Search results for: transcription factor binding sites

Authors: Karolis Leonavičius, Dalius Kučiauskas, Dangiras Lukošius, Arnoldas Jasiūnas, Kostas Zdanys, Rokas Stanislovas, Emilis Gegevičius, Žana Kapustina, Juozas Nainys

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Screening throughput is a common bottleneck in many research areas, including functional genomics, drug discovery, and directed evolution. High-throughput screening techniques can be classified into two main categories: (i) affinity-based screening and (ii) functional screening. The first one relies on binding assays that provide information about the affinity of a test molecule for a target binding site. Binding assays are relatively easy to establish; however, they reveal no functional activity. In contrast, functional assays show an effect triggered by the interaction of a ligand at a target binding site. Functional assays might be based on a broad range of readouts, such as cell proliferation, reporter gene expression, downstream signaling, and other effects that are a consequence of ligand binding. Screening of large cell or gene libraries based on direct activity rather than binding affinity is now a preferred strategy in many areas of research as functional assays more closely resemble the context where entities of interest are anticipated to act. Droplet sorting is the basis of high-throughput functional biological screening, yet its applicability is limited due to the technical complexity of integrating high-performance droplet analysis and manipulation systems. As a solution, the Droplet Genomics Styx platform enables custom droplet sorting workflows, which are necessary for the development of early-stage or complex biological therapeutics or industrially important biocatalysts. The poster will focus on the technical design considerations of Styx in the context of its application spectra.

Keywords: functional screening, droplet microfluidics, droplet sorting, dielectrophoresis

Procedia PDF Downloads 90

Authors: Minimol M. C.

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The study provides insights into the consumer’s trust on user generated brand recommendations on social networking sites and also investigates the role of ad scepticism in generating consumer trust in user generated brand recommendations. The work contributes to a better understanding of trust development in the context of social networking sites. Specifically, the study reveals that not all dimensions of trustworthiness are equal. The individual user characteristics vary according to the person. The major finding of this study is that high degrees of trust toward user generated brand recommendations can be generated on the basis of high trust toward social networking sites and ad scepticism. Consumers trust the user generated brand recommendations based on the individual’s trust in the particular social networking platform and the level of their individual ad-scepticism. The study pinpoints that as consumers’ trust in user generated brand recommendations is affected by their trust in social networking sites, it is influenced by benevolence, integrity, the propensity to trust, and individual user characteristics to a great extent, and hence, it is imperative for brands should attempt to build on these factors so that they can engage consumers to generate user generated content on social media.

Keywords: Consumer trust, user-generated brand recommendations, ad scepticism, social networking sites

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Authors: Srishty Gulati, Anju Singh, Shrikant Kukreti

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The manifestation of structural polymorphism in DNA depends on the sequence and surrounding environment. Ample of folded DNA structures have been found in the cellular system out of which DNA hairpins are very common, however, are indispensable due to their role in the replication initiation sites, recombination, transcription regulation, and protein recognition. We enumerate this approach in our study, where the two base substitutions and change in temperature embark destabilization of DNA structure and misbalance the equilibrium between two structures of a sequence present at the overlapping region of the human COMT gene and MIR4761 gene. COMT and MIR4761 gene encodes for catechol-O-methyltransferase (COMT) enzyme and microRNAs (miRNAs), respectively. Environmental changes and errors during cell division lead to genetic abnormalities. The COMT gene entailed in dopamine regulation fosters neurological diseases like Parkinson's disease, schizophrenia, velocardiofacial syndrome, etc. A 19-mer deoxyoligonucleotide sequence 5'-AGGACAAGGTGTGCATGCC-3' (COMT19) is located at exon-4 on chromosome 22 and band q11.2 at the intersection of COMT and MIR4761 gene. Bioinformatics studies suggest that this sequence is conserved in humans and few other organisms and is involved in recognition of transcription factors in the vicinity of 3'-end. Non-denaturating gel electrophoresis and CD spectroscopy of COMT sequences indicate the formation of hairpin type DNA structures. Temperature-dependent CD studies revealed an unusual shift in the slipped DNA-Hairpin DNA equilibrium with the change in temperature. Also, UV-thermal melting techniques suggest that the two base substitutions on the complementary strand of COMT19 did not affect the structure but reduces the stability of duplex. This study gives insight about the possibility of existing structurally polymorphic transient states within DNA segments present at the intersection of COMT and MIR4761 gene.

Keywords: base-substitution, catechol-o-methyltransferase (COMT), hairpin-DNA, structural polymorphism

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Authors: Matineh Sadat Hosseini Gheidari, Vahid Reza Yazdanpanah

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In this paper, we used the empirical tight-binding method (ETBM) with sp3s* approximation and considering the first nearest neighbor with spin-orbit interactions in order to model superlattice structure (SLS) of (AlₓGa₁₋ₓAs)ₘ/(GaAs)ₙ grown on GaAs (100) substrate at 300K. In the next step, we investigated the behavior of the energy gap and wavelength of this superlattice in terms of different thicknesses of core materials and Al mole fractions. As a result of this survey, we found out that as the Al composition increases, the energy gap of this superlattice has an upward trend and ranges from 1.42-1.63 eV. Also, according to the wavelength range that we gained from this superlattice in different Al mole fractions and various thicknesses, we can find a suitable semiconductor for a special light-emitting diode (LED) application.

