Search results for: drug discovery
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 2485

Search results for: drug discovery

1375 Differential Survival Rates of Pseudomonas aeruginosa Strains on the Wings of Pantala flavescens

Authors: Banu Pradheepa Kamarajan, Muthusamy Ananthasubramanian

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Biofilm forming Pseudomonads occupy the top third position in causing hospital acquired infections. P. aeruginosa is notoriously known for its tendency to develop drug resistance. Major classes of drug such as β-lactams, aminoglycosides, quinolones, and polymyxins are found ineffective against multi-drug resistance Pseudomonas. To combat the infections, rather than administration of a single antibiotic, use of combinations (tobramycin and essential oils from plants and/or silver nanoparticles, chitosan, nitric oxide, cis-2-decenoic acid) in single formulation are suggested to control P. aeruginosa biofilms. Conventional techniques to prevent hospital-acquired implant infections such as coatings with antibiotics, controlled release of antibiotics from the implant material, contact-killing surfaces, coating the implants with functional DNase I and, coating with glycoside hydrolase are being followed. Coatings with bioactive components besides having limited shelf-life, require cold-chain and, are likely to fail when bacteria develop resistance. Recently identified nano-scale physical architectures on the insect wings are expected to have potential bactericidal property. Nanopillars are bactericidal to Staphylococcus aureus, Bacillus subtilis, K. pnuemoniae and few species of Pseudomonas. Our study aims to investigate the survival rate of biofilm forming Pseudomonas aeruginosa strain over non-biofilm forming strain on the nanopillar architecture of dragonfly (Pantala flavescens) wing. Dragonflies were collected near house-hold areas and, insect identification was carried out by the Department of Entomology, Tamilnadu Agricultural University, Coimbatore, India. Two strains of P. aeruginosa such as PAO1 (potent biofilm former) and MTCC 1688 (non-weak biofilm former) were tested against the glass coverslip (control) and wings of dragonfly (test) for 48 h. The wings/glass coverslips were incubated with bacterial suspension in 48-well plate. The plates were incubated at 37 °C under static condition. Bacterial attachment on the nanopillar architecture of the wing surface was visualized using FESEM. The survival rate of P. aeruginosa was tested using colony counting technique and flow cytometry at 0.5 h, 1 h, 2 h, 7 h, 24 h, and 48 h post-incubation. Cell death was analyzed using propidium iodide staining and DNA quantification. The results indicated that the survival rate of non-biofilm forming P. aeruginosa is 0.2 %, whilst that of biofilm former is 45 % on the dragonfly wings at the end of 48 h. The reduction in the survival rate of biofilm and non-biofilm forming P. aeruginosa was 20% and 40% respectively on the wings compared to the glass coverslip. In addition, Fourier Transformed Infrared Radiation was used to study the modification in the surface chemical composition of the wing during bacterial attachment and, post-sonication. This result indicated that the chemical moieties are not involved in the bactericidal property of nanopillars by the conserved characteristic peaks of chitin pre and post-sonication. The nanopillar architecture of the dragonfly wing efficiently deters the survival of non-biofilm forming P. aeruginosa, but not the biofilm forming strain. The study highlights the ability of biofilm formers to survive on wing architecture. Understanding this survival strategy will help in designing the architecture that combats the colonization of biofilm forming pathogens.

Keywords: biofilm, nanopillars, Pseudomonas aeruginosa, survival rate

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1374 Analyzing the Plausible Alternatives in Contracting the Societal Fissure Caused by Digital Divide in Sri Lanka

Authors: Manuela Nayantara Jeyaraj

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'Digital Divide' is a concept that has existed in this paradigm ever since the discovery of the first-generation technologies. Before the turn of the century, it was basically used to describe the gap between those with telephone communication access and those without it. At present, it is plainly descriptive in itself to illustrate the cavity among those with Internet access and those without. Though the concept of digital divide has been merely lying in sight for as long as time itself, the friction it caused has not yet been fully realized to solve major crisis situations. Unlike well-developed countries, Sri Lanka is still in the verge of moving farther away from a developing country in the race towards reaching a developed state. Access to technological resources varies from region to region, even within the island itself, with one region having a considerable percentage of its community exposed to the Internet and its related technologies, and the other unaware of such. Thus, this paper intends to analyze the roots for the still-extant gap instigated based on the concept of ‘Digital Divide’ and explores the plausible potentials that could be brought about by narrowing this prevailing percentage among the population, specifically entrenching the advantages reaped towards an economic augmentation and culture or lifestyle revolution on the path towards development.

Keywords: communication, digital divide, society, Sri Lanka

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1373 TiO2 Adsorbed on Cement Balls for Effective Photomineralization of Organic Pollutants under UV Light Irradiation

Authors: Tarun Jain, Lovnish Gupta, Soumen Basu

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Organic pollutants like phenols and organic dyes present in industrial waste water are posing a hazardous threat to aquatic ecosystem. Several measures have been adopted for the neutralization and photodecomposition of these harmful organic moieties, among these semiconductor photocatalysis has been provided a major thrust after the discovery of Honda-Fujishema effect. Present study demonstrates the adsorption of TiO2- P25 in nano size (~36 nm) on cement balls for effective photodegradation of Alizarin and penta chlorophenol (PCP) under UV light illumination. Triton-X was used as a stabilizer for effective adsorption of TiO2 on cement balls (TCB) followed by calcination at ~300oC for 4 h. The TCB’s were dispersed randomly in a self designed reactor for phototcatalytic performance as shown in scheme 1. The change in concentration of alizarin and PCP was observed under UV-Vis spectroscopy, PCP was detoxified within 40 min while alizarin photodecomposed within 15 min of UV light irradiation. Taking into consideration the go green slogan and future prospective this technique can be also utilized under visible light and on mass scale because this is an effective tool for environmental remediation and waste water treatment.

Keywords: organic pollutants, TiO2 cement balls, photodegradation, UV light irradiation

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1372 The Efficacy of Albendazole against Soil-Transmitted Helminths and the Impact of Mass Drug Administration of Albendazole and Ivermectin on Health Status

Authors: Mike Yaw Osei-Atweneboana, John Asiedu Larbi, Edward Jenner Tettevi

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Background: The lymphatic filariasis (LF) control programme has been on-going in Ghana since 2000. This community-wide approach involves the use of ivermectin (IVM) and albendazole (ALB). Soil-transmitted helminth (STH) infections control is augmented within this programme; however, in areas where LF is not prevalent, albendazole alone is administered to school children. The purpose of this study was therefore, to determine the efficacy of albendazole against soils transmitted helminths and the impact of mass drug administration of albendazole and ivermectin on the health status of children of school going age and pregnant women. Material/Methods: This was a twelve months longitudinal study. A total of 412 subjects including school children (between the ages of 2-17 years) and pregnant women were randomly selected from four endemic communities in Kpandai district of the Northern region. Coprological assessment for parasites was based on the Kato–Katz technique in both dry and rainy seasons at baseline, 21 days and 3 months post-treatment. Single-dose albendazole treatment was administered to all patients at baseline. Preserved samples are currently under molecular studies to identify possible single nucleotide polymorphism (SNP) within the beta tubulin gene which is associated with benzimidazole resistance. Results: Of all the parasites found (hookworm, Trichuris trichiura, Hymenolepis nana, and Taenia sp.); hookworm was the most prevalent. In the dry season, the overall STHs prevalence at pre-treatment was 29%, while 9% and 13% prevalence was recorded at 21 days, and three months after treatment respectively. However, in the rainy season, the overall STHs prevalence was 8%, while 4% and 12% was recorded at 21 days and three months respectively after ALB treatment. In general, ALB treatment resulted in an overall hookworm egg count reduction rate of 89% in the dry season and 93% in the rainy season, while the T. trichiura egg count reduction rate was 100% in both seasons. Conclusions: STH infections still remains a significant public health burden in Ghana. Hookworm infection seems to respond poorly or sub-optimally to ALB, raising concerns of possible emergence of resistance which may lead to a major setback for the control and elimination of STH infections, especially hookworm infections.

