Search results for: active contour

Authors: M. M. Hefnawy, A. M. A. Homoda, M. A. Abounassif, A. M. Alanazia, A. Al-Majed, Gamal A. E. Mostafa

Abstract:

PVC membrane sensors using different approach e.g. ion-pair, ionophore, and Schiff-base has been used as testing membrane sensor. Analytical applications of membrane sensors for direct measurement of variety of different ions in complex biological and environmental sample are reported. The most important step of such PVC membrane sensor is the sensing active material. The potentiometric sensors have some outstanding advantages including simple design, operation, wide linear dynamic range, relative fast response time, and rotational selectivity. The analytical applications of these techniques to pharmaceutical compounds in dosage forms are also discussed. The construction and electrochemical response characteristics of Poly (vinyl chloride) membrane sensors for moxifloxacin HCl (MOX) are described. The sensing membranes incorporate ion association complexes of moxifloxacin cation and sodium tetraphenyl borate (NaTPB) (sensor 1), phosphomolybdic acid (PMA) (sensor 2) or phosphotungstic acid (PTA) (sensor 3) as electroactive materials. The sensors display a fast, stable and near-Nernstian response over a relative wide moxifloxacin concentration range (1 ×10-2-4.0×10-6, 1 × 10-2-5.0×10-6, 1 × 10-2-5.0×10-6 M), with detection limits of 3×10-6, 4×10-6 and 4.0×10-6 M for sensor 1, 2 and 3, respectively over a pH range of 6.0-9.0. The sensors show good discrimination of moxifloxacin from several inorganic and organic compounds. The direct determination of 400 µg/ml of moxifloxacin show an average recovery of 98.5, 99.1 and 98.6 % and a mean relative standard deviation of 1.8, 1.6 and 1.8% for sensors 1, 2, and 3 respectively. The proposed sensors have been applied for direct determination of moxifloxacin in some pharmaceutical preparations. The results obtained by determination of moxifloxacin in tablets using the proposed sensors are comparable favorably with those obtained using the US Pharmacopeia method. The sensors have been used as indicator electrodes for potentiometric titration of moxifloxacin.

Keywords: potentiometry, PVC, membrane sensors, ion-pair, ionophore, schiff-base, moxifloxacin HCl, sodium tetraphenyl borate, phosphomolybdic acid, phosphotungstic acid

Procedia PDF Downloads 439

Authors: Alessandro Poma, Kal Karim, Sergey Piletsky, Giuseppe Battaglia

Abstract:

The recent increasing emergency threat to public health of infectious influenza diseases has prompted interest in the detection of avian influenza virus (AIV) H5N1 in humans as well as animals. A variety of technologies for diagnosing AIV infection have been developed. However, various disadvantages (costs, lengthy analyses, and need for high-containment facilities) make these methods less than ideal in their practical application. Molecularly Imprinted Polymeric Nanoparticles (MIP NPs) are suitable to overcome these limitations by having high affinity, selectivity, versatility, scalability and cost-effectiveness with the versatility of post-modification (labeling – fluorescent, magnetic, optical) opening the way to the potential introduction of improved diagnostic tests capable of providing rapid differential diagnosis. Here we present our first results in the production and testing of MIP NPs for the detection of AIV H5N1. Recent developments in the solid-phase synthesis of MIP NPs mean that for the first time a reliable supply of ‘soluble’ synthetic antibodies can be made available for testing as potential biological or diagnostic active molecules. The MIP NPs have the potential to detect viruses that are widely circulating in farm animals and indeed humans. Early and accurate identification of the infectious agent will expedite appropriate control measures. Thus, diagnosis at an early stage of infection of a herd or flock or individual maximizes the efficiency with which containment, prevention and possibly treatment strategies can be implemented. More importantly, substantiating the practicability’s of these novel reagents should lead to an initial reduction and eventually to a potential total replacement of animals, both large and small, to raise such specific serological materials.

Keywords: influenza virus, molecular imprinting, nanoparticles, polymers

Procedia PDF Downloads 362

Authors: Deepshikha Shukla, C. H. Solanki, Mayank Desai

Abstract:

In the last few years, it has been observed that earthquake is proving a threat to the scientist across the world. With a large number of earthquakes occurring in day to day life, the threat to life and property has increased manifolds which call for an urgent attention of all the researchers globally to carry out the research in the field of Earthquake Engineering. Any hazard related to the earthquake and seismicity is considered to be seismic hazards. The common forms of seismic hazards are Ground Shaking, Structure Damage, Structural Hazards, Liquefaction, Landslides, Tsunami to name a few. Among all the natural hazards, the most devastating and damaging is the earthquake as all other hazards are triggered only after the occurrence of an earthquake. In order to quantify and estimate the seismicity and seismic hazards, many methods and approaches have been proposed in the past few years. Such approaches are Mathematical, Conventional and Computational. Convex Set Theory, Empirical Green’s Function are some of the Mathematical Approaches whereas the Deterministic and Probabilistic Approaches are the Conventional Approach for the estimation of the seismic Hazards. Ground response and Ground Shaking of a particular area or region plays an important role in the damage caused due to the earthquake. In this paper, seismic study using Deterministic Approach and 1 D Ground Response Analysis has been carried out for Madhya Pradesh Tourism Office in Indore Region in Madhya Pradesh in Central India. Indore lies in the seismic zone III (IS: 1893, 2002) in the Seismic Zoning map of India. There are various faults and lineament in this area and Narmada Some Fault and Gavilgadh fault are the active sources of earthquake in the study area. Deepsoil v6.1.7 has been used to perform the 1 D Linear Ground Response Analysis for the study area. The Peak Ground Acceleration (PGA) of the city ranges from 0.1g to 0.56g.

