Search results for: binding site
2562 Europium Chelates as a Platform for Biosensing
Authors: Eiman A. Al-Enezi, Gin Jose, Sikha Saha, Paul Millner
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Rare earth nanotechnology has gained a considerable amount of interest in the field of biosensing due to the unique luminescence properties of lanthanides. Chelating rare earth ions plays a significant role in biological labelling applications including medical diagnostics, due to their different excitation and emission wavelengths, variety of their spectral properties, sharp emission peaks and long fluorescence lifetimes. We aimed to develop a platform for biosensors based on Europium (Eu³⁺) chelates against biomarkers of cardiac injury (heart-type fatty acid binding protein; H-FABP3) and stroke (glial fibrillary acidic protein; GFAP). Additional novelty in this project is the use of synthetic binding proteins (Affimers), which could offer an excellent alternative targeting strategy to the existing antibodies. Anti-GFAP and anti-HFABP3 Affimer binders were modified to increase the number of carboxy functionalities. Europium nitrate then incubated with the modified Affimer. The luminescence characteristics of the Eu³⁺ complex with modified Affimers and antibodies against anti-GFAP and anti-HFABP3 were measured against different concentrations of the respective analytes on excitation wavelength of 395nm. Bovine serum albumin (BSA) was used as a control against the IgG/Affimer Eu³⁺ complexes. The emission spectrum of Eu³⁺ complex resulted in 5 emission peaks ranging between 550-750 nm with the highest intensity peaks were at 592 and 698 nm. The fluorescence intensity of Eu³⁺ chelates with the modified Affimer or antibodies increased significantly by 4-7 folder compared to the emission spectrum of Eu³⁺ complex. The fluorescence intensity of the Affimer complex was quenched proportionally with increased analyte concentration, but this did not occur with antibody complex. In contrast, the fluorescence intensity for Eu³⁺ complex increased slightly against increased concentration of BSA. These data demonstrate that modified Affimers Eu³⁺ complexes can function as nanobiosensors with potential diagnostic and analytical applications.Keywords: lanthanides, europium, chelates, biosensors
Procedia PDF Downloads 5262561 Synthesis and Characterization of Cyclic PNC-28 Peptide, Residues 17–26 (ETFSDLWKLL), A Binding Domain of p53
Authors: Deepshikha Verma, V. N. Rajasekharan Pillai
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The present study reports the synthesis of cyclic PNC-28 peptides with solid-phase peptide synthesis method. In the first step, we synthesize the linear PNC-28 Peptide and in the second step, we cyclize (N-to-C or head-to-tail cyclization) the linear PNC-28 peptide. The molecular formula of cyclic PNC-28 peptide is C64H88N12O16 and its m/z mass is ≈1233.64. Elemental analysis of cyclic PNC-28 is C, 59.99; H, 6.92; N, 13.12; O, 19.98. The characterization of LC-MS, CD, FT-IR, and 1HNMR has been done to confirm the successful synthesis and cyclization of linear PNC-28 peptides.Keywords: CD, FTIR, 1HNMR, cyclic peptide
Procedia PDF Downloads 1302560 Stabilizing a Failed Slope in Islamabad, Pakistan
Authors: Muhammad Umer Zubair, Kamran Akhtar, Muhammad Arsalan Khan
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This paper is based on a research carried out on a failed slope in Defence Housing Authority (DHA) Phase I, Islamabad. The research included determination of Soil parameters, Site Surveying and Cost Estimation. Apart from these, the use of three dimensional (3D) slope stability analysis in conjunction with two dimensional (2D) analysis was used determination of slope conditions. In addition collection of soil reports, a detailed survey was carried out to create a 3D model in Surfer 8 software. 2D cross-sections that needed to be analyzed for stability were generated from 3D model. Slope stability softwares, Rocscience Slide 6.0 and Clara-W were employed for 2D and 3D Analyses respectively which have the ability to solve complex mathematical functions. Results of the analyses were used to confirm site conditions and the threats were identified to recommend suitable remedies.The most effective remedy was suggested for slope stability after analyzing all remedies in software Slide 6 and its feasibility was determined through cost benefit analysis. This paper should be helpful to Geotechnical engineers, design engineers and the organizations working with slope stability.Keywords: slope stability, Rocscience, Clara W., 2d analysis, 3D analysis, sensitivity analysis
Procedia PDF Downloads 5262559 The Effects of Perceived Service Quality on Customers' Satisfaction, Trust and Loyalty in Online Shopping: A Case of Saudi Consumers' Perspectives
Authors: Nawt Almutairi, Ramzi El-Haddadeh
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With the extensive increase in the number of online shops, loyalty becomes the most purpose for e-retailers by which they can maintain their exit customers and regular income instead of spending large deal of money to target new segmentation. To obtain customers’ loyalty e-marketers should firstly satisfy customers by providing a high quality of services that could fulfil their demand. They have to satisfy them to trust the web-site then increase their intention to re-visit it. This study intends to investigate to what extend the elements of e-service quality presented in the literature affect customers’ satisfaction and how these influences contribute to customers’ trust and loyalty. Three dimensions of service quality are estimated. The first element is web-site interactivity, which is perceived the quality of interactive support and the accessible communications-tool. The second aspect is security/privacy, which is perceived the quality of controlling security and privacy while transaction over the web-site. The third element is web-design that perceived a pleasant user interface with visual appealing. These elements present positive effects on shoppers’ satisfaction. Thus, To examine the proposed constructs of this research, some measurements scale-items adapted from similar prior studies. Survey data collected online from Saudi customers (n=106) were utilized to test the research hypotheses. After that, the hypotheses were analyzed by using a variety of regression tools. The analytical results of this study propose that perceived quality of interactivity and security/privacy affects customers’ satisfaction. As well as trust seems to be a substantial construct that highly affects loyalty in online shopping. This study provides a developed model to obtain a simple understanding of the series of customers’ loyalty in online shopping. One construct presenting in the research model is web-design appears to be not important antecedent of satisfaction (the path to loyalty) in online shopping.Keywords: e-service, satisfaction, trust, loyalty
Procedia PDF Downloads 2592558 Intrabody Communication Using Different Ground Configurations in Digital Door Lock
Authors: Daewook Kim, Gilwon Yoon
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Intrabody communication (IBC) is a new way of transferring data using human body as a medium. Minute current can travel though human body without any harm. IBC can remove electrical wires for human area network. IBC can be also a secure communication network system unlike wireless networks which can be accessed by anyone with bad intentions. One of the IBC systems is based on frequency shift keying modulation where individual data are transmitted to the external devices for the purpose of secure access such as digital door lock. It was found that the quality of IBC data transmission was heavily dependent on ground configurations of electronic circuits. Reliable IBC transmissions were not possible when both of the transmitter and receiver used batteries as circuit power source. Transmission was reliable when power supplies were used as power source for both transmitting and receiving sites because the common ground was established through the grounds of instruments such as power supply and oscilloscope. This was due to transmission dipole size and the ground effects of floor and AC power line. If one site used battery as power source and the other site used the AC power as circuit power source, transmission was possible.Keywords: frequency shift keying, ground, intrabody, communication, door lock
