatoid Arthritis Mouse Model
Authors: Khairy M. A. Zoheir
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One of the most severe complications of Rheumatoid arthritis is delayed recovery. lipoic acid possesses antioxidant, hypoglycemic, and anti-inflammatory activity. In the present study, the effects of lipoic acid was investigated on the key mediators of Rheumatoid arthritis, namely, CD4+CD25+ T cell subsets, GITR expressing cells, CD4+CD25+Foxp3+ regulatory T (Treg) cells, T-helper-17 (Th17) cells, and pro-inflammatory cytokines Interleukin-1β (IL-1β), Interleukin-6 (IL-6) and Tumor Necrosis Factor- α (TNF-α)] through flow-cytometry and qPCR analyses. Lipoic acid treated mice showed a significant decrease in the Rheumatoid arthritis, the frequency of GITR-expressing cells, and Th1 cytokines (IL-17A, TNF-αand Interferon- γ (IFN-γ) compared with positive and negative controlled mice. Lipoic acid treatment also down regulated the mRNA expression of the inflammatory mediators compared with the Rheumatoid arthritis mouse model and untreated mice. The number of Tregs also found to be significantly upregulated in lipoic acid treated mice. Our results were confirmed by the histopathological examination. This study showed the beneficial role of lipoic acid in promoting a well-balanced tool for therapy Rheumatoid arthritis.Keywords: lipoic acid, chemokines, inflammatory, rheumatoid arthritis
Procedia PDF Downloads 1741358 A Parallel Cellular Automaton Model of Tumor Growth for Multicore and GPU Programming
Authors: Manuel I. Capel, Antonio Tomeu, Alberto Salguero
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Tumor growth from a transformed cancer-cell up to a clinically apparent mass spans through a range of spatial and temporal magnitudes. Through computer simulations, Cellular Automata (CA) can accurately describe the complexity of the development of tumors. Tumor development prognosis can now be made -without making patients undergo through annoying medical examinations or painful invasive procedures- if we develop appropriate CA-based software tools. In silico testing mainly refers to Computational Biology research studies of application to clinical actions in Medicine. To establish sound computer-based models of cellular behavior, certainly reduces costs and saves precious time with respect to carrying out experiments in vitro at labs or in vivo with living cells and organisms. These aim to produce scientifically relevant results compared to traditional in vitro testing, which is slow, expensive, and does not generally have acceptable reproducibility under the same conditions. For speeding up computer simulations of cellular models, specific literature shows recent proposals based on the CA approach that include advanced techniques, such the clever use of supporting efficient data structures when modeling with deterministic stochastic cellular automata. Multiparadigm and multiscale simulation of tumor dynamics is just beginning to be developed by the concerned research community. The use of stochastic cellular automata (SCA), whose parallel programming implementations are open to yield a high computational performance, are of much interest to be explored up to their computational limits. There have been some approaches based on optimizations to advance in multiparadigm models of tumor growth, which mainly pursuit to improve performance of these models through efficient memory accesses guarantee, or considering the dynamic evolution of the memory space (grids, trees,…) that holds crucial data in simulations. In our opinion, the different optimizations mentioned above are not decisive enough to achieve the high performance computing power that cell-behavior simulation programs actually need. The possibility of using multicore and GPU parallelism as a promising multiplatform and framework to develop new programming techniques to speed-up the computation time of simulations is just starting to be explored in the few last years. This paper presents a model that incorporates parallel processing, identifying the synchronization necessary for speeding up tumor growth simulations implemented in Java and C++ programming environments. The speed up improvement that specific parallel syntactic constructs, such as executors (thread pools) in Java, are studied. The new tumor growth parallel model is proved using implementations with Java and C++ languages on two different platforms: chipset Intel core i-X and a HPC cluster of processors at our university. The parallelization of Polesczuk and Enderling model (normally used by researchers in mathematical oncology) proposed here is analyzed with respect to performance gain. We intend to apply the model and overall parallelization technique presented here to solid tumors of specific affiliation such as prostate, breast, or colon. Our final objective is to set up a multiparadigm model capable of modelling angiogenesis, or the growth inhibition induced by chemotaxis, as well as the effect of therapies based on the presence of cytotoxic/cytostatic drugs.Keywords: cellular automaton, tumor growth model, simulation, multicore and manycore programming, parallel programming, high performance computing, speed up