Keywords: seismicity, seismic hazards, deterministic, probabilistic methods, ground response analysis

Procedia PDF Downloads 166

Authors: Mariame Taibi, Marouane Aouiji, Rachid Bengueddour

Abstract:

The Moroccan coastline is particularly rich in algae and constitutes a reserve of species with considerable economic, social and ecological potential. This work focuses on the research and characterization of algae bioactive compounds that can be used in pharmacology or phytopathology. The biochemical composition of the green alga Ulva lactuca (Ulvophyceae) was studied by determining the content of moisture, ash, phenols, flavonoids, total tannins, and chlorophyll. Seven solvents: distilled water, methanol, ethyl acetate, chloroform, benzene, petroleum ether, and hexane, were tested for their effectiveness in recovering chemical compounds. The identification of functional groupings, as well as the bioactive chemical compounds, was determined by FT-IR and GC-MS. The moisture content of the alga was 77%, while the ash content was 15%. Phenol content differed from one solvent studied to another, while chlorophyll a, b, and total chlorophyll were determined at 14%, 9.52%, and 25%, respectively. Carotenoid was present in a considerable amount (8.17%). The experimental results show that methanol is the most effective solvent for recovering bioactive compounds, followed by water. Moreover, the green alga Ulva lactuca is characterized by a high level of total polyphenols (45±3.24 mg GAE/gDM), average levels of total tannins and flavonoids (22.52±8.23 mg CE/gDM, 15.49±0.064 mg QE/gDM) respectively. The results of Fourier transform infrared spectroscopy (FT-IR) confirmed the presence of alcohol/phenol and amide functions in Ulva lactuca. The GC-MS analysis gave precisely the compounds contained in the various extracts, such as phenolic compounds, fatty acids, terpenoids, alcohols, alkanes, hydrocarbons, and steroids. All these results represent only a first step in the search for biologically active natural substances from seaweed. Additional tests are envisaged to confirm the bioactivity of seaweed.

Keywords: algae, Ulva lactuca, phenolic compounds, FTIR, GC-MS

Procedia PDF Downloads 108

Authors: Ł. Morawiński, C. Jasiński, M. Jurkiewicz, S. Bou Habib, M. Bondyra

Abstract:

With the development of optics, electronics, and computers, vision systems are increasingly used in various areas of life, science, and industry. Vision systems have a huge number of applications. They can be used in quality control, object detection, data reading, e.g., QR-code, etc. A large part of them is used for measurement purposes. Some of them make it possible to obtain a 3D reconstruction of the tested objects or measurement areas. 3D reconstruction algorithms are mostly based on creating depth maps from data that can be acquired from active or passive methods. Due to the specific appliance in airfield technology, only passive methods are applicable because of other existing systems working on the site, which can be blinded on most spectral levels. Furthermore, reconstruction is required to work long distances ranging from hundreds of meters to tens of kilometers with low loss of accuracy even with harsh conditions such as fog, rain, or snow. In response to those requirements, HRESS (Heliport REmote Safeguard System) was developed; which main part is a rotational head with a two-camera stereovision rig gathering images around the head in 360 degrees along with stereovision 3D reconstruction and point cloud combination. The sub-pixel analysis introduced in the HRESS system makes it possible to obtain an increased distance measurement resolution and accuracy of about 3% for distances over one kilometer. Ultimately, this leads to more accurate and reliable measurement data in the form of a point cloud. Moreover, the program algorithm introduces operations enabling the filtering of erroneously collected data in the point cloud. All activities from the programming, mechanical and optical side are aimed at obtaining the most accurate 3D reconstruction of the environment in the measurement area.

Keywords: airfield monitoring, artificial intelligence, stereovision, 3D reconstruction

Procedia PDF Downloads 125

Authors: Lidija Trandafilovic, Kirsten Leistner, Marie Stenfeldt, Louise Olsson

Abstract:

Ammonia Selective Catalytic Reduction (NH3 SCR), is one of the most efficient post combustion abatement technologies for removing NOx from diesel engines. In order to remove soot, diesel particulate filters (DPF) are used. Recently, SCR coated filters have been introduced, which captures soot and simultaneously is active for ammonia SCR. There are large advantages with using SCR coated filters, such as decreased volume and also better light off characteristics, since both the SCR function as well as filter function is close to the engine. The objective of this work was to examine the effect of soot, produced using an engine bench, on Cu/SSZ-13 catalysts. The impact of soot on Cu/SSZ-13 in standard SCR, NH3 oxidation, NH3 temperature programmed desorption (TPD), as well as soot oxidation (with and without water) was examined using flow reactor measurements. In all experiments, prior to the soot loading, the fresh activity of Cu/SSZ-13 was recorded with stepwise increasing the temperature from 100°C till 600°C. Thereafter, the sample was loaded with soot and the experiment was repeated in the temperature range from 100°C till 700°C. The amount of CO and CO2 produced in each experiment is used to calculate the soot oxidized at each steady state temperature. The soot oxidized during the heating to next temperature step is included, e.g. the CO+CO2 produced when increasing the temperature to 600°C is added to the 600°C step. The influence of the two factors seem to be of the most importance to soot oxidation: ammonia and water. The influence of water on soot oxidation shift the maximum of CO2 and CO production towards lower temperatures, thus water increases the soot oxidation. Moreover, when adding ammonia to the system it is clear that the soot oxidation is lowered in the presence of ammonia, resulting in larger integrated COx at 500°C for O2+H2O, while opposite results at 600 °C was received where more was oxidised for O2+H2O+NH3 case. To conclude the presence of ammonia reduces the soot oxidation, which is in line with the ammonia TPD results where we found ammonia storage on the soot. Interestingly, during ammonia SCR conditions the activity for soot oxidation is regained at 500°C. At this high temperature the SCR zone is very short, thus the majority of the catalyst is not exposed to ammonia and therefore the inhibition effect of ammonia is not observed.

Keywords: NH3-SCR, Cu/SSZ-13, soot, zeolite

Procedia PDF Downloads 236

Authors: Nadeem Munawar, Tariq Mahmood

Abstract:

Habitat manipulation is an important technique that can be used for controlling rodent damage in agricultural ecosystems. It involves intentionally manipulation of vegetation cover in adjacent habitats around the active burrows of rodents to reduce shelter, food availability and to increase predation pressure. The current study was conducted in the Pothwar Plateau during the respective non-crop period of wheat-groundnut (post-harvested and un-ploughed/non-crop fallow lands) with the aim to assess the impact of the reduction in vegetation height of adjacent habitats (field borders) on rodent’s richness and abundance. The study area was divided into two sites viz. treated and non-treated. At the treated sites, habitat manipulation was carried out by removing crop cache, and non-crop vegetation’s over 10 cm in height to a distance of approximately 20 m from the fields. The trapping sessions carried out at both treated and non-treated sites adjacent to wheat-groundnut fields were significantly different (F 2, 6 = 13.2, P = 0.001) from each other, which revealed that a maximum number of rodents were captured from non-treated sites. There was a significant difference in the overall abundance of rodents (P < 0.05) between crop stages and between treatments in both crops. The manipulation effect was significantly observed on damage to crops, and yield production resulted in the reduction of damage within the associated croplands (P < 0.05). The outcomes of this study indicated a significant reduction of rodent population at treated sites due to changes in vegetation height and cover which affect important components, i.e., food, shelter, movements and increased risk sensitivity in their feeding behavior; therefore, they were unable to reach levels where they cause significant crop damage. This method is recommended for being a cost-effective and easy application.

