Search results for: transcription factor binding sites

Authors: Alaa M. Badr Eldin, Mayar M. Shahen, Mohammed S. Sedeek, Marwa I. Ezzat, Sawsan M. ElSonbaty, Muhammed A. Saad, Manal S. Afifi, Omar M. Sabry

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Using HPLC-MS/MS technique, 133 polyphenolic compounds were identified in the methanol extract of pomegranate rind (Punica granatum L.). In-vitro cytotoxic activity against breast cancer cell line MCF-7 was investigated, with an IC50 of 54 ug/ml. In-silico molecular docking using ellagic acid, gallagic acid, and Punicalagin as model compounds identified in pomegranate rind extract confirmed the intriguing anti-estrogenic action of the key polyphenolic components in pomegranate rind extract. Surprisingly, taxol showed low activity compared to pomegranate compounds as ERα antagonist and ERβ agonist. Pomegranate rind extract enhanced apoptosis of breast cancer cells through upregulation of the caspase-3 expression and downregulation of NF-κB transcription factor.

Keywords: HPLC-MS/MS, pomegranate rind, cytotoxicity, MCF-7, ER, caspase-3, NF-kB

Procedia PDF Downloads 91

Authors: Gali Pesin, Yuliya Lipshits-Braziler, Sima Amram-Vaknin, Moshe Tatar

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The present study introduces four different patterns of seeking and providing help online among adolescents: (I) ‘Transceivers’ - adolescents who both seek as well as provide help online; (II) ‘Receivers’ - adolescents who seek help online, yet don’t provide it; (III) ‘Transmitters’ - adolescents who provide help online, yet don’t seek it; and (IV) ‘Idles’ - adolescents who refrain from seeking and providing help online. The study examined differences in seeking and providing help online between possible combinations of the four patterns, as well as gender differences within each pattern. Data was collected from 528 adolescents in Israel (59% were girls). Findings revealed that Transceivers are the largest group (45%) in this study, with higher representation of girls (65%). These adolescents seek help mainly around social difficulties, and they turn to peers who are both known and unknown to them. In addition, their preferred way to seek and provide help is through social network sites. Moreover, they often accept and give others emotional support. Receivers are the smallest group (5%) in this study. They turn to both known and unknown professionals more often than to friends and family. In addition, they seek help mostly around health and nutrition issues, and they usually receive instrumental support. For Receivers, the most important factor for seeking help online is anonymity, and the least important factor is familiarity with the help giver. Transmitters represent 16% of the adolescents in this study, with a greater representation of boys (52%). Their main reason to refrain from seeking help online is self-reliance. Nevertheless, these adolescents provide help to others online, mainly to those known to them through posting or responding to posts on social network sites. Idles represent 34% of the adolescents in this study. They refrain from seeking help online mainly due to their preference to seek help face to face, and due to their lack of trust in the internet or those using it. Idles and Transmitters are willing to seek help online mostly from friends and family. In addition, they are willing seek help online mainly regarding questions concerning military or civil service. They consider the most important facilitators for seeking help online as confidentiality and reliability. The present study’s main contribution is exploring the role of providing online help in understanding the adolescent behavior of seeking help online. In addition, the results of the present study have practical implications for the work of mental health providers, such as counseling psychologists and online mental health support.

Keywords: adolescents, counseling, online help-seeking, online help-providing

Procedia PDF Downloads 138

Authors: Chamnan Kumsap, Somsarit Sinnung, Suriyawate Boonthalarath, Teeranai Srithamarong

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This research paper addresses the GIS analysis approach to the investigation of suitable sites for a vertical takeoff and landing drone. The study manipulated GIS and terrain layers into a proper input before the spatial analysis that included slope, reclassify, classify, and buffer was applied to the individual layers. The output layers were weighted, and multi-criteria analyzed before those patches failing to comply with filtering out criteria were discarded. Field survey for each suitable candidate site was conducted to cross-check the proposed approach with the real world. Conclusion was extracted for the VTOL takeoff and landing sites, and discussion was provided with further study being suggested on the mission simulation of selected takeoff and landing sites.

Keywords: GIS approach, site selection, VTOL, takeoff and landing

Procedia PDF Downloads 76

Authors: Qintao Shen, Lei Luo, Jun Ma, Jie Yu, Qingbo Wu, Yongqi Ma, Zhengji Liu

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Control Flow Integrity (CFI) is one of the most promising technique to defend Code-Reuse Attacks (CRAs). Traditional CFI Systems and recent Context-Sensitive CFI use coarse control flow graphs (CFGs) to analyze whether the control flow hijack occurs, left vast space for attackers at indirect call-sites. Coarse CFGs make it difficult to decide which target to execute at indirect control-flow transfers, and weaken the existing CFI systems actually. It is an unsolved problem to extract CFGs precisely and perfectly from binaries now. In this paper, we present an algorithm to get a more precise CFG from binaries. Parameters are analyzed at indirect call-sites and functions firstly. By comparing counts of parameters prepared before call-sites and consumed by functions, targets of indirect calls are reduced. Then the control flow would be more constrained at indirect call-sites in runtime. Combined with CCFI, we implement our policy. Experimental results on some popular programs show that our approach is efficient. Further analysis show that it can mitigate COOP and other advanced attacks.

