Search results for: selective%20laser%20sintering

Authors: Gaurav Bhanjana, Ganga Ram Chaudhary, Sandeep Kumar, Neeraj Dilbaghi

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Main sources of endocrine disrupting compounds in the ecosystem are hormones, pesticides, phthalates, flame retardants, dioxins, personal-care products, coplanar polychlorinated biphenyls (PCBs), bisphenol A, and parabens. These endocrine disrupting compounds are responsible for learning disabilities, brain development problems, deformations of the body, cancer, reproductive abnormalities in females and decreased sperm count in human males. Although discharge of these chemical compounds into the environment cannot be stopped, yet their amount can be retarded through proper evaluation and detection techniques. The available techniques for determination of these endocrine disrupting compounds mainly include high performance liquid chromatography (HPLC), mass spectroscopy (MS) and gas chromatography-mass spectrometry (GC–MS). These techniques are accurate and reliable but have certain limitations like need of skilled personnel, time consuming, interference and requirement of pretreatment steps. Moreover, these techniques are laboratory bound and sample is required in large amount for analysis. In view of above facts, new methods for detection of endocrine disrupting compounds should be devised that promise high specificity, ultra sensitivity, cost effective, efficient and easy-to-operate procedure. Nowadays, electrochemical sensors/biosensors modified with nanomaterials are gaining high attention among researchers. Bioelement present in this system makes the developed sensors selective towards analyte of interest. Nanomaterials provide large surface area, high electron communication feature, enhanced catalytic activity and possibilities of chemical modifications. In most of the cases, nanomaterials also serve as an electron mediator or electrocatalyst for some analytes.

Keywords: electrochemical, endocrine disruptors, microscopy, nanoparticles, sensors

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Authors: G. Wagner, R. Herrmann

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Cytotoxic platinum compounds play a major role in the chemotherapy of a large number of human cancers. However, due to the severe side effects for the patient and other problems associated with their use, there is a need for the development of more efficient drugs and new methods for their selective delivery to the tumours. One way to achieve the latter could be in the use of nanoparticular substrates that can adsorb or chemically bind the drug. In the cell, the drug is supposed to be slowly released, either by physical desorption or by dissolution of the particle framework. Ideally, the cytotoxic properties of the platinum drug unfold only then, in the cancer cell and over a longer period of time due to the gradual release. In this paper, we report on our first steps in this direction. The binding properties of a series of cytotoxic Pt(II) oxadiazoline compounds to mesoporous silica particles has been studied by NMR and UV/vis spectroscopy. High loadings were achieved when the Pt(II) compound was relatively polar, and has been dissolved in a relatively nonpolar solvent before the silica was added. Typically, 6-10 hours were required for complete equilibration, suggesting the adsorption did not only occur to the outer surface but also to the interior of the pores. The untreated and Pt(II) loaded particles were characterised by C, H, N combustion analysis, BET/BJH nitrogen sorption, electron microscopy (REM and TEM) and EDX. With the latter methods we were able to demonstrate the homogenous distribution of the Pt(II) compound on and in the silica particles, and no Pt(II) bulk precipitate had formed. The in vitro cytotoxicity in a human cancer cell line (HeLa) has been determined for one of the new platinum compounds adsorbed to mesoporous silica particles of different size, and compared with the corresponding compound in solution. The IC50 data are similar in all cases, suggesting that the release of the Pt(II) compound was relatively fast and possibly occurred before the particles reached the cells. Overall, the platinum drug is chemically stable on silica and retained its activity upon prolonged storage.

Keywords: cytotoxicity, mesoporous silica, nanoparticles, platinum compounds

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Authors: Xavier Lorang, Ahmadali Tahmasebimoradi, Chetra Mang, Sylvain Girard