Procedia PDF Downloads 2441357 Impact of Simulated Brain Interstitial Fluid Flow on the Chemokine CXC-Chemokine-Ligand-12 Release From an Alginate-Based Hydrogel
Authors: Wiam El Kheir, Anais Dumais, Maude Beaudoin, Bernard Marcos, Nick Virgilio, Benoit Paquette, Nathalie Faucheux, Marc-Antoine Lauzon
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The high infiltrative pattern of glioblastoma multiforme cells (GBM) is the main cause responsible for the actual standard treatments failure. The tumor high heterogeneity, the interstitial fluid flow (IFF) and chemokines guides GBM cells migration in the brain parenchyma resulting in tumor recurrence. Drug delivery systems emerged as an alternative approach to develop effective treatments for the disease. Some recent studies have proposed to harness the effect CXC-lchemokine-ligand-12 to direct and control the cancer cell migration through delivery system. However, the dynamics of the brain environment on the delivery system remains poorly understood. Nanoparticles (NPs) and hydrogels are known as good carriers for the encapsulation of different agents and control their release. We studied the release of CXCL12 (free or loaded into NPs) from an alginate-based hydrogel under static and indirect perfusion (IP) conditions. Under static conditions, the main phenomena driving CXCL12 release from the hydrogel was diffusion with the presence of strong interactions between the positively charged CXCL12 and the negatively charge alginate. CXCL12 release profiles were independent from the initial mass loadings. Afterwards, we demonstrated that the release could tuned by loading CXCL12 into Alginate/Chitosan-Nanoparticles (Alg/Chit-NPs) and embedded them into alginate-hydrogel. The initial burst release was substantially attenuated and the overall cumulative release percentages of 21%, 16% and 7% were observed for initial mass loadings of 0.07, 0.13 and 0.26 µg, respectively, suggesting stronger electrostatic interactions. Results were mathematically modeled based on Fick’s second law of diffusion framework developed previously to estimate the effective diffusion coefficient (Deff) and the mass transfer coefficient. Embedding the CXCL12 into NPs decreased the Deff an order of magnitude, which was coherent with experimental data. Thereafter, we developed an in-vitro 3D model that takes into consideration the convective contribution of the brain IFF to study CXCL12 release in an in-vitro microenvironment that mimics as faithfully as possible the human brain. From is unique design, the model also allowed us to understand the effect of IP on CXCL12 release in respect to time and space. Four flow rates (0.5, 3, 6.5 and 10 µL/min) which may increase CXCL12 release in-vivo depending on the tumor location were assessed. Under IP, cumulative percentages varying between 4.5-7.3%, 23-58.5%, 77.8-92.5% and 89.2-95.9% were released for the three initial mass loadings of 0.08, 0.16 and 0.33 µg, respectively. As the flow rate increase, IP culture conditions resulted in a higher release of CXCL12 compared to static conditions as the convection contribution became the main driving mass transport phenomena. Further, depending on the flow rate, IP had a direct impact on CXCL12 distribution within the simulated brain tissue, which illustrates the importance of developing such 3D in-vitro models to assess the efficiency of a delivery system targeting the brain. In future work, using this very model, we aim to understand the impact of the different phenomenon occurring on GBM cell behaviors in response to the resulting chemokine gradient subjected to various flow while allowing them to express their invasive characteristics in an in-vitro microenvironment that mimics the in-vivo brain parenchyma.Keywords: 3D culture system, chemokines gradient, glioblastoma multiforme, kinetic release, mathematical modeling
Procedia PDF Downloads 841356 pH and Thermo-Sensitive Nanogels for Anti-Cancer Therapy
Authors: V. Naga Sravan Kumar Varma, H. G. Shivakumar