Keywords: contex-sensitive, CFI, binary analysis, code reuse attack

Procedia PDF Downloads 290

Authors: Jocelyn D. Perreault

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An exploratory study has been launched in 2013-2014 in the province of Quebec, the state of Vermont (USA) and the region of Zaer in Morocco. We have realized three first case studies in order to better understand the marketing strategies of starting up vineries, which are defined as having a maximum of five years of operations. The methodology used consisted of visiting the vineyards; conducting semi-directed interviews with owner-managers; visiting points-of-sale of the wines and analysing the web sites using an assessment grid. The results indicate many differences between the three firms in their use of their web sites. More precisely, we have noticed that: -The Quebec vineyard uses its web site in collaboration with the touristic actors of its region and the association of the wine makers of the province of Quebec.Positioning is as a touristic attraction. -In comparison,the Moroccan firm limits the content of the web site to itself and its activities and somehow to the wine industry.Positioning is as a wine specialist. -The american firm associated its web site more to farm markets actors and activities of the region.Positioning is as an agricultural actor. -The positionings of the three vineyards are very different from each others and will be discussed more thoroughly during the presentation to better understand the use of web sites, thus contributing to the «brand image». -Improvements to the three web sites have been identified and suggested by more than a hundred of persons using the same grid and comprising students of bachelor and MBA degrees from our university. In general, the web sites have been considered satisfying but requiring several improvements at different levels. Changes or updates have been observed for the Quebec winery web site but practically no changes have been made to the others in the last months. The assessment grid will be presented in more details as well as the global and the partial scores given by the respondents. In conclusion, we have noticed that only one winery is considered as a «heavy and strategic user» of its web site and of Facebook and Twitter.

Keywords: web site, wineries, marketing, positioning, starting up strategies

Procedia PDF Downloads 287

Authors: Mustafa Ali Abugila, Basma Nuri Kajruba, Hanan Elhadi, Rehab Ramadan Wali

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Iron deficiency anemia is characterized by a decrease of Hb (hemoglobin), serum iron, ferritin, and RBC (red blood cells) (shape and size). Also, it is characterized by an increase in total iron binding capacity (TIBC). Red blood cells become microctytic and hypochromic due to a decrease in iron content. This study was conducted in the north west of Libya and included 210 women in childbearing age (18-45 years) who were visiting women clinic. After filling the questionnaire, blood samples were taken and analyzed for hematological and biochemical profiles. Biochemical tests included measurement of serum iron, ferritin, and total iron binding capacity (TIBC). Among the total sample (210 women), there were 87 (41.42%) pregnant and 123 (58.57%) non-pregnant women (includes married and single). Pregnant women (87) were classified according to the gestational age into first, second, and third trimesters. The means of biochemical and hematological parameters in the studied samples were: Hb = 10.37± 2.02 g/dl, RBC = 3.78± 1.037 m/m3, serum iron 61.86± 40.28 µg/dl, and TIBC = 386.01 ± 94.91 µg/dl. In this study, we considered that any women have hemoglobin below 11.5 g/dl is anemic. 89.1%, 69.5%, and 47.8% of pregnant women who belong to third trimester had low (below normal value) Hb, serum iron, and ferritin, i.e. iron deficiency anemia was more common in third trimester among the first and the second trimesters. Third trimester pregnant women also had high TIBC more than first and second trimesters.

Keywords: red blood cells, hemoglobin, total iron binding capacity, ferritin

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Authors: Anika Chebrolu

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Mono-targeted drugs can be of limited efficacy against complex diseases. Recently, multi-target drug design has been approached as a promising tool to fight against these challenging diseases. However, the scope of current computational approaches for multi-target drug design is limited. DeepLig presents a de-novo drug discovery platform that uses reinforcement learning to generate and optimize novel, potent, and multitargeted drug candidates against protein targets. DeepLig’s model consists of two networks in interplay: a generative network and a predictive network. The generative network, a Stack- Augmented Recurrent Neural Network, utilizes a stack memory unit to remember and recognize molecular patterns when generating novel ligands from scratch. The generative network passes each newly created ligand to the predictive network, which then uses multiple Graph Attention Networks simultaneously to forecast the average binding affinity of the generated ligand towards multiple target proteins. With each iteration, given feedback from the predictive network, the generative network learns to optimize itself to create molecules with a higher average binding affinity towards multiple proteins. DeepLig was evaluated based on its ability to generate multi-target ligands against two distinct proteins, multi-target ligands against three distinct proteins, and multi-target ligands against two distinct binding pockets on the same protein. With each test case, DeepLig was able to create a library of valid, synthetically accessible, and novel molecules with optimal and equipotent binding energies. We propose that DeepLig provides an effective approach to design multi-targeted drug therapies that can potentially show higher success rates during in-vitro trials.

Keywords: drug design, multitargeticity, de-novo, reinforcement learning

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Authors: Farnoosh Faal

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The trend among smart cities is to incorporate technological advancements to better manage and protect their cultural heritage sites. This study investigates how smart city solutions can improve the cultural and historical significance of urban heritage sites and assesses present practices and potential for the future. The paper delves into the literature to examine how smart city technologies can be utilized to increase knowledge and respect for cultural heritage, as well as promote sustainable tourism and economic growth. The article reviews various instances of smart city initiatives across different regions of the world, pinpointing innovative tactics and best practices in improving the cultural and historical worth of urban heritage sites. Additionally, it analyzes the difficulties and limitations associated with implementing these solutions, including community involvement, privacy concerns, and data management issues. The conclusions drawn from this paper propose that smart city solutions offer a substantial opportunity to augment the cultural and historical value of urban heritage sites. By effectively integrating technology into heritage management, there can be greater comprehension and admiration for cultural heritage, enhanced visitor experience, and support for sustainable tourism. However, to fully exploit the potential of smart city solutions in this context, it is crucial to prioritize community engagement and participation, as well as ensure that data management practices are transparent, responsible, and respectful of privacy. In summary, this paper offers guidance and advice to policymakers, urban planners, and heritage management professionals who want to increase the cultural and historical significance of urban heritage sites through the application of smart city solutions. It emphasizes the significance of creating comprehensive and cooperative strategies, as well as ensuring that efforts to preserve heritage are sustainable, fair, and efficient.