Keywords: agricultural ecosystems, crop damage, habitat manipulation, rodents, trapping

Procedia PDF Downloads 165

Authors: Kabange Kasumbwe, Viresh Mohanlall, Bharti Odhav, Venu Narayanaswamy

Abstract:

Coumarins are naturally occurring plant metabolites known for their pharmacological properties such as anticoagulant, antimicrobial, anticancer, antioxidant, anti-inflammatory and antiviral properties. The pharmacological and biochemical properties and curative applications of coumarins depend on the substitution around the coumarin core structure. In the present study, seven halogenated coumarins CMRN1-CMRN7 were synthesized and evaluated for their anticancer activity. The cytotoxicity potential of the test compounds was evaluated against UACC62 (Melanoma), MCF-7 (Breast cancer) and PBM (Peripheral Blood Mononuclear) cell lines using MTT assay keeping doxorubicin as standard drug. The apoptotic potential of the coumarin compounds was evaluated against UACC62 (Melanoma) cell by assessing their morphological changes, membrane change, mitochondria membrane potential; pro-apoptotic changes were investigated using the AnnexinV-PI staining, JC-1, caspase-3 enzyme kits respectively on flow cytometer. The synthetic coumarin has strongly suppressed the cell proliferation of UACC-62 (Melanoma) and MCF-7 (Breast) Cancer cells, the higher toxicity of these compounds against UACC-62 (Melanoma) and MCF-7 (Breast) were CMRN3, CMRN4, CMRN5, CMRN6. However, compounds CMRN1, CMRN2, and CMRN7 had no significant inhibitory effect. Furthermore the active compounds CMRN3, CMRN4, CMRN5, CMRN6 exerted antiproliferative effects through apoptosis induction against UACC-62 (Melanoma), suggesting their potential could be considered as attractive lead molecules in the future for the development of potential anticancer agents since one of the important criteria in the development of therapeutic drugs for cancer treatment is to have high selectivity and less or no side-effects on normal cells and these compounds had no inhibitory effect against the PBMC cells.

Keywords: coumarin, MTT, apoptosis, cytotoxicity

Procedia PDF Downloads 238

Authors: Rod Davis, Sara Saminfar

Abstract:

Earthquakes can induce dynamic earth pressures on retaining walls, which are in addition to the static earth pressures. This raises questions about how to effectively combine the seismic lateral earth pressure with other loads on buildings, including static lateral earth pressure. When basement walls retain soil with differing exterior grades on opposite sides, the seismic increment of active earth pressure should be considered. Additionally, buildings situated on sloped sites with stepped retention may experience unique dynamic effects due to soil-structure interactions, potentially amplifying the lateral pressures exerted on the retaining walls and influencing the building's response during seismic events. To account for the dynamic effects of the retained soil on the building's responses, it is essential to interconnect the building structure with the surrounding soil to facilitate their interaction as the embedded structure and the surrounding soil move together during an earthquake. Consequently, a finite element model of the building is developed, with the rigid retaining walls and restrained to the floor diaphragms. This paper aims to explore the dynamic effects of retained soil on the lateral stability of buildings and the sensitivity of the building's responses to differences in the retained heights on opposite sides of the building basement. Furthermore, the results are compared with those from a sloped site to evaluate the impact of stepped retention on dynamic soil pressure. These findings will help establish a minimum threshold for differences in retained heights on opposite sides of a building that necessitates the inclusion of dynamic soil pressure in the building's lateral stability analysis.

Keywords: dynamic earth pressures, soil-structure interaction, stepped retention, building retention

Procedia PDF Downloads 12

Authors: Azusa Katsumata

Abstract:

Where there is collaboration between universities and companies in the educational context, companies seek ‘knowledge’ from universities and provide a ‘place of practice’ to them. Several universities have introduced activities aimed at the mutual enlightenment of a diversity of people in career education. However, several programs emphasize on delivering results, and on practicing the prepared materials as planned. Few programs focus on unexpected failures and setbacks. This way of learning is important in career education so that classmates can help each other, overcome difficulties, draw out each other’s strengths, and learn from them. Seijo University in Tokyo offered Tokyo Tourism, a Project-Based Learning course, as a first-year career education course until 2016. In cooperation with a travel agency, students participate in planning actual tourism products for foreigners visiting Japan, undertake tours serving as guides. This paper aims to study the 'learning platform' created by a series of processes such as the fieldwork, planning tours, the presentation, selling the tourism products, and guiding the tourists. We conducted a questionnaire to measure the development of work-related skills in class. From the results of the questionnaire, we can see, in the example of this class, that students demonstrated an increased desire to be pro-active and an improved motivation to learn. Students have not, however, acquired policy or business skills. This is appropriate for first-year careers education, but we need to consider how this can be incorporated into future courses. In the questionnaire filled out by the students after the class, the following results were found. Planning and implementing travel products while learning from each other, and helping the teams has led to improvements in the student workforce. This course is a collaborative project between Japanese universities and the 2020 Tokyo Olympics and Paralympic Games committee.

Keywords: university career education, platform of learning, project-based learning, collaboration between university and company

Procedia PDF Downloads 161

Authors: G. Ultanbekova, Zh. Suleimenova, Zh. Rakhmetova, G. Mombekova, S. Mantieva

Abstract:

Plant Growth Promoting Rhizobacteria (PGPR) are a group of free-living bacteria that colonize the rhizosphere, enhance plant growth of many cereals and other important agricultural crops and protect plants from disease and abiotic stresses through a wide variety of mechanisms. The use of PGPR has been proven to be an environmentally sound way of increasing crop yields by facilitating plant growth. In the present study, strain improvement of PGPR isolates were carried out by chemical mutagenesis for the improvement of growth and yield of lima bean. Induced mutagenesis is widely used for the selection of microorganisms producing biologically active substances and further improving their activities. Strain improvement is usually done by classical mutagenesis which involves exposing the microbes to chemical or physical mutagens. The strains of Pseudomonas putida 4/1, Azotobacter chroococcum Р-29 and Bacillus subtilis were subjected to mutation process for strain improvement by treatment with a chemical agent (sodium nitrite) to cause mutation and were observed for its consequent action on the seeds germination and plant growth of lima bean (Phaseolus lunatus). Bacterial mutant strains of Pseudomonas putida M-1, Azotobacter chroococcum M-1 and Bacillus subtilis M-1, treated with sodium nitrite in the concentration of 5 mg/ml for 120 min, were found effective to enhance the germination of lima bean seeds compared to parent strains. Moreover, treatment of the lima bean seeds with a mutant strain of Bacillus subtilis M-1 had a significant stimulation effect on plant growth. The length of the stems and roots of lima bean treated with Bacillus subtilis M-1 increased significantly in comparison with parent strain in 1.6 and 1.3 times, respectively.