Procedia PDF Downloads 4202557 Life Cycle Analysis (LCA) for Transportation of Cross-Laminated Timber (CLT) Panels Comparing Two Origin Points of Supply
Authors: Mahboobeh Hemmati, Tahar Messadi, Hongmei Gu
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This overall research is targeted at the assessment of the new CLT-built Adohi Hall residential building located on the campus of the University of Arkansas in Fayetteville, Arkansas. The purpose of the Life Cycle Assessment (LCA) study is to analyze the environmental impacts resulting from the transportation route of the Austrian imported CLT to the construction site with those of the CLT assumed to be originating from Conway, Arkansas. The Global Warming Potential (GWP) of CLT from Europe (Styria-Graz in Austria) to the site was first investigated. The results were then compared with the GWP of the CLT produced in Conway, Arkansas. The impacts of each scenario, using the Ecoinvent database, are then calculated and compared against each other to find the most environmentally efficient scenario in terms of global warming impacts. The quantification of GWP is associated with different transportation systems, water, road, and rail. Obtained through comparison, the findings reveal that the use of local materials is more efficient. In addition, transportation by water produces less Greenhouse Gas (GHG) emission in comparison to freight transportation by rail and road. Thus, besides the travel distance, the utilized transportation system is still a significant factor and should be seriously considered in making decisions for moving materials.Keywords: comparative analysis, GWP, LCA, transportation
Procedia PDF Downloads 2432556 Building User Behavioral Models by Processing Web Logs and Clustering Mechanisms
Authors: Madhuka G. P. D. Udantha, Gihan V. Dias, Surangika Ranathunga
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Today Websites contain very interesting applications. But there are only few methodologies to analyze User navigations through the Websites and formulating if the Website is put to correct use. The web logs are only used if some major attack or malfunctioning occurs. Web Logs contain lot interesting dealings on users in the system. Analyzing web logs has become a challenge due to the huge log volume. Finding interesting patterns is not as easy as it is due to size, distribution and importance of minor details of each log. Web logs contain very important data of user and site which are not been put to good use. Retrieving interesting information from logs gives an idea of what the users need, group users according to their various needs and improve site to build an effective and efficient site. The model we built is able to detect attacks or malfunctioning of the system and anomaly detection. Logs will be more complex as volume of traffic and the size and complexity of web site grows. Unsupervised techniques are used in this solution which is fully automated. Expert knowledge is only used in validation. In our approach first clean and purify the logs to bring them to a common platform with a standard format and structure. After cleaning module web session builder is executed. It outputs two files, Web Sessions file and Indexed URLs file. The Indexed URLs file contains the list of URLs accessed and their indices. Web Sessions file lists down the indices of each web session. Then DBSCAN and EM Algorithms are used iteratively and recursively to get the best clustering results of the web sessions. Using homogeneity, completeness, V-measure, intra and inter cluster distance and silhouette coefficient as parameters these algorithms self-evaluate themselves to input better parametric values to run the algorithms. If a cluster is found to be too large then micro-clustering is used. Using Cluster Signature Module the clusters are annotated with a unique signature called finger-print. In this module each cluster is fed to Associative Rule Learning Module. If it outputs confidence and support as value 1 for an access sequence it would be a potential signature for the cluster. Then the access sequence occurrences are checked in other clusters. If it is found to be unique for the cluster considered then the cluster is annotated with the signature. These signatures are used in anomaly detection, prevent cyber attacks, real-time dashboards that visualize users, accessing web pages, predict actions of users and various other applications in Finance, University Websites, News and Media Websites etc.Keywords: anomaly detection, clustering, pattern recognition, web sessions
Procedia PDF Downloads 2882555 Effect of Chemical Modification of Functional Groups on Copper(II) Biosorption by Brown Marine Macroalgae Ascophyllum nodosum
Authors: Luciana P. Mazur, Tatiana A. Pozdniakova, Rui A. R. Boaventura, Vitor J. P. Vilar
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The principal mechanism of metal ions sequestration by brown algae involves the formation of complexes between the metal ion and functional groups present on the cell wall of the biological material. To understand the role of functional groups on copper(II) uptake by Ascophyllum nodosum, some functional groups were chemically modified. The esterification of carboxylic groups was carried out by suspending the biomass in a methanol/HCl solution under stirring for 48 h and the blocking of the sulfonic groups was performed by repeating the same procedure for 4 cycles of 48 h. The methylation of amines was conducted by suspending the biomass in a formaldehyde/formic acid solution under shaking for 6 h and the chemical modification of sulfhydryl groups on the biomass surface was achieved using dithiodipyridine for 1 h. Equilibrium sorption studies for Cu2+ using the raw and esterified algae were performed at pH 2.0 and 4.0. The experiments were performed using an initial copper concentration of 300 mg/L and algae dose of 1.0 g/L. After reaching the equilibrium, the metal in solution was quantified by atomic absorption spectrometry. The biological material was analyzed by Fourier Transform Infrared Spectroscopy and Potentiometric Titration techniques for functional groups identification and quantification, respectively. The results using unmodified algae showed that the maximum copper uptake capacity at pH 4.0 and 2.0 was 1.17 and 0.52 mmol/g, respectively. At acidic pH values most carboxyl groups are protonated and copper sorption suffered a significant reduction of 56%. Blocking the carboxylic, sulfonic, amines and sulfhydryl functional groups, copper uptake decreased by 24/26%, 69/81%, 1/23% and 40/27% at pH 2.0/4.0, respectively, when compared to the unmodified biomass. It was possible to conclude that the carboxylic and sulfonic groups are the main functional groups responsible for copper binding (>80%). This result is supported by the fact that the adsorption capacity is directly related to the presence of carboxylic groups of the alginate polymer, and the second most abundant acidic functional group in brown algae is the sulfonic acid of fucoidan that contributes, to a lower extent, to heavy metal binding, particularly at low pH.Keywords: biosorption, brown marine macroalgae, copper, ion-exchange
Procedia PDF Downloads 3272554 Investigating Ancient Technology and Ceramic Composition at Al-Khidr Site (Failaka Island, Kuwait): Geochemical Analyses of Bronze Age Pottery by pXRF and Thin-section Petrographic Analyses
Authors: Hasan Ashkanani