Keywords: smart city, Urban heritage, sustainable tourism, heritage preservation

Procedia PDF Downloads 68

Authors: Islam Nowisser, Noha Farag, Mohamed El Azizi

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Helicobacter pylori is a highly important human pathogen which inhabits about 50% of the population worldwide. Infection with this bacteria is very hard to treat, with high probability of recurrence. H. pylori causes severe gastric diseases, including peptic ulcer, gastritis, and gastric cancer, which has been linked to chronic inflammation. The infection has been reported to be associated with high levels of pro-inflammatory cytokines, especially IL-1β and TNF-α. The aim of the current study is to investigate the molecular mechanisms by which H. pylori activates NLRP3 inflammasome and its contribution to Il-1 β production in an innate cellular model. H. pylori PMSS1 and G27 standard strains, as well as the PMSS1 isogenic mutant strain PMSS1ΔVacA and G27ΔVacA, G27ΔCagA in addition to clinical isolates obtained from biopsy samples from the antrum and corpus mucosa of chronic gastritis patients, were used to establish infection in RAW-264.7 macrophages. The production levels of TNF-α and IL-1β was assessed using ELISA. Since expression of these cytokines is often regulated by the transcription factor complex, nuclear factor-kB (NF-kB), the activation of NF-κB in H. pylori infected cells was also evaluated by luciferase assay. Genomic DNA was extracted from bacterial cultures of H. pylori clinical isolates as well as the standard strains and their corresponding mutants, where they were evaluated for the cagA pathogenicity island and vacA expression. The correlation between these findings and expression of the cagA Pathogenicity Island and vacA in the bacteria was also investigated. The results showed IL-1β, and TNF-α production significantly increased in raw macrophages following H. pylori infection. The cagA+ and vacA+ H. pylori strains induced significant production of IL-1β compared to cagA- and vacA- strains. The activation pattern of NF-κB was correlated in the isolates to their cagA and vacA expression profiles. A similar finding could not be confirmed for TNF-α production. Our study shows the ability of H. pylori to activate NF-kB and induce significant IL-1β production as a possible mechanism for the augmented inflammatory response seen in subjects infected with cagA+ and vacA+ H. pylori strains that would lead to the progression to more severe form of the disease.

Keywords: Helicobacter pylori, IL-1β, inflammatory cytokines, nuclear factor KB, TNF-α

Procedia PDF Downloads 101

Authors: Hari Bezwada, Michelle Cheon, Ryan Divan, Hannah Escritor, Michelle Kagramian, Isha Korgaonkar, Maya MacAdams, Udgita Pamidigantam, Richard Pilny, Eleanor Race, Angadh Singh, Nathan Zhang, LeeAnn Nguyen, Fina Liotta

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Malaria is a deadly disease caused by the Plasmodium parasite, which continues to develop resistance to current antimalarial drugs. In this research project, the effectiveness of numerous thiazole derivatives was explored in inhibiting the PfPKG, a crucial part of the Plasmodium life cycle. This study involved the synthesis of six thiazole-derived amides to inhibit the PfPKG pathway. Nuclear Magnetic Resonance (NMR) spectroscopy and Infrared (IR) spectroscopy were used to characterize these compounds. Furthermore, AutoDocking software was used to predict binding affinities of these thiazole-derived amides in silico. In silico, compound 6 exhibited the highest predicted binding affinity to PfPKG, while compound 5 had the lowest affinity. Compounds 1-4 displayed varying degrees of predicted binding affinity. In-vitro, it was found that compound 4 had the best percent inhibition, while compound 5 had the worst percent inhibition. Overall, all six compounds had weak inhibition (approximately 30-39% at 10 μM), but these results provide a foundation for future drug discovery experiments.

Keywords: Medicinal Chemistry, Malaria, drug discovery, PfPKG, Thiazole, Plasmodium

Procedia PDF Downloads 64

Authors: Tassia Batista Pessato, Francielli Pires Ribeiro Morais, Fernanda Guimaraes Drummond Silva, Flavia Maria Netto

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Proteins and phenolic compounds can interact mainly by hydrophobic interactions. Those interactions may lead to structural changes in both molecules, which in turn could affect positively or negatively their functional and nutritional properties. Here, the structural changes of whey proteins (WPI) due to interaction with caffeic acid (CA) were investigated by intrinsic and extrinsic fluorescence. The effects of protein-phenolic compounds interactions on the total phenolic content and antioxidant activity were also assessed. The WPI-CA complexes were obtained by mixture of WPI and CA stock solutions in deionized water. The complexation was carried out at room temperature during 60 min, using 0.1 M NaOH to adjust pH at 7.0. The WPI concentration was fixed at 5 mg/mL, whereas the CA concentration varied in order to obtain four different WPI:CA molar relations (1:1; 2:1; 5:1; 10:1). WPI and phenolic solutions were used as controls. Intrinsic fluorescence spectra of the complexes (mainly due to Trp fluorescence emission) were obtained at λex = 280 nm and the emission intensities were measured from 290 to 500 nm. Extrinsic fluorescence was obtained as the measure of protein surface hydrophobicity (S0) using ANS as a fluorescence probe. Total phenolic content was determined by Folin-Ciocalteau and the antioxidant activity by FRAP and ORAC methods. Increasing concentrations of CA resulted in decreasing of WPI intrinsic fluorescence. The emission band of WPI red shifted from 332 to 354 nm as the phenolic concentration increased, which is related to the exposure of Trp residue to the more hydrophilic environment and unfolding of protein structure. In general, the complexes presented lower S0 values than WPI, suggesting that CA hindered ANS binding to hydrophobic sites of WPI. The total phenolic content in the complexes was lower than the sum of two compounds isolated. WPI showed negligible AA measured by FRAP. However, as the relative concentration of CA increased in the complexes, the FRAP values enhanced, indicating that AA measure by this technique comes mainly from CA. In contrast, the WPI ORAC value (82.3 ± 1.5 µM TE/g) suggest that its AA is related to the capacity of H+ transfer. The complexes exhibited no important improvement of AA measured by ORAC in relation to the isolated components, suggesting complexation partially suppressed AA of the compounds. The results hereby presented indicate that interaction of WPI and CA occurred, and this interaction caused a structural change in the proteins. The complexation can either hide or expose antioxidant sites of both components. In conclusion, although the CA can undergo an AA suppression due to the interaction with proteins, the AA of WPI could be enhanced due to protein unfolding and exposure of antioxidant sites.