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The aim of the study was to develop dual sensitive poly (N-isopropylacrylamide-co-acrylic acid) (PNA) nanogels(NGs) and studying its applications for Anti-Cancer therapy. NGs were fabricated by free radical polymerization using different amount of N-isopropylacrylamide and acrylic acid. A study for polymer composition over the effect on LCST in different pH was evaluated by measuring the absorbance at 500nm using UV spectrophotometer. Further selected NG’s were evaluated for change in hydrodynamic diameters in response to pH and temperature. NGs which could sharply respond to low pH value of cancer cells at body temperature were loaded with Fluorouracil (5-FU) using equilibrium swelling method and studied for drug release behaviour in different pH. A significant influence of NGs polymer composition over pH dependent LCST was observed. NGs which were spherical with an average particle size of 268nm at room temperature, shrinked forming an irregular shape when heated above to their respective LCST. 5FU loaded NGs did not intervene any difference in pH depended LCST behaviour of NGs. The in vitro drug release of NGs exhibited a pH and thermo-dependent control release. The cytoxicity study of blank carrier to MCF7 cell line showed no cytotoxicity. The results indicated that PNA NGs could be used as a potential drug carrier for anti-cancer therapy.Keywords: pH and thermo-sensitive, nanogels, P(NIPAM-co-AAc), anti-cancer, 5-FU
Procedia PDF Downloads 3501355 Thymoquinone Prevented the Development of Symptoms in Animal Model of Parkinson’s Disease
Authors: Kambiz Hassanzadeh, Seyedeh Shohreh Ebrahimi, Shahrbanoo Oryan, Arman Rahimmi, Esmael Izadpanah
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Parkinson’s disease is one of the most prevalent neurodegenerative diseases which occurs in elderly. There are convincing evidences that oxidative stress has an important role in both the initiation and progression of Parkinson’s disease. Thymoquinone (TQ) is shown to have antioxidant and anti-inflammatory properties in invitro and invivo studies. It is well documented that TQ acts as a free radical scavenger and prevents the cell damage. Therefore this study aimed to evaluate the effect of TQ on motor and non-motor symptoms in animal model of Parkinson’s disease. Male Wistar rats (10-12 months) received rotenone (1mg/kg/day, sc) to induce Parkinson’s disease model. Pretreatment with TQ (7.5 and 15 mg/kg/day, po) was administered one hour before the rotenone injection. Three motor tests (rotarod, rearing and bar tests) and two non-motor tests (forced swimming and elevated plus maze) were performed for behavioral assessment. Our results indicated that TQ significantly ameliorated the rotenone-induced motor dysfunction in rotarod and rearing tests also it could prevent the non-motor dysfunctions in forced swimming and elevated plus maze tests. In conclusion we found that TQ delayed the Parkinson's disease induction by rotenone and this effect might be related to its proved antioxidant effect.Keywords: Parkinson's disease, thymoquinone, motor and non-motor symptoms, neurodegenerative disease
Procedia PDF Downloads 5471354 Rock-Bed Thermocline Storage: A Numerical Analysis of Granular Bed Behavior and Interaction with Storage Tank
Authors: Nahia H. Sassine, Frédéric-Victor Donzé, Arnaud Bruch, Barthélemy Harthong
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Thermal Energy Storage (TES) systems are central elements of various types of power plants operated using renewable energy sources. Packed bed TES can be considered as a cost–effective solution in concentrated solar power plants (CSP). Such a device is made up of a tank filled with a granular bed through which heat-transfer fluid circulates. However, in such devices, the tank might be subjected to catastrophic failure induced by a mechanical phenomenon known as thermal ratcheting. Thermal stresses are accumulated during cycles of loading and unloading until the failure happens. For instance, when rocks are used as storage material, the tank wall expands more than the solid medium during charge process, a gap is created between the rocks and tank walls and the filler material settles down to fill it. During discharge, the tank contracts against the bed, resulting in thermal stresses that may exceed the wall tank yield stress and generate plastic deformation. This phenomenon is repeated over the cycles and the tank will be slowly ratcheted outward until it fails. This paper aims at studying the evolution of tank wall stresses over granular bed thermal cycles, taking into account both thermal and mechanical loads, with a numerical model based on the discrete element method (DEM). Simulations were performed to study two different thermal configurations: (i) the tank is heated homogeneously along its height or (ii) with a vertical gradient of temperature. Then, the resulting loading stresses applied on the tank are compared as well the response of the internal granular material. Besides the study of the influence of different thermal configurations on the storage tank response, other parameters are varied, such as the internal angle of friction of the granular material, the dispersion of particles diameters as well as the tank’s dimensions. Then, their influences on the kinematics of the granular bed submitted to thermal cycles are highlighted.Keywords: discrete element method (DEM), thermal cycles, thermal energy storage, thermocline