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Pottery assemblages from the site of Al-Khidr on Failaka Island, Kuwait, were analysed in order to reconstruct the chemical composition of Bronze Age wares and to build a mineralogical database of Bronze Age pottery dated from Failaka Periods 1–3B (2000–1650 BCE). A total of 145 ceramic sherds from Al-Khidr, as well as reference groups, were analysed by non-destructive portable X-ray fluorescence (pXRF) spectrometry. Preliminarily petrographic thin-section analysis was applied to four samples to reconstruct possible clay paste recipes and to identify raw materials. The results indicate that geochemical analyses can successfully distinguish subgroups within a typological category of ceramic assemblages. The results identified two subgroups within the Al-Khidr typological category: the Dilmun Barbar tradition and the Mesopotamian tradition. Future comparative compositional studies can be conducted to explore other aspects of craft specialisation, such as ceramic technological choices and possibly the influence of sociopolitical unitsKeywords: Kuwait archaeology, pottery, pXRF, Dilmun
Procedia PDF Downloads 1412553 University Short Courses Web Application Using ASP.Net
Authors: Ahmed Hariri
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E-Learning has become a necessity in the advanced education. It is easier for the student and teacher communication also it speed up the process with less time and less effort. With the progress and the enormous development of distance education must keep up with this age of making a website that allows students and teachers to take all the advantages of advanced education. In this regards, we developed University Short courses web application which is specially designed for Faculty of computing and information technology, Rabigh, Kingdom of Saudi Arabia. After an elaborate review of the current state-of-the-art methods of teaching and learning, we found that instructors deliver extra short courses and workshop to students to enhance the knowledge of students. Moreover, this process is completely manual. The prevailing methods of teaching and learning consume a lot of time; therefore in this context, University Short courses web application will help to make process easy and user friendly. The site allows for students can view and register short courses online conducted by instructor also they can see courses starting dates, finishing date and locations. It also allows the instructor to put things on his courses on the site and see the students enrolled in the study material. Finally, student can print the certificate after finished the course online. ASP.NET, SQLSERVER, JavaScript SQL SERVER Database will use to develop the University Short Courses web application.Keywords: e-learning, short courses, ASP.NET, SQL SERVER
Procedia PDF Downloads 1352552 Waste Generation in Iranian Building Industry: Addressing a Theory
Authors: Golnaz Moghimi, Alireza Afsharghotli, Alireza Rezaei
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Construction waste has been gradually increased as a result of upsizing construction projects which are occurred within the lifecycle of buildings. Since waste management is a major priority and has profound impacts on the volume of waste generated in construction stage, the majority of efforts have been attempted to reuse, recycle and reduce waste. However, there is still room to study on lack of sufficient knowledge about waste management in construction industry. This paper intends to provide an insight into the effect of project management knowledge areas on waste management solely on construction stage. To this end, a survey among Iranian building construction industry contractors was conducted to identify the effectiveness of project management knowledge areas on three jobsite key factors including ‘Site activity’, ‘Training’, and ‘Awareness’. As a result, four management disciplines were identified as most influential ones on amount of construction waste. These disciplines were Project Cost Management, Quality Management, Human Resource Management, and Integration Management. Based on the research findings, a new model was presented to develop effective construction waste strategies.Keywords: awareness, PMBOK, site activity, training, waste management
Procedia PDF Downloads 3602551 Composition Dependence of Ni 2p Core Level Shift in Fe1-xNix Alloys
Authors: Shakti S. Acharya, V. R. R. Medicherla, Rajeev Rawat, Komal Bapna, Deepnarayan Biswas, Khadija Ali, K. Maiti
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The discovery of invar effect in 35% Ni concentration Fe1-xNix alloy has stimulated enormous experimental and theoretical research. Elemental Fe and low Ni concentration Fe1-xNix alloys which possess body centred cubic (bcc) crystal structure at ambient temperature and pressure transform to hexagonally close packed (hcp) phase at around 13 GPa. Magnetic order was found to be absent at 11K for Fe92Ni8 alloy when subjected to a high pressure of 26 GPa. The density functional theoretical calculations predicted substantial hyperfine magnetic fields, but were not observed in Mossbaur spectroscopy. The bulk modulus of fcc Fe1-xNix alloys with Ni concentration more than 35%, is found to be independent of pressure. The magnetic moment of Fe is also found be almost same in these alloys from 4 to 10 GPa pressure. Fe1-xNix alloys exhibit a complex microstructure which is formed by a series of complex phase transformations like martensitic transformation, spinodal decomposition, ordering, mono-tectoid reaction, eutectoid reaction at temperatures below 400°C. Despite the existence of several theoretical models the field is still in its infancy lacking full knowledge about the anomalous properties exhibited by these alloys. Fe1-xNix alloys have been prepared by arc melting the high purity constituent metals in argon ambient. These alloys have annealed at around 3000C in vacuum sealed quartz tube for two days to make the samples homogeneous. These alloys have been structurally characterized by x-ray diffraction and were found to exhibit a transition from bcc to fcc for x > 0.3. Ni 2p core levels of the alloys have been measured using high resolution (0.45 eV) x-ray photoelectron spectroscopy. Ni 2p core level shifts to lower binding energy with respect to that of pure Ni metal giving rise to negative core level shifts (CLSs). Measured CLSs exhibit a linear dependence in fcc region (x > 0.3) and were found to deviate slightly in bcc region (x < 0.3). ESCA potential model fails correlate CLSs with site potentials or charges in metallic alloys. CLSs in these alloys occur mainly due to shift in valence bands with composition due to intra atomic charge redistribution.Keywords: arc melting, core level shift, ESCA potential model, valence band
Procedia PDF Downloads 3802550 21st Century Computer Technology for the Training of Early Childhood Teachers: A Study of Second-Year Education Students Challenged with Building a Kindergarten Website
Authors: Yonit Nissim, Eyal Weissblueth