Keywords: bioactive properties, milk proteins, phenolic acids, protein-phenolic compounds complexation

Procedia PDF Downloads 516

Authors: Chinmayee Choudhury

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Human Melanocortin 4 Receptor (HMC4R) is one of the most potential drug targets for the treatment of obesity which controls the appetite. A deletion of the residues 88-92 in HMC4R is sometimes the cause of severe obesity in the humans. In this study, two homology models are constructed for the normal as well as mutated HMC4Rs and some phytochemicals present in Green Tea, Honey and Cinnamon have been docked to them to study their differential binding to the normal and mutated HMC4R as compared to the natural agonist α- MSH. Two homology models have been constructed for the normal as well as mutated HMC4Rs using the Modeller9v7. Some of the phytochemicals present in Green Tea, Honey, and Cinnamon, which have appetite suppressant activities are constructed, minimized and docked to these normal and mutated HMC4R models using ArgusLab 4.0.1. The mode of binding of the phytochemicals with the Normal and Mutated HMC4Rs have been compared. Further, the mode of binding of these phytochemicals with that of the natural agonist α- Melanocyte Stimulating Hormone(α-MSH) to both normal and mutated HMC4Rs have also been studied. It is observed that the phytochemicals Kaempherol, Epigallocatechin-3-gallate (EGCG) present in Green Tea and Honey, Isorhamnetin, Chlorogenic acid, Chrysin, Galangin, Pinocambrin present in Honey, Cinnamaldehyde, Cinnamyl acetate and Cinnamyl alcohol present in Cinnamon have capacity to form more stable complexes with the Mutated HMC4R as compared to α- MSH. So they may be potential agonists of HMC4R to suppress the appetite.

Keywords: HMC4R, α-MSH, docking, photochemical, appetite suppressant, homology modelling

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Authors: H. Abu-Ali, A. Nabok, T. Smith

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Aptamers are single-strand of DNA or RNA nucleotides sequence which is designed in vitro using selection process known as SELEX (systematic evolution of ligands by exponential enrichment) were developed for the selective detection of many toxic materials. In this work, we have developed an electrochemical biosensor for highly selective and sensitive detection of Hg2+ and Pb2+ using a specific aptamer probe (SAP) labelled with ferrocene (or methylene blue) in (5′) end and the thiol group at its (3′) termini, respectively. The SAP has a specific coil structure that matching with G-G for Pb2+ and T-T for Hg2+ interaction binding nucleotides ions, respectively. Aptamers were immobilized onto surface of screen-printed gold electrodes via SH groups; then the cyclic voltammograms were recorded in binding buffer with the addition of the above metal salts in different concentrations. The resulted values of anode current increase upon binding heavy metal ions to aptamers and analyte due to the presence of electrochemically active probe, i.e. ferrocene or methylene blue group. The correlation between the anodic current values and the concentrations of Hg2+ and Pb2+ ions has been established in this work. To the best of our knowledge, this is the first example of using a specific DNA aptamers for electrochemical detection of heavy metals. Each increase in concentration of 0.1 μM results in an increase in the anode current value by simple DC electrochemical test i.e (Cyclic Voltammetry), thus providing an easy way of determining Hg2+ and Pb2+concentration.

Keywords: aptamer, based, biosensor, DNA, electrochemical, highly, specific

Procedia PDF Downloads 136

Authors: Mozhgan Bahadory, Gholam-Hossein Rostami

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Over the next quarter of a century, the US government and the private sector will spend billions of dollars annually to clean the contaminated sites from pollution such as petroleum products, heavy metals, and solvents organic compounds. During the past three decades, almost 750,000 sites that require remediation have been reported to the United States federal and state agencies. Out of these contamination sites, approximately 300,000 are still in need of remediation. In these sites, the most widespread forms of contamination are petroleum products and heavy metals. At least half of US Department of Defense, US Department of Energy, Superfund sites, and Resource Conservation and Recovery Act (RCRA) sites have been reported to contain heavy metals. Heavy metals most often found in the contaminated water are lead, mercury, chromium, cadmium, arsenic, and zinc. This investigation emphasizes the elimination of arsenic and cadmium from aqueous solution. During the past several years, we developed a novel material called Alkali-Activated fly ash Material Permeable Reactive Barrier (AAM-PRB), which includes fly ash, fine aggregates, coarse aggregates, activating chemicals, and water. AAM can be produced with high permeability, 10-1 cm/s, then crushed into pelletized form. Laboratory experiments showed that water containing 10 ppm, 100 ppm, and 1000 ppm of arsenic and cadmium ion passing through AAM-PRB reduced to less than 0.1 ppm. However, water containing 10,000 ppm arsenic ion passing through AAM- PRB shows that the breakthrough was achieved. The removal of the mixture of arsenic and cadmium from aqueous solutions was also tested by using AAM-PRB. The results indicate that the efficiency of AAM-PRB for simultaneous removal of arsenic and cadmium from 10 ppm, 100 ppm, and 1,000 ppm were marginally below that of arsenic alone. Still, it was significantly lower for cadmium from the aqueous solution. The basic science behind removing heavy metal and microstructural investigation AAM-PRB will be the focus of our future work.

