Search results for: gene circuit
1709 Rooting Out Breast Cancer by Repressing ER Gene Expression: Correlating Bioactivity of Pomegranate Rind with Chemical Constituents Identified by HPLC-MS/MS
Authors: Alaa M. M. Badr Eldin, Marwa I. Ezzat, Mohammed S. Sedeek, Manal S. Afifi, Omar M. Sabry
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Cytotoxic activity of the total methanol extract against breast cancer cell line MCF-7 was amazing IC50 at 54 ug/ml. 130 polyphenolic compounds were tentatively identified in pomegranate peel (Punica granatum L.) methanol extract using HPLC-MS/MS technique. The antiestrogenic activity of the polyphenolic constituents found in pomegranate extract was confirmed experimentally in-vitro and by the in-silico molecular docking using gallagic acid, ellagic acid, and Punicalagin as these are considered model compounds confirmed in pomegranate peel extract. The methanolic extract was found to suppress ER, TGF-β, and NF-kB in-vitro gene expression strongly, and that was verified by qPCR and Western Blot gel electrophoresis techniques.Keywords: HPLC-MS/MS, pomegranate, breast cancer, ovarian cancer, ER, TGF-β, NF-kB
Procedia PDF Downloads 1021708 Loss of Function of Only One of Two CPR5 Paralogs Causes Resistance Against Rice Yellow Mottle Virus
Authors: Yugander Arra, Florence Auguy, Melissa Stiebner, Sophie Chéron, Michael M. Wudick, Van Schepler-Luu, Sébastien Cunnac, Wolf B. Frommer, Laurence Albar
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Rice yellow mottle virus (RYMV) is one of the most important diseases affecting rice in Africa. The most promising strategy to reduce yield losses is the use of highly resistant varieties. The resistance gene RYMV2 is homolog of the Arabidopsis constitutive expression of pathogenesis related protein-5 (AtCPR5) nucleoporin gene. Resistance alleles are originating from African cultivated rice Oryza glaberrima, rarely cultivated, and are characterized by frameshifts or early stop codons, leading to a non-functional or truncated protein. Rice possesses two paralogs of CPR5 and function of these genes are unclear. Here, we evaluated the role of the two rice candidate nucleoporin paralogs OsCPR5.1 (pathogenesis-related gene 5; RYMV2) and OsCPR5.2 by CRISPR/Cas9 genome editing. Despite striking sequence and structural similarity, only loss-of-function of OsCPR5.1 led to full resistance, while loss-of-function oscpr5.2 mutants remained susceptible. Short N-terminal deletions in OsCPR5.1 also did not lead to resistance. In contrast to Atcpr5 mutants, neither OsCPR5.1 nor OsCPR5.2 knock out mutants showed substantial growth defects. Taken together, the candidate nucleoporin OsCPR5.1, but not its close homolog OsCPR5.2, plays a specific role for the susceptibility to RYMV, possibly by impairing the import of viral RNA or protein into the nucleus. Whereas gene introgression from O. glaberrima to high yielding O. sativa varieties is impaired by strong sterility barriers and the negative impact of linkage drag, genome editing of OsCPR5.1, while maintaining OsCPR5.2 activity, thus provides a promising strategy to generate O. sativa elite lines that are resistant to RYMV.Keywords: CRISPR Cas9, genome editing, knock out mutant, recessive resistance, rice yellow mottle virus
Procedia PDF Downloads 1201707 Study of seum Tumor Necrosis Factor Alpha in Pediatric Patients with Hemophilia A
Authors: Sara Mohammad Atef Sabaika
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Background: The development of factor VIII (FVIII) inhibitor and hemophilic arthropathy in patients with hemophilia A (PWHA) are a great challenge for hemophilia care. Both genetic and environmental factors led to complications in PWHA. The development of inhibitory antibodies is usually induced by the immune response. Tumor necrosis factor α (TNF-α), one of the cytokines, might contribute to its polymorphism. Aim: Study the association between tumor necrosis alpha level and genotypes in pediatric patients with hemophilia A and its relation to inhibitor development and joint status. Methods: A cross-sectional study was conducted among a sufficient number of PWHA attending the Pediatric Hematology and Oncology Unit, Pediatric department in Menoufia University hospital. The clinical parameters, FVIII, FVIII inhibitor, and serum TNF-α level were assessed. The genotyping of −380G > A TNF-α gene polymorphism was performed using real time polymerase chain reaction. Results: Among the 50 PWHA, 28 (56%) were identified as severe PWHA. The FVIII inhibitor was identified in 6/28 (21.5%) of severe PWHA. There was a significant correlation between serum TNF-α level and the development of inhibitor (p = 0:043). There was significant correlation between polymorphisms of −380G > A TNF-α gene and hemophilic arthropathy development (p = 0:645). Conclusion: The prevalence of FVIII inhibitor in severe PWHA in Menoufia was 21.5%. The frequency of replacement therapy is a risk factor for inhibitor development. Serum TNF-α level and its gene polymorphism might be used to predict inhibitor development and joint status in pediatric patients with hemophilia A.Keywords: hemophilic arthropathy, TNF alpha., patients witb hemophilia A PWHA, inhibitor
Procedia PDF Downloads 951706 Compact Dual-Band Bandpass Filter Based on Quarter Wavelength Stepped Impedance Resonators
Authors: Yu-Fu Chen, Zih-Jyun Dai, Chen-Te Chiu, Shiue-Chen Chiou, Yung-Wei Chen, Yu-Ming Lin, Kuan-Yu Chen, Hung-Wei Wu, Hsin-Ying Lee, Yan-Kuin Su, Shoou-Jinn Chang
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This paper presents a compact dual-band bandpass filter that involves using the quarter wavelength stepped impedance resonators (SIRs) for achieving simultaneously compact circuit size and good dual-band performance. The filter is designed at 2.4 / 3.5 GHz and constructed by two pairs of quarter wavelength SIRs and source-load lines. By properly tuning the impedance ratio, length ratio and radius of via hole of the SIRs, dual-passbands performance can be easily determined. To improve the passband selectivity, the use of source-load lines is to increase coupling energy between the resonators. The filter is showing simple configuration, effective design method and small circuit size. The measured results are in good agreement with the simulation results.Keywords: dual-band, bandpass filter, stepped impedance resonators, SIR
Procedia PDF Downloads 5171705 Nuclear Mitochondrial Pseudogenes in Anastrepha fraterculus Complex
Authors: Pratibha Srivastava, Ayyamperumal Jeyaprakash, Gary Steck, Jason Stanley, Leroy Whilby
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Exotic, invasive tephritid fruit flies (Diptera: Tephritidae) are a major threat to fruit and vegetable industries in the United States. The establishment of pest fruit fly in the agricultural industries and produce severe ecological and economic impacts on agricultural diversification and trade. Detection and identification of these agricultural pests in a timely manner will facilitate the possibility of eradication from newly invaded areas. Identification of larval stages to species level is difficult, but is required to determine pest loads and their pathways into the United States. The aim of this study is the New World genus, Anastrepha which includes pests of major economic importance. Mitochondrial cytochrome c oxidase I (COI) gene sequences were amplified from Anastrepha fraterculus specimens collected from South America (Ecuador and Peru). Phylogenetic analysis was performed to characterize the Anastrepha fraterculus complex at a molecular level. During phylogenetics analysis numerous nuclear mitochondrial pseudogenes (numts) were discovered in different specimens. The numts are nonfunctional copies of the mtDNA present in the nucleus and are easily coamplified with the mitochondrial COI gene copy by using conserved universal primers. This is problematic for DNA Barcoding, which attempts to characterize all living organisms by using the COI gene. This study is significant for national quarantine use, as morphological diagnostics to separate larvae of the various members remain poorly developed.Keywords: tephritid, Anastrepha fraterculus, COI, numts