Keywords: chemical mutagenesis, germination, kidney bean, plant growth promoting rhizobacteria (PGPR)

Procedia PDF Downloads 198

Authors: Jean Hugé, Francisco Benitez-Capistros, Giorgia Camperio-Ciani

Abstract:

Addressing conservation conflicts requires the consideration of multiple stakeholders' perspectives and knowledge claims, in order to inform complex and possibly contentious decision-making dilemmas. Hence, a better understanding of why people in particular contexts act in a particular way in a conservation conflict is needed. First, this contribution aims at providing and applying an approach to map and interpret the diversity of subjective viewpoints with regard to iconic species in conservation conflicts. Secondly, this contribution aims to feed the reflection on the possible consequences of the diversity of perspectives for the future management of wildlife (in particular iconic species), based on case studies in Galapagos and Malaysia. The use of the semi-quantitative Q methodology allowed us to identify various perspectives on conservation in different social-ecological contexts. While the presence of iconic species may lead to a more passionate and emotional debate, it may also provide more opportunities for finding common ground and for jointly developing acceptable management solutions that will depolarize emergent, long-lasting or latent conservation conflicts. Based on the research team’s experience in the field, and on the integration of ecological and social knowledge, methodological and management recommendations are made with regard to conservation conflicts involving iconic wildlife. The mere presence of iconic wildlife does not guarantee its centrality in conservation conflicts, and comparisons will be drawn between the cases of the giant tortoises (Chelonoidis spec.) in Galapagos, Ecuador and the Milky Stork (Mycteria cinerea) in western peninsular Malaysia. Acknowledging the diversity of viewpoints, reflecting how different stakeholders see, act and talk about wildlife management, highlights the need to develop pro-active and resilient strategies to deal with these issues.

Keywords: conservation conflicts, Q methodology, Galapagos, Malaysia, giant tortoise, milky stork

Procedia PDF Downloads 285

Authors: Judith Klostermann, Miguel Segura, Wilma Jans, Dragana Bojovic, Isadora Christel Jimenez, Francisco Doblas-Reyees, Judit Snethlage

Abstract:

The Climate Data Store (CDS), developed by the Copernicus Climate Change Service (C3S) implemented by the European Centre for Medium-Range Weather Forecasts (ECMWF) on behalf of the European Union, is intended to become a key instrument for exploring climate data. The CDS contains both raw and processed data to provide information to the users about the past, present and future climate of the earth. It allows for easy and free access to climate data and indicators, presenting an important asset for scientists and stakeholders on the path for achieving a more sustainable future. The C3S Evaluation and Quality Control (EQC) is assessing the quality of the CDS by undertaking a comprehensive user requirement assessment to measure the users’ satisfaction. Recommendations will be developed for the improvement and expansion of the CDS datasets and products. User requirements will be identified on the fitness of the datasets, the toolbox, and the overall CDS service. The EQC function of the CDS will help C3S to make the service more robust: integrated by validated data that follows high-quality standards while being user-friendly. This function will be closely developed with the users of the service. Through their feedback, suggestions, and contributions, the CDS can become more accessible and meet the requirements for a diverse range of users. Stakeholders and their active engagement are thus an important aspect of CDS development. This will be achieved with direct interactions with users such as meetings, interviews or workshops as well as different feedback mechanisms like surveys or helpdesk services at the CDS. The results provided by the users will be categorized as a function of CDS products so that their specific interests will be monitored and linked to the right product. Through this procedure, we will identify the requirements and criteria for data and products in order to build the correspondent recommendations for the improvement and expansion of the CDS datasets and products.

Keywords: climate data store, Copernicus, quality, user engagement

Procedia PDF Downloads 146

Authors: Vincent Jones

Abstract:

The North African country of Libya is in crisis and is currently a humanitarian disaster. The current American ‘hands off’ foreign policy appear to have contributed to this crisis. The research upon which this paper is based focused on a qualitative analysis of migration to Libya and its history with slavery, current conditions that have contributed to the re-emergence of slavery, an analysis of available resources in the effected region, and an analysis of legal remedies pursuant to international law. In addition, a qualitative analysis of American foreign policy from the Reagan Administration through the current Trump administration has been a focus of analysis. The major findings of this research are: (1) Since the removal of Muammar Gadhafi, a move that the United States played a major role in achieving, the nation of Libya has been in free fall and the rule of law has all but disappeared. As a major port stop for refugees and migrants fleeing atrocities in sub-Saharan African states, Libya has become the gate way to European ports of asylum. The problem is these migrant refugees are unwanted, caught between rival and often ineffective governments, profiteers, and inaction from the international community. (2) The outlook for these refugees is bleak: the ineffective government of Libya is ill-equipped to handle the large influx, European refugee destination states like Italy and Greece are already overburdened by the Syrian refugee crisis and are reluctant to accept more refugees, leaving the powerful and armed Libyan militia in control of a situation that is ripe for exploitation. (3) The combined intervention of the international community, led by a newly committed and engaged American foreign policy. In conclusion, a new American foreign policy approach along with the active engagement of the United Nations, EU, and the African Union can effectively resolve this humanitarian crisis.

Keywords: slavery, Libya, migrants, slave auction

Procedia PDF Downloads 234

Authors: Ashit Syngle, Inderjit Verma, Pawan Krishan

Abstract:

Therapeutic approaches used previously relied on disease-modifying antirheumatic drugs (DMARDs) that had only partial clinical benefit and were associated with significant toxicity. Spironolactone, an oral aldosterone antagonist, suppresses inflammatory mediators. Clinical efficacy of spironolactone compared with placebo in patients with active psoriatic arthritis despite treatment with prior traditional DMARDs. In the 24-week, placebo-controlled study patients (n=31) were randomized to placebo and spironolactone (2 m/kg/day). Patients on background concurrent DMARDs continued stable doses (methotrexate, leflunomide, and/or sulfasalazine). Primary outcome measures were the assessment of disease activity measures i.e. 28-joint disease activity score (DAS28) and diseases activity in psoriatic arthritis (DAPSA) at week 24. The key secondary endpoint was change from baseline in Health Assessment Questionnaire–Disability Index (HAQ-DI) at week 24. Additional efficacy outcome measures at week 24 included improvements in the markers of inflammation (ESR and CRP) and pro-inflammatory cytokines TNF-α, IL-6 and IL-1. At week 24, spironolactone significantly reduced disease activity measure DAS-28 (p<0.001) and DAPSA (p=0.001) compared with placebo. Significant improvements in key secondary measures HAQ-DI (disability index) were evident with spironolactone (p=0.02) versus placebo. After week 24, there was significant reduction in pro-inflammatory cytokines level TNF-α, IL-6 (p<0.01) as compared with placebo group. However, there was no significant improvement in IL-1 in both treatment and placebo groups. There were minor side effects which did not mandate stopping of spironolactone. No change in any biochemical profile was noted after spironolactone treatment. Spironolactone was effective in the treatment of PsA, improving disease activity, physical function and suppressing the level of pro-inflammatory cytokines. Spironolactone demonstrated an acceptable safety profile and was well tolerated.