Keywords: hookworm, sub-optimal response, albendazole, trichuriasis, soil-transmitted helminths

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1371 Mapping Identity: Algerian Diasporic Voices in Literature

Authors: Salma Kaouthar Letaief

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This article investigates the experience of diaspora in the writings of Algerian diasporic writers, namely: Leila Sebbar’s Silence on the Shores (2000), Keltoum Staali’ December’s Mimosa (2012). The study discusses the collective trauma of violence in Algeria and overseas. The experience of displacement of the characters to an alien territory compel their journey with issues related to nostalgia, identity crisis, alienation, racism, and in-betweeness. The focus in this research is, thus, on Algerian immigrants’ experience in the host country and their psychological conflicts. The theories Multiculturalism and Psychoanalysis are used to analyse the novels in this paper. While Multiculturalism examines how characters negotiate and navigate their identities in multicultural settings, Psychoanalysis enables the analysis of how characters in diasporic novels grapple with issues of identity, belonging, and self-discovery. Hence, interweaving multiculturalism and psychoanalysis provides an interdisciplinary framework that addresses both the socio-cultural and psychological aspects of the diasporic experience. Accordingly, this paper is an attempt to examine the diasporic experience and cultural dialectics.

Keywords: diaspora, algerian diasporic writers, trauma, algeria, displacement, identity crisis, cultural dialects

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1370 Biosynthesis of a Nanoparticle-Antibody Phthalocyanine Photosensitizer for Use in Targeted Photodynamic Therapy of Cervical Cancer

Authors: Elvin P. Chizenga, Heidi Abrahamse

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Cancer cell resistance to therapy is the main cause of treatment failures and the poor prognosis of cancer convalescence. The progression of cervical cancer to other parts of the genitourinary system and the reported recurrence rates are overwhelming. Current treatments, including surgery, chemo and radiation have been inefficient in eradicating the tumor cells. These treatments are also associated with poor prognosis and reduced quality of life, including fertility loss. This has inspired the need for the development of new treatment modalities to eradicate cervical cancer successfully. Photodynamic Therapy (PDT) is a modern treatment modality that induces cell death by photochemical interactions of light and a photosensitizer, which in the presence of molecular oxygen, yields a set of chemical reactions that generate Reactive Oxygen Species (ROS) and other free radical species causing cell damage. Enhancing PDT using modified drug delivery can increase the concentration of the photosensitizer in the tumor cells, and this has the potential to maximize its therapeutic efficacy. In cervical cancer, all infected cells constitutively express genes of the E6 and E7 HPV viral oncoproteins, resulting in high concentrations of E6 and E7 in the cytoplasm. This provides an opportunity for active targeting of cervical cancer cells using immune-mediated drug delivery to maximize therapeutic efficacy. The use of nanoparticles in PDT has also proven effective in enhancing therapeutic efficacy. Gold nanoparticles (AuNps) in particular, are explored for their use in biomedicine due to their biocompatibility, low toxicity, and enhancement of drug uptake by tumor cells. In this present study, a biomolecule comprising of AuNPs, anti-E6 monoclonal antibodies, and Aluminium Phthalocyanine photosensitizer was synthesized for use in targeted PDT of cervical cancer. The AuNp-Anti-E6-Sulfonated Aluminium Phthalocyanine mix (AlPcSmix) photosensitizing biomolecule was synthesized by coupling AuNps and anti-E6 monoclonal antibodies to the AlPcSmix via Polyethylene Glycol (PEG) chemical links. The final product was characterized using Transmission Electron Microscope (TEM), Zeta Potential, Uv-Vis Spectrophotometry, Fourier Transform Infrared Spectroscopy (FTIR), and X-ray diffraction (XRD), to confirm its chemical structure and functionality. To observe its therapeutic role in treating cervical cancer, cervical cancer cells, HeLa cells were seeded in 3.4 cm² diameter culture dishes at a concentration of 5x10⁵ cells/ml, in vitro. The cells were treated with varying concentrations of the photosensitizing biomolecule and irradiated using a 673.2 nm wavelength of laser light. Post irradiation cellular responses were performed to observe changes in morphology, viability, proliferation, cytotoxicity, and cell death pathways induced. Dose-Dependent response of the cells to treatment was demonstrated as significant morphologic changes, increased cytotoxicity, and decreased cell viability and proliferation This study presented a synthetic biomolecule for targeted PDT of cervical cancer. The study suggested that PDT using this AuNp- Anti-E6- AlPcSmix photosensitizing biomolecule is a very effective treatment method for the eradication of cervical cancer cells, in vitro. Further studies in vivo need to be conducted to support the use of this biomolecule in treating cervical cancer in clinical settings.

Keywords: anti-E6 monoclonal antibody, cervical cancer, gold nanoparticles, photodynamic therapy

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1369 Human Trafficking and Terrorism: A Study on the Security Challenges Imposed upon Countries in Conflict

Authors: Christopher Holroyd

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With the various terrorist organizations and drug cartels that are currently active, there is a myriad of security concerns facing countries around the world. Organizations that focus their attacks on others through terror, such as what is seen with the Islamic State of Iraq and the Levant (ISIS), have no boundaries when it comes to doing what is needed to fulfill their desired intent. For countries such as Iraq, who have been trying to rebuild their country since the fall of the Saddam Hussein Regime, organizations such as Al-Qaeda and ISIS have been impeding the country’s efforts toward peace and stability. One method utilized by terrorist organizations around the world is human trafficking. This method is one that is seen around the world; modern slavery is still exploited by those who have no concern for human decency and morality, their only concern is to achieve their goals by any means. It is understandable that some people may not have even heard of 'modern slavery', or they just might not believe that it is even an issue in today’s world. Organizations such as ISIS are not the only ones in the world that seek to benefit from the immoral trading of humans. Various drug cartels in the world, such as those seen in Mexico and Central America, have recently begun to take part in the trade – moving humans from state to state, or country to country, to better fuel their overall operations. This now makes the possibility of human trafficking more real for those in the United States because of the proximity of the cartels to the southern border of the country. An issue that, at one time, might have only seen as a distant threat, is now close to home for those in the United States. Looking at these two examples is how we begin to understand why human trafficking is utilized by various organizations around the world. This trade of human beings and the violation of basic human rights is a plague that effects the entire world and not just those that are in a country other than your own. One of the security issues that stem from the trade includes the movement and recruitment of members of the organizations. With individuals being smuggled from one location to another in secrecy, this only puts those trying to combat this trade at a disadvantage. This creates concern over the accurate number of potential recruits, combatants, and other individuals who are working against the host nation, and for the mission of the cartel or terrorist organization they are a part of. An uphill battle is created, and the goals of peace and stability are now harder to reach. Aside from security aspects, it cannot be forgotten that those being traded and forced into slavery, are being done so against their will. Families are separated, children trained to be fighters or worse. This makes the goal of eradicating human trafficking even more dire and important.