Keywords: energy gap, empirical tight-binding method, light-emitting diode, superlattice, wavelength

Procedia PDF Downloads 159

Authors: Phakit Treesukol

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The purpose of this investigation is to ascertain Internet users’ behaviours towards companies’ public relations activities on social networking sites. In order to conduct a study of Internet users’ behaviour, data was collected using the quota sampling method from a total of 100 Internet users who are members of SNS and used the Internet during the period 10 December 2009 to 9 January 2010. An online self-administrated questionnaire was distributed through Facebook, Hi5 and Twitter to Internet users by using snowball sampling technique. Results of the study showed that the majority of the respondents were using social networking sites with the main purpose to contact their friends. Presently, most of the respondents were not regularly receiving companies’ public relations activities on social networking sites. The highest frequency of survey responses by the respondents was for hiding or deleting information introducing new products or services from companies on SNS also as well.

Keywords: media uses and gratification, online activities, public relations activities, social networking sites

Procedia PDF Downloads 225

Authors: Nancy Ibrahim Abdalla, Abdelaziz Karamalla Gaiballa

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Rangelands in semi-arid areas provide a good source for feeding huge numbers of animals and serving environmental, economic and social importance; therefore, these areas are considered economically very important for the pastoral sector in Sudan. This paper investigates the means of differentiating between different rangelands sites according to soil types using principal component analysis to assist in monitoring and assessment purposes. Three rangeland sites were identified in the study area as flat sandy sites, sand dune site, and hard clay site. Principal component analysis (PCA) was used to reduce the number of factors needed to distinguish between rangeland sites and produce a new set of data including the most useful spectral information to run satellite image processing. It was performed using selected types of data (two vegetation indices, topographic data and vegetation surface reflectance within the three bands of MODIS data). Analysis with PCA indicated that there is a relatively high correspondence between vegetation and soil of the total variance in the data set. The results showed that the use of the principal component analysis (PCA) with the selected variables showed a high difference, reflected in the variance and eigenvalues and it can be used for differentiation between different range sites.

Keywords: principal component analysis, PCA, rangeland sites, semi-arid areas, soil types

Procedia PDF Downloads 145

Authors: Jafar Ahmadi, Zhohreh Asiaban, Sedigheh Fabriki Ourang

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Brassinosteroids (BRs) regulate cell elongation, vascular differentiation, senescence and stress responses. BRs signal through the BES1/BZR1 family of transcription factors, which regulate hundreds of target genes involved in this pathway. In this research a comprehensive genome-wide analysis was carried out in BES1/BZR1 gene family in Arabidopsis thaliana, Cucumis sativus, Vitis vinifera, Glycin max, and Brachypodium distachyon. Specifications of the desired sequences, dot plot and hydropathy plot were analyzed in the protein and genome sequences of five plant species. The maximum amino acid length was attributed to protein sequence Brdic3g with 374aa and the minimum amino acid length was attributed to protein sequence Gm7g with 163aa. The maximum Instability index was attributed to protein sequence AT1G19350 equal with 79.99 and the minimum Instability index was attributed to protein sequence Gm5g equal with 33.22. Aliphatic index of these protein sequences ranged from 47.82 to 78.79 in Arabidopsis thaliana, 49.91 to 57.50 in Vitis vinifera, 55.09 to 82.43 in Glycin max, 54.09 to 54.28 in Brachypodium distachyon 55.36 to 56.83 in Cucumis sativus. Overall, data obtained from our investigation contributes a better understanding of the complexity of the BES1/BZR1 gene family and provides the first step towards directing future experimental designs to perform systematic analysis of the functions of the BES1/BZR1 gene family.

Keywords: BES1/BZR1, brassinosteroids, phylogenetic analysis, transcription factor

Procedia PDF Downloads 307

Authors: Kah Yan How, Peh Fern Ong, Keang Peng Song

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Porphyromonas gingivalis is a black-pigmented, anaerobic Gram-negative bacterium that is important in the progression of chronic and severe periodontitis. This organism has an essential requirement for iron, which is usually obtained from hemin, using specific membrane receptors, proteases, and lipoproteins. In this study, we report the characterization of a novel 24 kDa hemin-binding protein, HmuX, in P. gingivalis W50. The hmuX gene is 651 bp long which encodes for a 217 amino acid protein. HmuX was found to be identical at the C-terminus to the previously reported HmuY protein, differing by an additional 74 amino acids at the N-terminus. Recombinant HmuX demonstrated hemin-binding ability by LDS- PAGE and TMBZ staining. Sequence analysis of HmuX revealed a putative lipoprotein attachment site, suggesting its possible role as a lipoprotein. HmuX was also localized to the outer cell surface by transmission electron microscopy. Northern analysis showed hmuX to be transcribed as a single gene and that hmuX mRNA was tightly regulated by the availability of extra-cellular hemin. P. gingivalis isogenic mutant deficient in hmuX gene exhibited significant growth retardation under hemin-limited conditions. Taken together, these results suggest that HmuX is a hemin-binding lipoprotein, important in hemin utilization for the growth of P. gingivalis.