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The additive manufacturing processes (e.g. selective laser melting) allow us to produce lattice structures which have less weight, higher impact absorption capacity, and better thermal exchange property compared to the classical structures. Unfortunately, geometric imperfections (defects) in the lattice structures are by-products results of the manufacturing process. These imperfections decrease the lifetime and the strength of the lattice structures and alternate their mechanical responses. The objective of the paper is to present a simulation strategy which allows us to take into account the effect of the geometric imperfections on the mechanical response of the lattice structure. In the first part, an identification method of geometric imperfection parameters of the lattice structure based on point clouds is presented. These point clouds are based on tomography measurements. The point clouds are fed into the platform LATANA (LATtice ANAlysis) developed by IRT-SystemX to characterize the geometric imperfections. This is done by projecting the point clouds of each microbeam along the beam axis onto a 2D surface. Then, by fitting an ellipse to the 2D projections of the points, the geometric imperfections are characterized by introducing three parameters of an ellipse; semi-major/minor axes and angle of rotation. With regard to the calculated parameters of the microbeam geometric imperfections, a statistical analysis is carried out to determine a probability density law based on a statistical hypothesis. The microbeam samples are randomly drawn from the density law and are used to generate lattice structures. In the second part, a finite element model for the lattice structure with the simplified geometric imperfections (ellipse parameters) is presented. This numerical model is used to simulate the generated lattice structures. The propagation of the uncertainties of geometric imperfections is shown through the distribution of the computed mechanical responses of the lattice structures.

Keywords: additive manufacturing, finite element model, geometric imperfections, lattice structures, propagation of uncertainty

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Authors: Ibrahim Hakeem

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Biosolids are stabilised sewage sludge produced from wastewater treatment processes. Biosolids contain valuable plant nutrient which facilitates their beneficial reuse in agricultural land. However, the increasing levels of legacy and emerging contaminants such as heavy metals (HMs), PFAS, microplastics, pharmaceuticals, microbial pathogens etc., are restraining the direct land application of biosolids. Pyrolysis of biosolids can effectively degrade microbial and organic contaminants; however, HMs remain a persistent problem with biosolids and their pyrolysis-derived biochar. In this work, we demonstrated the integrated processing of biosolids involving the acid pre-treatment for HMs removal and selective reduction of ash-forming elements followed by the bench-scale pyrolysis of the treated biosolids to produce quality biochar and bio-oil enriched with valuable platform chemicals. The pre-treatment of biosolids using 3% v/v H₂SO₄ at room conditions for 30 min reduced the ash content from 30 wt% in raw biosolids to 15 wt% in the treated sample while removing about 80% of limiting HMs without degrading the organic matter. The preservation of nutrients and reduction of HMs concentration and mobility via the developed hydrometallurgical process improved the grade of the treated biosolids for beneficial land reuse. The co-removal of ash-forming elements from biosolids positively enhanced the fluidised bed pyrolysis of the acid-treated biosolids at 700 ℃. Organic matter devolatilisation was improved by 40%, and the produced biochar had higher surface area (107 m²/g), heating value (15 MJ/kg), fixed carbon (35 wt%), organic carbon retention (66% dry-ash free) compared to the raw biosolids biochar with surface area (56 m²/g), heating value (9 MJ/kg), fixed carbon (20 wt%) and organic carbon retention (50%). Pre-treatment also improved microporous structure development of the biochar and substantially decreased the HMs concentration and bioavailability by at least 50% relative to the raw biosolids biochar. The integrated process is a viable approach to enhancing value recovery from biosolids.

Keywords: biosolids, pyrolysis, biochar, heavy metals

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Authors: Atif Zafar Khan, Swarnendra Singh, Imrana Naseem

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Breast cancer is one of the most frequent malignancies in women worldwide and a leading cause of cancer-related deaths among women. Therefore, there is a need to identify new chemotherapeutic strategies for cancer treatment. Unlike normal cells, cancer cells contain elevated copper levels which play an integral role in angiogenesis. Copper is an important metal ion associated with the chromatin DNA, particularly with guanine. Thus, targeting copper via copper-specific chelators in cancer cells can serve as effective anticancer strategy. Keeping in view these facts, we evaluated the anticancer activity and copper-dependent cytotoxic effect of coumestrol (phytoestrogen in soybean products) in breast cancer MCF-7 cells. Coumestrol inhibited proliferation and induced apoptosis in MCF-7 cells, which was prevented by copper chelator neocuproine and ROS scavengers. Coumestrol treatment induced ROS generation coupled to DNA fragmentation, up-regulation of p53/p21, cell cycle arrest at G1/S phase, mitochondrial membrane depolarization and caspases 9/3 activation. All these effects were suppressed by ROS scavengers and neocuproine. These results suggest that coumestrol targets elevated copper for redox cycling to generate ROS leading to DNA fragmentation. DNA damage leads to p53 up-regulation which directs the cell cycle arrest at G1/S phase and promotes caspase-dependent apoptosis of MCF-7 cells. In conclusion, coumestrol induces pro-oxidant cell death by chelating cellular copper to produce copper-coumestrol complexes that engages in redox cycling in breast cancer cells. Thus, targeting elevated copper levels might be a potential therapeutic strategy for selective cytotoxic action against malignant cells.