Procedia PDF Downloads 2391704 Medical Neural Classifier Based on Improved Genetic Algorithm
Authors: Fadzil Ahmad, Noor Ashidi Mat Isa
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This study introduces an improved genetic algorithm procedure that focuses search around near optimal solution corresponded to a group of elite chromosome. This is achieved through a novel crossover technique known as Segmented Multi Chromosome Crossover. It preserves the highly important information contained in a gene segment of elite chromosome and allows an offspring to carry information from gene segment of multiple chromosomes. In this way the algorithm has better possibility to effectively explore the solution space. The improved GA is applied for the automatic and simultaneous parameter optimization and feature selection of artificial neural network in pattern recognition of medical problem, the cancer and diabetes disease. The experimental result shows that the average classification accuracy of the cancer and diabetes dataset has improved by 0.1% and 0.3% respectively using the new algorithm.Keywords: genetic algorithm, artificial neural network, pattern clasification, classification accuracy
Procedia PDF Downloads 4741703 Q Eqchi Mayan Piper and Cissampelos Species Alter Reporter Genes and Endogenous Genes Expression in Mc-7 Cells
Authors: Sheila M. Wicks, Gail Mahady, Udesh Patel, Joanna Michel, Armando Caceres
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Introduction: The genus piperaceae contains approximately 1000 species of herbs scrubs small trees and hanging vines distributed in both hemispheres. During our ethno medical work in Guatemala of the 27 plant families documented for us e by the Qeqchi Maya for reproductive disorders the most prominent were the Piperaceae (15%) and Menispermiaceae. Our Previous work showed that extracts from form Piper and Cissampelos species bound to both and progesterone and the estrogen receptors. In this work active extracts from Piper aeruginosibaccum Trelease, P auritum, P tuerckheimii and Cissampels tropaeolifolia were tested in functionalized cell based assays including a SEAP reporter gene and by qPCR of ER-responsive gene expression in MCF-7cells. In the reporter gene assay P aeruginosibaccum was estrogenic and enhanced E2 EFFECTS IN MCF-7 CELLS. P. tuerckheimi was not estrogenic alone but significantly enhanced the effects of E2 on SEAP reporter gene expression. Both altered mRNA expression of E2 responsive genes in MCF-7. Methods: this is collaborative project between University of Illinois at Chicago and University of San Carlos Guatemala City. 144 spices of plants were collected in Guatemala of which 57 used to treat a variety of women's reproductive health. The Genus Piperaraceae contains approximately 1000 species of herbs scrubs and small trees. Active extracts of the plants were tested in functionalized in cell-based bioassays including SEAP reporter genes. Results demonstrated altered mRNA expression of E2 responsive genes in MC-7 cells plants were collected in Guatemala of which 57 used. Conclusion of the 5 plants tested all were shown to contain components of binding to estrogenic receptor to a greater or lesser degree. These effects support the use of QEqchi Maya women in Guatemala for reproductive.Keywords: reporter genes, MC7, guatemala piperaceae, reproductive health
Procedia PDF Downloads 2481702 Oxide Based Memristor and Its Potential Application in Analog-Digital Electronics
Authors: P. Michael Preetam Raj, Souri Banerjee, Souvik Kundu
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Oxide based memristors were fabricated in order to establish its potential applications in analog/digital electronics. BaTiO₃-BiFeO₃ (BT-BFO) was employed as an active material, whereas platinum (Pt) and Nb-doped SrTiO₃ (Nb:STO) were served as a top and bottom electrodes, respectively. Piezoelectric force microscopy (PFM) was utilized to present the ferroelectricity and repeatable polarization inversion in the BT-BFO, demonstrating its effectiveness for resistive switching. The fabricated memristors exhibited excellent electrical characteristics, such as hysteresis current-voltage (I-V), high on/off ratio, high retention time, cyclic endurance, and low operating voltages. The band-alignment between the active material BT-BFO and the substrate Nb:STO was experimentally investigated using X-Ray photoelectron spectroscopy, and it attributed to staggered heterojunction alignment. An energy band diagram was proposed in order to understand the electrical transport in BT-BFO/Nb:STO heterojunction. It was identified that the I-V curves of these memristors have several discontinuities. Curve fitting technique was utilized to analyse the I-V characteristic, and the obtained I-V equations were found to be parabolic. Utilizing this analysis, a non-linear BT-BFO memristors equivalent circuit model was developed. Interestingly, the obtained equivalent circuit of the BT-BFO memristors mimics the identical electrical performance, those obtained in the fabricated devices. Based on the developed equivalent circuit, a finite state machine (FSM) design was proposed. Efforts were devoted to fabricate the same FSM, and the results were well matched with those in the simulated FSM devices. Its multilevel noise filtering and immunity to external noise characteristics were also studied. Further, the feature of variable negative resistance was established by controlling the current through the memristor.Keywords: band alignment, finite state machine, polarization inversion, resistive switching
Procedia PDF Downloads 1361701 ACTN3 Genotype Association with Motoric Performance of Roma Children
Authors: J. Bernasovska, I. Boronova, J. Poracova, M. Mydlarova Blascakova, V. Szabadosova, P. Ruzbarsky, E. Petrejcikova, I. Bernasovsky
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The paper presents the results of the molecular genetics analysis in sports research, with special emphasis to use genetic information in diagnosing of motoric predispositions in Roma boys from East Slovakia. The ability and move are the basic characteristics of all living organisms. The phenotypes are influenced by a combination of genetic and environmental factors. Genetic tests differ in principle from the traditional motoric tests, because the DNA of an individual does not change during life. The aim of the presented study was to examine motion abilities and to determine the frequency of ACTN3 (R577X) gene in Roma children. Genotype data were obtained from 138 Roma and 155 Slovak boys from 7 to 15 years old. Children were investigated on physical performance level in association with their genotype. Biological material for genetic analyses comprised samples of buccal swabs. Genotypes were determined using Real Time High resolution melting PCR method (Rotor-Gene 6000 Corbett and Light Cycler 480 Roche). The software allows creating reports of any analysis, where information of the specific analysis, normalized and differential graphs and many information of the samples are shown. Roma children of analyzed group legged to non-Romany children at the same age in all the compared tests. The % distribution of R and X alleles in Roma children was different from controls. The frequency of XX genotype was 9.26%, RX 46.33% and RR was 44.41%. The frequency of XX genotype was 9.26% which is comparable to a frequency of an Indian population. Data were analyzed with the ANOVA test.Keywords: ACTN3 gene, R577X polymorphism, Roma children, sport performance, Slovakia