Keywords: arsenic, cadmium, contaminated water, fly ash, permeability, reactive barrier

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Authors: Lin Huang, Bo Wang, Armando Borgna

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Dehydration of glycerol to acrolein was conducted with solid acid catalysts in liquid phase in a batch reactor and in gas phase in a fix-bed reactor, respectively. In the liquid-phase reaction, ZSM-5, H3PO4-modified ZSM-5 and heteropolyacids including H3PW12O40•xH2O (HPW) and Cs2.5H0.5PW12O40 (CsPW) were studied as catalysts. High temperatures and high boiling point solvents such as sulfolane improved the selectivity to acrolein through suppressing the formation of polyglycerols and coke. Catalytic results and temperature-programmed desorption of ammonia showed that the yield of acrolein increased with increasing catalyst acidity within the range of weak acid strength. Weak acid sites favored the selectivity to acrolein whereas strong acid sites promoted the formation of coke. ZSM-5 possessing only acid sites led to a high acrolein yield, while heteropolyacid catalysts with strong acid sites produced a low acrolein yield. In the gas-phase reaction, HPW and CsPW supported on metal oxides such as SiO2, γ-Al2O3, SiO2-Al2O3, ZrO2 and silicate TUD-1 were studied as catalysts. HPW/TUD-1 was most active for the production of acrolein, followed by HPW/SiO2. An acrolein yield of 61 % was obtained over HPW/TUD-1. X-ray diffraction study suggested that HPW and CsPW were stable and more dispersed on SiO2, silicate TUD-1 and SiO2-Al2O3. It was found that the structures of HPW and CsPW were destroyed by interaction with γ-Al2O3 and ZrO2. Compared to CsPW/TUD-1, the higher acrolein yield with HPW/TUD-1 may be attributed to more Brønsted acid sites on HPW/TUD-1, based on preliminary pyridine adsorption IR study.

Keywords: dehydration, glycerol, acrolein, solid acid catalysts, gas-phase, liquid-phase

Procedia PDF Downloads 239

Authors: Amna J. Ghith, Khaled Abu Zid, Khairia Youssef, Nasser Saad

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Backgrounds: The multikinase and vascular endothelial growth factor (VEGF) receptor inhibitors interrupt the pathway by which angiogenesis becomes established and promulgated, resulting in the inadequate nourishment of metastatic disease. VEGFR-2 has been the principal target of anti-angiogenic therapies. We disclose the new thieno pyrimidines as inhibitors of VEGFR-2 designed by a molecular modeling approach with increased synergistic activity and decreased side effects. Purpose: 2-substituted thieno pyrimidines are designed and synthesized with anticipated anticancer activity based on its in silico molecular docking study that supports the initial pharmacophoric hypothesis with a same binding mode of interaction at the ATP-binding site of VEGFR-2 (PDB 2QU5) with high docking score. Methods: A series of compounds were designed using discovery studio 4.1/CDOCKER with a rational that mimic the pharmacophoric features present in the reported active compounds that targeted VEGFR-2. An in silico ADMET study was also performed to validate the bioavailability of the newly designed compounds. Results: The Compounds to be synthesized showed interaction energy comparable to or within the range of the benzimidazole inhibitor ligand when docked with VEGFR-2. ADMET study showed comparable results most of the compounds showed absorption within (95-99) zone varying according to different substitutions attached to thieno pyrimidine ring system. Conclusions: A series of 2-subsituted thienopyrimidines are to be synthesized with anticipated anticancer activity and according to docking study structure requirement for the design of VEGFR-2 inhibitors which can act as powerful anticancer agents.

Keywords: docking, discovery studio 4.1/CDOCKER, heterocycles based anticancer agents, 2-subsituted thienopyrimidines

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Authors: Mohd Farooq Naqshbandi

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The four fractions of aqueous extract of Sesame Seeds (Sesamum indicum L.) were studied for invitro DNA fragmentation, cell migration, and cellular apoptosis on SW480 and HTC116 human colorectal cancer cell lines. The seeds of Sesamum indicum were extracted with six solvents, including Methanol, Ethanol, Aqueous, Chloroform, Acetonitrile, and Hexane. The aqueous extract (IC₅₀ value 154 µg/ml) was found to be the most active in terms of cytotoxicity with SW480 human colorectal cancer cell lines. Further fractionation of this aqueous extract on flash chromatography gave four fractions. These four fractions were studied for anticancer and DNA binding studies. Cell viability was assessed by colorimetric assay (MTT). IC₅₀ values for all these four fractions ranged from 137 to 548 µg/mL for the HTC116 cancer cell line and 141 to 402 µg/mL for the SW480 cancer cell line. The four fractions showed good anticancer and DNA binding properties. The DNA binding constants ranged from 10.4 ×10⁴ 5 to 28.7 ×10⁴, showing good interactions with DNA. The DNA binding interactions were due to intercalative and π-π electron forces. The results indicate that aqueous extract fractions of sesame showed inhibition of cell migration of SW480 and HTC116 human colorectal cancer cell lines and induced DNA fragmentation and apoptosis. This was demonstrated by calculating the low wound closure percentage in cells treated with these fractions as compared to the control (80%). Morphological features of nuclei of cells treated with fractions revealed chromatin compression, nuclear shrinkage, and apoptotic body formation, which indicate cell death by apoptosis. The flow cytometer of fraction-treated cells of SW480 and HTC116 human colorectal cancer cell lines revealed death due to apoptosis. The results of the study indicate that aqueous extract of sesame seeds may be used to treat colorectal cancer.