Keywords: human trafficking, reconstruction, security, terrorism

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1368 Emergence of Fluoroquinolone Resistance in Pigs, Nigeria

Authors: Igbakura I. Luga, Alex A. Adikwu

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A comparison of resistance to quinolones was carried out on isolates of Shiga toxin-producing Escherichia coliO157:H7 from cattle and mecA and nuc genes harbouring Staphylococcus aureus from pigs. The isolates were separately tested in the first and current decades of the 21st century. The objective was to demonstrate the dissemination of resistance to this frontline class of antibiotic by bacteria from food animals and bring to the limelight the spread of antibiotic resistance in Nigeria. A total of 10 isolates of the E. coli O157:H7 and 9 of mecA and nuc genes harbouring S. aureus were obtained following isolation, biochemical testing, and serological identification using the Remel Wellcolex E. coli O157:H7 test. Shiga toxin-production screening in the E. coli O157:H7 using the verotoxin E. coli reverse passive latex agglutination (VTEC-RPLA) test; and molecular identification of the mecA and nuc genes in S. aureus. Detection of the mecA and nuc genes were carried out using the protocol by the Danish Technical University (DTU) using the following primers mecA-1:5'-GGGATCATAGCGTCATTATTC-3', mecA-2: 5'-AACGATTGTGACACGATAGCC-3', nuc-1: 5'-TCAGCAAATGCATCACAAACAG-3', nuc-2: 5'-CGTAAATGCACTTGCTTCAGG-3' for the mecA and nuc genes, respectively. The nuc genes confirm the S. aureus isolates and the mecA genes as being methicillin-resistant and so pathogenic to man. The fluoroquinolones used in the antibiotic resistance testing were norfloxacin (10 µg) and ciprofloxacin (5 µg) in the E. coli O157:H7 isolates and ciprofloxacin (5 µg) in the S. aureus isolates. Susceptibility was tested using the disk diffusion method on Muller-Hinton agar. Fluoroquinolone resistance was not detected from isolates of E. coli O157:H7 from cattle. However, 44% (4/9) of the S. aureus were resistant to ciprofloxacin. Resistance of up to 44% in isolates of mecA and nuc genes harbouring S. aureus is a compelling evidence for the rapid spread of antibiotic resistance from bacteria in food animals from Nigeria. Ciprofloxacin is the drug of choice for the treatment of Typhoid fever, therefore widespread resistance to it in pathogenic bacteria is of great public health significance. The study concludes that antibiotic resistance in bacteria from food animals is on the increase in Nigeria. The National Food and Drug Administration and Control (NAFDAC) agency in Nigeria should implement the World Health Organization (WHO) global action plan on antimicrobial resistance. A good starting point can be coordinating the WHO, Office of International Epizootics (OIE), Food and Agricultural Organization (FAO) tripartite draft antimicrobial resistance monitoring and evaluation (M&E) framework in Nigeria.

Keywords: Fluoroquinolone, Nigeria, resistance, Staphylococcus aureus

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1367 Formulation, Preparation, and Evaluation of Coated Desloratadine Oral Disintegrating Tablets

Authors: Mohamed A. Etman, Mona G. Abd-Elnasser, Mohamed A. Shams-Eldin, Aly H. Nada

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Orally disintegrating tablets (ODTs) are gaining importance as new drug delivery systems and emerged as one of the popular and widely accepted dosage forms, especially for the pediatric and geriatric patients. Their advantages such as administration without water, anywhere, anytime lead to their suitability to geriatric and pediatric patients. They are also suitable for the mentally ill, the bed-ridden and patients who do not have easy access to water. The benefits, in terms of patient compliance, rapid onset of action, increased bioavailability, and good stability make these tablets popular as a dosage form of choice in the current market. These dosage forms dissolve or disintegrate in the oral cavity within a matter of seconds without the need of water or chewing. Desloratadine is a tricyclic antihistaminic, which has a selective and peripheral H1-antagonist action. It is an antagonist at histamine H1 receptors, and an antagonist at all subtypes of the muscarinic acetylcholine receptor. Desloratadine is the major metabolite of loratadine. Twelve different placebos ODT were prepared (F1-F12) using different functional excipients. They were evaluated for their compressibility, hardness and disintegration time. All formulations were non sticky except four formulations; namely (F8, F9, F10, F11). All formulations were compressible with the exception of (F2). Variable disintegration times were found ranging between 20 and 120 seconds. It was found that (F12) showed the least disintegration time (20 secs) without showing any sticking which could be due to the use of high percentage of superdisintegrants. Desloratadine showed bitter taste when formulated as ODT without any treatment. Therefore, different techniques were tried in order to mask its bitter taste. Using Eudragit EPO resulted in complete masking of the bitter taste of the drug and increased the acceptability to volunteers. The compressible non sticky formulations (F1, F3, F4, F5, F6, F7 and F12) were subjected to further evaluation tests after addition of coated desloratadine, including weight uniformity, wetting time, and friability testing.. Fairly good weight uniformity values were observed in all the tested formulations. F12 exhibiting the shortest wetting time (14.7 seconds) and consequently the lowest (20 seconds) disintegration time. Dissolution profile showed that 100% desloratadine release was attained after only 2.5 minutes from the prepared ODT (F12) with dissolution efficiency of 95%.

Keywords: Desloratadine, orally disintegrating tablets (ODTs), formulations, taste masking

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1366 Towards a Distributed Computation Platform Tailored for Educational Process Discovery and Analysis

Authors: Awatef Hicheur Cairns, Billel Gueni, Hind Hafdi, Christian Joubert, Nasser Khelifa

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Given the ever changing needs of the job markets, education and training centers are increasingly held accountable for student success. Therefore, education and training centers have to focus on ways to streamline their offers and educational processes in order to achieve the highest level of quality in curriculum contents and managerial decisions. Educational process mining is an emerging field in the educational data mining (EDM) discipline, concerned with developing methods to discover, analyze and provide a visual representation of complete educational processes. In this paper, we present our distributed computation platform which allows different education centers and institutions to load their data and access to advanced data mining and process mining services. To achieve this, we present also a comparative study of the different clustering techniques developed in the context of process mining to partition efficiently educational traces. Our goal is to find the best strategy for distributing heavy analysis computations on many processing nodes of our platform.

Keywords: educational process mining, distributed process mining, clustering, distributed platform, educational data mining, ProM

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1365 Directional Search for Dark Matter Using Nuclear Emulsion

Authors: Ali Murat Guler

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A variety of experiments have been developed over the past decades, aiming at the detection of Weakly Interactive Massive Particles (WIMPs) via their scattering in an instrumented medium. The sensitivity of these experiments has improved with a tremendous speed, thanks to a constant development of detectors and analysis methods. Detectors capable of reconstructing the direction of the nuclear recoil induced by the WIMP scattering are opening a new frontier to possibly extend Dark Matter searches beyond the neutrino background. Measurement of WIMP’s direction will allow us to detect the galactic origin of dark matter and, therefore to have a clear signal-background separation. The NEWSdm experiment, based on nuclear emulsions, is intended to measure the direction of WIMP-induced nuclear coils with a solid-state detector, thus with high sensitivity. We discuss the discovery potential of a directional experiment based on the use of a solid target made of newly developed nuclear emulsions and novel read-out systems achieving nanometric resolution. We also report results of a technical test conducted in Gran Sasso.