Procedia PDF Downloads 3351700 Application of IED to Condition Based Maintenance of Medium Voltage GCB/VCB
Authors: Ming-Ta Yang, Jyh-Cherng Gu, Chun-Wei Huang, Jin-Lung Guan
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Time base maintenance (TBM) is conventionally applied by the power utilities to maintain circuit breakers (CBs), transformers, bus bars and cables, which may result in under maintenance or over maintenance. As information and communication technology (ICT) industry develops, the maintenance policies of many power utilities have gradually changed from TBM to condition base maintenance (CBM) to improve system operating efficiency, operation cost and power supply reliability. This paper discusses the feasibility of using intelligent electronic devices (IEDs) to construct a CB CBM management platform. CBs in power substations can be monitored using IEDs with additional logic configuration and wire connections. The CB monitoring data can be sent through intranet to a control center and be analyzed and integrated by the Elipse Power Studio software. Finally, a human-machine interface (HMI) of supervisory control and data acquisition (SCADA) system can be designed to construct a CBM management platform to provide maintenance decision information for the maintenance personnel, management personnel and CB manufacturers.Keywords: circuit breaker, condition base maintenance, intelligent electronic device, time base maintenance, SCADA
Procedia PDF Downloads 3301699 Spatial Architecture Impact in Mediation Open Circuit Voltage Control of Quantum Solar Cell Recovery Systems
Authors: Moustafa Osman Mohammed
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The photocurrent generations are influencing ultra-high efficiency solar cells based on self-assembled quantum dot (QD) nanostructures. Nanocrystal quantum dots (QD) provide a great enhancement toward solar cell efficiencies through the use of quantum confinement to tune absorbance across the solar spectrum enabled multi-exciton generation. Based on theoretical predictions, QDs have potential to improve systems efficiency in approximate regular electrons excitation intensity greater than 50%. In solar cell devices, an intermediate band formed by the electron levels in quantum dot systems. The spatial architecture is exploring how can solar cell integrate and produce not only high open circuit voltage (> 1.7 eV) but also large short-circuit currents due to the efficient absorption of sub-bandgap photons. In the proposed QD system, the structure allows barrier material to absorb wavelengths below 700 nm while multi-photon processes in the used quantum dots to absorb wavelengths up to 2 µm. The assembly of the electronic model is flexible to demonstrate the atoms and molecules structure and material properties to tune control energy bandgap of the barrier quantum dot to their respective optimum values. In terms of energy virtual conversion, the efficiency and cost of the electronic structure are unified outperform a pair of multi-junction solar cell that obtained in the rigorous test to quantify the errors. The milestone toward achieving the claimed high-efficiency solar cell device is controlling the edge causes of energy bandgap between the barrier material and quantum dot systems according to the media design limits. Despite this remarkable potential for high photocurrent generation, the achievable open-circuit voltage (Voc) is fundamentally limited due to non-radiative recombination processes in QD solar cells. The orientation of voltage recovery system is compared theoretically with experimental Voc variation in mediation upper–limit obtained one diode modeling form at the cells with different bandgap (Eg) as classified in the proposed spatial architecture. The opportunity for improvement Voc is valued approximately greater than 1V by using smaller QDs through QD solar cell recovery systems as confined to other micro and nano operations states.Keywords: nanotechnology, photovoltaic solar cell, quantum systems, renewable energy, environmental modeling
Procedia PDF Downloads 1571698 Prenatal Diagnosis of Beta Thalassemia Intermedia in Vietnamese Family: Case Report
Authors: Ha T. T. Ly, Truc B. Truc, Hai N. Truong, Mai P. T. Nguyen, Ngoc D. Ngo, Khanh V. Tran, Hai T. Le
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Beta thalassemia is one of the most common inherited blood disorders, which is characterized by decreased or absent in beta globin expression. Patients with Beta thalassemia whose anemia is not so severe as to necessitate transfusions are said to have thalassemia intermedia. Objective: The goal of this study is prenatal diagnosis for pregnancy woman with Beta thalassemia intermedia and her husband with Beta thalassemia carrier at high risk of Beta thalassemia major in Northern of Vietnam. Material and method: The family has a 6 years-old compound heterozygous thalassemia major for CD71/72(+A) and Hbb:c. -78A>G/nt-28(A>G) male child. The father was heterozygous for CD71/72(+A) mutation which is Beta plus type and the mother was compound heterozygosity of two different variants, namely, Hbb: c. -78A>G/nt-28(A>G) and CD26(A-G) HbE. Prenatal Beta thalassemia mutation detection in fetal DNA was carried out using multiplex Amplification-refractory mutation system ARMS-PCR and confirmed by direct Sanger-sequencing Hbb gene. Prenatal diagnoses were perfomed by amniotic fluid sampling from pregnant woman in the 16-18th week of pregnancy after the genotypes of parents of the probands were identified. Result: When amniotic fluid sample was analyzed for Beta globin gene (Hbb), we found that the genotype is heterozygous for CD71/72(+A) and CD26(A-G) HbE. This genotype is different from the 1st child of this family. Conclusion: Prenatal diagnosis helps the parents to know the genotype and the thalassemia status of the fetus, so they can have early decision on their pregnancy. Genetic diagnosis provided a useful method in diagnosis for familial members in pedigree, genetic counseling and prenatal diagnosis.Keywords: beta thalassemia intermedia, Hbb gene, pedigree, prenatal diagnosis
Procedia PDF Downloads 3831697 Transcriptomic Analyses of Kappaphycus alvarezii under Different Wavelengths of Light
Authors: Vun Yee Thien, Kenneth Francis Rodrigues, Clemente Michael Vui Ling Wong, Wilson Thau Lym Yong