Keywords: Sesamum indicum, cell migration inhibition, apoptosis induction, anticancer activity, colorectal cancer

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Authors: Geetakshi Arora, Danish Malhotra

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Diabetic wounds are serious health issues and often fail to heal, leading to limb amputation that makes the life of the patient miserable. Delayed wound healing has been characterized by an increase in matrix metalloproteinase-9 (MMP-9). Thus research throughout the world has been going on to develop selective MMP-9 inhibitors for aiding diabetic wound healing. Bioactive constituents from natural sources always served as potential leads in drug development with high rates of success. Considering the need for novel selective MMP-9 inhibitors and the importance of natural bioactive compounds in drug development, we have screened a library of bioactive constituents from plant sources that were effective in diabetic wound healing on human MMP-9 (hMMP-9) using molecular docking studies. Screened constituents are ranked according to their dock score, ∆G value (binding affinity), and Ligand efficiency evaluated from FleXX docking and Hyde scoring modules available with drug designing platform LeadIT. Rhamnocitrin showed the highest correlation between dock score, ∆G value (binding affinity), and Ligand efficiency was further explored for binding interactions with hMMP-9. The overall study suggest that Rhamnocitrin is sufficiently decorated with both hydrophilic and hydrophobic substitutions that perfectly block hMMP-9 and act as a potential lead in the design and development of selective hMMP-9 inhibitors.

Keywords: MMP-9, diabetic wound, molecular docking, phytoconstituents

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Authors: Nihar Ranjan, Derrick Watkins, Dev P. Arya

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Current methods in the study of antibiotic activity of ribosome targeted antibiotics are dependent on cell based bacterial inhibition assays or various forms of ribosomal binding assays. These assays are typically independent of each other and little direct correlation between the ribosomal binding and bacterial inhibition is established with the complementary assay. We have developed novel high-throughput capable assays for ribosome targeted drug discovery. One such assay examines the compounds ability to bind to a model ribosomal RNA A-site. We have also coupled this assay to other functional orthogonal assays. Such analysis can provide valuable understanding of the relationships between two complementary drug screening methods and could be used as standard analysis to correlate the affinity of a compound for its target and the effect the compound has on a cell.

Keywords: bacterial resistance, aminoglycosides, screening, drugs

Procedia PDF Downloads 342

Authors: Wuthichai Wongthatsanekorn, Nuntana Matheekrieangkrai

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This research proposes Bee Algorithm (BA) to optimize Ready Mixed Concrete (RMC) truck scheduling problem from single batch plant to multiple construction sites. This problem is considered as an NP-hard constrained combinatorial optimization problem. This paper provides the details of the RMC dispatching process and its related constraints. BA was then developed to minimize total waiting time of RMC trucks while satisfying all constraints. The performance of BA is then evaluated on two benchmark problems (3 and 5construction sites) according to previous researchers. The simulation results of BA are compared in term of efficiency and accuracy with Genetic Algorithm (GA) and all problems show that BA approach outperforms GA in term of efficiency and accuracy to obtain optimal solution. Hence, BA approach could be practically implemented to obtain the best schedule.

Keywords: bee colony optimization, ready mixed concrete problem, ruck scheduling, multiple construction sites

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Authors: M. Said Ahmed, M. Lebrini, J. Pellé, S. Rioual, B. Lescop, C. Roos

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The corrosion behavior of copper exposed in a marine atmosphere polluted and unpolluted by gases, mainly hydrogen sulphide (H2S), from the decomposition of Sargassum algae was studied using the mass loss method and electrochemical measurements. MEB/EDX and XRD were also used for the observation of morphology and surface analysis. To study the impact of this on copper corrosion, four sites more or less impacted by Sargassum algae strandings were selected. The samples were exposed for up to six months. The mass loss results showed that the average corrosion rate of copper was 528 µm/year for the site most affected by Sargassum algae and 9.4 µm/year for the least impacted site after three months of exposure, implying that the presence of Sargassum algae caused an important copper degradation. The morphological structures and properties of the corrosion products obtained at the impacted and non-impacted sites differed significantly. In the absence of Sargassum algae, we obtained mainly Cu2O and Cu2Cl(OH)3. Whereas in the atmosphere with Sargassum algae, CuS product is the main corrosion product obtained. Electrochemical analyses showed that the protection offered by the corrosion product layer was more important and improved with time for the non-impacted sites, whereas on the impacted sites, this protection deteriorated.

Keywords: atmospheric-corrosion, sargassum algae, copper, electrochemical techniques, SEM/EDX and XRD

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Authors: S. Mohamadi, T. Boudina, A. Rouabeh, A. Seridi

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Equivalent linear and non-linear ground response analyses are conducted at many representative sites at the mosque of Algeria, to compare the free field acceleration spectra with local code of practice. Spectral Analysis of Surface Waves (SASW) technique was adopted to measure the in-situ shear wave velocity profile at the representative sites. The seismic movement imposed on the rock is the NS component of Keddara station recorded during the earthquake in Boumerdes 21 May 2003. The site-specific elastic design spectra for each site are determined to further obtain site specific non-linear acceleration spectra. As a case study, the results of site-specific evaluations are presented for two building sites (site of minaret and site of the prayer hall) to demonstrate the influence of local geological conditions on ground response at Algerian sites. A comparison of computed response with the standard code of practice being used currently in Algeria for the seismic zone of Algiers indicated that the design spectra is not able to capture site amplification due to local geological conditions.