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This research is the continuation of a process that began in 2010 with the goal of redesigning the training program for future early childhood teachers at the Ohalo College, to integrate technology and provide 21st-century skills. The article focuses on a study of the processes involved in developing a special educational unit which challenged students with the task of designing, planning and building an internet site for kindergartens. This project was part of their second-year studies in the early childhood track of an interdisciplinary course entitled 'Educating for the Future.' The goal: enabling students to gain experience in developing an internet site specifically for kindergartens, and gain familiarity with Google platforms, the acquisition and use of innovative skills and the integration of technology in pedagogy. Research questions examined how students handled the task of building an internet site. The study explored whether the guided process of building a site helped them develop proficiency in creativity, teamwork, evaluation and learning appropriate to the 21st century. The research tool was a questionnaire constructed by the researchers and distributed online to the students. Answers were collected from 50-course participants. Analysis of the participants’ responses showed that, along with the significant experience and benefits that students gained from building a website for kindergarten, ambivalence was shown toward the use of new, unfamiliar and complex technology. This attitude was characterized by unease and initial emotional distress triggered by the departure from routine training to an island of uncertainty. A gradual change took place toward the adoption of innovation with the help of empathy, training, and guidance from the instructors, leading to the students’ success in carrying out the task. Initial success led to further successes, resulting in a quality product and a feeling of personal competency among the students. A clear and extreme emotional shift was observed on the spectrum from a sense of difficulty and dissatisfaction to feelings of satisfaction, joy, competency and cognitive understanding of the importance of facing a challenge and succeeding. The findings of this study can contribute to increased understanding of the complex training process of future kindergarten teachers, coping with a changing world, and pedagogy that is supported by technology.Keywords: early childhood teachers, educating for the future, emotions, kindergarten website
Procedia PDF Downloads 1562549 Synthesis, Inhibitory Activity, and Molecular Modelling of 2-Hydroxy-3-Oxo-3-Phenylpropionate Derivatives as HIV-1-Integrase Inhibitors
Authors: O. J. Jesumoroti, Faridoon, R. Klein, K. A. Iobb, D. Mnkadhla, H. C. Hoppe, P. T. Kaye
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The 1, 3-aryl diketo acids (DKA) based agents represent an important class of HIV integrase (IN) strand transfer inhibitors. In other to study the chelating role of the divalent metal ion in the inhibition of IN strand transfer, we designed and synthesized a series of 2-hydroxy-3-oxo-3-phenyl propionate derivatives with the notion that such compounds could interact with the divalent ion in the active site of IN. The synthetic sequence to the desired compounds involves the concept of Doebner knoevenagel condensation, Fischer esterification and ketohydroxylation using neuclophilic re-oxidant; compounds were characterized by their IR, IHNMR, 13CNMR, HRMS spectroscopic data and melting point determination. Also, molecular docking was employed in this study and it was revealed that there is interaction with the active site of the enzyme. However, there is disparity in the corresponding anti-HIV activity determined by the experimental bioassay. These compounds lack potency at low micromolar concentration when compared to the results of the docking studies. Nevertheless, the results of the study suggest modification of the aryl ring with one or two hydroxyl groups to improve the inhibitory activity.Keywords: anti-HIV-1 integrase, ketohydroxylation, molecular docking, propionate derivatives
Procedia PDF Downloads 1952548 On-Site Coaching on Freshly-Graduated Nurses to Improves Quality of Clinical Handover and to Avoid Clinical Error
Authors: Sau Kam Adeline Chan
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World Health Organization had listed ‘Communication during Patient Care Handovers’ as one of its highest 5 patient safety initiatives. Clinical handover means transfer of accountability and responsibility of clinical information from one health professional to another. The main goal of clinical handover is to convey patient’s current condition and treatment plan accurately. Ineffective communication at point of care is globally regarded as the main cause of the sentinel event. Situation, Background, Assessment and Recommendation (SBAR), a communication tool, is extensively regarded as an effective communication tool in healthcare setting. Nonetheless, just by scenario-based program in nursing school or attending workshops on SBAR would not be enough for freshly graduated nurses to apply it competently in a complex clinical practice. To what extend and in-depth of information should be conveyed during handover process is not easy to learn. As such, on-site coaching is essential to upgrade their expertise on the usage of SBAR and ultimately to avoid any clinical error. On-site coaching for all freshly graduated nurses on the usage of SBAR in clinical handover was commenced in August 2014. During the preceptorship period, freshly graduated nurses were coached by the preceptor. After that, they were gradually assigned to take care of a group of patients independently. Nurse leaders would join in their shift handover process at patient’s bedside. Feedback and support were given to them accordingly. Discrepancies on their clinical handover process were shared with them and documented for further improvement work. Owing to the constraint of manpower in nurse leader, about coaching for 30 times were provided to a nurse in a year. Staff satisfaction survey was conducted to gauge their feelings about the coaching and look into areas for further improvement. Number of clinical error avoided was documented as well. The nurses reported that there was a significant improvement particularly in their confidence and knowledge in clinical handover process. In addition, the sense of empowerment was developed when liaising with senior and experienced nurses. Their proficiency in applying SBAR was enhanced and they become more alert to the critical criteria of an effective clinical handover. Most importantly, accuracy of transferring patient’s condition was improved and repetition of information was avoided. Clinical errors were prevented and quality patient care was ensured. Using SBAR as a communication tool looks simple. The tool only provides a framework to guide the handover process. Nevertheless, without on-site training, loophole on clinical handover still exists, patient’s safety will be affected and clinical error still happens.Keywords: freshly graduated nurse, competency of clinical handover, quality, clinical error
Procedia PDF Downloads 1502547 The Molecular Rationale for Steroid Based Therapy of Leukemia: Diagnostic and Therapeutic Implications
Authors: Eitan Yefenof
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Glucocorticoid (GC) hormones, e.g. Dexamethasone and Prednisone, are widely used in the therapy of leukemia and lymphoma owing to their apoptogenic effect on lymphoid cells. However, the emergence of GC resistant cells during therapy is a major cause for treatment failure, urging the need for novel strategies that maintain leukemia sensitivity to the pro-apoptotic activity of GCs. GCs act by binding to the GC receptor (GR), which, in its inactive state, is sequestered in the cytosol by a multi-subunit complex of heat shock proteins. Upon ligand binding, the complex dissociates, allowing GR activation and translocation to the nucleus, where it regulates transcription of multiple genes. We demonstrated that in addition to gene expression, GR also regulates microRNA (miR) expression. Deep-sequencing analysis revealed 14 miRs that are regulated in GC-sensitive but resistant leukemias upon treatment with GC. GC up-regulates miR-103, miR-15~16 and miR-30e/d, while down-regulates miR-17, mir-18a, miR-19a, miR-19b, miR-20a and miR-92a (members of the miR-17∼92a multi-cistron). Upon transfection, miR-103 confers GC apoptotic sensitivity to otherwise GC-resistant cell. Furthermore, knocking down miR-103 expression reduces the GC apoptotic response of sensitive cells. miR-103 abrogates c-Myc expression, an oncogenic transcription factor which is deregulated in many cancers. In addition, miR-103 up-regulates Bim, a pro-apoptotic protein crucial for GC-induced death. Activated glycogen synthase kinase 3 (GSK3) is also crucial for GC-induced apoptosis. GSK3 is active in GC-sensitive but not in GC-resistant cells. We found that GSK3 associates with the GR multi-subunit complex. Upon GC exposure, it dissociates from the GR and interacts with Bim to enable activation of the mitochondrial apoptosis pathway. miR-103 mediated c-Myc ablation is followed by down-regulation of the multi-cistron miR-17~92a, in particular miR-18a and miR-20a. miR-18a targets GR for degradation whereas miR-20a targets Bim degradation. Hence, miR-103 acts, in concert with Bim and GR, as a "tumor suppressor" that leads to reduced proliferation, cell-cycle arrest and cell death. We suggest that miR-103 can provide a diagnostic tool that predicts the sensitivity of leukemia to GC based therapy. Furthermore, exosomal delivery of miR-103 or up-regulation of the endogenous miR-103 could confer apoptotic sensitivity to resistant cells at the outset, thus becoming a useful therapeutic tool combined with GCs.Keywords: apoptosis, leukemia, micro-RNA, steroids