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Transcriptomes associated with the process of photosynthesis have offered insights into the mechanism of gene regulation in terrestrial plants; however, limited information is available as far as macroalgae are concerned. This investigation aims to decipher the underlying mechanisms associated with photosynthesis in the red alga, Kappaphycus alvarezii, by performing a differential expression analysis on a de novo assembled transcriptomes. Comparative analysis of gene expression was designed to examine the alteration of light qualities and its effect on physiological mechanisms in the red alga. High-throughput paired-end RNA-sequencing was applied to profile the transcriptome of K. alvarezii irradiated with different wavelengths of light (blue 492-455 nm, green 577-492 nm and red 780-622 nm) as compared to the full light spectrum, resulted in more than 60 million reads individually and assembled using Trinity and SOAPdenovo-Trans. The transcripts were annotated in the NCBI non-redundant (nr) protein, SwissProt, KEGG and COG databases with a cutoff E-value of 1e-5 and nearly 30% of transcripts were assigned to functional annotation by Blast searches. Differential expression analysis was performed using edgeR. The DEGs were designated to six categories: BL (blue light) regulated, GL (green light) regulated, RL (red light) regulated, BL or GL regulated, BL or RL regulated, GL or RL regulated, and either BL, GL or RL regulated. These DEGs were mapped to terms in KEGG database and compared with the whole transcriptome background to search for genes that regulated by light quality. The outcomes of this study will enhance our understanding of molecular mechanisms underlying light-induced responses in red algae.Keywords: de novo transcriptome sequencing, differential gene expression, Kappaphycus alvareziired, red alga
Procedia PDF Downloads 5091696 An Attenuated Quadruple Gene Mutant of Mycobacterium tuberculosis Imparts Protection against Tuberculosis in Guinea Pigs
Authors: Shubhita Mathur, Ritika Kar Bahal, Priyanka Chauhan, Anil K. Tyagi
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Mycobacterium tuberculosis, the causative agent of human tuberculosis, is a major cause of mortality. Bacillus Calmette-Guérin (BCG), the only licensed vaccine available for protection against tuberculosis confers highly variable protection ranging from 0%-80%. Thus, novel vaccine strains need to be evaluated for their potential as a vaccine against tuberculosis. We had previously constructed a triple gene mutant of M. tuberculosis (MtbΔmms), having deletions in genes encoding for phosphatases mptpA, mptpB, and sapM that are involved in host-pathogen interaction. Though vaccination with Mtb∆mms strain induced protection in the lungs of guinea pigs, the mutant strain was not able to control the hematogenous spread of the challenge strain to the spleens. Additionally, inoculation with Mtb∆mms resulted in some pathological damage to the spleens in the early phase of infection. In order to overcome the pathology caused by MtbΔmms in the spleens of guinea pigs and also to control the dissemination of the challenge strain, MtbΔmms was genetically modified by disrupting bioA gene to generate MtbΔmmsb strain. Further, in vivo attenuation of MtbΔmmsb was evaluated, and its protective efficacy was assessed against virulent M. tuberculosis challenge in guinea pigs. Our study demonstrates that Mtb∆mmsb mutant was highly attenuated for growth and virulence in guinea pigs. Vaccination with Mtb∆mmsb mutant generated significant protection in comparison to sham-immunized animals at 4 and 12 weeks post-infection in lungs and spleens of the infected animals. Our findings provide evidence that deletion of genes involved in signal transduction and biotin biosynthesis severely attenuates the pathogen and the single immunization with the auxotroph was able to provide significant protection as compared to sham-immunized animals. The protection imparted by Mtb∆mmsb fell short in comparison to the protection observed in BCG-immunized animals. This study nevertheless indicates the importance of attenuated multiple gene deletion mutants of M. tuberculosis in generating protection against tuberculosis.Keywords: Mycobacterium tuberculosis, BCG, MtbΔmmsb, bioA, guinea pigs
Procedia PDF Downloads 1401695 Adapting the Chemical Reaction Optimization Algorithm to the Printed Circuit Board Drilling Problem
Authors: Taisir Eldos, Aws Kanan, Waleed Nazih, Ahmad Khatatbih
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Chemical Reaction Optimization (CRO) is an optimization metaheuristic inspired by the nature of chemical reactions as a natural process of transforming the substances from unstable to stable states. Starting with some unstable molecules with excessive energy, a sequence of interactions takes the set to a state of minimum energy. Researchers reported successful application of the algorithm in solving some engineering problems, like the quadratic assignment problem, with superior performance when compared with other optimization algorithms. We adapted this optimization algorithm to the Printed Circuit Board Drilling Problem (PCBDP) towards reducing the drilling time and hence improving the PCB manufacturing throughput. Although the PCBDP can be viewed as instance of the popular Traveling Salesman Problem (TSP), it has some characteristics that would require special attention to the transactions that explore the solution landscape. Experimental test results using the standard CROToolBox are not promising for practically sized problems, while it could find optimal solutions for artificial problems and small benchmarks as a proof of concept.Keywords: evolutionary algorithms, chemical reaction optimization, traveling salesman, board drilling
Procedia PDF Downloads 5191694 Inheritance, Stability, and Validation of Provitamin a Markers in Striga Hermonthica-Resistant Maize
Authors: Fiston Masudi Tambwe, Lwanga Charles, Arfang Badji, Unzimai Innocent
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The development of maize varieties combining Provitamin A (PVA), high yield, and Striga resistance is an effective and affordable strategy to contribute to food security in sub-Saharan Africa, where maize is a staple food crop. There has been limited research on introgressing PVA genes into Striga-resistant maize genotypes. The objectives of this study were to: i) determine the mode of gene action controlling PVA carotenoid accumulation in Striga-resistant maize, ii) identify Striga-resistant maize hybrids with high PVA content and stable yield, and iii) validate the presence of PVA functional markers in offspring. Six elite, Striga-resistant inbred females were crossed with six high-PVA inbred males in a North Carolina Design II and their offspring were evaluated in four environments, following a 5x8 alpha lattice design with four hybrid checks. Results revealed that both additive and non-additive gene action control carotenoid accumulation in the present study, with a predominance of non-additive gene effects for PVA. Hybrids STR1004xCLHP0352 and STR1004xCLHP0046 - identified as Striga-resistant because they supported fewer Striga plants – were the highest-yielding genotypes with a moderate PVA concentration of 5.48 and 5.77 µg/g, respectively. However, those two hybrids were not stable in terms of yield across all environments. Hybrid STR1007xCLHP0046, however, supported fewer Striga plants, had a yield of 4.52 T/ha, a PVA concentration of 4.52 µg/g, and was also stable. Gel-based marker systems of CrtRB1 and LCYE were used to screen the hybrids and favorable alleles of CrtRB1 primers were detected in 20 hybrids, confirming good levels of PVA carotenoids. Hybrids with favorable alleles of LCYE had the highest concentration of non-PVA carotenoids. These findings will contribute to the development of high-yielding PVA-rich maize varieties in Uganda.Keywords: gene action, stability, striga resistance, provitamin A markers, beta-carotene hydroxylase 1, CrtRB1, beta-carotene, beta-cryptoxanthin, lycopene epsilon cyclase, LCYE
Procedia PDF Downloads 721693 Analysis of Saudi Breast Cancer Patients’ Primary Tumors using Array Comparative Genomic Hybridization