Keywords: Porphyromonas gingivalis, periodontal diseases, HmuX, protein characterization

Procedia PDF Downloads 192

Authors: Sinethemba Yakobi, Lindiwe Zuma, Ofentse Pooe

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Gonococcal infections present a notable public health issue, and the major approach for treatment involves using β-lactam antibiotics that specifically target penicillin-binding protein 2 (PBP2) in Neisseria gonorrhoeae. This study examines the influence of flavonoids, namely rutin, on the structural changes of PBP2 in both penicillin-resistant (FA6140) and penicillin-susceptible (FA19) strains. The research clarifies the structural effects of particular mutations, such as inserting an aspartate residue at position 345 (Asp-345a) in the PBP2 protein. The strain FA6140, which is resistant to penicillin, shows specific changes that lead to a decrease in penicillin binding. These mutations, namely P551S and F504L, significantly impact the pace at which acylation occurs and the stability of the strain under high temperatures. Molecular docking analyses investigate the antibacterial activities of rutin and other phytocompounds, emphasizing its exceptional binding affinity and potential as an inhibitor of PBP2. Quercetin and protocatechuic acid have encouraging antibacterial effectiveness, with quercetin displaying characteristics similar to those of drugs. Molecular dynamics simulations offer a detailed comprehension of the interactions between flavonoids and PBP2, highlighting rutin's exceptional antioxidant effects and strong affinity for the substrate binding site. The study's wider ramifications pertain to the pressing requirement for antiviral treatments in the context of the ongoing COVID-19 epidemic. Flavonoids have a strong affinity for binding to PBP2, indicating their potential as inhibitors to impair cell wall formation in N. gonorrhoeae. Ultimately, this study provides extensive knowledge on the interactions between proteins and ligands, the dynamics of the structure, and the ability of flavonoids to combat penicillin-resistant N. gonorrhoeae bacteria. The verified simulation outcomes establish a basis for creating potent inhibitors and medicinal therapies to combat infectious illnesses.

Keywords: phytochemicals, penicillin-binding protein 2, gonococcal infection, ligand-protein interaction, binding energy, neisseria gonorrhoeae FA19, neisseria gonorrhoeae FA6140, flavonoids

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Authors: Pui-sze Yeung, Connie Suk-han Ho, David Wai-ock Chan, Kevin Kien-hoa Chung

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Background: Recent findings have shown that transcription skills play a unique and significant role in Chinese word reading and spelling (i.e. word dictation), and written composition development. The interrelationships among component skills of transcription, word reading, word spelling, and written composition in Chinese have rarely been examined in the literature. Is the contribution of component skills of transcription to Chinese written composition mediated by word level skills (i.e., word reading and spelling)? Methods: The participants in the study were 249 Chinese children in Grade 1, Grade 3, and Grade 5 in Hong Kong. They were administered measures of general reasoning ability, orthographic knowledge, stroke sequence knowledge, word spelling, handwriting fluency, word reading, and Chinese narrative writing. Orthographic knowledge- orthographic knowledge was assessed by a task modeled after the lexical decision subtest of the Hong Kong Test of Specific Learning Difficulties in Reading and Writing (HKT-SpLD). Stroke sequence knowledge: The participants’ performance in producing legitimate stroke sequences was measured by a stroke sequence knowledge task. Handwriting fluency- Handwriting fluency was assessed by a task modeled after the Chinese Handwriting Speed Test. Word spelling: The stimuli of the word spelling task consist of fourteen two-character Chinese words. Word reading: The stimuli of the word reading task consist of 120 two-character Chinese words. Written composition: A narrative writing task was used to assess the participants’ text writing skills. Results: Analysis of covariance results showed that there were significant between-grade differences in the performance of word reading, word spelling, handwriting fluency, and written composition. Preliminary hierarchical multiple regression analysis results showed that orthographic knowledge, word spelling, and handwriting fluency were unique predictors of Chinese written composition even after controlling for age, IQ, and word reading. The interaction effects between grade and each of these three skills (orthographic knowledge, word spelling, and handwriting fluency) were not significant. Path analysis results showed that orthographic knowledge contributed to written composition both directly and indirectly through word spelling, while handwriting fluency contributed to written composition directly and indirectly through both word reading and spelling. Stroke sequence knowledge only contributed to written composition indirectly through word spelling. Conclusions: Preliminary hierarchical regression results were consistent with previous findings about the significant role of transcription skills in Chinese word reading, spelling and written composition development. The fact that orthographic knowledge contributed both directly and indirectly to written composition through word reading and spelling may reflect the impact of the script-sound-meaning convergence of Chinese characters on the composing process. The significant contribution of word spelling and handwriting fluency to Chinese written composition across elementary grades highlighted the difficulty in attaining automaticity of transcription skills in Chinese, which limits the working memory resources available for other composing processes.