Procedia PDF Downloads 4021353 Numerical Analysis of Real-Scale Polymer Electrolyte Fuel Cells with Cathode Metal Foam Design
Authors: Jaeseung Lee, Muhammad Faizan Chinannai, Mohamed Hassan Gundu, Hyunchul Ju
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In this paper, we numerically investigated the effect of metal foams on a real scale 242.57cm2 (19.1 cm × 12.7 cm) polymer electrolyte membrane fuel cell (PEFCs) using a three-dimensional two-phase PEFC model to substantiate design approach for PEFCs using metal foam as the flow distributor. The simulations were conducted under the practical low humidity hydrogen, and air gases conditions in order to observe the detailed operation result in the PEFCs using the serpentine flow channel in the anode and metal foam design in the cathode. The three-dimensional contours of flow distribution in the channel, current density distribution in the membrane and hydrogen and oxygen concentration distribution are provided. The simulation results revealed that the use of highly porous and permeable metal foam can be beneficial to achieve a more uniform current density distribution and better hydration in the membrane under low inlet humidity conditions. This study offers basic directions to design channel for optimal water management of PEFCs.Keywords: polymer electrolyte fuel cells, metal foam, real-scale, numerical model
Procedia PDF Downloads 2391352 A Furaneol-Containing Glass-Ionomer Cement for Enhanced Antibacterial Activity
Authors: Dong Xie, Yuling Xu, Leah Howard
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Secondary caries is found to be one of the main reasons to the restoration failure of dental restoratives. To prevent secondary caries formation, dental restoratives ought to be made antibacterial. In this study, a natural fruit component furaneol was tethered onto polyacid, the formed polyacid was used to formulate the light-curable glass-ionomer cements, and then the effect of this new antibacterial compound on compressive strength (CS) and antibacterial activity of the formed cement was evaluated. Fuji II LC glass powders were used as fillers. Compressive strength (CS) and S. mutans viability were used to evaluate the mechanical strength and antibacterial activity of the formed cement. The experimental cement showed a significant antibacterial activity, accompanying with an initial CS reduction. Increasing the compound loading significantly decreased the S. mutans viability from 5 to 81% and also reduced the initial CS of the formed cements from 4 to 58%. The cement loading with 7% antibacterial polymer showed 168 MPa, 7.8 GPa, 243 MPa, 46 MPa, and 57 MPa in yield strength, modulus, CS, diametral tensile strength and flexural strength, respectively, as compared to 141, 6.9, 236, 42 and 53 for Fuji II LC. The cement also showed an antibacterial function to other bacteria. No human saliva effect was noticed. It is concluded that the experimental cement may potentially be developed to a permanent antibacterial cement.Keywords: antibacterial, dental materials, strength, cell viability
Procedia PDF Downloads 3171351 Meticulous Doxorubicin Release from pH-Responsive Nanoparticles Entrapped within an Injectable Thermoresponsive Depot
Authors: Huayang Yu, Nicola Ingram, David C. Green, Paul D. Thornton