Keywords: dark matter, direct detection, nuclear emulsion, WIMPS

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1364 Genome Sequencing and Analysis of the Spontaneous Nanosilver Resistant Bacterium Proteus mirabilis Strain scdr1

Authors: Amr Saeb, Khalid Al-Rubeaan, Mohamed Abouelhoda, Manojkumar Selvaraju, Hamsa Tayeb

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Background: P. mirabilis is a common uropathogenic bacterium that can cause major complications in patients with long-standing indwelling catheters or patients with urinary tract anomalies. In addition, P. mirabilis is a common cause of chronic osteomyelitis in diabetic foot ulcer (DFU) patients. Methodology: P. mirabilis SCDR1 was isolated from a diabetic ulcer patient. We examined P. mirabilis SCDR1 levels of resistance against nano-silver colloids, the commercial nano-silver and silver containing bandages and commonly used antibiotics. We utilized next generation sequencing techniques (NGS), bioinformatics, phylogenetic analysis and pathogenomics in the identification and characterization of the infectious pathogen. Results: P. mirabilis SCDR1 is a multi-drug resistant isolate that also showed high levels of resistance against nano-silver colloids, nano-silver chitosan composite and the commercially available nano-silver and silver bandages. The P. mirabilis-SCDR1 genome size is 3,815,621 bp with G+C content of 38.44%. P. mirabilis-SCDR1 genome contains a total of 3,533 genes, 3,414 coding DNA sequence genes, 11, 10, 18 rRNAs (5S, 16S, and 23S), and 76 tRNAs. Our isolate contains all the required pathogenicity and virulence factors to establish a successful infection. P. mirabilis SCDR1 isolate is a potential virulent pathogen that despite its original isolation site, wound, it can establish kidney infection and its associated complications. P. mirabilis SCDR1 contains several mechanisms for antibiotics and metals resistance including, biofilm formation, swarming mobility, efflux systems, and enzymatic detoxification. Conclusion: P. mirabilis SCDR1 is the spontaneous nano-silver resistant bacterial strain. P. mirabilis SCDR1 strain contains all reported pathogenic and virulence factors characteristic for the species. In addition, it possesses several mechanisms that may lead to the observed nano-silver resistance.

Keywords: Proteus mirabilis, multi-drug resistance, silver nanoparticles, resistance, next generation sequencing techniques, genome analysis, bioinformatics, phylogeny, pathogenomics, diabetic foot ulcer, xenobiotics, multidrug resistance efflux, biofilm formation, swarming mobility, resistome, glutathione S-transferase, copper/silver efflux system, altruism

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1363 Chemicals to Remove and Prevent Biofilm

Authors: Cynthia K. Burzell

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Aequor's Founder, a Marine and Medical Microbiologist, discovered novel, non-toxic chemicals in the ocean that uniquely remove biofilm in minutes and prevent its formation for days. These chemicals and over 70 synthesized analogs that Aequor developed can replace thousands of toxic biocides used in consumer and industrial products and, as new drug candidates, kill biofilm-forming bacteria and fungi Superbugs -the antimicrobial-resistant (AMR) pathogens for which there is no cure. Cynthia Burzell, PhD., is a Marine and Medical Microbiologist studying natural mechanisms that inhibit biofilm formation on surfaces in contact with water. In 2002, she discovered a new genus and several new species of marine microbes that produce small molecules that remove biofilm in minutes and prevent its formation for days. The molecules include new antimicrobials that can replace thousands of toxic biocides used in consumer and industrial products and can be developed into new drug candidates to kill the biofilm-forming bacteria and fungi -- including the antimicrobial-resistant (AMR) Superbugs for which there is no cure. Today, Aequor has over 70 chemicals that are divided into categories: (1) Novel natural chemicals. Lonza validated that the primary natural chemical removed biofilm in minutes and stated: "Nothing else known can do this at non-toxic doses." (2) Specialty chemicals. 25 of these structural analogs are already approved under the U.S. Environmental Protection Agency (EPA)'s Toxic Substances Control Act, certified as "green" and available for immediate sale. These have been validated for the following agro-industrial verticals: (a) Surface cleaners: The U.S. Department of Agriculture validated that low concentrations of Aequor's formulations provide deep cleaning of inert, nano and organic surfaces and materials; (b) Water treatments: NASA validated that one dose of Aequor's treatment in the International Space Station's water reuse/recycling system lasted 15 months without replenishment. DOE validated that our treatments lower energy consumption by over 10% in buildings and industrial processes. Future validations include pilot projects with the EPA to test efficacy in hospital plumbing systems. (c) Algae cultivation and yeast fermentation: The U.S. Department of Energy (DOE) validated that Aequor's treatment boosted biomass of renewable feedstocks by 40% in half the time -- increasing the profitability of biofuels and biobased co-products. DOE also validated increased yields and crop protection of algae under cultivation in open ponds. A private oil and gas company validated decontamination of oilfield water. (3) New structural analogs. These kill Gram-negative and Gram-positive bacteria and fungi alone, in combinations with each other, and in combination with low doses of existing, ineffective antibiotics (including Penicillin), "potentiating" them to kill AMR pathogens at doses too low to trigger resistance. Both the U.S. National Institutes for Health (NIH) and Department of Defense (DOD) has executed contracts with Aequor to provide the pre-clinical trials needed for these new drug candidates to enter the regulatory approval pipelines. Aequor seeks partners/licensees to commercialize its specialty chemicals and support to evaluate the optimal methods to scale-up of several new structural analogs via activity-guided fractionation and/or biosynthesis in order to initiate the NIH and DOD pre-clinical trials.

Keywords: biofilm, potentiation, prevention, removal

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1362 Methotrexate Associated Skin Cancer: A Signal Review of Pharmacovigilance Center

Authors: Abdulaziz Alakeel, Abdulrahman Alomair, Mohammed Fouda

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Introduction: Methotrexate (MTX) is an antimetabolite used to treat multiple conditions, including neoplastic diseases, severe psoriasis, and rheumatoid arthritis. Skin cancer is the out-of-control growth of abnormal cells in the epidermis, the outermost skin layer, caused by unrepaired DNA damage that triggers mutations. These mutations lead the skin cells to multiply rapidly and form malignant tumors. The aim of this review is to evaluate the risk of skin cancer associated with the use of methotrexate and to suggest regulatory recommendations if required. Methodology: Signal Detection team at Saudi Food and Drug Authority (SFDA) performed a safety review using National Pharmacovigilance Center (NPC) database as well as the World Health Organization (WHO) VigiBase, alongside with literature screening to retrieve related information for assessing the causality between skin cancer and methotrexate. The search conducted in July 2020. Results: Four published articles support the association seen while searching in literature, a recent randomized control trial published in 2020 revealed a statistically significant increase in skin cancer among MTX users. Another study mentioned methotrexate increases the risk of non-melanoma skin cancer when used in combination with immunosuppressant and biologic agents. In addition, the incidence of melanoma for methotrexate users was 3-fold more than the general population in a cohort study of rheumatoid arthritis patients. The last article estimated the risk of cutaneous malignant melanoma (CMM) in a cohort study shows a statistically significant risk increase for CMM was observed in MTX exposed patients. The WHO database (VigiBase) searched for individual case safety reports (ICSRs) reported for “Skin Cancer” and 'Methotrexate' use, which yielded 121 ICSRs. The initial review revealed that 106 cases are insufficiently documented for proper medical assessment. However, the remaining fifteen cases have extensively evaluated by applying the WHO criteria of causality assessment. As a result, 30 percent of the cases showed that MTX could possibly cause skin cancer; five cases provide unlikely association and five un-assessable cases due to lack of information. The Saudi NPC database searched to retrieve any reported cases for the combined terms methotrexate/skin cancer; however, no local cases reported up to date. The data mining of the observed and the expected reporting rate for drug/adverse drug reaction pair is estimated using information component (IC), a tool developed by the WHO Uppsala Monitoring Centre to measure the reporting ratio. Positive IC reflects higher statistical association, while negative values translated as a less statistical association, considering the null value equal to zero. Results showed that a combination of 'Methotrexate' and 'Skin cancer' observed more than expected when compared to other medications in the WHO database (IC value is 1.2). Conclusion: The weighted cumulative pieces of evidence identified from global cases, data mining, and published literature are sufficient to support a causal association between the risk of skin cancer and methotrexate. Therefore, health care professionals should be aware of this possible risk and may consider monitoring any signs or symptoms of skin cancer in patients treated with methotrexate.