Keywords: orthographic knowledge, transcription skills, word reading, writing

Procedia PDF Downloads 390

Authors: Mohammadjavad Sotoudeheian, Navid Farahmandian

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Cardiac hypertrophy arises in response to persistent increases in hemodynamic loads. In comparison, diabetic cardiomyopathy is defined by an abnormal myocardial changes without other cardiac-related risk factors. Pathological cardiac hypertrophy and myocardial remodeling are hallmarks of cardiovascular diseases and are risk factors for heart failure. The transcription factor forkhead box class O (FOXOs) can protect heart tissue by hostile oxidative stress and stimulating apoptosis and autophagy. FOXO proteins, as sensitive elements and mediators in response to environmental changes, have been revealed to prevent and inverse cardiac hypertrophy. FOXOs are inhibited by insulin and are critical mediators of insulin action. Insulin deficiency and uncontrolled diabetes lead to a catabolic state. FOXO1 acts downstream of the insulin-dependent pathways, which are dysregulated in diabetes. It regulates cardiomyocyte hypertrophy downstream of IGF1R/PI3K/Akt activation, which are critical regulators of cardiac hypertrophy. The complex network of signaling pathways comprising insulin/IGF-1 signaling, AMPK, JNK, and Sirtuins regulate the development of cardiovascular dysfunction by modulating the activity of FOXOs. Insulin receptors and IGF1R act via the PI3k/Akt and the MAPK/ERK pathways. Activation of Akt in response to insulin or IGF-1 induces phosphorylation of FOXOs. Increased protein synthesis induced by activation of the IGF-I/Akt/mTOR signaling pathway leads to hypertrophy. This pathway and the myostatin/Smad pathway are potent negative muscle development regulators. In cardiac muscle, insulin receptor substrates (IRS)-1 or IRS-2 activates the Akt signaling pathway and inactivate FOXO1. Under metabolic stress, p38 MAPK promotes degradation of IRS-1 and IRS-2 in cardiac myocytes and activates FOXO1, leading to cardiomyopathy. Sirt1 and FOXO1 interaction play an essential role in starvation-induced autophagy in cardiac metabolism. Inhibition of Angiotensin-II induced cardiomyocyte hypertrophy is associated with reduced FOXO1 acetylation and activation of Sirt1. The NF-κB, ERK, and FOXOs are de-acetylated by SIRT1. De-acetylation of FOXO1 induces the expression of genes involved in autophagy and stimulates autophagy flux. Therefore, under metabolic stress, FOXO1 can cause diabetic cardiomyopathy. The overexpression of FOXO1 leads to decreased cardiomyocyte size and suppresses cardiac hypertrophy through inhibition of the calcineurin–NFAT pathway. Diabetes mellitus is associated with elevation of O-GlcNAcylation. Some of its binding partners regulate the substrate selectivity of O-GlcNAc transferase (OGT). O-GlcNAcylation of essential contractile proteins may inhibit protein-protein interactions, reduce calcium sensitivity, and modulate contractile function. Uridine diphosphate (UDP)-GlcNAc is the obligatory substrate of OGT, which catalyzes a reversible post-translational protein modification. The increase of O-GlcNAcylation is accompanied by impaired cardiac hypertrophy in diabetic hearts. Inhibition of O-GlcNAcylation blocks activation of ERK1/2 and hypertrophic growth. O-GlcNAc modification on NFAT is required for its translocation from the cytosol to the nucleus, where NFAT stimulates the transcription of various hypertrophic genes. Inhibition of O-GlcNAcylation dampens NFAT-induced cardiac hypertrophic growth. Transcriptional activity of FOXO1 is enriched by improved O-GlcNAcylation upon high glucose stimulation or OGT overexpression. In diabetic conditions, the modification of FOXO1 by O-GlcNAc is promoted in cardiac troponin I and myosin light chain 2. Therefore targeting O-GlcNAcylation represents a potential therapeutic option to prevent hypertrophy in the diabetic heart.

Keywords: diabetes, cardiac hypertrophy, O-GlcNAcylation, FOXO1, Akt, PI3K, AMPK, insulin

Procedia PDF Downloads 81

Authors: Sara Arafeh, Kovriguine Evguine

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Cytochromes P450 are enzymes that require a supply of electrons to catalyze the synthesis of steroid hormones, fatty acids, and prostaglandin hormone. Cytochrome P450 Oxidoreductase (CYPOR), a membrane bound enzyme, provides these electrons in its open conformation. CYPOR has two cytosolic domains (FAD domain and FMN domain) and an N-terminal in the membrane. In its open conformation, electrons flow from NADPH, FAD, and finally to FMN where cytochrome P450 picks up these electrons. In the closed conformation, cytochrome P450 does not bind to the FMN domain to take the electrons. It was found that when the cytosolic domains are isolated, CYPOR could not bind to cytochrome P450. This suggested that the membrane environment is important for CYPOR function. This project takes the initiative to better understand the dynamics of CYPOR in its full length. Here, we determine the distance between specific sites in the FAD and FMN binding domains in CYPOR by Forster Resonance Energy Transfer (FRET) and Ultrafast TA spectroscopy with and without NADPH. The approach to determine these distances will rely on labeling these sites with red and infrared fluorophores. Mimic membrane attachment is done by inserting CYPOR in lipid nanodiscs. By determining the distances between the donor-acceptor sites in these domains, we can observe the open/closed conformations upon reducing CYPOR in the presence and absence of cytochrome P450. Such study is important to better understand CYPOR mechanism of action in various endosomal membranes including hepatic CYPOR which is vital in plasma cholesterol homeostasis. By investigating the conformational cycles of CYPOR, we can synthesize drugs that would be more efficient in affecting the steroid hormonal levels and metabolism of toxins catalyzed by Cytochrome P450.

Keywords: conformational cycle of CYPOR, cytochrome P450, cytochrome P450 oxidoreductase, FAD domain, FMN domain, FRET, Ultrafast TA Spectroscopy

Procedia PDF Downloads 244

Authors: Rohan V. Ambekar, Shrirang N. Tande

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The present study estimates the seismic response reduction factor (R) of reinforced concrete special moment resisting frame (SMRF) with and without shear wall using static nonlinear (pushover) analysis. Calculation of response reduction factor (R) is done as per the new formulation of response reduction factor (R) given by Applied Technology Council (ATC)-19 which is the product of strength factor (Rs), ductility factor (Rµ) and redundancy factor (RR). The analysis revealed that these three factors affect the actual value of response reduction factor (R) and therefore they must be taken into consideration while determining the appropriate response reduction factor to be used during the seismic design process. The actual values required for determination of response reduction factor (R) is worked out on the basis of pushover curve which is a plot of base shear verses roof displacement. Finally, the calculated values of response reduction factor (R) of reinforced concrete special moment resisting frame (SMRF) with and without shear wall are compared with the codal values.