Keywords: apoptosis, breast cancer, copper chelation, coumestrol, reactive oxygens species, redox cycling

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Authors: Chi-Hsuan Cheng

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This research aims to evaluate public-private partnerships against cyberattacks by comparing the UK and Taiwan. First, the study analyses major cyberattacks and factors influencing cybersecurity in both countries. Second, it assesses the effectiveness of current cyber defence strategies in combating cyberattacks by comparing the approaches taken in the UK and Taiwan, while also evaluating the cyber resilience of both nations. Lastly, the research evaluates existing public-private partnerships by comparing those in the UK and Taiwan, and proposes recommendations for enhancing cooperation and collaboration mechanisms in tackling cyberattacks. Grounded theory serves as the core research method. Theoretical sampling is used to recruit participants in both the UK and Taiwan, including investigators, police officers, and professionals from cybersecurity firms. Semi-structured interviews are conducted in English in the UK and Mandarin in Taiwan, recorded with consent, and pseudonymised for privacy. Data analysis involves open coding, grouping excerpts into codes, and categorising codes. Axial coding connects codes into categories, leading to the development of a codebook. The process continues iteratively until theoretical saturation is reached. Finally, selective coding identifies the core topic, evaluating public-private cooperation against cyberattacks and its implications for social and policing strategies in the UK and Taiwan, which highlights the current status of the cybersecurity industry, governmental plans for cybersecurity, and contributions to cybersecurity from both government sectors and cybersecurity firms, with a particular focus on public-private partnerships. In summary, this research aims to offer practical recommendations to law enforcement, private sectors, and academia for reflecting on current strategies and tailoring future approaches in cybersecurity

Keywords: cybersecurity, cybercrime, public private partnerships, cyberattack

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Authors: Kashan Bashir, Salah Naji Ahmed Sufyan, Mirza Umar Baig

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In this study, n-dodecane, tetralin, decalin, and tetramethybenzene (TMBE) were used as model compounds of alkanes, naphthenic-aromatic, cycloalkanes and alkyl-benzenes presented in hydro-diesel. The catalytic cracking properties of four model compounds over Y zeolite catalyst (Y-Cat.) and ZSM-5 zeolite catalysts (ZSM-5-Cat.) were probed. The experiment results revealed that high conversion of macromolecular paraffin and naphthenic aromatics were achieved over Y-Cat, whereas its low cracking activity of intermediate products micromolecules paraffin and olefin and high activity of hydride transfer reaction goes against the production of value-added products (light olefin and gasoline). In contrast, despite the fact that the hydride transfer reaction was greatly inhabited over ZSM-5-Cat, the low conversion of macromolecules was observed attributed to diffusion limitations. Interestingly, the mixed catalyst compensates for the shortcomings of the two catalysts, and a “relay reaction” between Y-Cat and ZSM-5-Cat was proposed. Specifically, the added Y-Cat acts as a “pre-cracking booster site” and promotes macromolecules conversion. The addition of ZSM-5-Cat not only significantly suppresses the hydride transfer reaction but also contributes to the cracking of immediate products paraffin and olefin into ethylene and propylene, resulting in a high yield of alkyl-benzene (gasoline), ethylene, and propylene with a low yield of naphthalene (LCO) and coke. The catalytic cracking evaluation experiments of mixed hydro-LCO were also performed to further clarify the “relay reaction” above, showing the highest yield of LPG and gasoline over mixed catalyst. The results indicate that the Y-cat and ZSM-5-cat have a synergistic effect on the conversion of hydro-diesel and corresponding value-added product yield and selective coke yield.