Authors: L. M. Al-Harbi, A. M. Shokry, J. S. M. Sabir, A. Chaudhary, J. Manikandan, K. S. Saini
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Breast cancer is the second most common cause of cancer death worldwide and is the most common malignancy among Saudi females. During breast carcinogenesis, a wide-array of cytogenetic changes involving deletions, or amplification, or translocations, of part or whole of chromosome regions have been observed. Because of the limitations of various earlier technologies, newer tools are developed to scan for changes at the genomic level. Recently, Array Comparative Genomic Hybridization (aCGH) technique has been applied for detecting segmental genomic alterations at molecular level. In this study, aCGH was performed on twenty breast cancer tumors and their matching non-tumor (normal) counterparts using the Agilent 2x400K. Several regions were identified to be either amplified or deleted in a tumor-specific manner. Most frequent alterations were amplification of chromosome 1q, chromosome 8q, 20q, and deletions at 16q were also detected. The amplification of genetic events at 1q and 8q were further validated using FISH analysis using probes targeting 1q25 and 8q (MYC gene). The copy number changes at these loci can potentially cause a significant change in the tumor behavior, as deletions in the E-Cadherin (CDH1)-tumor suppressor gene as well as amplification of the oncogenes-Aurora Kinase A. (AURKA) and MYC could make these tumors highly metastatic. This study validates the use of aCGH in Saudi breast cancer patients and sets the foundations necessary for performing larger cohort studies searching for ethnicity-specific biomarkers and gene copy number variations.Keywords: breast cancer, molecular biology, ecology, environment
Procedia PDF Downloads 3761692 Smart and Active Package Integrating Printed Electronics
Authors: Joana Pimenta, Lorena Coelho, José Silva, Vanessa Miranda, Jorge Laranjeira, Rui Soares
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In this paper, the results of R&D on an innovative food package for increased shelf-life are presented. SAP4MA aims at the development of a printed active device that enables smart packaging solutions for food preservation, targeting the extension of the shelf-life of the packed food through the controlled release of active natural antioxidant agents at the onset of the food degradation process. To do so, SAP4MA focuses on the development of active devices such as printed heaters and batteries/supercapacitors in a label format to be integrated on packaging lids during its injection molding process, promoting the passive release of natural antioxidants after the product is packed, during transportation and in the shelves, and actively when the end-user activates the package, just prior to consuming the product at home. When the active device present on the lid is activated, the release of the natural antioxidants embedded in the inner layer of the packaging lid in direct contact with the headspace atmosphere of the food package starts. This approach is based on the use of active functional coatings composed of nano encapsulated active agents (natural antioxidants species) in the prevention of the oxidation of lipid compounds in food by agents such as oxygen. Thus keeping the product quality during the shelf-life, not only when the user opens the packaging, but also during the period from food packaging up until the purchase by the consumer. The active systems that make up the printed smart label, heating circuit, and battery were developed using screen-printing technology. These systems must operate under the working conditions associated with this application. The printed heating circuit was studied using three different substrates and two different conductive inks. Inks were selected, taking into consideration that the printed circuits will be subjected to high pressures and temperatures during the injection molding process. The circuit must reach a homogeneous temperature of 40ºC in the entire area of the lid of the food tub, promoting a gradual and controlled release of the antioxidant agents. In addition, the circuit design involves a high level of study in order to guarantee maximum performance after the injection process and meet the specifications required by the control electronics component. Furthermore, to characterize the different heating circuits, the electrical resistance promoted by the conductive ink and the circuit design, as well as the thermal behavior of printed circuits on different substrates, were evaluated. In the injection molding process, the serpentine-shaped design developed for the heating circuit was able to resolve the issues connected to the injection point; in addition, the materials used in the support and printing had high mechanical resistance against the pressure and temperature inherent to the injection process. Acknowledgment: This research has been carried out within the Project “Smart and Active Packing for Margarine Product” (SAP4MA) running under the EURIPIDES Program being co-financed by COMPETE 2020 – the Operational Programme for Competitiveness and Internationalization and under Portugal 2020 through the European Regional Development Fund (ERDF).Keywords: smart package, printed heat circuits, printed batteries, flexible and printed electronic
Procedia PDF Downloads 1101691 Oncogenic Functions of Long Non-Coding RNA XIST in Human Nasopharyngeal Carcinoma by Targeting MiR-34a-5p
Authors: Cheng-Cao Sun, Shu-Jun Li, De-Jia Li
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Long non-coding RNA (lncRNA) X inactivate-specific transcript (XIST) has been verified as an oncogenic gene in several human malignant tumors, and its dysregulation was closed associated with tumor initiation, development and progression. Nevertheless, whether the aberrant expression of XIST in human nasopharyngeal carcinoma (NPC) is corrected with malignancy, metastasis or prognosis has not been elaborated. Here, we discovered that XIST was up-regulated in NPC tissues and higher expression of XIST contributed to a markedly poorer survival time. In addition, multivariate analysis demonstrated XIST was an independent risk factor for prognosis. XIST over-expression enhanced, while XIST silencing hampered the cell growth in NPC. Additionally, mechanistic analysis revealed that XIST up-regulated the expression of miR-34a-5p targeted gene E2F3 through acting as a competitive ‘sponge’ of miR-34a-5p. Taking all into account, we concluded that XIST functioned as an oncogene in NPC through up-regulating E2F3 in part through ‘spongeing’ miR-34a-5p.Keywords: X inactivate-specific transcript; hsa-miRNA-34a-5p, miR-34a-5p; E2F3, nasopharyngeal carcinoma, tumorigenesis
Procedia PDF Downloads 2411690 Design of Process Parameters in Electromagnetic Forming Apparatus by FEM
Authors: Hyeong-Gyu Park, Hak-Gon Noh, Beom-Soo Kang, Jeong Kim
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Electromagnetic forming (EMF) process is one of a high-speed forming process, which uses an electromagnetic body (Lorentz) force to deform work-piece. Advantages of EMF are summarized as improvement of formability, reduction in wrinkling, non-contact forming. In this study, the spiral coil is considered to evaluate formability in terms of pressure distribution of the forming process. It also is represented forming results of numerical analysis using ANSYS code. In the numerical simulation, RLC circuit coupled with spiral coil was made to consider the design parameters such as system input current and electromagnetic force. The simulation results show that even though input peak currents level are same level in each case, forming condition is certainly different because of frequency of input current and magnitude of current density and magnetic flux density. Finally, the simulation results appear that electromagnetic forming force apparently affected by input current frequency which determines magnitude of current density and magnetic flux density.Keywords: electromagnetic forming, high-speed forming, RLC circuit, Lorentz force