Procedia PDF Downloads 2462546 Anatomical Features of Internal Pudendal Artery
Authors: Adel Yasky, Waseem Al-Talalwah, Shorok Al Dorazi, Roger Soames
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The internal pudendal artery is a standard branch of the anterior division of the internal iliac artery. The current study includes 41 cadavers to investigate the origin and branches of the internal pudendal artery and its clinical significances. The internal pudendal artery arose directly from the anterior division of the internal iliac artery in 48.3% while it arose indirectly in 48.5%. However, the internal pudendal artery arose from the posterior division of internal iliac artery in 1.6%. Moreover, it arose internal iliac artery bifurcation site in 1.6%. Further, the internal pudendal artery supplied the urinary bladder in 17.1%. Also, the internal pudendal artery supplied the rectum 33.5% respectively. It gave uterine and vaginal arteries in 9.4% and 7.8% respectively. Finally, it supplied the sciatic nerve via giving lateral sacral branch in 1.6%. Internists, surgeons and radiologists have to be aware of the variability to decrease iatrogenic injury. Therefore, unnecessary proximal ligation should be avoided at the site of indirect origin of the internal pudendal artery to prevent sciatic neuropathy. Further, intrapelvic bleeding as result of laceration of internal pudendal branches during hysterectomy, prostatectomy or proctectomy should be expected. Therefore, this study increases the awareness of surgeons leading to minimize iatrogenic faults,Keywords: internal pudendal artery, inferior gluteal artery, superior gluteal artery, internal iliac artery, impotence, decreased libido
Procedia PDF Downloads 3562545 Spatial Assessment of Soil Contamination from Informal E-Waste Recycling Site in Agbogbloshie, Ghana
Authors: Kyere Vincent Nartey, Klaus Greve, Atiemo Sampson
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E-waste is discarded electrical electronic equipment inclusive of all components, sub-assemblies and consumables which are part of the product at the time of discarding and known to contain both hazardous and valuable fractions. E-waste is recycled within the proposed ecological restoration of the Agbogbloshie enclave using crude and rudimental recycling procedures such as open burning and manual dismantling which result in pollution and contamination of soil, water and air. Using GIS, this study was conducted to examine the spatial distribution and extent of soil contamination by heavy metals from the e-waste recycling site in Agbogbloshie. From the month of August to November 2013, 146 soil samples were collected in addition to their coordinates using GPS. Elemental analysis performed on the collected soil samples using X-Ray fluorescence revealed over 30 elements including, Ni, Cr, Zn, Cu, Pb and Mn. Using geostatistical techniques in ArcGIS 10.1 spatial assessment and distribution maps were generated. Mathematical models or equations were used to estimate the degree of contamination and pollution index. Results from soil analysis from the Agbogbloshie enclave showed that levels of measured or observed elements were significantly higher than the Canadian EPA and Dutch environmental standards.Keywords: e-waste, geostatistics, soil contamination, spatial distribution
Procedia PDF Downloads 5152544 Surgical Site Infections Post Ventriculoperitoneal (VP) Shunting: A Matched Healthcare Cost and Length of Stay Study
Authors: Issa M. Hweidi, Saba W. Al-Ibraheem
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This study aimed to assess the increased hospital length of stay and healthcare costs associated with SSIs among ventriculoperitoneal shunting surgery patients in Jordan. This study adopted a retrospective and nested 1:1 matched case-control design. A non-probability convenient sample of 48 VP shunt patients was recruited for the purpose of the study. The targeted groups of the study basically used to cross-match the variables investigated to minimize the risk of confounding. Information was extracted from the text of patients' electronic health records. As compared to the non-SSI group, the SSI group had an extra mean healthcare cost of $13,696.53 (p=0.001) and longer hospital length of stay (22.64 mean additional days). Furthermore, Acinetobacter baumannii and Klebsiella pneumonia were identified as being the most predominant causative agents of SSIs. The results of this study may provide baseline data for national and regional benchmarking to evaluate the quality of care provided to likewise patients. Adherence to infection control strategies and protocols considering new surveillance methods of SSIs is encouraged.Keywords: ventriculoperitoneal shunt, health care cost, length of stay, neurosurgery, surgical site infections
Procedia PDF Downloads 772543 In-silico DFT Study, Molecular Docking, ADMET Predictions, and DMS of Isoxazolidine and Isoxazoline Analogs with Anticancer Properties
Authors: Moulay Driss Mellaoui, Khadija Zaki, Khalid Abbiche, Abdallah Imjjad, Rachid Boutiddar, Abdelouahid Sbai, Aaziz Jmiai, Souad El Issami, Al Mokhtar Lamsabhi, Hanane Zejli
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This study presents a comprehensive analysis of six isoxazolidine and isoxazoline derivatives, leveraging a multifaceted approach that combines Density Functional Theory (DFT), AdmetSAR analysis, and molecular docking simulations to explore their electronic, pharmacokinetic, and anticancer properties. Through DFT analysis, using the B3LYP-D3BJ functional and the 6-311++G(d,p) basis set, we optimized molecular geometries, analyzed vibrational frequencies, and mapped Molecular Electrostatic Potentials (MEP), identifying key sites for electrophilic attacks and hydrogen bonding. Frontier Molecular Orbital (FMO) analysis and Density of States (DOS) plots revealed varying stability levels among the compounds, with 1b, 2b, and 3b showing slightly higher stability. Chemical potential assessments indicated differences in binding affinities, suggesting stronger potential interactions for compounds 1b and 2b. AdmetSAR analysis predicted favorable human intestinal absorption (HIA) rates for all compounds, highlighting compound 3b superior oral effectiveness. Molecular docking and molecular dynamics simulations were conducted on isoxazolidine and 4-isoxazoline derivatives targeting the EGFR receptor (PDB: 1JU6). Molecular docking simulations confirmed the high affinity of these compounds towards the target protein 1JU6, particularly compound 3b, among the isoxazolidine derivatives, compound 3b exhibited the most favorable binding energy, with a g score of -8.50 kcal/mol. Molecular dynamics simulations over 100 nanoseconds demonstrated the stability and potential of compound 3b as a superior candidate for anticancer applications, further supported by structural analyses including RMSD, RMSF, Rg, and SASA values. This study underscores the promising role of compound 3b in anticancer treatments, providing a solid foundation for future drug development and optimization efforts.Keywords: isoxazolines, DFT, molecular docking, molecular dynamic, ADMET, drugs.