Keywords: spironolactone, inflammation, inflammatory cytokine, psoriatic arthritis

Procedia PDF Downloads 337

Authors: Samaneh Pouyanfar, Michael Oliff

Abstract:

The industry of home appliances may beone of theindustries which has the highest competition, and actually what can guarantee the survival of this industry is discovering the superior services. A trend to provide quality products and services plays an important role in this industry because discovering the services is counted as a vital affair for Manufacturing Organizations’ survival and profitability. Given the importance of the topic, this paper attempts to investigate the relative priority of the factors influencing the customer satisfaction in gaining the competitive advantage in Pars-Khazar Company. In sum, 96 executives of Pars-Khazar Company where investigated in a census. For this purpose, after reviewing the research literature and performing deep interviews between pundits and experts active in the industry, the research questionnaire was made based on variables affecting customer satisfaction and components determining business competitive advantage. Determining the content validity took place by judgement of the experts. The reliability of each structure was measured based on Cronbach’s alpha coefficient. Since the value of Cronbach's alpha was higher than 0.7 for each structure, internal consistency of statements was high and the reliability of the questionnaire was acceptable. The data analysis was also done with Kulmgrf-asmyrnf test and Friedman test using SPSS software. The results showed that in dimension of factors affecting customer satisfaction, the History of trade name (brand), Familiarity with the product brand, Brand reputation and Safety have the highest value of priority respectively, and the variable of firm growth has the highest value of priority among the components determining the performance of competitive advantage.

Keywords: customer satisfaction, competitive advantage, brand history, safety, growth

Procedia PDF Downloads 230

Authors: Caiwei Chen, Jianhao Li, Jiasong Zhu

Abstract:

The reform and opening-up stimulated economic and technological take-off in China while resulting in massive urbanization and motorization. Wujiaochang area was set as a secondary business district in Shanghai to meet the growing demand, with the reconstruction of Wujiaochang Plaza in 2005 being a milestone of this intended urban renewal. Wujiaochang is now an economically dynamic area providing much larger traffic and transit capacity transportation-wise. However, this rebuilding has completely changed the face of the district. It is, therefore, appropriate to evaluate its impact on neighborhoods and communities while assessing the overall sustainability of such an operation. In this study, via an online questionnaire survey among local residents and daily visitors, we assess the perceptions and the estimated impact of Wujiaochang Plaza's reconstruction. We then confront these results to the 62 answers from local residents to a questionnaire collected on paper. The analysis of our data, along with observation and other forms of information -such as maps analysis or online applications (Dianping)- demonstrate major improvement in economic sustainability but also significant losses in environmental sustainability, especially in terms of active transportation. As for the social viewpoint, local residents' opinions tend to be rather positive, especially regarding traffic safety and access to consumption, despite the lack of connectivity and radical changes induced by Wujiaochang massive transformations. In general, our investigation exposes the overall positive outcomes of Wujiaochang Plaza reconstruction but also unveils major drawbacks, especially in terms of soft mobility and traffic fluidity. We gather that our approach could be of tremendous help for future major urban interventions, as such approaches in municipal regeneration are widely implemented in Chinese cities and yet still need to be thoroughly assessed in terms of sustainability.

Keywords: China's reform and opening-up, economical revitalization, neighborhood identity, sustainability assessment, urban renewal

Procedia PDF Downloads 237

Authors: Alexis Thouki

Abstract:

In our post-Christian societies, ecclesiastical heritage acquired a new extrovert profile aiming to reach out an increasingly diverse audience. In this context, the various motivations, interests, personalities and cultural exchanges, found in the ‘post-modern pilgrimage’, bequeath a hybrid and multidimensional character to religious tourism education. In consequence, churches have acquired the challenging role of enriching visitors cultural and spiritual capital. Despite this promising diversification to relate, reveal and provoke constructive discourses, due to the various ‘conflicting interests’, practitioners attempt to tame the rich in symbolism and meanings religious environment through ‘neutral interpretations’. This paper aims to present the results of an ongoing developing strategy related to the presentation of contentious meanings in English churches. The paper will explore some of the underlying issues related to the capacity of ‘neutrality’ to spark, downplay or eliminate contentious conversations relating to the cultural, religious, and social dimension of Christian cultural heritage thematology. In an effort to understand this issue, the paper examines the concept of neutrality and what it stands for, executing a discourse analysis in the semantic context in which the theological lexicon is interwoven with the cultural and social meanings of sacred sites. Following that, the paper examines whether the preferable interpretive strategies meet the post-modern interpretative framework which is marked by polysemy and critical active engagement. The ultimate aim of the paper is to investigate the hypothesis that the preferable neutral strategies, managing the ‘conflicting’ demands of worshippers and visitors, result in the uneven treatment of both, the religious and historical spirit of the place.

Keywords: contentious dialogue, interpretation, meaning making, religious tourism

Procedia PDF Downloads 156

Authors: D. Motlhanka, M. Mine, T. Bagaketse, T. Ngakane

Abstract:

There is a plethora of evidence from numerous sources that highlights the triumph of naturally derived medicinal plant metabolites with antioxidant capability for repurposed therapeutics. As post-COVID-19 syndromes and non-communicable diseases are on the rise, there is an urgent need to come up with new therapeutic strategies to address the problem. Non-communicable diseases and Post COVID-19 syndromes are classified as socio-economic diseases and are ranked high among threats to health security due to the economic burden they pose to any government budget commitment. Research has shown a strong link between accumulation of free radicals and oxidative stress critical for pathogenesis of non-communicable diseases and COVID-19 syndromes. Botswana has embarked on a robust programme derived from ethno-pharmacognosy and drug repurposing to address these threats to health security. In the current approach, a number of medicinally active plant-derived polyphenolics are repurposed and combined into new medicinal tools to target diabetes, Hypertension, Prostate Cancer and oxidative stress induced Post COVID 19 syndromes such as “brain fog”. All four formulants demonstrated Free Radical scavenging capacities above 95% at 200µg/ml using the diphenylpicryalhydrazyl free radical scavenging assay and the total phenolic contents between 6899-15000GAE(g/L) using the folin-ciocalteau assay respectively. These repurposed medicinal tools offer new hope and potential in the fight against emerging health threats driven by hyper-inflammation and free radical-induced oxidative stress.