Keywords: synergistic effect, hydro-diesel cracking, FCC, zeolite catalyst, ethylene and propylene

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Authors: André C. Silva, Izabela L. A. Moraes, Elenice M. S. Silva, Carlos M. Silva Filho

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In Brazil, most soils are acidic and low in essential nutrients required for the growth and development of plants, making fertilizers essential for agriculture. As the biggest producer of soy in the world and a major producer of coffee, sugar cane and citrus fruits, Brazil is a large consumer of phosphate. Brazilian’s phosphate ores are predominantly from igneous rocks showing a complex mineralogy, associated with carbonites and oxides, typically iron, silicon and barium. The adopted industrial concentration circuit for this type of ore is a mix between magnetic separation (both low and high field) to remove the magnetic fraction and a froth flotation circuit composed by a reverse flotation of apatite (barite’s flotation) followed by direct flotation circuit (rougher, cleaner and scavenger circuit). Since the 70’s fatty acids obtained from vegetable oils are widely used as lower-cost collectors in apatite froth flotation. This is a very effective approach to the apatite family of minerals, being that this type of collector is both selective and efficient (high recovery). This paper presents Jatropha curcas L. oil (JCO) as a renewable and sustainable source of fatty acids with high selectivity in froth flotation of apatite. JCO is considerably rich in fatty acids such as linoleic, oleic and palmitic acid. The experimental campaign involved 216 tests using a modified Hallimond tube and two different minerals (apatite and quartz). In order to be used as a collector, the oil was saponified. The results found were compared with the synthetic collector, Fotigam 5806 produced by Clariant, which is composed mainly by soy oil. JCO showed the highest selectivity for apatite flotation with cold saponification at pH 8 and concentration of 2.5 mg/L. In this case, the mineral recovery was around 95%.

Keywords: froth flotation, jatropha curcas, microflotation, selectivity

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Authors: Nagui A. Abdel-Khalek, Khaled A. Selim, Ahmed Hamdy

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Kaolin is naturally occurring ore predominantly containing kaolinite mineral in addition to some gangue minerals. Typical impurities present in kaolin ore are quartz, iron oxides, titanoferrous minerals, mica, feldspar, organic matter, etc. The main coloring impurity, particularly in the ultrafine size range, is titanoferrous minerals. Kaolin is used in many industrial applications such as sanitary ware, table ware, ceramic, paint, and paper industries, each of which should be of certain specifications. For most industrial applications, kaolin should be processed to obtain refined clay so as to match with standard specifications. For example, kaolin used in paper and paint industries need to be of high brightness and low yellowness. Egyptian kaolin is not subjected to any beneficiation process and the Egyptian companies apply selective mining followed by, in some localities, crushing and size reduction only. Such low quality kaolin can be used in refractory and pottery production but not in white ware and paper industries. This paper aims to study the amenability of beneficiation of an Egyptian kaolin ore of El-Teih locality, Sinai, to be suitable for different industrial applications. Attrition scrubbing and classification followed by magnetic separation are applied to remove the associated impurities. Attrition scrubbing and classification are used to separate the coarse silica and feldspars. Wet high intensity magnetic separation was applied to remove colored contaminants such as iron oxide and titanium oxide. Different variables affecting of magnetic separation process such as solid percent, magnetic field, matrix loading capacity, and retention time are studied. The results indicated that substantial decrease in iron oxide (from 1.69% to 0.61% ) and TiO2 (from 3.1% to 0.83%) contents as well as improving iso-brightness (from 63.76% to 75.21% and whiteness (from 79.85% to 86.72%) of the product can be achieved.