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The dual stimuli-controlled release of doxorubicin from gel-embedded nanoparticles is reported. Non-cytotoxic polymer nanoparticles are formed from poly(ethylene glycol)-b-poly(benzyl glutamate) that, uniquely, contain a central ester link. This connection renders the nanoparticles pH-responsive, enabling extensive doxorubicin release in acidic solutions (pH 6.5), but not in solutions of physiological pH (pH 7.4). Doxorubicin loaded nanoparticles were found to be stable for at least 31 days and lethal against the three breast cancer cell lines tested. Furthermore, doxorubicin-loaded nanoparticles could be incorporated within a thermoresponsive poly(2-hydroxypropyl methacrylate) gel depot, which forms immediately upon injection of poly(2-hydroxypropyl methacrylate) into aqueous solution. The combination of the poly(2-hydroxypropyl methacrylate) gel and poly(ethylene glycol)-b-poly(benzyl glutamate) nanoparticles yields an injectable doxorubicin delivery system that facilities near-complete drug release when maintained at elevated temperatures (37 °C) in acidic solution (pH 6.5). In contrast, negligible payload release occurs when the material is stored at room temperature in a non-acidic solution (pH 7.4). The system has great potential as a vehicle for the prolonged, site-specific release of chemotherapeutics.Keywords: biodegradable, nanoparticle, polymer, thermoresponsive
Procedia PDF Downloads 1361350 Effect of Loop Diameter, Height and Insulation on a High Temperature CO2 Based Natural Circulation Loop
Authors: S. Sadhu, M. Ramgopal, S. Bhattacharyya
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Natural circulation loops (NCLs) are buoyancy driven flow systems without any moving components. NCLs have vast applications in geothermal, solar and nuclear power industry where reliability and safety are of foremost concern. Due to certain favorable thermophysical properties, especially near supercritical regions, carbon dioxide can be considered as an ideal loop fluid in many applications. In the present work, a high temperature NCL that uses supercritical carbon dioxide as loop fluid is analysed. The effects of relevant design and operating variables on loop performance are studied. The system operating under steady state is modelled taking into account the axial conduction through loop fluid and loop wall, and heat transfer with surroundings. The heat source is considered to be a heater with controlled heat flux and heat sink is modelled as an end heat exchanger with water as the external cold fluid. The governing equations for mass, momentum and energy conservation are normalized and are solved numerically using finite volume method. Results are obtained for a loop pressure of 90 bar with the power input varying from 0.5 kW to 6.0 kW. The numerical results are validated against the experimental results reported in the literature in terms of the modified Grashof number (Grm) and Reynolds number (Re). Based on the results, buoyancy and friction dominated regions are identified for a given loop. Parametric analysis has been done to show the effect of loop diameter, loop height, ambient temperature and insulation. The results show that for the high temperature loop, heat loss to surroundings affects the loop performance significantly. Hence this conjugate heat transfer between the loop and surroundings has to be considered in the analysis of high temperature NCLs.Keywords: conjugate heat transfer, heat loss, natural circulation loop, supercritical carbon dioxide
Procedia PDF Downloads 2411349 Transmission Line Protection Challenges under High Penetration of Renewable Energy Sources and Proposed Solutions: A Review
Authors: Melake Kuflom
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European power networks involve the use of multiple overhead transmission lines to construct a highly duplicated system that delivers reliable and stable electrical energy to the distribution level. The transmission line protection applied in the existing GB transmission network are normally independent unit differential and time stepped distance protection schemes, referred to as main-1 & main-2 respectively, with overcurrent protection as a backup. The increasing penetration of renewable energy sources, commonly referred as “weak sources,” into the power network resulted in the decline of fault level. Traditionally, the fault level of the GB transmission network has been strong; hence the fault current contribution is more than sufficient to ensure the correct operation of the protection schemes. However, numerous conventional coal and nuclear generators have been or about to shut down due to the societal requirement for CO2 emission reduction, and this has resulted in a reduction in the fault level on some transmission lines, and therefore an adaptive transmission line protection is required. Generally, greater utilization of renewable energy sources generated from wind or direct solar energy results in a reduction of CO2 carbon emission and can increase the system security and reliability but reduces the fault level, which has an adverse effect on protection. Consequently, the effectiveness of conventional protection schemes under low fault levels needs to be reviewed, particularly for future GB transmission network operating scenarios. The proposed paper will evaluate the transmission line challenges under high penetration of renewable energy sources andprovides alternative viable protection solutions based on the problem observed. The paper will consider the assessment ofrenewable energy sources (RES) based on a fully rated converter technology. The DIgSILENT Power Factory software tool will be used to model the network.Keywords: fault level, protection schemes, relay settings, relay coordination, renewable energy sources