Keywords: response reduction factor, ductility ratio, base shear, special moment resisting frames

Procedia PDF Downloads 454

Authors: Hong Su, Qiuju Yan, Wei Du, En Hu, Zhaoyu Yang, Wei Zhang, Yusheng Li, Tao Tang, Wang yang, Shushan Zhao

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Osteoarthritis (OA) is a severe chronic inflammatory disease. As the main active component of Astragalus mongholicus Bunge, a classic traditional ethnic herb, calycosin exhibits anti-inflammatory action and its mechanism of exact targets for OA have yet to be determined. In this study, we established an anterior cruciate ligament transection (ACLT) mouse model. Mice were randomized to sham, OA, and calycosin groups. Cartilage synthesis markers type II collagen (Col-2) and SRY-Box Transcription Factor 9 (Sox-9) increased significantly after calycosin gavage. While cartilage matrix degradation index cyclooxygenase-2 (COX-2), phosphor-epidermal growth factor receptor (p-EGFR), and matrix metalloproteinase-9 (MMP9) expression were decreased. With the help of network pharmacology and molecular docking, these results were confirmed in chondrocyte ATDC5 cells. Our results indicated that the calycosin treatment significantly improved cartilage damage, this was probably attributed to reversing the imbalance between chondrocyte synthesis and catabolism.

Keywords: calycosin, osteoarthritis, network pharmacology, molecular docking, inflammatory, cyclooxygenase 2

Procedia PDF Downloads 62

Authors: Jer-Yuh Liu, Je-Chiuan Ye, Jin-Ming Hwang

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Protein kinase C alpha (PKCα) is a key signaling molecule in human cancer development. As a therapeutic strategy, targeting PKCα is difficult because the molecule is ubiquitously expressed in non-malignant cells. PKCα is regulated by the cooperative interaction of the transcription factors myeloid zinc finger 1 (MZF-1) and Ets-like protein-1 (Elk-1) in human cancer cells. By conducting tissue array analysis, herein, we determined the protein expression of MZF-1/Elk-1/PKCα in various cancers. The data show that the expression of MZF-1/Elk-1 is correlated with that of PKCα in hepatocellular carcinoma (HCC), but not in bladder and lung cancers. In addition, the PKCα down-regulation by shRNA Elk-1 was only observed in the HCC SK-Hep-1 cells. Blocking the interaction between MZF-1 and Elk-1 through the transfection of their binding domain MZF-160–72 decreased PKCα expression. This step ultimately depressed the epithelial-mesenchymal transition potential of the HCC cells. These findings could be used to develop an alternative therapeutic strategy for patients with the PKCα-derived HCC.

Keywords: protein kinase C alpha, myeloid zinc finger 1, ets-like protein-1, hepatocellular carcinoma

Procedia PDF Downloads 198

Authors: Somkiat Korbuakaew, Winai Mankhatitham, Anchan Chongcharoen, Wichar Kunkum

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This research’s objective is to evaluate the online broadcasting of Suan Dusit Rajabhat Univeristy by CIPP model. The evaluation was separated into 4 parts: context factor, input factor, process factor and product factor. Sample group in this research were 399 participants who were university’s executive, staff and students. Questionnaires and interview were the research tools. Data were analyzed by computer program. Statistics used here were percentage, mean, and standard deviation. Findings are as follows: 1. Context factor: The context factor here in this research was university’s executives, staff and students. The study shows that they would like to use online broadcasting to be the educational tool and IT development. 2. Input factor: The input factor was the modern IT equipment to create interesting teaching materials and develop education in general. 3. Process factor: The process factor in this study was the publication of the program that it should be promoted more among students and should be more objective. 4. Product factor: The product factor in this study was the purpose of the program that it expands the educational channel for students.

Keywords: evaluation, project, internet, online broadcasting

Procedia PDF Downloads 487

Authors: Abdul Musaweer Habib, Habibul Hasan Mazumder, Saiful Islam, Sohel Sikder, Omar Faruk Sikder

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The plethora of genome sequence information of bacteria in recent times has ushered in many novel strategies for antibacterial drug discovery and facilitated medical science to take up the challenge of the increasing resistance of pathogenic bacteria to current antibiotics. In this study, we adopted subtractive genomics approach to analyze the whole genome sequence of the Fusobacterium nucleatum, a human oral pathogen having association with colorectal cancer. Our study divulged 1499 proteins of Fusobacterium nucleatum, which has no homolog in human genome. These proteins were subjected to screening further by using the Database of Essential Genes (DEG) that resulted in the identification of 32 vitally important proteins for the bacterium. Subsequent analysis of the identified pivotal proteins, using the KEGG Automated Annotation Server (KAAS) resulted in sorting 3 key enzymes of F. nucleatum that may be good candidates as potential drug targets, since they are unique for the bacterium and absent in humans. In addition, we have demonstrated the 3-D structure of these three proteins. Finally, determination of ligand binding sites of the key proteins as well as screening for functional inhibitors that best fitted with the ligands sites were conducted to discover effective novel therapeutic compounds against Fusobacterium nucleatum.

Keywords: colorectal cancer, drug target, Fusobacterium nucleatum, homology modeling, ligands

Procedia PDF Downloads 357

Authors: Nicole C. Valdez, Vincent L. Borromeo, Conrad C. Chong, Ahmad F. Mazahery