Keywords: methotrexate, skin cancer, signal detection, pharmacovigilance

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1361 Chinese Language Teaching as a Second Language: Immersion Teaching

Authors: Lee Bih Ni, Kiu Su Na

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This paper discusses the Chinese Language Teaching as a Second Language by focusing on Immersion Teaching. Researchers used narrative literature review to describe the current states of both art and science in focused areas of inquiry. Immersion teaching comes with a standard that teachers must reliably meet. Chinese language-immersion instruction consists of language and content lessons, including functional usage of the language, academic language, authentic language, and correct Chinese sociocultural language. Researchers used narrative literature reviews to build a scientific knowledge base. Researchers collected all the important points of discussion, and put them here with reference to the specific field where this paper is originally based on. The findings show that Chinese Language in immersion teaching is not like standard foreign language classroom; immersion setting provides more opportunities to teach students colloquial language than academic. Immersion techniques also introduce a language’s cultural and social contexts in a meaningful and memorable way. It is particularly important that immersion teachers connect classwork with real-life experiences. Immersion also includes more elements of discovery and inquiry based learning than do other kinds of instructional practices. Students are always and consistently interpreted the conclusions and context clues.

Keywords: a second language, Chinese language teaching, immersion teaching, instructional strategies

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1360 Targetting T6SS of Klebsiella pneumoniae for Assessment of Immune Response in Mice for Therapeutic Lead Development

Authors: Sweta Pandey, Samridhi Dhyani, Susmita Chaudhuri

Abstract:

Klebsiella pneumoniae bacteria is a global threat to human health due to an increase in multi-drug resistance among strains. The hypervirulent strains of Klebsiella pneumoniae is a major trouble due to their association with life-threatening infections in a healthy population. One of the major virulence factors of hyper virulent strains of Klebsiella pneumoniae is the T6SS (Type six secretary system) which is majorly involved in microbial antagonism and causes interaction with the host eukaryotic cells during infections. T6SS mediates some of the crucial factors for establishing infection by the bacteria, such as cell adherence, invasion, and subsequent in vivo colonisation. The antibacterial activity and the cell invasion property of the T6SS system is a major requirement for the establishment of K. pneumoniae infections within the gut. The T6SS can be an appropriate target for developing therapeutics. The T6SS consists of an inner tube comprising hexamers of Hcp (Haemolysin -regulated protein) protein, and at the top of this tube sits VgrG (Valine glycine repeat protein G); the tip of the machinery consists of PAAR domain containing proteins which act as a delivery system for bacterial effectors. For this study, immune response to recombinant VgrG protein was generated to establish this protein as a potential immunogen for the development of therapeutic leads. The immunogenicity of the selected protein was determined by predicting the B cell epitopes by the BCEP analysis tool. The gene sequence for multiple domains of VgrG protein (phage_base_V, T6SS_Vgr, DUF2345) was selected and cloned in pMAL vector in E. coli. The construct was subcloned and expressed as a fusion protein of 203 residue protein with mannose binding protein tag (MBP) to enhance solubility and purification of this protein. The purified recombinant VgrG fusion protein was used for mice immunisation. The antiserum showed reactivity with the recombinant VgrG in ELISA and western blot. The immunised mice were challenged with K. pneumoniae bacteria and showed bacterial clearance in immunised mice. The recombinant VgrG protein can further be used for studying downstream signalling of VgrG protein in mice during infection and for therapeutic MAb development to eradicate K. pneumoniae infections.

Keywords: immune response, Klebsiella pneumoniae, multi-drug resistance, recombinant protein expression, T6SS, VgrG

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1359 Rheological Characteristics of Ice Slurries Based on Propylene- and Ethylene-Glycol at High Ice Fractions

Authors: Senda Trabelsi, Sébastien Poncet, Michel Poirier

Abstract:

Ice slurries are considered as a promising phase-changing secondary fluids for air-conditioning, packaging or cooling industrial processes. An experimental study has been here carried out to measure the rheological characteristics of ice slurries. Ice slurries consist in a solid phase (flake ice crystals) and a liquid phase. The later is composed of a mixture of liquid water and an additive being here either (1) Propylene-Glycol (PG) or (2) Ethylene-Glycol (EG) used to lower the freezing point of water. Concentrations of 5%, 14% and 24% of both additives are investigated with ice mass fractions ranging from 5% to 85%. The rheological measurements are carried out using a Discovery HR-2 vane-concentric cylinder with four full-length blades. The experimental results show that the behavior of ice slurries is generally non-Newtonian with shear-thinning or shear-thickening behaviors depending on the experimental conditions. In order to determine the consistency and the flow index, the Herschel-Bulkley model is used to describe the behavior of ice slurries. The present results are finally validated against an experimental database found in the literature and the predictions of an Artificial Neural Network model.

Keywords: ice slurry, propylene-glycol, ethylene-glycol, rheology

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1358 Self-Assembled ZnFeAl Layered Double Hydroxides as Highly Efficient Fenton-Like Catalysts

Authors: Marius Sebastian Secula, Mihaela Darie, Gabriela Carja

Abstract:

Ibuprofen is a non-steroidal anti-inflammatory drug (NSAIDs) and is among the most frequently detected pharmaceuticals in environmental samples and among the most widespread drug in the world. Its concentration in the environment is reported to be between 10 and 160 ng L-1. In order to improve the abatement efficiency of this compound for water source prevention and reclamation, the development of innovative technologies is mandatory. AOPs (advanced oxidation processes) are known as highly efficient towards the oxidation of organic pollutants. Among the promising combined treatments, photo-Fenton processes using layered double hydroxides (LDHs) attracted significant consideration especially due to their composition flexibility, high surface area and tailored redox features. This work presents the self-supported Fe, Mn or Ti on ZnFeAl LDHs obtained by co-precipitation followed by reconstruction method as novel efficient photo-catalysts for Fenton-like catalysis. Fe, Mn or Ti/ZnFeAl LDHs nano-hybrids were tested for the degradation of a model pharmaceutical agent, the anti-inflammatory agent ibuprofen, by photocatalysis and photo-Fenton catalysis, respectively, by means of a lab-scale system consisting of a batch reactor equipped with an UV lamp (17 W). The present study presents comparatively the degradation of Ibuprofen in aqueous solution UV light irradiation using four different types of LDHs. The newly prepared Ti/ZnFeAl 4:1 catalyst results in the best degradation performance. After 60 minutes of light irradiation, the Ibuprofen removal efficiency reaches 95%. The slowest degradation of Ibuprofen solution occurs in case of Fe/ZnFeAl 4:1 LDH, (67% removal efficiency after 60 minutes of process). Evolution of Ibuprofen degradation during the photo Fenton process is also studied using Ti/ZnFeAl 2:1 and 4:1 LDHs in the presence and absence of H2O2. It is found that after 60 min the use of Ti/ZnFeAl 4:1 LDH in presence of 100 mg/L H2O2 leads to the fastest degradation of Ibuprofen molecule. After 120 min, both catalysts Ti/ZnFeAl 4:1 and 2:1 result in the same value of removal efficiency (98%). In the absence of H2O2, Ibuprofen degradation reaches only 73% removal efficiency after 120 min of degradation process. Acknowledgements: This work was supported by a grant of the Romanian National Authority for Scientific Research and Innovation, CNCS - UEFISCDI, project number PN-II-RU-TE-2014-4-0405.