Keywords: drug repurposed plant polyphenolics, free radical damage, non-communicable diseases, post COVID 19 syndromes

Procedia PDF Downloads 128

Authors: Hsiao-Chien Tsai, Yu-Pin Chen, Ruei-Ming Chen

Abstract:

Introduction: Osteoarthritis (OA) is characterized by joint destruction and causes chronic disability. One of the prominent symptoms is pain. Alleviating the pain is necessary and urgent for the therapy of OA patients. However, currently, understanding the mechanisms that drive OA-induced pain remains challenging, which hampers the optimistic management of pain in OA patients. Semaphorin 4D (Sema4D) participates in axon guidance pathway and bone remodeling, thus, may play a role in the regulation of pain in OA. In this study, we have established a rat model of OA to find out the mechanisms of OA-induced pain and to deliberate the roles of Sema4D. Methods: Behavioral changes and the pro-inflammatory cytokines (IL-1β, TNF-α, and IL-17) associated with pain were measured during the development of OA. Sema4D expression in cartilage and synovial membrane at 1, 4, and 12 weeks after inducing OA was analyzed. To assess if Sema4D is related to the neurogenesis in OA as an axon repellant, we analyzed the expression of PGP9.5 as well. Results: Synovitis and cartilage degradation were evident histologically during the development of OA. Mechanical hyperalgesia was most severe at week 1, then persisted thereafter. It was associated with stress coping strategies. Similar to the pain behavioral results, levels of IL-1β and TNF-α in synovial lavage fluid were significantly elevated in the OA group at weeks 1 and 4, respectively. Sema4D expression in cartilage and the synovial membrane was also enhanced in the OA group and was correlated with pain and pro-inflammatory cytokines. The marker of neurogenesis, PGP9.5, was also enhanced during the development of OA. Discussion: OA induced mechanical hyperalgesia, which might be through upregulating IL-1β/TNF-α-mediated Sema4D expressions. If anti-Sema4D treatment could reduce OA-induced mechanical hyperalgesia and prevent the subsequent progression of OA needs to be further investigated. Significance: OA can induce mechanical hyperalgesia through upregulation of IL-1β/TNF-α-mediated Sema4D and PGP9.5 expressions. And the upregulation of Sema4D may indicate the severity or active status of OA and OA-induced pain.

Keywords: traumatic osteoarthritis, mechanical hyperalgesia, Sema4D, inflammatory cytokines

Procedia PDF Downloads 78

Authors: Elham Shakerian, Reza Afarin

Abstract:

The hepatic disease causes approximately 2 million deaths/year worldwide. Liver fibrosis is the last stage of numerous chronic liver diseases, and until now there is no definite cure or drug for it. Activation of hepatic stellate cells (HSCs) is the main reason for fibrosis. Transforming growth factor (TGF-β), as a main profibrogenic cytokine, if increased in these cells, leads to liver fibrosis through smad3 signaling pathways and increasing the expressions of Collagen type I and III, and actin-alpha smooth muscle (αSMA) genes. Curcumin (CUR) is a polyphenolic compound and an active ingredient derived from the rhizome of the turmeric plant that exerts effective antioxidant, anti-inflammatory, and antimicrobial activity. It has been shown that daily consumption of curcumin may have a protective effect on the liver against oxidative stress associated with alcohol consumption. In this study, we investigate the role of Curcumin in decreasing HSC activation and treating liver fibrosis. First, the human HSCs were treated with 2 ng/ml of (TGF-β) for 24 hours to become activated, then with Silibinin for 24 hours. Total RNAs were extracted, reversely transcribed into cDNA, Quantitative Real-time PCR, and western blot were performed. The mRNA expression levels of Collagen type I and III, αSMA genes, and the level of smad3 phosphorylation in TGF-β activated human HSCs treated with Curcumin were significantly reduced compared to human HSCs untreated with Curcumin. Curcumin is effective in reducing the expression of fibrogenic genes in the activated human HSCs treated with TGFB through downregulation of the TGF-β/smad3 signaling pathway. Therefore, Curcumin possesses significant antifibrotic properties in hepatic fibrosis

Keywords: hepatic fibrosis, human HSCs, curcumin, fibrogenic genes

Procedia PDF Downloads 122

Authors: S. P. Bansal, Mukesh Kumar Sharma, Ankit Prabhakar

Abstract:

Luhri Hydroelectric Project Stage-I (210 MW) is a run of the river type development with a dam toe surface powerhouse (122m long, 50.50m wide, and 65.50m high) on the right bank of river Satluj in Himachal Pradesh, India. The project is located in the inner lesser Himalaya between Dhauladhar Range in the south and higher Himalaya in the north in the seismically active region. At the project, the location river is confined within narrow V-shaped valleys with little or no flat areas close to the river bed. Nearly 120m high cut slopes behind the powerhouse are proposed from the powerhouse foundation level of 795m to ± 915m to accommodate the surface powerhouse. The stability of 120m high cut slopes is a prime concern for the reason of risk involved. The slopes behind the powerhouse will be excavated in mainly in augen gneiss, fresh to weathered in nature, and biotite rich at places. The foliation joints are favorable and dipping inside the hill. Two valleys dipping steeper joints will be encountered on the slopes, which can cause instability during excavation. Geological exploration plays a vital role in designing and optimization of cut slopes. SWEDGE software has been used to analyze the geometry and stability of surface wedges in cut slopes. The slopes behind powerhouse have been analyzed in three zones for stability analysis by providing a break in the continuity of cut slopes, which shall provide quite substantial relief for slope stabilization measure. Pseudo static analysis has been carried out for the stabilization of wedges. The results indicate that many large wedges are forming, which have a factor of safety less than 1. The stability measures (support system, bench width, slopes) have been planned so that no wedge failure may occur in the future.