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Breast cancer is the most prevalent cancer worldwide, where the majority of cases are estrogen-receptor positive and involve 2 receptor proteins. The binding of estrogen to estrogen receptor alpha (ERα) promotes breast cancer growth, while it's binding to estrogen-receptor beta (ERβ) inhibits tumor growth. While natural products have been a promising source of chemotherapeutic agents, the challenge remains in finding a bioactive compound that specifically targets cancer cells, minimizing side effects on normal cells. Flavonoids are natural products that act as phytoestrogens and induce the same response as estrogen. They are able to compete with estrogen for binding to ERα; however, it has a higher binding affinity for ERβ. Their abundance in nature and low toxicity make them a potential candidate for breast cancer treatment. This study aimed to determine which particular flavonoids can specifically recognize ERβ and potentially be used for breast cancer treatment through molecular docking. A total of 206 flavonoids comprised of 97 isoflavones and 109 flavanones were collected from ZINC15, while the 3D structures of ERβ and ERα were obtained from Protein Data Bank. These flavonoid subclasses were chosen as they bind more strongly to ERs due to their chemical structure. The structures of the flavonoid ligands were converted using Open Babel, while the estrogen receptor protein structures were prepared using Autodock MGL Tools. The optimal binding site was found using BIOVIA Discovery Studio Visualizer before docking all flavonoids on both ERβ and ERα through Autodock Vina. Genistein is a flavonoid that exhibits anticancer effects by binding to ERβ, so its binding affinity was used as a baseline. Eriodictyol and 4”,6”-Di-O-Galloylprunin both exceeded genistein’s binding affinity for ERβ and was lower than its binding affinity for ERα. Of the two, eriodictyol was pursued due to its antitumor properties on a lung cancer cell line and on glioma cells. It is able to arrest the cell cycle at the G2/M phase by inhibiting the mTOR/PI3k/Akt cascade and is able to induce apoptosis via the PI3K/Akt/NF-kB pathway. Protein pathway and gene analysis were also conducted using ChEMBL and PANTHER and it was shown that eriodictyol might induce anticancer effects through the ROS1, CA7, KMO, and KDM1A genes which are involved in cell proliferation in breast cancer, non-small cell lung cancer, and other diseases. The high binding affinity of eriodictyol to ERβ, as well as its potential affected genes and antitumor effects, therefore, make it a candidate for the development of new breast cancer treatment. Verification through in vitro experiments such as checking the upregulation and downregulation of genes through qPCR and checking cell cycle arrest using a flow cytometry assay is recommended.

Keywords: breast cancer, estrogen receptor, flavonoid, molecular docking

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Authors: Sultan Ali Suleiman AlMazrouei

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Purpose: The purpose of this paper is to examine the effect of communication through social networking sites (Facebook, Twitter) on employee engagement. Methodology: A quantitative survey was used to collect data from 440 employees from the Ministry of Education in Oman. SPSS software was used to analyze the data. Findings: The results revealed a positive significant relationship between communication via Facebook and employee engagement. However, communication via Twitter does not influence employee engagement significantly. Practical implications: Managers can benefit from the study by understanding the importance of communication via Facebook with employees in order to increase their engagement. They should post their views and thoughts on Facebook and encourage their employees to be members which would be reflected on their psychological side positively. That gives them a feeling of belonging to a network. Originality/value: The study enriches the human resources management literature by examining a theoretical framework about the influence of social networking sites usage on employee engagement. This is one of the few studies that focus on the relationship of social networking sites usage with employees' engagement. It is the first study in an Omani context.

Keywords: employee engagement, social networking sites, Facebook, Twitter

Procedia PDF Downloads 314

Authors: Nazanin Naderi, Milton Smith

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Since worldwide demand for renewable energy is increasing rapidly because of the climate problem and the limitation of fossil fuels, technologies of alternative energy sources have been developed and the electric power network now includes renewable energy resources such as wind energy. Because of the huge advantages that wind energy has, like reduction in natural gas use, price pressure, emissions of greenhouse gases and other atmospheric pollutants, electric sector water consumption and many other contributions to the nation’s economy like job creation it has got too much attention these days from different parts of the world especially in the United States which is trying to provide 20% of the nation’s energy from wind by 2030. This study is trying to evaluate the effect of splitting wind farms on power output. We are trying to find if we can get more output by installing wind turbines in different sites rather than installing all wind turbines in one site. Five potential sites in Texas have been selected as a case study and two years wind data has been gathered for these sites. Wind data are analyzed and effect of correlation between sites on power output has been evaluated. Standard deviation and autocorrelation effect has also been considered for this study. The paper has been organized as follows: After the introduction the second section gives a brief overview of wind analysis. The third section addresses the case study and evaluates correlation between sites, auto correlation of sites and standard deviation of power output. In section four we describe the results.

Keywords: auto correlation, correlation between sites, splitting wind farms, power output, standard deviation

Procedia PDF Downloads 566

Authors: K. A. Ghazaryan, G. A. Gevorgyan, H. S. Movsesyan, N. P. Ghazaryan, K. V. Grigoryan

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The heavy metal pollution degree in the soils around the Zangezur copper and molybdenum combine in Syunik Marz, Armenia was aessessed. The results of the study showed that heavy metal pollution degree in the soils mainly decreased with increasing distance from the open mine and the ore enrichment combine which indicated that the open mine and the ore enrichment combine were the main sources of heavy metal pollution. The only exception was observed in the northern part of the open mine where pollution degree in the sites (along the open mine) situated 600 meters far from the mine was higher than that in the sites located 300 meters far from the mine. This can be explained by the characteristics of relief and air currents as well as the weak vegetation cover of these sites and the characteristics of soil structure. According to geo-accumulation index (I-geo), contamination factor (Cf), contamination degree (Cd) and pollution load index (PLI) values, the pollution degree in the soils around the open mine and the ore enrichment combine was higher than that in the soils around the tailing dumps which was due to the proper and accurate operation of the Artsvanik tailing damp and the recultivation of the Voghji tailing dump. The high Cu and Mo pollution of the soils was conditioned by the character of industrial activities, the moving direction of air currents as well as the physicochemical peculiarities of the soils.