Keywords: layered double hydroxide, advanced oxidation process, micropollutant, heterogeneous Fenton

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1357 Wellbore Spiraling Induced through Systematic Micro-Sliding

Authors: Christopher Viens, Bosko Gajic, Steve Krase

Abstract:

Stick-Slip is a term that is often overused and commonly diagnosed from surface drilling parameters of torque and differential pressure, but the actual magnitude of the condition is rarely captured at the BHA level as the necessary measurements are seldom deployed. Deployment of an accurate stick-slip measurement downhole has led to an interesting discovery that goes against long held traditional drilling lore. A divide has been identified between stick-slip as independent bit and BHA conditions. This phenomenon in horizontal laterals is common, but few M/LWD systems have been able to capture it. Utilizing measurements of downhole RPM bore pressure, high-speed magnetometer data, bending moment, and continuous inclination, the wellbore spiraling phenomenon is able to be captured, quantified, and intimately tied back to systematic effects of BHA stalling and micro-sliding. An operator in the Permian Basin has identified that this phenomenon is contributing to increased tortuosity and drag. Utilizing downhole torque measurements the root causes of the stick-slip and spiraling phenomenon were identified and able to engineered out of the system.

Keywords: bending moment, downhole dynamics measurements, micro sliding, wellbore spiraling

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1356 Design of a Service-Enabled Dependable Integration Environment

Authors: Fuyang Peng, Donghong Li

Abstract:

The aim of information systems integration is to make all the data sources, applications and business flows integrated into the new environment so that unwanted redundancies are reduced and bottlenecks and mismatches are eliminated. Two issues have to be dealt with to meet such requirements: the software architecture that supports resource integration, and the adaptor development tool that help integration and migration of legacy applications. In this paper, a service-enabled dependable integration environment (SDIE), is presented, which has two key components, i.e., a dependable service integration platform and a legacy application integration tool. For the dependable platform for service integration, the service integration bus, the service management framework, the dependable engine for service composition, and the service registry and discovery components are described. For the legacy application integration tool, its basic organization, functionalities and dependable measures taken are presented. Due to its service-oriented integration model, the light-weight extensible container, the service component combination-oriented p-lattice structure, and other features, SDIE has advantages in openness, flexibility, performance-price ratio and feature support over commercial products, is better than most of the open source integration software in functionality, performance and dependability support.

Keywords: application integration, dependability, legacy, SOA

Procedia PDF Downloads 354
1355 Gut Microbiota in Patients with Opioid Use Disorder: A 12-week Follow up Study

Authors: Sheng-Yu Lee

Abstract:

Aim: Opioid use disorder is often characterized by repetitive drug-seeking and drug-taking behaviors with severe public health consequences. Animal model showed that opioid-induced perturbations in the gut microbiota causally relate to neuroinflammation, deficits in reward responding, and opioid tolerance, possibly due to changes in gut microbiota. Therefore, we propose that the dysbiosis of gut microbiota can be associated with pathogenesis of opioid dependence. In this current study, we explored the differences in gut microbiota between patients and normal controls and in patients before and after initiation of methadone treatment program for 12 weeks. Methods: Patients with opioid use disorder between 20 and 65 years were recruited from the methadone maintenance outpatient clinic in 2 medical centers in the Southern Taiwan. Healthy controls without any family history of major psychiatric disorders (schizophrenia, bipolar disorder and major depressive disorder) were recruited from the community. After initial screening, 15 patients with opioid use disorder joined the study for initial evaluation (Week 0), 12 of them completed the 12-week follow-up while receiving methadone treatment and ceased heroin use (Week 12). Fecal samples were collected from the patients at baseline and the end of 12th week. A one-time fecal sample was collected from the healthy controls. The microbiota of fecal samples were investigated using 16S rRNA V3V4 amplicon sequencing, followed by bioinformatics and statistical analyses. Results: We found no significant differences in species diversity in opioid dependent patients between Week 0 and Week 12, nor compared between patients at both points and controls. For beta diversity, using principal component analysis, we found no significant differences between patients at Week 0 and Week 12, however, both patient groups showed significant differences compared to control (P=0.011). Furthermore, the linear discriminant analysis effect size (LEfSe) analysis was used to identify differentially enriched bacteria between opioid use patients and healthy controls. Compared to controls, the relative abundance of Lactobacillaceae Lactobacillus (L. Lactobacillus), Megasphaera Megasphaerahexanoica (M. Megasphaerahexanoica) and Caecibacter Caecibactermassiliensis (C Caecibactermassiliensis) were increased in patients at Week 0, while Coriobacteriales Atopobiaceae (C. Atopobiaceae), Acidaminococcus Acidaminococcusintestini (A. Acidaminococcusintestini) and Tractidigestivibacter Tractidigestivibacterscatoligenes (T. Tractidigestivibacterscatoligenes) were increased in patients at Week 12. Conclusion: In conclusion, we suggest that the gut microbiome community maybe linked to opioid use disorder, such differences may not be altered even after 12-week of cessation of opioid use.

Keywords: opioid use disorder, gut microbiota, methadone treatment, follow up study

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1354 Effect of a Synthetic Platinum-Based Complex on Autophagy Induction in Leydig TM3 Cells

Authors: Ezzati Givi M., Hoveizi E., Nezhad Marani N.