Keywords: cut slopes, geotechnical investigations, Himalayan geology, surface powerhouse, wedge failure

Procedia PDF Downloads 118

Authors: Ruqaiya Khalil, Saman Usmani, Zaheer Ul-Haq

Abstract:

The accurate characterization of ligand binding affinity is indispensable for designing molecules with optimized binding affinity. Computational tools help in many directions to predict quantitative correlations between protein-ligand structure and their binding affinities. Molecular dynamics (MD) simulation is a modern state-of-the-art technique to evaluate the underlying basis of ligand-protein interactions by characterizing dynamic and energetic properties during the event. Autoimmune diseases arise from an abnormal immune response of the body against own tissues. The current regimen for the described condition is limited to immune-modulators having compromised pharmacodynamics and pharmacokinetics profiles. One of the key player mediating immunity and tolerance, thus invoking autoimmunity is Interleukin-2; a cytokine influencing the growth of T cells. Molecular dynamics simulation techniques are applied to seek insight into the inhibitory mechanisms of newly synthesized compounds that manifested immunosuppressant potentials during in silico pipeline. In addition to estimation of free energies associated with ligand binding, MD simulation yielded us a great deal of information about ligand-macromolecule interactions to evaluate the pattern of interactions and the molecular basis of inhibition. The present study is a continuum of our efforts to identify interleukin-2 inhibitors of both natural and synthetic origin. Herein, we report molecular dynamics simulation studies of Interluekin-2 complexed with different antagonists previously reported by our group. The study of protein-ligand dynamics enabled us to gain a better understanding of the contribution of different active site residues in ligand binding. The results of the study will be used as the guide to rationalize the fragment based synthesis of drug-like interleukin-2 inhibitors as immune-modulators.

Keywords: immuno-modulators, MD simulation, protein-ligand interaction, structure-based drug design

Procedia PDF Downloads 262

Authors: Suelen C. Lima, André C. de Oliveira, Rosemary A. Roque

Abstract:

Dengue is fatal arboviruses transmitted by the A. aegypti mosquito to more than 100 countries, for which the WHO estimates that 2.5 million people will be infected by these disease. The widespread of these diseases is due, among other factors, to the resistance that A. aegypti has to several commercial insecticides. On the other hand, natural products based on plants of the genus Piper (Piperaceae) are characterized by their insecticidal activities against mosquitoes. Piper longepetiolatum and Piper brachypetiolatum are species with wide distribution in the State of Amazonas. However, there is no investigation of phytochemical or biological of these plants against mosquitoes such as A. aegypti. The main of this study was to identify the chemical composition of the essential oil (EOs) from P. longepetiolatum and P. brachypetiolatum and to evaluate the biological activity against A. aegypti. The EOs were extracted by hydrodistillation from leaves (200 g) of P. longepetiolatum and P. brachypetiolatum and analyzed by GC-MS and GC-FID. The main compounds β-caryophyllene (99.9% of purity) and E-nerolidol (99.4% of purity) were purchased from Sigma-Aldrich® Brazil. The larvicidal activity of EOs (20 to 100 ppm), β-caryophyllene and E-nerolidol (10 to 50 ppm) was performed according to WHO protocol against A. aegypti larvae. The GC-MS and GC-FID analysis of EOs from P. longepetiolatum and P. brachypetiolatum indicated the majority presence of β-caryophyllene (35.42%) and E-nerolidol (49.79%), respectively. The results showed that all natural products presented larvicidal activity against A. aegypti. In this aspect, the OE from P. brachypetiolatum (LC50 of 15.51 ppm and LC90 of 22.79 ppm) was more active than the OE from P. longepetiolatum (LC50 of 47.17 ppm and LC90 of 69.60 ppm) (p < 0.05). Regarding of main compounds, E-nerolidol (LC50 of 9.50 ppm and LC90 of 23.89 ppm) showed higher larvicidal activity than the β-caryophyllene compound (LC50 of 79.00 ppm and LC90 of 230.91 ppm) (p < 0.05). The larvae treated with these natural products showed tremors and lethargic movements, suggesting that these natural products have neurotoxic action. These observations support studies to investigate the mechanism of action. This is the first record of the chemical composition and larvicidal activity of the EO from P. longepetiolatum and P. brachypetiolatum rich in β-caryophyllene and E-nerolidol against A. aegypti larvae.

Keywords: piperaceae, aedes, sesquiterpenes, biological control

Procedia PDF Downloads 76

Authors: Magdy Abouzeid

Abstract:

Introduction: Physical activity has been shown to have a positive effect on bone mineral density (BMD) and bone mineral content (BMC) among children, adolescents, and adults. Sports characterized by little or moderate weight bearing or impact have a low osteogenic effect. However, the action of such sports on bone turnover remains unclear. Swimming, as a non-weight-bearing sport, has been considered to be insignificant in the maintenance of bone mass. Purpose: To examine this issue we measured (BMD) and(BMC) of the lumbar spine, proximal femur via dual energy x-ray absorptiometry in the group of elite male swimmers, and determine the effect of swimming training on bone health and compared the results with matched controls group in age, body weight and height. Materials and Methods: Twenty-five male swimmers (age 20.7+/-0.8 years) training for 12-15 hours/week; and the controls group consisted of 25 non-active male (age 21.3 +/-1.3 years) were studied BMD and BMC of lumbar spine, femur were assessed via (DXA) absorptiometry. Results: There was significant difference between swimmers and control group in BMD and BMC, BMD of Swimmers was significantly greater than controls at all sites. The lumbar spine (1, 08 +/-0.202 vs., 0717+0.57 gxcm (-2), right proximal femur (1, 02 +/-, 044 vs., 771+/-, 027 gxcm (-2), and left proximal femur (1.374+/-0.212 vs. 1.01 +/-0.141 gxcm (-2). Swimmers were significantly taller, and had greater BMC and BMD compared to the controls group (P<0.001). Conclusions: These results suggest that swimming training may be beneficial in the prevention or therapy of OSTEOPENIA, and may lead to increased (BMD) and (BMC) for male swimmers. Swimming may be an effective non-pharmacological intervention for the adults and adolescent. Further research with younger athletes of another type of aquatics sport is warranted to better identify the periods of BMD development during which Aquatics sport has the greatest impact on bone health.

Keywords: bone mineral density, lumbar spine, femur, swimming, DXA absorptiometry

Procedia PDF Downloads 322

Authors: Asteria Nsamba

Abstract:

Social networking applications and tools have become compelling platforms for generating and sharing knowledge across the world. Social networking applications and tools refer to a variety of social media platforms which include Facebook, Twitter WhatsApp, blogs and Wikis. The most popular of these platforms are Facebook, with 2.41 billion active users on a monthly basis, followed by WhatsApp with 1.6 billion users and Twitter with 330 million users. These communication platforms have not only impacted social lives but have also impacted students’ learning, across different delivery modes in higher education: distance, conventional and blended learning modes. With this amount of interest in these platforms, knowledge sharing has gained importance within the context in which it is required. In open distance learning (ODL) contexts, social networking platforms can offer students and teachers the platform on which to create and share knowledge, and form learning collaborations. Thus, they can serve as support mechanisms to increase interactions and reduce isolation and loneliness inherent in ODL. Despite this potential and opportunity, research indicates that many ODL teachers are not inclined to using social media tools in learning. Although it is unclear why these tools are uncommon in these environments, concerns raised in the literature have indicated that many teachers have not mastered the art of teaching with technology. Using technological, pedagogical content knowledge (TPCK) and product quality theory, and Bloom’s Taxonomy as lenses, this paper is aimed at; firstly, assessing the quality of three social media applications: Facebook, Twitter and WhatsApp, in order to determine the extent to which they are suitable platforms for teaching and learning, in terms of content generation, information sharing and learning collaborations. Secondly, the paper demonstrates the application of teaching, learning and assessment using Bloom’s Taxonomy.