Procedia PDF Downloads 4561689 Obesity, Leptin Levels and Leptin Receptor Gene Polymorphisms in Afro-Caribbean Subjects
Authors: Lydia Foucan, Christine Rambhojan, Rachel Billy, Christophe Armand, Carl-Thony Michel, Jean-Marc Lacorte, Laurent Larifla
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Leptin, an adipocyte-derived hormone, modulates insulin secretion and action via the leptin receptor (LEPR) that is expressed in pancreatic beta cells, adipose tissue, and muscle. Several polymorphisms have been described in the human LEPR gene including p.K109R (rs1137100), p.Q223R (rs1137101) and p.K656N (rs1805094) polymorphisms. The role of these polymorphisms is not yet studied in Guadeloupian population. Our aim was to explore the association of LEPR polymorphisms (K109R, Q223R and K656N) with leptin levels and obesity in non-diabetic Afro-Caribbean subjects. Genotypic analysis of the three polymorphisms was performed in 425 subjects using TaqMan and KASPar Assays. Serum leptin was measured with ELISA kits Biovendor® (RD191001100). Logistic regressions were used for assessment of statistical associations. Mean age was 47.6 ± 12.7 years. Among the participants, 238 (56 %) were women, 124 (30%) were obese and 155 (36.5%) had abdominal obesity. Carriers of LEPR K656N rs1805094 rare allele had significant higher frequencies of obesity (P = 0.007), abdominal obesity (P = 0.004) and metabolic syndrome (P = 0.021) but mean leptin level was not significantly different between both groups (P = 0.075). Odds ratios, adjusted for age and sex associated with presence of rs1805094 rare allele were 1.8 (1.1-2.9), P = 0.012 for obesity, 2.0 (1.2-3.3), P = 0.008 for abdominal obesity and 1.8 (1.1-3.0), P = 0.031 for MetS. No significant association was found with K109R, Q223R. These findings suggest that the K656N polymorphism (but not the K109R or Q223R polymorphism) of LEPR is associated with obesity, abdominal obesity and metabolic syndrome in this Afro-Caribbean non-diabetic population.Keywords: Afro-Caribbean, leptin levels, leptin receptor gene polymorphisms, obesity
Procedia PDF Downloads 3791688 Impact of CYP3A5 Polymorphism on Tacrolimus to Predict the Optimal Initial Dose Requirements in South Indian Renal Transplant Recipients
Authors: S. Sreeja, Radhakrishnan R. Nair, Noble Gracious, Sreeja S. Nair, M. Radhakrishna Pillai
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Background: Tacrolimus is a potent immunosuppressant clinically used for the long term treatment of antirejection of transplanted organs in liver and kidney transplant recipients though dose optimization is poorly managed. However, So far no study has been carried out on the South Indian kidney transplant patients. The objective of this study is to evaluate the potential influence of a functional polymorphism in CYP3A5*3 gene on tacrolimus physiological availability/dose ratio in South Indian renal transplant patients. Materials and Methods: Twenty five renal transplant recipients receiving tacrolimus were enrolled in this study. Their body weight, drug dosage, and therapeutic concentration of Tacrolimus were observed. All patients were on standard immunosuppressive regime of Tacrolimus-Mycophenolate mofetil along with steroids on a starting dose of Tac 0.1 mg/kg/day. CYP3A5 genotyping was performed by PCR followed with RFLP. Conformation of RFLP analysis and variation in the nucleotide sequence of CYP3A5*3 gene were determined by direct sequencing using a validated automated generic analyzer. Results: A significant association was found between tacrolimus per dose/kg/d and CYP3A5 gene (A6986G) polymorphism in the study population. The CYP3A5 *1/*1, *1/*3 and *3/*3 genotypes were detected in 5 (20 %), 5 (20 %) and 15 (60 %) of the 25 graft recipients, respectively. CYP3A5*3 genotypes were found to be a good predictor of tacrolimus Concentration/Dose ratio in kidney transplant recipients. Significantly higher L/D was observed among non-expressors 9.483 ng/mL(4.5- 14.1) as compared with the expressors 5.154 ng/mL (4.42-6.5 ) of CYP3A5. Acute rejection episodes were significantly higher for CYP3A5*1 homozygotes compared to patients with CYP3A5*1/*3 and CYP3A5*3/*3 genotypes (40 % versus 20 % and 13 %, respectively ). The dose normalized TAC concentration (ng/ml/mg/kg) was significantly lower in patients having CYP3A5*1/*3 polymorphism. Conclusion: This is the first study to extensively determine the effect of CYP3A5*3 genetic polymorphism on tacrolimus pharmacokinetics in South Indian renal transplant recipients and also shows that majority of our patients carry mutant allele A6986G in CYP3A5*3 gene. Identification of CYP3A5 polymorphism prior to transplantation could contribute to evaluate the appropriate initial dosage of tacrolimus for each patient.Keywords: kidney transplant patients, CYP3A5 genotype, tacrolimus, RFLP
Procedia PDF Downloads 3021687 hsa-miR-1204 and hsa-miR-639 Prominent Role in Tamoxifen's Molecular Mechanisms on the EMT Phenomenon in Breast Cancer Patients
Authors: Mahsa Taghavi
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In the treatment of breast cancer, tamoxifen is a regularly prescribed medication. The effect of tamoxifen on breast cancer patients' EMT pathways was studied. In this study to see if it had any effect on the cancer cells' resistance to tamoxifen and to look for specific miRNAs associated with EMT. In this work, we used continuous and integrated bioinformatics analysis to choose the optimal GEO datasets. Once we had sorted the gene expression profile, we looked at the mechanism of signaling, the ontology of genes, and the protein interaction of each gene. In the end, we used the GEPIA database to confirm the candidate genes. after that, I investigated critical miRNAs related to candidate genes. There were two gene expression profiles that were categorized into two distinct groups. Using the expression profile of genes that were lowered in the EMT pathway, the first group was examined. The second group represented the polar opposite of the first. A total of 253 genes from the first group and 302 genes from the second group were found to be common. Several genes in the first category were linked to cell death, focal adhesion, and cellular aging. Two genes in the second group were linked to cell death, focal adhesion, and cellular aging. distinct cell cycle stages were observed. Finally, proteins such as MYLK, SOCS3, and STAT5B from the first group and BIRC5, PLK1, and RAPGAP1 from the second group were selected as potential candidates linked to tamoxifen's influence on the EMT pathway. hsa-miR-1204 and hsa-miR-639 have a very close relationship with the candidates genes according to the node degrees and betweenness index. With this, the action of tamoxifen on the EMT pathway was better understood. It's important to learn more about how tamoxifen's target genes and proteins work so that we can better understand the drug.Keywords: tamoxifen, breast cancer, bioinformatics analysis, EMT, miRNAs
Procedia PDF Downloads 1291686 Intrabody Communication Using Different Ground Configurations in Digital Door Lock