Procedia PDF Downloads 492542 Using Contingency Valuation Approaches to Assess Community Benefits through the Use of Great Zimbabwe World Heritage Site as a Tourism Attraction
Authors: Nyasha Agnes Gurira, Patrick Ngulube
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Heritage as an asset can be used to achieve cultural and socio-economic development through its careful use as a tourist attraction. Cultural heritage sites, especially those listed as World Heritage sites generate a lot of revenue through their use as tourist attractions. According to article 5(a) of the World Heritage Convention, World Heritage Sites (WHS) must serve a function in the life of the communities. This is further stressed by the International Council on Monuments and Sites (ICOMOS) charter on cultural heritage tourism which recognizes the positive effects of tourism on cultural heritage and underlines that domestic and international tourism is among the foremost vehicles for cultural exchange, conservation should thus provide for responsible and well-managed opportunities for local communities. The inclusion of communities in the world heritage agenda identifies them as the owners of the heritage and partners in the management planning process. This reiterates the need to empower communities and enable them to participate in the decisions which relate to the use of their heritage divorcing from the ideals of viewing communities as beneficiaries from the heritage resource. It recognizes community ownership rights to cultural heritage an element enshrined in Zimbabwe’ national constitution. Through the use of contingency valuation approaches, by assessing the Willingness to pay for visitors at the site the research determined the tourism use value of Great Zimbabwe (WHS). It assessed the extent to which the communities at Great Zimbabwe (WHS) have been developed through the tourism use of the WHS. Findings show that the current management mechanism in place regards communities as stakeholders in the management of the WHS, their ownership and property rights are not fully recognized. They receive indirect benefits from the tourism use of the WHS. This paper calls for a shift in management approach where community ownership rights are fully recognized and more inclusive approaches are adopted to ensure that the goal of sustainable development is achieved. Pro-poor benefits of tourism are key to enhancing the livelihoods of communities and can only be achieved if their rights are recognized and respected.Keywords: communities, cultural heritage tourism, development, property ownership rights, pro-poor benefits, sustainability, world heritage site
Procedia PDF Downloads 2592541 Scheduling Building Projects: The Chronographical Modeling Concept
Authors: Adel Francis
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Most of scheduling methods and software apply the critical path logic. This logic schedule activities, apply constraints between these activities and try to optimize and level the allocated resources. The extensive use of this logic produces a complex an erroneous network hard to present, follow and update. Planning and management building projects should tackle the coordination of works and the management of limited spaces, traffic, and supplies. Activities cannot be performed without the resources available and resources cannot be used beyond the capacity of workplaces. Otherwise, workspace congestion will negatively affect the flow of works. The objective of the space planning is to link the spatial and temporal aspects, promote efficient use of the site, define optimal site occupancy rates, and ensures suitable rotation of the workforce in the different spaces. The Chronographic scheduling modelling belongs to this category and models construction operations as well as their processes, logical constraints, association and organizational models, which help to better illustrate the schedule information using multiple flexible approaches. The model defined three categories of areas (punctual, surface and linear) and four different layers (space creation, systems, closing off space, finishing, and reduction of space). The Chronographical modelling is a more complete communication method, having the ability to alternate from one visual approach to another by manipulation of graphics via a set of parameters and their associated values. Each individual approach can help to schedule a certain project type or specialty. Visual communication can also be improved through layering, sheeting, juxtaposition, alterations, and permutations, allowing for groupings, hierarchies, and classification of project information. In this way, graphic representation becomes a living, transformable image, showing valuable information in a clear and comprehensible manner, simplifying the site management while simultaneously utilizing the visual space as efficiently as possible.Keywords: building projects, chronographic modelling, CPM, critical path, precedence diagram, scheduling
Procedia PDF Downloads 1552540 DNpro: A Deep Learning Network Approach to Predicting Protein Stability Changes Induced by Single-Site Mutations
Authors: Xiao Zhou, Jianlin Cheng
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A single amino acid mutation can have a significant impact on the stability of protein structure. Thus, the prediction of protein stability change induced by single site mutations is critical and useful for studying protein function and structure. Here, we presented a deep learning network with the dropout technique for predicting protein stability changes upon single amino acid substitution. While using only protein sequence as input, the overall prediction accuracy of the method on a standard benchmark is >85%, which is higher than existing sequence-based methods and is comparable to the methods that use not only protein sequence but also tertiary structure, pH value and temperature. The results demonstrate that deep learning is a promising technique for protein stability prediction. The good performance of this sequence-based method makes it a valuable tool for predicting the impact of mutations on most proteins whose experimental structures are not available. Both the downloadable software package and the user-friendly web server (DNpro) that implement the method for predicting protein stability changes induced by amino acid mutations are freely available for the community to use.Keywords: bioinformatics, deep learning, protein stability prediction, biological data mining
Procedia PDF Downloads 4712539 BIM-based Construction Noise Management Approach With a Focus on Inner-City Construction
Authors: Nasim Babazadeh
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Growing demand for a quieter dwelling environment has turned the attention of construction companies to reducing the propagated noise of their project. In inner-city constructions, close distance between the construction site and surrounding buildings lessens the efficiency of passive noise control methods. Dwellers of the nearby areas may file complaints and lawsuits against the construction companies due to the emitted construction noise, thereby leading to the interruption of processes, compensation costs, or even suspension of the project. Therefore, construction noise should be predicted along with the project schedule. The advantage of managing the noise in the pre-construction phase is two-fold. Firstly, changes in the time plan and construction methods can be applied more flexibly. Thus, the costs related to rescheduling can be avoided. Secondly, noise-related legal problems are expected to be reduced. To implement noise mapping methods for the mentioned prediction, the required detailed information (such as the location of the noisy process, duration of the noisy work) can be exported from the 4D BIM model. The results obtained from the noise maps would be used to help the planners to define different work scenarios. The proposed approach has been applied for the foundation and earthwork of a site located in a residential area, and the obtained results are discussed.Keywords: building information modeling, construction noise management, noise mapping, 4D BIM