Keywords: equivalent linear, non-linear, ground response analysis, design response spectrum

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Authors: Pennuel P. Togonave, Bartholomew S. Apis, Emma Kiup, Gure Tumae, Johannes Pakatul, Michael Webb

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Interplanting food crops in coffee gardens has increased in recent years. The purpose of this study was to quantify the nutrient management implications of growing food crops within the coffee garden and to investigate the sustainability of this practice through field surveys in two accessible sites (Asaro and Bena) and two remote sites (Marawaka and Baira), in Eastern Highlands Province of Papua New Guinea. Coffee gardens were selected at each site and surveys were conducted to assess the status of intercropping in each of the smallholder coffee gardens. Food crops in the coffee gardens were sampled for nutrient analysis Survey results indicate intercropping as a common practice in coffee gardens and entailed mixed cropping of food crops in an irregular pattern and spacing. More than 40% of the farmers used 40-60% of their total coffee garden area for intercropping. In remote sites, more than 50% of the coffee garden areas closest to the house were intercropped with food crops compared to 40% of inaccessible sites. In both remote and accessible sites, the most common intercropped food crops were 90% banana (Musa spp) varieties and 50% sugarcane (Saccharum spp). Nutrient analysis of the by-products and residuals of some common intercrops shows the potential to replenish the coffee plant's deficient nutrients like Potassium, Magnesium, Phosphorus, Boron and Zinc. Intercropping of coffee gardens is increasing due to land pressure, marketing opportunities, food security and labor supply

Keywords: by-products, coffee, crops, intercropping, nutrients, soil

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Authors: D. R. Apoorva

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Ichthyosis follicularis, alopecia, and photophobia (IFAP) syndrome is a rare oculocutaneous disorder of genetic origin. This disorder results from mutations in the membrane-bound transcription factor protease site, two genes that impair cholesterol homeostasis, and the ability to cope with endoplasmic reticulum stress. We report a rare case of IFAP syndrome with an atypical presentation, and it was interesting to note that the child had patchy non-scarring alopecia over the scalp along with unilateral madarosis. To our best knowledge, this unique presentation has not been described earlier. The child presented with photophobia and unilateral ptosis. The child also had short stature and intellectual disability. Skin histopathology was nonspecific and consisted of dilated hair follicles with keratin plugs extending above the skin surface. This rare oculocutaneous disorder requires proper documentation so that identification of its variants may be possible in the future. Early recognition of atypical presentations can help in preventing cardiovascular complications, which remain the major cause of death.

Keywords: alopecia, photophobia, ichthyosis follicularis, IFAP syndrome

Procedia PDF Downloads 53

Authors: Qi Liu, Jiqin Yao, Xiaohu Zhou, Bo Zheng

Abstract:

The first artificial cell was produced by Thomas Chang in the 1950s when he was trying to make a mimic of red blood cells. Since then, many different types of artificial cells have been constructed from one of the two approaches: a so-called bottom-up approach, which aims to create a cell from scratch, and a top-down approach, in which genes are sequentially knocked out from organisms until only the minimal genome required for sustaining life remains. In this project, bottom-up approach was used to build a new cell-free expression system which mimics artificial cell that capable of protein expression and communicate with each other. The artificial cells constructed from the bottom-up approach are usually lipid vesicles, polymersomes, hydrogels or aqueous droplets containing the nucleic acids and transcription-translation machinery. However, lipid vesicles based artificial cells capable of communication present several issues in the cell communication research: (1) The lipid vesicles normally lose the important functions such as protein expression within a few hours. (2) The lipid membrane allows the permeation of only small molecules and limits the types of molecules that can be sensed and released to the surrounding environment for chemical communication; (3) The lipid vesicles are prone to rupture due to the imbalance of the osmotic pressure. To address these issues, the hydrogel-based artificial cells were constructed in this work. To construct the artificial cell, polyacrylamide hydrogel was functionalized with Acrylate PEG Succinimidyl Carboxymethyl Ester (ACLT-PEG2000-SCM) moiety on the polymer backbone. The proteinaceous factors can then be immobilized on the polymer backbone by the reaction between primary amines of proteins and N-hydroxysuccinimide esters (NHS esters) of ACLT-PEG2000-SCM, the plasmid template and ribosome were encapsulated inside the hydrogel particles. Because the artificial cell could continuously express protein with the supply of nutrients and energy, the artificial cell-artificial cell communication and artificial cell-natural cell communication could be achieved by combining the artificial cell vector with designed plasmids. The plasmids were designed referring to the quorum sensing (QS) system of bacteria, which largely relied on cognate acyl-homoserine lactone (AHL) / transcription pairs. In one communication pair, “sender” is the artificial cell or natural cell that can produce AHL signal molecule by synthesizing the corresponding signal synthase that catalyzed the conversion of S-adenosyl-L-methionine (SAM) into AHL, while the “receiver” is the artificial cell or natural cell that can sense the quorum sensing signaling molecule form “sender” and in turn express the gene of interest. In the experiment, GFP was first immobilized inside the hydrogel particle to prove that the functionalized hydrogel particles could be used for protein binding. After that, the successful communication between artificial cell-artificial cell and artificial cell-natural cell was demonstrated, the successful signal between artificial cell-artificial cell or artificial cell-natural cell could be observed by recording the fluorescence signal increase. The hydrogel-based artificial cell designed in this work can help to study the complex communication system in bacteria, it can also be further developed for therapeutic applications.

Keywords: artificial cell, cell-free system, gene circuit, synthetic biology

Procedia PDF Downloads 125

Authors: Abdullahi Garba Abu, Muhammad Bello Sada, Aminu Abubakar

Abstract:

Facebook and Twitter/X platforms are preferred and largely patronized by Youths in Nigeria. The simplicity and popularity of Facebook and Twitter/X have made them preferred social networking sites for Youths to handle or execute different political activities in favor of their chosen candidates or political parties. This is largely related to their interest in using the platform for the purposes of participation in 2023 political activities and general elections. The two Social Networking Sites were used to vigorously pursue party activities on the eve of the 2023 general elections. Youths engaged the two platforms in campaigning for their candidates and political parties and succeeded in reaching a wide audience, shared the policies and manifestos of their parties, engaged with supporters and even posted advertising campaigns for specific demographics. However, the utilization of Facebook and Twitter /X platforms during the 2023 elections was largely seen in two lights: positive and negative lights/intentions. Therefore, this research investigates the motivating factors for which largely Nigerian Youths engage Facebook and Twitter platforms in political activities, with reference to the 2023 general elections. The research uses a survey method through which it reaches out to respondents from all six geo-politial zones. The research found that Nigerian Youths utilize the two social media sites to campaign for politicians voluntarily based on their belief in the capabilities of the candidates. It also found out that Youths were lured into using Facebook and Twitter/X sites to campaign through tribal, religious, and ethnic factors. More so, the research found out that eagerness to share political materials in support of candidates made Youths in Nigeria share unverifiable content on Facebook and Twitter sites.