Authors: Daewook Kim, Gilwon Yoon
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Intrabody communication (IBC) is a new way of transferring data using human body as a medium. Minute current can travel though human body without any harm. IBC can remove electrical wires for human area network. IBC can be also a secure communication network system unlike wireless networks which can be accessed by anyone with bad intentions. One of the IBC systems is based on frequency shift keying modulation where individual data are transmitted to the external devices for the purpose of secure access such as digital door lock. It was found that the quality of IBC data transmission was heavily dependent on ground configurations of electronic circuits. Reliable IBC transmissions were not possible when both of the transmitter and receiver used batteries as circuit power source. Transmission was reliable when power supplies were used as power source for both transmitting and receiving sites because the common ground was established through the grounds of instruments such as power supply and oscilloscope. This was due to transmission dipole size and the ground effects of floor and AC power line. If one site used battery as power source and the other site used the AC power as circuit power source, transmission was possible.Keywords: frequency shift keying, ground, intrabody, communication, door lock
Procedia PDF Downloads 4201685 Fault-Tolerant Configuration for T-Type Nested Neutral Point Clamped Converter
Authors: S. Masoud Barakati, Mohsen Rahmani Haredasht
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Recently, the use of T-type nested neutral point clamped (T-NNPC) converter has increased in medium voltage applications. However, the T-NNPC converter architecture's reliability and continuous operation are at risk by including semiconductor switches. Semiconductor switches are a prone option for open-circuit faults. As a result, fault-tolerant converters are required to improve the system's reliability and continuous functioning. This study's primary goal is to provide a fault-tolerant T-NNPC converter configuration. In the proposed design utilizing the cold reservation approach, a redundant phase is considered, which replaces the faulty phase once the fault is diagnosed in each phase. The suggested fault-tolerant configuration can be easily implemented in practical applications due to the use of a simple PWM control mechanism. The performance evaluation of the proposed configuration under different scenarios in the MATLAB-Simulink environment proves its efficiency.Keywords: T-type nested neutral point clamped converter, reliability, continuous operation, open-circuit faults, fault-tolerant converters
Procedia PDF Downloads 1211684 FDX1, a Cuproptosis-Related Gene, Identified as a Potential Target for Human Ovarian Aging
Authors: Li-Te Lin, Chia-Jung Li, Kuan-Hao Tsui
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Cuproptosis, a newly identified cell death mechanism, has attracted attention for its association with various diseases. However, the genetic interplay between cuproptosis and ovarian aging remains largely unexplored. This study aims to address this gap by analyzing datasets related to ovarian aging and cuproptosis. Spatial transcriptome analyses were conducted in the ovaries of both young and aged female mice to elucidate the role of FDX1. Comprehensive bioinformatics analyses, facilitated by R software, identified FDX1 as a potential cuproptosis-related gene with implications for ovarian aging. Clinical infertility biopsies were examined to validate these findings, showing consistent results in elderly infertile patients. Furthermore, pharmacogenomic analyses of ovarian cell lines explored the intricate association between FDX1 expression levels and sensitivity to specific small molecule drugs. Spatial transcriptome analyses revealed a significant reduction in FDX1 expression in aging ovaries, supported by consistent findings in biopsies from elderly infertile patients. Pharmacogenomic investigations indicated that modulating FDX1 could influence drug responses in ovarian-related therapies. This study pioneers the identification of FDX1 as a cuproptosis-related gene linked to ovarian aging. These findings not only contribute to understanding the mechanisms of ovarian aging but also position FDX1 as a potential diagnostic biomarker and therapeutic target. Further research may establish FDX1's pivotal role in advancing precision medicine and therapies for ovarian-related conditions.Keywords: cuproptosis, FDX1, ovarian aging, biomarker
Procedia PDF Downloads 421683 Molecular Characterisation and Expression of Glutathione S-Transferase of Fasciola Gigantica
Authors: J. Adeppa, S. Samanta, O. K. Raina
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Fasciolosis is a widespread economically important parasitic infection throughout the world caused by Fasciola hepatica and F. gigantica. In order to identify novel immunogen conferring significant protection against fasciolosis, currently, research has been focused on the defined antigens viz. glutathione S-transferase, fatty acid binding protein, cathepsin-L, fluke hemoglobin, paramyosin, myosin and F. hepatica- Kunitz Type Molecule. Among various antigens, GST which plays a crucial role in detoxification processes, i.e. phase II defense mechanism of this parasite, has a unique position as a novel vaccine candidate and a drug target in the control of this disease. For producing the antigens in large quantities and their purification to complete homogeneity, the recombinant DNA technology has become an important tool to achieve this milestone. RT- PCR was carried out using F. gigantica total RNA as template, and an amplicon of 657 bp GST gene was obtained. TA cloning vector was used for cloning of this gene, and the presence of insert was confirmed by blue-white selection for recombinant colonies. Sequence analysis of the present isolate showed 99.1% sequence homology with the published sequence of the F. gigantica GST gene of cattle origin (accession no. AF112657), with six nucleotide changes at 72, 74, 423, 513, 549 and 627th bp found in the present isolate, causing an overall change of 4 amino acids. The 657 bp GST gene was cloned at BamH1 and HindIII restriction sites of the prokaryotic expression vector pPROEXHTb in frame with six histidine residues and expressed in E. coli DH5α. Recombinant protein was purified from the bacterial lysate under non-denaturing conditions by the process of sonication after lysozyme treatment and subjecting the soluble fraction of the bacterial lysate to Ni-NTA affinity chromatography. Western blotting with rabbit hyper-immune serum showed immuno-reactivity with 25 kDa recombinant GST. Recombinant protein detected F. gigantica experimental as well as field infection in buffaloes by dot-ELISA. However, cross-reactivity studies on Fasciola gigantica GST antigen are needed to evaluate the utility of this protein in the serodiagnosis of fasciolosis.Keywords: fasciola gigantic, fasciola hepatica, GST, RT- PCR
Procedia PDF Downloads 1871682 Association between a Serotonin Re-Uptake Transporter Gene Polymorphism and Mucosal Serotonin Level in Women Patients with Irritable Bowel Syndrome and Healthy Control: A Pilot Study from Northern India
Authors: Sunil Kumar, Uday C. Ghoshal