Keywords: Armenia, Zangezur copper and molybdenum combine, soil, heavy metal pollution degree

Procedia PDF Downloads 274

Authors: Christine Mappala

Abstract:

Social Networking Sites has an undeniable contribution but also a downgrading effect in our society when used inappropriately. It has effects on an individual’s physical, academic, social, emotional, and behavioral aspects in life, a reason to take account to the possible risks it can have with the future generations, specifically the Generation Z. Determining if SNS Usage has an effect on an individual’s Narcissistic Tendencies, how common narcissism is among these individuals and to provide additional information about the Generation Z in the Philippines is the purpose of this study. A total of 342 participants were gathered. Results indicated that there is a low significance of SNS as a predictor to Narcissism. Also, results showed that there is a low level of narcissism among Generation Z.

Keywords: narcissism, social networking sites, Generation Z, normal narcissism

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Authors: Feten Chihi, Gabriella Varga

Abstract:

The world's most prevalent waste management strategy is landfills. However, it grew more difficult due to a lack of acceptable waste sites. In order to develop larger landfills and extend their lifespan, the purpose of this article is to expand the capacity of the construction by varying the slope's inclination and to examine its effect on the safety factor. The capacity change with tilt is mathematically determined. Using a new probabilistic calculation method that takes into account the heterogeneity of waste layers, the safety factor for various slope angles is examined. To assess the effect of slope variation on the overall safety of landfills, over a hundred computations were performed for each angle. It has been shown that capacity increases significantly with increasing inclination. Passing from 1:3 to 2:3 slope angles and from 1:3 to 1:2 slope angles, the volume of garbage that can be deposited increases by 40 percent and 25 percent, respectively, of the initial volume. The results of the safety factor indicate that slopes of 1:3 and 1:2 are safe when the standard method (homogenous waste) is used for computation. Using the new approaches, a slope with an inclination of 2:3 can be deemed safe, despite the fact that the calculation does not account for the safety-enhancing effect of daily cover layers. Based on the study reported in this paper, the malty layered nonhomogeneous calculating technique better characterizes the safety factor. As it more closely resembles the actual state of landfills, the employed technique allows for more flexibility in design parameters. This work represents a substantial advance in limiting both safe and economical landfills.

Keywords: landfill, municipal solid waste, slope inclination, capacity, safety factor

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Authors: Kai-Cheng Hsu, Tzu-Ying Sung, Jinn-Moon Yang

Abstract:

Colorectal cancer (CRC) is one of the main causes of cancer death in the world. Although several drugs have been developed to treat colorectal cancer, such as Regorafenib and 5-FU, their efficacy is often limited by the development of drug resistance. Therefore, development of new drugs with new scaffolds is necessary to treat CRC. Here, we used site-moiety maps to identify inhibitors against PIM1, LIMK1, SRC, and mTOR, which are often overexpressed in CRC. A site-moiety map represents physicochemical properties and moiety preferences of a binding site through anchors. An anchor contains three elements: (1) conserved interacting residues of a binding pocket; (2) moiety preference of the binding pocket; and (3) the type (e.g., hydrogen-bonding or van der Waals interactions) of interaction between the moieties and the binding pocket. Then, we performed a structure-based virtual screening of ~260,000 compounds and selected compound candidates with high site-moiety map scores for bioassays. Among these candidates, compound 1 and compound 2 inhibited the growth of CRC cells with IC50 values of <10 μM. The experimental result of enzyme-based assays indicated that compound 1 is a dual inhibitor against PIM1 (IC50 6 μM) and LIMK1(IC50 11 μM). Compound 2 was predicted as a SRC inhibitor and will be further validated. The compounds inhibited different protein targets compared to the current drugs. We believe that the compounds provide a starting point to design new drugs for CRC treatment.

Keywords: colorectal cancer, drug discovery, site-moiety map, virtual screening, PIM1, LIMK1

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Authors: David Wuepper, Marc Patry

Abstract:

UNESCO’s World Heritage program requests the inscribed locations to promote the World Heritage brand by clearly presenting information about it on-site. Based on feedback from over 319,000 visitors at 791 locations, we create an index that shows how much the World Heritage sites actually brand themselves as such. We find great heterogeneity throughout the list and explain this econometrically mostly with the economic benefit for the sites but also with cultural brand preferences, which are highest in Asia, followed by Europe and North America. We also find a positive relationship between World Heritage branding and conservation status and a U-shaped relationship between visitor numbers and WH branding. Based on our findings, we recommend to make clear World Heritage branding mandatory for all sites.

Keywords: UNESCO World Heritage, collective brand, cultural tourism, heritage conservation, brand equity, spatial econometrics

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Authors: Xing Lu, Yi-ming Wu, Yan-hong Zhu, Zhen-feng Chen, Hong Liang, Yan Peng

Abstract:

[Eu(BMQ)2(NO3)3(CH3OH)(H2O)] (1),and [Er(BMQ)2(NO3)3(CH3OH)(H2O)] (2),were synthesized. Compounds 1 and 2 exhibit a certain extent cytotoxicity against Hep G2, Hela 229, MGC80-3 and BEL-7404 cell lines invitro, with IC50 values in the14.51±1.41μM to 52.49±4.01μM range. Compound 1 exhibited significantly enhanced cytotoxicity against MGC80-3 cell line, comparing with free 3-(1H-benzimidazol-2-yl)-6-methyl-2(1H)- quinolinone. The binding abilities of 1 to DNA were stronger than that of 2. Intercalation is the most probable binding mode for both the complexes.

Keywords: quinolinone, Eu(II) complex, Er(III) complex, cytotoxicity.