Procedia PDF Downloads 2061348 Photodegradation of Profoxydim Herbicide in Amended Paddy Soil-Water System
Authors: A. Cervantes-Diaz, B. Sevilla-Moran, Manuel Alcami, Al Mokhtar Lamsabhi, J. L. Alonso-Prados, P. Sandin-España
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Profoxydim is a post-emergence herbicide belonging to the cyclohexanedione oxime family, used to control weeds in rice crops. The use of soil organic amendments has increased significantly in the last decades, and their effects on the behavior of many herbicides are still unknown. Additionally, it is known that photolysis is an important degradation process to be considered when evaluating the persistence of this family of herbicides in the environment. In this work, the photodegradation of profoxydim in an amended paddy soil-water system with alperujo compost was studied. Photodegradation experiments were carried out under laboratory conditions using simulated solar light (Suntest equipment) in order to evaluate the reaction kinetics of the active substance. The photochemical behavior of profoxydim was investigated in soil with and without alperujo amendment. Furthermore, due to the rice crop characteristics, profoxydim photodegradation in water in contact with these types of soils was also studied. Determination of profoxydim degradation kinetics was performed by High-Performance Liquid Chromatography with Diode-Array Detection (HPLC-DAD). Furthermore, we followed the evolution of resulting transformation by-products, and their tentative identification was achieved by mass spectrometry. All the experiments allowed us to fit the data of profoxydim photodegradation to a first-order kinetic. Photodegradation of profoxydim was very rapid in all cases. The half-lives in aqueous matrices were in the range of 86±0.3 to 103±0.5 min. The addition of alperujo amendment to the soil produced an increase in the half-life from 62±0.2 min (soil) to 75±0.3 min (amended soil). In addition, a comparison to other organic amendments was also performed. Results showed that the presence of the organic amendment retarded the photodegradation in paddy soil and water. Regarding degradation products, the main process involved was the cleavage of the oxime moiety giving rise to the formation of the corresponding imine compound.Keywords: by-products, herbicide, organic amendment, photodegradation, profoxydim
Procedia PDF Downloads 791347 Identification of a Panel of Epigenetic Biomarkers for Early Detection of Hepatocellular Carcinoma in Blood of Individuals with Liver Cirrhosis
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
Procedia PDF Downloads 3041346 Nonclassical Antifolates: Synthesis, Biological Evaluation and Molecular Modeling Study of Some New Quinazolin-4-One Analogues as Dihydrofolate Reductase Inhibitors
Authors: Yomna Ibrahim El-Gazzar, Hussien Ibrahim El-Subbagh, Hanan Hanaa Georgey, Ghada S. Hassan Hassan
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Dihydrofolate reductase (DHFR) is an enzyme that has pivotal importance in biochemistry and medicinal chemistry. It catalyzes the reduction of dihydrofolate to tetrahydrofolate and intimately couples with thymidylate synthase. Thymidylate synthase is a crucial enzyme that catalyzes the reductive methylation of (dUMP) to (dTMP) utilizing N5, N10-methylenetetrahydrofolate as a cofactor. A new series of 2-substituted thio-quinazolin-4-one analogs was designed that possessed electron withdrawing or donating functional groups (Cl or OCH3) at position 6- or 7-, 4-methoxyphenyl function at position 3-.The thiol function is used to connect to either 1,2,4-triazole, or 1,3,4-thiadiazole via a methylene bridge. Most of the functional groups designed to be accommodated on the quinazoline ring such as thioether, alkyl to increase lipid solubility of polar compounds, a character very much needed in the nonclassical DHFR inhibitors. The target compounds were verified with spectral data and elemental analysis. DHFR inhibitions, as well as antitumor activity, were applied on three cell lines (MCF-7, CACO-2, HEPG-2).Keywords: nonclassical antifolates, DHFR Inhibitors, antitumor activity, quinazoline ring
Procedia PDF Downloads 394