Keywords: distance education, quality, social networking tools, TPACK

Procedia PDF Downloads 124

Authors: E. A. Alaswad, H. M. Choudhry, F. Z. Filimban

Abstract:

Sickle Cell Anemia (SCA) is one type of blood diseases related to autosomal disorder. The sickle shaped red blood cells are the main cause of many problems in the blood vessels and capillaries. Aerva Javanica (J) and Ficus Palmata (P) are medicinal plants that have many popular uses and have been proved their efficacy. The aim of this study was to assess the antioxidants activity and the antisickling effect of J and P extractions. The period of this study, air-dried leaves of J, and P plants were ground and the active components were extracted by maceration in water (W) and methanol (M) as solvents. The antioxidants activity of JW, PW, JM, and PM were assessed by way of the radical scavenging method using 2,2-diphenyl-1-picrylhydrazyl (DPPH). To determine the antisickling effect of J and P extracts. 20 samples were collected from sickle cell anemia patients. Different concentrations of J and P extracts (200 and 110 μg/mL) were added on the sample and incubated. A drop of each sample was examined with light microscope. Normal and sickled RBCs were calculated and expressed as the percent of sickling. The stabilization effect of the extracts was measured by the osmotic fragility test for erythrocytes. The finding suggests as estimated by DPPH method, all the extracts showed an antioxidant activity with a significant inhibition of the DPPH radicals. PM has the least IC50% with 71.49 μg/ml while JM was the most with 408.49 μg/ml. Sickle cells treated with extracts at different concentrations significantly reduced the percentage of sickling compering to control samples. However, JM 200 μg/mL give the highest anti-sickling affect with 17.4% of sickling compared to control 67.5 of sickling while PM at 200 μg/mL showed the highest membrane cell stability. In a conclusion, the results showed that J and P extracts have antisickling effects. Therefore, the Aerva javanica and Ficus palmata may have a role in SCA management and a good impact on the patient's lives.

Keywords: Aerva javanica, antioxidant, antisickling, Ficus palmata, sickle cell anemia

Procedia PDF Downloads 168

Authors: Sofia Ait Bouazza

Abstract:

We consider the problem of finding a minimum identifying code in a graph. This problem was initially introduced in 1998 and has been since fundamentally connected to a wide range of applications (fault diagnosis, location detection …). Suppose we have a building into which we need to place fire alarms. Suppose each alarm is designed so that it can detect any fire that starts either in the room in which it is located or in any room that shares a doorway with the room. We want to detect any fire that may occur or use the alarms which are sounding to not only to not only detect any fire but be able to tell exactly where the fire is located in the building. For reasons of cost, we want to use as few alarms as necessary. The first problem involves finding a minimum domination set of a graph. If the alarms are three state alarms capable of distinguishing between a fire in the same room as the alarm and a fire in an adjacent room, we are trying to find a minimum locating domination set. If the alarms are two state alarms that can only sound if there is a fire somewhere nearby, we are looking for a differentiating domination set of a graph. These three areas are the subject of much active research; we primarily focus on the third problem. An identifying code of a graph G is a dominating set C such that every vertex x of G is distinguished from other vertices by the set of vertices in C that are at distance at most r≥1 from x. When only vertices out of the code are asked to be identified, we get the related concept of a locating dominating set. The problem of finding an identifying code (resp a locating dominating code) of minimum size is a NP-hard problem, even when the input graph belongs to a number of specific graph classes. Therefore, we study this problem in some restricted classes of undirected graphs like split graph, line graph and path in a directed graph. Then we present some results on the identifying code by giving an exact value of upper total locating domination and a total 2-identifying code in directed and undirected graph. Moreover we determine exact values of locating dominating code and edge identifying code of thin headless spider and locating dominating code of complete suns.

Keywords: identiying codes, locating dominating set, split graphs, thin headless spider

Procedia PDF Downloads 480

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

Abstract:

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

Procedia PDF Downloads 246

Authors: Pureun-Haneul Lee, Byeong-Gon Kim, Sun-Hye Lee, An-Soo Jang

Abstract:

Background: Nanoparticles may pose adverse health effects due to particulate matter inhalation. Nanoparticle exposure induces cell and tissue damage, causing local and systemic inflammatory responses. The inflammasome is a major regulator of inflammation through its activation of pro-caspase-1, which cleaves pro-interleukin-1β (IL-1β) into its mature form and may signal acute and chronic immune responses to nanoparticles. Objective: The aim of the study was to identify whether nanoparticles exaggerates inflammasome pathway leading to airway inflammation and hyperresponsiveness in an allergic mice model of asthma. Methods: Mice were treated with saline (sham), OVA-sensitized and challenged (OVA), or titanium dioxide nanoparticles. Lung interleukin 1 beta (IL-1β), interleukin 18 (IL-18), NACHT, LRR and PYD domains-containing protein 3 (NLRP3) and caspase-1 levels were assessed with Western Blot. Caspase-1 was checked by immunohistochemical staining. Reactive oxygen species were measured for the marker 8-isoprostane and carbonyl by ELISA. Results: Airway inflammation and hyperresponsiveness increased in OVA-sensitized/challenged mice and these responses were exaggerated by TiO2 nanoparticles exposure. TiO2 nanoparticles treatment increased IL-1β and IL-18 protein expression in OVA-sensitized/challenged mice. TiO2 nanoparticles augmented the expression of NLRP3 and caspase-1 leading to the formation of an active caspase-1 in the lung. Lung caspase-1 expression was increased in OVA-sensitized/challenged mice and these responses were exaggerated by TiO2 nanoparticles exposure. Reactive oxygen species was increased in OVA-sensitized/challenged mice and in OVA-sensitized/challenged plus TiO2 exposed mice. Conclusion: Our data demonstrate that inflammasome pathway activates in asthmatic lungs following nanoparticles exposure, suggesting that targeting the inflammasome may help control nanoparticles-induced airway inflammation and responsiveness.

Keywords: bronchial asthma, inflammation, inflammasome, nanoparticles

Procedia PDF Downloads 375