Procedia PDF Downloads 1862538 The Environmental Impact Assessment of Land Use Planning (Case Study: Tannery Industry in Al-Garma District)
Authors: Husam Abdulmuttaleb Hashim
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The environmental pollution problems represent a great challenge to the world, threatening to destroy all the evolution that mankind has reached, the organizations and associations that cares about environment are trying to warn the world from the forthcoming danger resulted from excessive use of nature resources and consuming it without looking to the damage happened as a result of unfair use of it. Most of the urban centers suffers from the environmental pollution problems and health, economic, and social dangers resulted from this pollution, and while the land use planning is responsible for distributing different uses in urban centers and controlling the interactions between these uses to reach a homogeneous and perfect state for the different activities in cities, the occurrence of environmental problems in the shade of existing land use planning operation refers to the disorder or insufficiency in this operation which leads to presence of such problems, and this disorder lays in lack of sufficient importance to the environmental considerations during the land use planning operations and setting up the master plan, so the research start to study this problem and finding solutions for it, the research assumes that using accurate and scientific methods in early stages of land use planning operation will prevent occurring of environmental pollution problems in the future, the research aims to study and show the importance of the environmental impact assessment method (EIA) as an important planning tool to investigate and predict the pollution ranges of the land use that has a polluting pattern in land use planning operation. This research encompasses the concept of environmental assessment and its kinds and clarifies environmental impact assessment and its contents, the research also dealt with urban planning concept and land use planning, it also dealt with the current situation of the case study (Al-Garma district) and the land use planning in it and explain the most polluting use on the environment which is the industrial land use represented in the tannery industries and then there was a stating of current situation of this land use and explaining its contents and environmental impacts resulted from it, and then we analyzed the tests applied by the researcher for water and soil, and perform environmental evaluation through applying environmental impact assessment matrix using the direct method to reveal the pollution ranges on the ambient environment of industrial land use, and we also applied the environmental and site limits and standards by using (GIS) and (AUTOCAD) to select the site of the best alternative of the industrial region in Al-Garma district after the research approved the unsuitability of its current site location for the environmental and site limitations, the research conducted some conclusions and recommendations regard clarifying the concluded facts and to set the proper solutions.Keywords: EIA, pollution, tannery industry, land use planning
Procedia PDF Downloads 4502537 Comparative Functional Analysis of Two Major Sterol-Biosynthesis Regulating Transcription Factors, Hob1 and Sre1, in Pathogenic Cryptococcus Species Complex
Authors: Dong-Gi Lee, Suyeon Cha, Yong-Sun Bahn
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Sterol lipid is essential for cell membrane structure in eukaryotic cells. In mammalian cells, sterol regulatory element binding proteins (SREBPs) act as principal regulators of cellular cholesterol which is essential for proper cell membrane fluidity and structure. SREBP and sterol regulation are related to levels of cellular oxygen because it is a major substrate for sterol synthesis. Upon cellular sterol and oxygen levels are depleted, SREBP is translocated to the Golgi where it undergoes proteolytic cleavage of N terminus, then it travels to the nucleus to play a role as transcription factor. In yeast cells, synthesis of ergosterol is also highly oxygen consumptive, and Sre1 is a transcription factor known to play a central role in adaptation to growth under low oxygen condition and sterol homeostasis in Cryptococcus neoformans. In this study, we observed phenotypes in other strains of Cryptococcus species by constructing hob1Δ and sre1Δ mutants to confirm whether the functions of both genes are conserved in most serotypes. As a result, hob1Δ showed no noticeable phenotype under treatment of antifungal drugs and most environmental stresses in R265 (C. gattii) and XL280 (C. neoformans), suggesting that Hob1 is related to sterol regulation only in H99 (serotype A). On the other hand, the function of Sre1 was found to be conserved in most serotypes. Furthermore, mating experiment of hob1Δ or sre1Δ showed dramatic defects in serotype A (H99) and D (XL280). It revealed that Hob1 and Sre1 related to mating ability in Cryptococcus species, especially cell fusion efficiency. In conclusion, HOB1 and SRE1 play crucial role in regulating sterol-homeostasis and differentiation in C. neoformans, moreover, Hob1 is specific gene in Cryptococcus neoformans. It suggests that Hob1 is considered as potent factor-targeted new safety antifungal drug.Keywords: cryptococcus neoformans, Hob1, Sre1, sterol regulatory element binding proteins
Procedia PDF Downloads 2512536 Geotechnical Investigation of Soil Foundation for Ramps of Dawar El-Tawheed Bridge in Jizan City, Kingdom of Saudi Arabia
Authors: Ali H. Mahfouz, Hossam E. M. Sallam, Abdulwali Wazir, Hamod H. Kharezi
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The soil profile at site of the bridge project includes soft fine grained soil layer located between 5.0 m to 11.0 m in depth, it has high water content, low SPT no., and low bearing capacity. The clay layer induces high settlement due to surcharge application of earth embankment at ramp T1, ramp T2, and ramp T3 especially at heights from 9m right 3m. Calculated settlement for embankment heights less than 3m may be accepted regarding Saudi Code for soil and foundation. The soil and groundwater at the project site comprise high contents of sulfates and chlorides of high aggressively on concrete and steel bars, respectively. Regarding results of the study, it has been recommended to use stone column piles or new technology named PCC piles as soil improvement to improve the bearing capacity of the weak layer. The new technology is cast in-situ thin wall concrete pipe piles (PCC piles), it has economically advantageous and high workability. The technology can save time of implementation and cost of application is almost 30% of other types of piles.Keywords: soft foundation soil, bearing capacity, bridge ramps, soil improvement, geogrid, PCC piles