Abstract:

Platinum-based anticancer therapeutics are the most widely used drugs in clinical chemotherapy but have major limitations and various side effects in clinical applications. Gonadotoxicity and sterility is one of the most common complications for cancer survivors, which seem to be drug-specific and dose-related. Therefore, many efforts have been dedicated to discovering a new structure of platinum-based anticancer agents with improved therapeutic index, fewer side effects. In this regard, new Pt(II)-phosphane complexes containing heterocyclic thionate ligands (PCTL) have been synthesized, which show more potent antitumor activities in comparison to cisplatin. Cisplatin, the best leading metal-based antitumor drug in the field, induces testicular toxicity on Leydig and Sertoli cells leading to serious side effects such as azoospermia and infertility. Therefore in the present study, we aimed to investigate the cytotoxicity effect of PCTL on mice TM4 Sertoli cells with particular emphasis on the role of autophagy in comparison to cisplatin. In this study, an MTT assay was performed to evaluate the IC50 of PCTL and to analyze the TM3 Leydig cell's viability. Cells morphology was evaluated via invert microscope and Changing in morphology for nuclei swelling or autophagic vacuoles formation were assessed by DAPI and MDC staining. Testosterone production in the culture medium was measured using an ELISA kit. Finally, the expression of Autophagy-related genes, Atg5, Beclin1 and p62, were analyzed by qPCR. Based on the obtained results by MTT, the IC50 value of PCTL was 50 μM in TM3 cells and cytotoxic effects was in a dose- and time-dependent manner. Cells morphological changes investigated by inverted microscopy, DAPI, and MDC staining which showed the cytotoxic concentrations of PCTL was significantly higher than cisplatin in the treated TM3 Leydig cells. The results of PCR showed a lack of expression of the p62, Atg5 and Beclin1 gene in TM3 cells treated with PCTL in comparison to cisplatin and control groups. It should be noted that the effects of 25 μM PCTL concentration on TM3 cells have been associated with increased testosterone production and secretion, which requires further study to explain the possible causes and involved molecular mechanisms. The results of the study showed that the PCTL had less-lethal effects on TM3 cells in comparison to cisplatin and probably did not induce autophagy in TM3 cells.

Keywords: platinum-based anticancer agents, cisplatin, Leydig TM3 cells, autophagy

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1353 Harnessing Entrepreneurial Opportunities for National Security

Authors: Itiola Kehinde Adeniran

Abstract:

This paper investigated the influence of harnessing entrepreneurial opportunities on the national security in Nigeria with a specific focus on the security situation of the post-amnesty programmes of the Federal Government in Ondo State. The self-administered structured questionnaire was employed to collect data from one hundred and twenty participants through purposive sampling method. Inferential statistics was used to analyze the data, specifically; ordinary least squares linear regression method was employed with the aid of statistical package for social science (SPSS) version 20 in order to determine the influence of independent variable (entrepreneurial opportunities) on dependent variable (national security). The result showed that business opportunities have a significant influence on the rate of criminal activities. The study also revealed that entrepreneurial opportunity creation and discovery as well as providing a model on how these entrepreneurial opportunities could be effectively and efficiently utilized jointly predict better national security, which counted for 69% variance of crime rate reduction. The paper, therefore, recommended that citizens should be encouraged to develop an interest in the skill-based activities in order to change their mindset towards self-employment which can motivate them in identify entrepreneurial opportunities.

Keywords: entrepreneurship, entrepreneurial opportunities, national security, unemployment

Procedia PDF Downloads 317
1352 Comparison Of Data Mining Models To Predict Future Bridge Conditions

Authors: Pablo Martinez, Emad Mohamed, Osama Mohsen, Yasser Mohamed

Abstract:

Highway and bridge agencies, such as the Ministry of Transportation in Ontario, use the Bridge Condition Index (BCI) which is defined as the weighted condition of all bridge elements to determine the rehabilitation priorities for its bridges. Therefore, accurate forecasting of BCI is essential for bridge rehabilitation budgeting planning. The large amount of data available in regard to bridge conditions for several years dictate utilizing traditional mathematical models as infeasible analysis methods. This research study focuses on investigating different classification models that are developed to predict the bridge condition index in the province of Ontario, Canada based on the publicly available data for 2800 bridges over a period of more than 10 years. The data preparation is a key factor to develop acceptable classification models even with the simplest one, the k-NN model. All the models were tested, compared and statistically validated via cross validation and t-test. A simple k-NN model showed reasonable results (within 0.5% relative error) when predicting the bridge condition in an incoming year.

Keywords: asset management, bridge condition index, data mining, forecasting, infrastructure, knowledge discovery in databases, maintenance, predictive models

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1351 Clonal Evaluation of Malignant Mesothelioma

Authors: Sabahattin Comertpay, Sandra Pastorino, Rosanna Mezzapelle, Mika Tanji, Oriana Strianese, Andrea Napolitano, Tracey Weigel, Joseph Friedberg, Paul Sugarbaker, Thomas Krausz, Ena Wang, Amy Powers, Giovanni Gaudino, Harvey I. Pass, Fatmagul Ozcelik, Barbara L. Parsons, Haining Yang, Michele Carbone

Abstract:

Tumors are thought to be monoclonal in origin. This paradigm arose decades ago, primarily from the study of hematopoietic malignancies and sarcomas. The clonal origin of malignant mesothelioma (MM), a deadly cancer resistant to the current therapies, has not been investigated. Examination of the pleura from patients with MM shows often the presence of multiple pleural nodules, raising the question of whether they represent independent or metastatic growth processes. To investigate the clonality patterns of MM, we used the HUMARA (Human Androgen Receptor) assay to examine 14 sporadic and 2 familial Malignant Mesotheliomas (MM). Of 16 specimens studied, 15 were informative and 14/15 revealed two electrophoretically distinct methylated HUMARA alleles, indicating a polyclonal origin for these tumors. This discovery has important clinical implications, because an accurate assessment of tumor clonality is key to the design of novel molecular strategies for the treatment of MM.

Keywords: malignant mesothelioma, clonal origin, HUMARA, sarcomas

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1350 Synthesis of Gold Nanoparticles Stabilized in Na-Montmorillonite for Nitrophenol Reduction

Authors: Fatima Ammari, Meriem Chenouf

Abstract:

Synthesis of gold nano particles has attracted much attention since the pioneering discovery of the high catalytic activity of supported gold nano particles in the reaction of CO oxidation at low temperature. In this research field, we used Na-montmorillonite for gold nanoparticles stabilization; different loading percentage 1, 2 and 5%. The gold nano particles were obtained using chemical reduction method using NaBH4 as reductant agent. The obtained gold nano particles Au-mont stabilized in Na-montmorillonite were used as catalysts for reduction of 4-nitrophenol to aminophenol with sodium borohydride at room temperature. The UV-Vis results confirm directly the gold nano particles formation. The XRD and N2 adsorption results showed the formation of gold nano particles in the pores of montmorillonite with an average size of 5 nm obtained on samples with 2%Au-mont. The gold particles size increased with the increase of gold loading percentage. The reduction reaction of 4-nitrophenol into 4-aminophenol with NaBH4 catalyzed by Au-Na-montmorillonite catalyst exhibits remarkably a high activity; the reaction was completed within 9 min for 1Au-mont and within 3 min for 2Au-mont.

Keywords: chemical reduction, gold, montmorillonite, nano particles, 4-nitrophenol

Procedia PDF Downloads 318
1349 Theoretical Study of Carbonic Anhydrase-Ii Inhibitors for Treatment of Glaucoma

Authors: F. Boukli Hacene, W. Soufi, S. Ghalem

Abstract:

Glaucoma disease is a progressive degenerative optic neuropathy, with irreversible visual field deficits and high eye pressure being one of the risk factors. Sulfonamides are carbonic anhydrase-II inhibitors that aim to decrease the secretion of aqueous humor by direct inhibition of this enzyme at the level of the ciliary processes. These drugs present undesirable effects that are difficult to accept by the patient. In our study, we are interested in the inhibition of carbonic anhydrase-II by different natural ligands (curcumin analogues) using molecular modeling methods using molecular operating environment (MOE) software to predict their interaction with this enzyme.