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Background and aims: Serotonin (5-hydroxtryptamine, 5-HT) is an important factor in gut function, playing key roles in intestinal peristalsis and secretion, and in sensory signaling in the brain-gut axis. Removal from its sites of action is mediated by a specific protein called the serotonin reuptake transporter (SERT). Polymorphisms in the promoter region of the SERT gene have effects on transcriptional activity, resulting in altered 5-HT reuptake efficiency. Functional polymorphisms may underlie disturbance in gut function in individuals suffering with disorders such as irritable bowel syndrome (IBS). The aim of this study was to assess the potential association between SERT polymorphisms and the diarrhea predominant IBS (D-IBS) phenotype Subjects: A total of 36 northern Indian female patients and 55 female northern Indian healthy controls (HC) were subjected to genotyping. Methods: Leucocyte DNA of all subjects was analyzed by polymerase chain reaction based technologies for SERT polymorphisms, specifically the insertion/deletion polymorphism in the promoter (SERT-P). Statistical analysis was performed to assess association of SERT polymorphism allele with the D-IBS phenotype. Results: The frequency of distribution of SERT-P gene was comparable between female patients with IBS and HC (p = 0.086). However, frequency of SERT-P deletion/deletion genotype was significantly higher in female patients with D-IBS compared to C-IBS and A-IBS [17/19 (89.5%) vs. 4/12 (33.3%) vs. 1/5 (20%), p=0.001, respectively]. The mucosal level of serotonin was higher in D-IBS compared to C-IBS and A-IBS [Median, range (159.26, 98.78–212.1) vs. 110.4, 67.87–143.53 vs. 92.34, 78.8–166.3 pmol/mL, p=0.001, respectively]. The mucosal level of serotonin was higher in female patients with IBS with SERT-P deletion/deletion genotype compared deletion/insertion and insertion/insertion [157.65, 67.87–212.1 vs. 110.4, 78.1–143.32 vs. 100.5, 69.1–132.03 pmol/mL, p=0.001, respectively]. Patients with D-IBS with deletion/deletion genotype more often reported symptoms of abdominal pain, discomfort (p=0.025) and bloating (p=0.039). Symptoms development following lactose ingestion was strongly associated with D-IBS and SERT-P deletion/deletion genotype (p=0.004). Conclusions: Significant association was observed between D-IBS and the SERT-P deletion/deletion genotype, suggesting that the serotonin transporter is a potential candidate gene for D-IBS in women.Keywords: serotonin, SERT, inflammatory bowel disease, genetic polymorphism
Procedia PDF Downloads 3331681 Identification of the Target Genes to Increase the Immunotherapy Response in Bladder Cancer Patients using Computational and Experimental Approach
Authors: Sahar Nasr, Lin Li, Edwin Wang
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Bladder cancer (BLCA) is known as the 13th cause of death among cancer patients worldwide, and ~575,000 new BLCA cases are diagnosed each year. Urothelial carcinoma (UC) is the most prevalent subtype among BLCA patients, which can be categorized into muscle-invasive bladder cancer (MIBC) and non-muscle-invasive bladder cancer (NMIBC). Currently, various therapeutic options are available for UC patients, including (1) transurethral resection followed by intravesical instillation of chemotherapeutics or Bacillus Calmette-Guérin for NMIBC patients, (2) neoadjuvant platinum-based chemotherapy (NAC) plus radical cystectomy is the standard of care for localized MIBC patients, and (3) systematic chemotherapy for metastatic UC. However, conventional treatments may lead to several challenges for treating patients. As an illustration, some patients may suffer from recurrence of the disease after the first line of treatment. Recently, immune checkpoint therapy (ICT) has been introduced as an alternative treatment strategy for the first or second line of treatment in advanced or metastatic BLCA patients. Although ICT showed lucrative results for a fraction of BLCA patients, ~80% of patients were not responsive to it. Therefore, novel treatment methods are required to augment the ICI response rate within BLCA patients. It has been shown that the infiltration of T-cells into the tumor microenvironment (TME) is positively correlated with the response to ICT within cancerous patients. Therefore, the goal of this study is to enhance the infiltration of cytotoxic T-cells into TME through the identification of target genes within the tumor that are responsible for the non-T-cell inflamed TME and their inhibition. BLCA bulk RNA-sequencing data from The Cancer Genome Atlas (TCGA) and immune score for TCGA samples were used to determine the Pearson correlation score between the expression of different genes and immune score for each sample. The genes with strong negative correlations were selected (r < -0.2). Thereafter, the correlation between the expression of each gene and survival in BLCA patients was calculated using the TCGA data and Cox regression method. The genes that are common in both selected gene lists were chosen for further analysis. Afterward, BLCA bulk and single-cell RNA-sequencing data were ranked based on the expression of each selected gene and the top and bottom 25% samples were used for pathway enrichment analysis. If the pathways related to the T-cell infiltration (e.g., antigen presentation, interferon, or chemokine pathways) were enriched within the low-expression group, the gene was included for downstream analysis. Finally, the selected genes will be used to calculate the correlation between their expression and the infiltration rate of the activated CD+8 T-cells, natural killer cells and the activated dendric cells. A list of potential target genes has been identified and ranked based on the above-mentioned analysis and criteria. SUN-1 got the highest score within the gene list and other identified genes in the literature as benchmarks. In conclusion, inhibition of SUN1 may increase the tumor-infiltrating lymphocytes and the efficacy of ICI in BLCA patients. BLCA tumor cells with and without SUN-1 CRISPR/Cas9 knockout will be injected into the syngeneic mouse model to validate the predicted SUN-1 effect on increasing tumor-infiltrating lymphocytes.Keywords: data analysis, gene expression analysis, gene identification, immunoinformatic, functional genomics, transcriptomics
Procedia PDF Downloads 1561680 Phylogenetic Relationships of the Malaysian Primates Cercopithecine Based on COI Gene Sequences
Authors: B. M. Md-Zain, N. A. Rahman, M. A. B. Abdul-Latiff, W. M. R. Idris
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We conducted molecular research to portray phylogenetic relationships of Malaysian primates particularly in the genus of Macaca. We have sequenced cytochrome C oxidase subunit I (COI) of mitochondrial DNA of several individuals from M. fascicularis and M. arctoides. PCR amplifications were performed and COI DNA sequences were aligned using ClustalW. Phylogenetic trees were constructed using distance analyses by employing neighbor-joining algorithm (NJ). We managed to sequence 700 bp of COI DNA sequences. The tree topology showed that M. fascicularis did not clump based on phyleogeography division in Peninsular Malaysia. Individuals from Negeri Sembilan merged together with samples from Perak and Penang into one clade. In addition, phylogenetic analyses indicated that M. arctoides was classified into sinica group instead of fascicularis group supported by genetic distance data. COI gene is an effective locus to clarify phylogenetic position of M. arctoides but not in discriminating M. fascicularis population in Peninsular Malaysia.Keywords: cercopithecine, long-tailed macaque, Macaca fascicularis, Macaca arctoides
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