Keywords: Facebook, Twitter/X, Nigerian youths, 2023 elections

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Authors: Kamal Ameis

Abstract:

This study aims to further improve our understanding of the underlying mechanism of local injury that occurs after manual acupuncture needle manipulation, and that initiates the muscle regeneration process, which is essential for muscle maintenance and adaptation. Skeletal muscle is maintained by resident stem cells called muscle satellite cells. These cells are normally in quiescent state, but following muscle injury, they re-enter the cell cycle and execute a myogenic program resulting in muscle fiber regeneration. Our previous work in young rats demonstrated that acupuncture treatment induced injury that activated resident satellite (stem) cells, which leads to muscle regeneration. Skeletal muscle regeneration is an adaptive response to injury that requires a tightly orchestrated event between signaling pathways activated by growth factor and intrinsic regulatory program controlled by myogenic transcription factor. We identified several gene expressions uniquely important for muscle regeneration in response to acupuncture treatment at different time course using different biological techniques, including Immunocytochemistry, western blotting, and Real Time PCR. This study uses a novel but non-invasive model of injury induced by manual acupuncture to further our current understanding of regenerative mechanism of muscle stem cells. From a clinical perspective, this model of injury induced by manual acupuncture may be easily translatable into a clinical tool that can be used as an alternative to physical exercise for patients challenged by bed rest or forced inactivity. Finally, the knowledge gained from this research could be useful for studies of the local effects of various modalities of induced injury, such as the traditional method of healing by cupping (hijamah), which may enhanced muscle stem cells and muscle fiber regeneration.

Keywords: acupuncture, injury, regeneration, muscle stem cells

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Authors: Hamid Rostami, Ali Fallah Yeznabad, Mohammad H. Baziar

Abstract:

The energy-based method for evaluating seismic soil liquefaction has two main sections. First is the demand energy, which is dissipated energy of earthquake at a site, and second is the capacity energy as a representation of soil resistance against liquefaction hazard. In this study, using a statistical analysis of recorded data by 14 down-hole array sites in California, an empirical equation was developed to estimate the demand energy at sites. Because determination of capacity energy at a site needs to calculate several site calibration factors, which are obtained by experimental tests, in this study the standard penetration test (SPT) N-value was assumed as an alternative to the capacity energy at a site. Based on this assumption, the empirical equation was employed to calculate the demand energy for 193 liquefied and no-liquefied sites and then these amounts were plotted versus the corresponding SPT numbers for all sites. Subsequently, a discrimination analysis was employed to determine the equations of several boundary curves for various liquefaction likelihoods. Finally, a comparison was made between the probabilistic model and the commonly used stress method. As a conclusion, the results clearly showed that energy-based method can be more reliable than conventional stress-based method in evaluation of liquefaction occurrence.

Keywords: energy demand, liquefaction, probabilistic analysis, SPT number

Procedia PDF Downloads 343

Authors: Mohamed Moussaoui

Abstract:

A series of thirty-one potential inhibitors targeting the epidermal growth factor receptor kinase (EGFR), derived from quinazoline, underwent 3D-QSAR analysis using CoMFA and CoMSIA methodologies. The training and test sets of quinazoline derivatives were utilized to construct and validate the QSAR models, respectively, with dataset alignment performed using the lowest energy conformer of the most active compound. The best-performing CoMFA and CoMSIA models demonstrated impressive determination coefficients, with R² values of 0.981 and 0.978, respectively, and Leave One Out cross-validation determination coefficients, Q², of 0.645 and 0.729, respectively. Furthermore, external validation using a test set of five compounds yielded predicted determination coefficients, R² test, of 0.929 and 0.909 for CoMFA and CoMSIA, respectively. Building upon these promising results, eighteen new compounds were designed and assessed for drug likeness and ADMET properties through in silico methods. Additionally, molecular docking studies were conducted to elucidate the binding interactions between the selected compounds and the enzyme. Detailed molecular dynamics simulations were performed to analyze the stability, conformational changes, and binding interactions of the quinazoline derivatives with the EGFR kinase. These simulations provided deeper insights into the dynamic behavior of the compounds within the active site. This comprehensive analysis enhances the understanding of quinazoline derivatives as potential anti-cancer agents and provides valuable insights for lead optimization in the early stages of drug discovery, particularly for developing highly potent anticancer therapeutics

Keywords: 3D-QSAR, CoMFA, CoMSIA, ADMET, molecular docking, quinazoline, molecular dynamic, egfr inhibitors, lung cancer, anticancer

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Authors: K. Farheen, A. Munir

Abstract:

Seismic response of the multi-storey buildings is created by the interaction of both the structure and underlying soil medium. The seismic design philosophy is incorporated using response modification factor 'R'. Current code based values of 'R' factor does not reflect the SSI problem as it is based on fixed base condition. In this study, the modified values of 'R' factor for moment resisting frame (MRF) considering SSI are evaluated. The response of structure with and without SSI has been compared using equivalent linear static and nonlinear static pushover analyses for 10-storied moment resisting frame building. The building is located in seismic zone 2B situated on different soils with shear wave velocity (Vₛ) of 300m/sec (SD) and 1200m/s (SB). Code based 'R' factor value for building frame system has been taken as 5.5. Soil medium is modelled using identical but mutually independent horizontal and vertical springs. It was found that the modified 'R' factor values have been decreased by 47% and 43% for soil SD and SB respectively as compared to that of code based 'R' factor.

Keywords: buildings, SSI, shear wave velocity, R factor

Procedia PDF Downloads 186