Keywords: carbonic anhydrase-II, curcumin analogues, drug research, molecular modeling

Procedia PDF Downloads 82
1348 Bioactivities and Phytochemical Studies of Acrocarpus fraxinifolius Bark Wight and Arn

Authors: H. M. El-Rafie, A. H. Abou Zeid, R. S. Mohammed, A. A. Sleem

Abstract:

Acrocarpus is a genus of flowering plants in the legume family Fabaceae which considered as a large and economically important family. This study aimed to investigate the phytoconstituents of the petroleum ether extract (PEE) of Acrocarpus fraxinofolius bark by Gas chromatography coupled with mass spectrometry (GC/MS) analysis of its fractions (fatty acid and unsaponifiable matter). Concerning this, identification of 52 compounds constituting 97.03 % of the total composition of the unsaponifiable matter fraction. Cycloeucalenol was found to be the major compound representing 32.52% followed by 4a, 14a-dimethyl-A8~24(28)-ergostadien (26.50%) and ß-sitosterol(13.74%), furthermore Gas liquid chromatography (GLC) analysis of the sterol fraction revealed the identification of cholesterol (7.22 %), campesterol (13.30 %), stigmasterol (10.00 %) and β - sitosterol (69.48 %). Meanwhile, the identification of 33 fatty acids representing 90.71% of the total fatty acid constituents. Methyl-9,12-octadecadienoate (40.39%) followed by methyl hexadecanoate (23.64%) were found to be the major compounds. On the other hand, column chromatography and Thin layer chromatography (TLC) fractionation of PEE separate the triterpenoid: 21β-hydroxylup-20(29)-en-3-one and β- amyrin which were structurally identified by spectroscopic analysis (NMR, MS and IR). PEE has been biologically evaluated for 1: management of diabetes in alloxan induced diabetic rats 2: cytotoxic activity against four human tumor cell lines (Cervix carcinoma cell line[HELA], Breast carcinoma cell line [MCF7], Liver carcinoma cell line[HEPG2] and Colon carcinoma cell line[HCT-116] 3: hepatoprotective activity against CCl4-induced hepatotoxicity in rats and the activity was studied by assaying the serum marker enzymes like AST, ALT, and ALP. Concerning this, the anti-diabetic activity exhibited by 100mg of PEE extract was 74.38% relative to metformin (100% potency). It also showed a significant anti-proliferative activity against MCF-7 (IC50= 2.35µg), Hela(IC50=3.85µg) and HEPG-2 (IC50= 9.54µg) compared with Doxorubicin as reference drug. The hepatoprotective activity was evidenced by significant decrease in liver function enzymes, i.e. AST, ALT and ALP by (29.18%, 28.26%, and 34.11%, respectively using silymarin as the reference drug, compared to their concentration levels in an untreated group with liver damage induced by CCl₄. This study was performed for the first time on the bark of this species.

Keywords: Acrocarpus fraxinofolius, antidiabetic, cytotoxic, hepatoprotective

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1347 Bioefficiency of Cinnamomum verum Loaded Niosomes and Its Microbicidal and Mosquito Larvicidal Activity against Aedes aegypti, Anopheles stephensi and Culex quinquefasciatus

Authors: Aasaithambi Kalaiselvi, Michael Gabriel Paulraj, Ekambaram Nakkeeran

Abstract:

Emergences of mosquito vector-borne diseases are considered as a perpetual problem globally in tropical countries. The outbreak of several diseases such as chikungunya, zika virus infection and dengue fever has created a massive threat towards the living population. Frequent usage of synthetic insecticides like Dichloro Diphenyl Trichloroethane (DDT) eventually had its adverse harmful effects on humans as well as the environment. Since there are no perennial vaccines, prevention, treatment or drugs available for these pathogenic vectors, WHO is more concerned in eradicating their breeding sites effectively without any side effects on humans and environment by approaching plant-derived natural eco-friendly bio-insecticides. The aim of this study is to investigate the larvicidal potency of Cinnamomum verum essential oil (CEO) loaded niosomes. Cholesterol and surfactant variants of Span 20, 60 and 80 were used in synthesizing CEO loaded niosomes using Transmembrane pH gradient method. The synthesized CEO loaded niosomes were characterized by Zeta potential, particle size, Fourier Transform Infrared Spectroscopy (FT-IR), GC-MS and SEM analysis to evaluate charge, size, functional properties, the composition of secondary metabolites and morphology. The Z-average size of the formed niosomes was 1870.84 nm and had good stability with zeta potential -85.3 meV. The entrapment efficiency of the CEO loaded niosomes was determined by UV-Visible Spectrophotometry. The bio-potency of CEO loaded niosomes was treated and assessed against gram-positive (Bacillus subtilis) and gram-negative (Escherichia coli) bacteria and fungi (Aspergillus fumigatus and Candida albicans) at various concentrations. The larvicidal activity was evaluated against II to IV instar larvae of Aedes aegypti, Anopheles stephensi and Culex quinquefasciatus at various concentrations for 24 h. The mortality rate of LC₅₀ and LC₉₀ values were calculated. The results exhibited that CEO loaded niosomes have greater efficiency against mosquito larvicidal activity. The results suggest that niosomes could be used in various applications of biotechnology and drug delivery systems with greater stability by altering the drug of interest.

Keywords: Cinnamomum verum, niosomes, entrapment efficiency, bactericidal and fungicidal, mosquito larvicidal activity

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1346 Phytochemical Screening and Assessment of Hepatoprotective Activity of Geigeria alata Leaves Ethanolic Extract on Wistar Rats

Authors: Girgis Younan, Ikram Eltayeb

Abstract:

Geigeria alata belongs to the family Asteraceae, is an effective plant traditionally used in Sudan as a therapy for hepatic disease and as an antiepileptic, antispasmodic and to treat cough and intestinal complaints.The liver is responsible for many critical functions within the body and any liver disease or injury will result in the loss of those functions leading to significant damage in the body. Liver diseases cause increase in liver enzymes (AST, ALP ALT) and total bilirubin and a decrease in total blood protein level. The objective of this study is to investigate the hepato-protective activity of Geigeria alata leaves ethanolic extract. The plant leaves were extracted using 96% ethanol using Soxhlet apparatus. The hepatoprotective effect was determined using 25 wistar rats, the rats was divided to 5 groups, each group contain 5 rats: [Normal control group] receiving purified water, liver damage was induced in wistar rats by administering a 1:1 (v/v) mixture of CCl4 (1.25 ml/kg) and olive oil once at day four of the experiment [negative control group]. Two doses of extract [400mg/kg and 200mg/kg] was applied daily for 7 days, and standard drug Silymarin (200 mg/kg) were administered daily for 7 days to CCl4-treated rats. The degree of hepato-protective activity was evaluated by determining the hepatic marker enzymes AST, ALP, ALT, total Bilirubin and total proteins (TP). Results have shown that, the extract of G.alata leaves reduced the level of liver enzymes ALT, AST, ALP, total bilirubin and increased the level of total proteins. Since the levels of liver enzymes; bilirubin and total protein are considered as markers of liver function, the extract has proven to reduce the detrimental effects of liver toxicity induced using CCl4. The hepato-protective effect of extract on liver was found to be dose dependent, where the 400mg/kg dose of the extract exhibited higher activity than 200mg/kg dose. In addition, the effect of the higher dose (400mg/kg) of the extract was found to be higher than Silymarin standard drug. The result concludes that, G.alata leaves extract was found to exhibit profound hepato-protective activity, which justifies the traditional use of the plant for the treatment of hepatic diseases.

Keywords: alata, extract, geigeria, hepatoprotective

Procedia PDF Downloads 221