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Authors: Muhammad Dawood Idrees, Arsalan Ansari

Abstract:

Construction industry is considered as one of the most dangerous industry because workers' safety is always a major concern due to extensive number of accidents, injuries, and casualties at worksites. There are various causes of accidents at construction sites, several factors are influencing on the perception of safety of workers and psychological factors are one of them. Perception of safety varies from region to region and it also varies by demographics of workers, such as gender, age, education, job level, etc. However, research on different level of workers, such as labor and managerial staff to evaluate the impact of psychological factor is limited. Objective of this research is to evaluate the effect of psychological factors with different job level of workers. An extensive literature review was conducted to find the casual relationship between psychological factors and perception of safety, and a hypothetical structure model was developed based upon literature review. A survey instrument based upon psychological factors was developed and data was obtained from several construction sites. Structure Equation Modeling (SEM) technique was adopted in order to examine the effect of psychological factors on the perception of safety of workers with different job levels of workers. The results of this analysis reveal that job security and organizational relationships are most affecting factors in labor staff, therefore job satisfaction, mental stress, and workload are dominant in managerial staff.

Keywords: accidents, job level of workers, perception of safety, structural equation modeling

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Authors: Hyun Lim, Dong Sook Min, Han Eul Yun, Kil Tae Kim, Ya Nan Sun, Young Ho Kim, Hyun Pyo Kim

Abstract:

Matrix metalloproteinase (MMP)-13 has an important role for degrading cartilage materials under inflammatory conditions such as arthritis. Since the 70% ethanol extract of Acanthopanax koreanum inhibited MMP-13 expression in IL-1β-treated human chondrocyte cell line, SW1353, two major constituents including acanthoic acid and impressic acid were initially isolated from the same plant materials and their MMP-13 down-regulating capacity was examined. In IL-1β-treated SW1353 cells, acanthoic acid and impressic acid significantly and concentration-dependently inhibited MMP-13 expression at 10 – 100 μM and 0.5 – 10 μM, respectively. The potent one, impressic acid, was found to inhibit MMP-13 expression by blocking the phosphorylation of signal transducer and activator of transcription-1/-2 (STAT-1/-2) and activation of c-Jun and c-Fos among cellular signaling pathway involved, but did not affect the activation of mitogen-activated protein kinases (MAPKs) and nuclear transcription factor-κB (NF-κB). Further, impressic acid was also found to inhibit the expression of MMP-13 mRNA (47.7% inhibition at 10 μM), the glycosaminoglycan release (42.2% reduction at 10 μM) and proteoglycan loss in IL-1-treated rabbit cartilage explants culture. For a further study, 21 impressic acid derivatives were isolated from the same plant materials and their suppressive activities against MMP-13 expression were examined. Among the derivatives, 3α-hydroxy-lup-20(29)-en-23-oxo,28-oic acid, (20R)-3α-hydroxy-29-dimethoxylupan-23,28-dioic acid, acankoreoside F and acantrifoside A clearly down-regulated MMP-13 expression, but impressic acid being most potent. All these results suggest that impressic acid, 3α-hydroxy-lup-20(29)-en-23-oxo,28-oic acid, (20R)-3α-hydroxy-29-dimethoxylupan-23,28-dioic acid, acankoreoside F, acantrifoside A and A. koreanum may have a potential for therapeutic agents to prevent cartilage degradation possibly by inhibiting matrix protein degradation.

Keywords: acanthoic acid, Acanthopanax koreanum, cartilage, impressic acid, matrix metalloproteinase

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Authors: Motonori Tamura

Abstract:

The hydrogen barrier properties of the coatings of diamond-like carbon (DLC) were evaluated. Using plasma chemical vapor deposition and sputtering, DLC coatings were deposited on Type 316L stainless steels. The hydrogen permeation rate was reduced to 1/1000 or lower by the DLC coatings. The DLC coatings with high hydrogen content had high hydrogen barrier function. For hydrogen diffusion in coatings, the movement of atoms through hydrogen trap sites such as pores in coatings, and crystal defects such as dislocations, is important. The DLC coatings are amorphous, and there are both sp3 and sp2 bonds, and excess hydrogen could be found in the interstitial space and the hydrogen trap sites. In the DLC coatings with high hydrogen content, these hydrogen trap sites are likely already filled with hydrogen atoms, and the movement of new hydrogen atoms could be limited.

Keywords: hydrogen permeation, stainless steels, diamond-like carbon, hydrogen trap sites

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Authors: Oluwatayomi Daniel Fadumo, Chinyere Celestina Esimone

Abstract:

The construction industry, as a massive human capital-related sector, requires an always motivated workforce. The inability to maintain this state has been found to hamper productivity which ultimately leads to poor project delivery, infrastructural development decline, and low morale among citizens. The need to develop an approach to keep this set of people inspired before, during, and after work becomes a necessity; this paper aims to evaluate the key benefits and cautions in integrating music on construction sites in Nigeria to improve effective project delivery. In attaining this, the study identified the advantages of music on construction sites, evaluated the key considerations in introducing music on construction sites, and recommended measures for the effective integration of music on construction sites in Nigeria. The study is a descriptive research through the use of secondary data gleaned from relevant literature, journals, and research sites. The study concluded that different forms of music genres can be implemented ranging from Pop music, rock, metal, and classical music. Introducing music has the advantage of industrial branding, improving workers` morale, setting the pace for working, helping in information retention, and improving mental health and happiness. The key consideration, however, is to provide the right volume and music that doesn’t pose health and safety challenges. The study finally recommended that for effective integration of music on construction sites in Nigeria, policies should be drafted regulating its use, specific radio customized for the site be introduced and that research-based music, proven to have previously helped, should be given to a group of workers.

Keywords: music, construction sites, workers, construction industry, construction management practice

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