Procedia PDF Downloads 3992535 CSRFDtool: Automated Detection and Prevention of a Reflected Cross-Site Request Forgery
Authors: Alaa A. Almarzuki, Nora A. Farraj, Aisha M. Alshiky, Omar A. Batarfi
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The number of internet users is dramatically increased every year. Most of these users are exposed to the dangers of attackers in one way or another. The reason for this lies in the presence of many weaknesses that are not known for native users. In addition, the lack of user awareness is considered as the main reason for falling into the attackers’ snares. Cross Site Request Forgery (CSRF) has placed in the list of the most dangerous threats to security in OWASP Top Ten for 2013. CSRF is an attack that forces the user’s browser to send or perform unwanted request or action without user awareness by exploiting a valid session between the browser and the server. When CSRF attack successes, it leads to many bad consequences. An attacker may reach private and personal information and modify it. This paper aims to detect and prevent a specific type of CSRF, called reflected CSRF. In a reflected CSRF, a malicious code could be injected by the attackers. This paper explores how CSRF Detection Extension prevents the reflected CSRF by checking browser specific information. Our evaluation shows that the proposed solution succeeds in preventing this type of attack.Keywords: CSRF, CSRF detection extension, attackers, attacks
Procedia PDF Downloads 4142534 Culvert Blockage Evaluation Using Australian Rainfall And Runoff 2019
Authors: Rob Leslie, Taher Karimian
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The blockage of cross drainage structures is a risk that needs to be understood and managed or lessened through the design. A blockage is a random event, influenced by site-specific factors, which needs to be quantified for design. Under and overestimation of blockage can have major impacts on flood risk and cost associated with drainage structures. The importance of this matter is heightened for those projects located within sensitive lands. It is a particularly complex problem for large linear infrastructure projects (e.g., rail corridors) located within floodplains where blockage factors can influence flooding upstream and downstream of the infrastructure. The selection of the appropriate blockage factors for hydraulic modeling has been subject to extensive research by hydraulic engineers. This paper has been prepared to review the current Australian Rainfall and Runoff 2019 (ARR 2019) methodology for blockage assessment by applying this method to a transport corridor brownfield upgrade case study in New South Wales. The results of applying the method are also validated against asset data and maintenance records. ARR 2019 – Book 6, Chapter 6 includes advice and an approach for estimating the blockage of bridges and culverts. This paper concentrates specifically on the blockage of cross drainage structures. The method has been developed to estimate the blockage level for culverts affected by sediment or debris due to flooding. The objective of the approach is to evaluate a numerical blockage factor that can be utilized in a hydraulic assessment of cross drainage structures. The project included an assessment of over 200 cross drainage structures. In order to estimate a blockage factor for use in the hydraulic model, a process has been advanced that considers the qualitative factors (e.g., Debris type, debris availability) and site-specific hydraulic factors that influence blockage. A site rating associated with the debris potential (i.e., availability, transportability, mobility) at each crossing was completed using the method outlined in ARR 2019 guidelines. The hydraulic results inputs (i.e., flow velocity, flow depth) and qualitative factors at each crossing were developed into an advanced spreadsheet where the design blockage level for cross drainage structures were determined based on the condition relating Inlet Clear Width and L10 (average length of the longest 10% of the debris reaching the site) and the Adjusted Debris Potential. Asset data, including site photos and maintenance records, were then reviewed and compared with the blockage assessment to check the validity of the results. The results of this assessment demonstrate that the estimated blockage factors at each crossing location using ARR 2019 guidelines are well-validated with the asset data. The primary finding of the study is that the ARR 2019 methodology is a suitable approach for culvert blockage assessment that has been validated against a case study spanning a large geographical area and multiple sub-catchments. The study also found that the methodology can be effectively coded within a spreadsheet or similar analytical tool to automate its application.Keywords: ARR 2019, blockage, culverts, methodology
Procedia PDF Downloads 3662533 Canthin-6-One Alkaloid Inhibits NF-κB and AP-1 Activity: An Inhibitory Action At Transcriptional Level
Authors: Fadia Gafri, Kathryn Mckintosh, Louise Young, Alan Harvey, Simon Mackay, Andrew Paul, Robin Plevin
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Nuclear factor-kappa B (NF-κB) is a ubiquitous transcription factor found originally to play a key role in regulating inflammation. However considerable evidence links this pathway to the suppression of apoptosis, cellular transformation, proliferation and invasion (Aggarwal et al., 2006). Moreover, recent studies have also linked inflammation to cancer progression making NF-κB overall a promising therapeutic target for drug discovery (Dobrovolskaia & Kozlov, 2005). In this study we examined the effect of the natural product canthin-6-one (SU182) as part of a CRUK small molecule drug discovery programme for effects upon the NF-κB pathway. Initial studies demonstrated that SU182 was found to have good potency against the inhibitory kappa B kinases (IKKs) at 30M in vitro. However, at concentrations up to 30M, SU182 had no effect upon TNFα stimulated loss in cellular IκBα or p65 phosphorylation in the keratinocyte cell line NCTC2544. Nevertheless, 30M SU182 reduced TNF-α / PMA-induced NF-κB-linked luciferase reporter activity to (22.9 ± 5%) and (34.6± 3 %, P<0.001) respectively, suggesting an action downstream of IKK signalling. Indeed, SU182 neither decreased NF-κB-DNA binding as assayed by EMSA nor prevented the translocation of p65 (NF-κB) to the nucleus assessed by immunofluorescence and subcellular fractionation. In addition to the inhibition of transcriptional activity of TNFα-induced NF-κB reporter activity SU182 significantly reduced PMA-induced AP-1-linked luciferase reporter activity to about (48± 9% at 30M, P<0.001) . This mode of inhibition was not sufficient to prevent the activation of NF-κB dependent induction of other proteins such as COX-2 and iNOS, or activated MAP kinases (p38, JNK and ERK1/2) in LPS stimulated RAW 264.7 macrophages. Taken together these data indicate the potential for SU182 to interfere with the transcription factors NF-κB and AP-1 at transcriptional level. However, no potential anti-inflammatory effect was indicated, further investigation for other NF-κB dependent proteins linked to survival are also required to identify the exact mechanism of action.Keywords: Canthin-6-one, NF-κB, AP-1, phosphorylation, Nuclear translocation, DNA-binding activity, inflammatory proteins.
Procedia PDF Downloads 458