Keywords: Kaolin, titanoferrous minerals, beneficiation, magnetic separation, attrition scrubbing, classification

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Authors: Elitsa Kolentsova, Dimitar Dimitrov, Vasko Idakiev, Tatyana Tabakova, Krasimir Ivanov

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Formaldehyde production by selective oxidation of methanol is an important industrial process. The main by-products in the waste gas are CO and dimethyl ether (DME). The idea of this study is to combine the advantages of both Cu-Mn and Cu-Co catalytic systems by obtaining a new mixed Cu-Mn-Co catalyst with high activity and selectivity at the simultaneous oxidation of CO, methanol, and DME. Two basic Cu-Mn samples with high activity were selected for further investigation: (i) manganese-rich Cu-Mn/γ–Al2O3 catalyst with Cu/Mn molar ratio 1:5 and (ii) copper-rich Cu-Mn/γ-Al2O3 catalyst with Cu/Mn molar ratio 2:1. Manganese in these samples was replaced by cobalt in the whole concentration region, and catalytic properties were determined. The results show a general trend of decreasing the activity toward DME oxidation and increasing the activity toward CO and methanol oxidation with the increase of cobalt up to 60% for both groups of catalyst. This general trend, however, contains specific features, depending on the composition of the catalyst and the nature of the oxidized gas. The catalytic activity of the sample with Cu/(Mn+Co) molar ratio of 2:1 is gradually changed with increasing the cobalt content. The activity of the sample with Cu/(Mn+Co) molar ratio of 1: 5 passes through a maximum at 60% manganese replacement by cobalt, probably due to the formation of highly dispersed Co-based spinel structures (Co3O4 and/or MnCo2O4). In conclusion, the present study demonstrates that the Cu-Mn-Co/γ–alumina supported catalysts have enhanced activity toward CO, methanol and DME oxidation. Cu/(Mn+Co) molar ratio 1:5 and Co/Mn molar ratio 1.5 in the active component can ensure successful oxidation of CO, CH3OH and DME. The active component of the mixed Cu-Mn-Co/γ–alumina catalysts consists of at least six compounds - CuO, Co3O4, MnO2, Cu1.5Mn1.5O4, MnCo2O4 and CuCo2O4, depending on the Cu/Mn/Co molar ratio. Chemical composition strongly influences catalytic properties, this effect being quite variable with regards to the different processes.

Keywords: Cu-Mn-Co catalysts, oxidation, carbon oxide, VOCs

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Authors: Nour S. Abdelrahman, Seunghyun Hong, Hassan A. Arafat, Daniel Choi, Faisal Al Marzooqi

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Abstract—The advancement of lithium extraction methods from water sources, particularly saltwater brine, is gaining prominence in the lithium recovery industry due to its cost-effectiveness. Traditional techniques like recrystallization, chemical precipitation, and solvent extraction for metal recovery from seawater or brine are energy-intensive and exhibit low efficiency. Moreover, the extensive use of organic solvents poses environmental concerns. As a result, there's a growing demand for environmentally friendly lithium recovery methods. Membrane-based separation technology has emerged as a promising alternative, offering high energy efficiency and ease of continuous operation. In our study, we explored the potential of lithium-selective sieve channels constructed from layers of 2D graphene oxide and MXene (transition metal carbides and nitrides), integrated with surface – SO₃₋ groups. The arrangement of these 2D sheets creates interplanar spacing ranging from 0.3 to 0.8 nm, which forms a barrier against multivalent ions while facilitating lithium-ion movement through nano capillaries. The introduction of the sulfonate group provides an effective pathway for Li⁺ ions, with a calculated binding energy of Li⁺ – SO³⁻ at – 0.77 eV, the lowest among monovalent species. These modified membranes demonstrated remarkably rapid transport of Li⁺ ions, efficiently distinguishing them from other monovalent and divalent species. This selectivity is achieved through a combination of size exclusion and varying binding affinities. The graphene oxide channels in these membranes showed exceptional inter-cation selectivity, with a Li⁺/Mg²⁺ selectivity ratio exceeding 104, surpassing commercial membranes. Additionally, these membranes achieved over 94% rejection of MgCl₂.

Keywords: ion permeation, lithium extraction, membrane-based separation, nanotechnology

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Authors: Oluyomi Stephen Adeyemi, Kentaro Kato

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Toxoplasma gondii is the etiological agent of toxoplasmosis, a common parasitic disease capable of infecting a range of hosts, including nearly one-third of the human population. Current treatment options for toxoplasmosis patients are limited. In consequence, toxoplasmosis represents a large global burden that is further enhanced by the shortcomings of the current therapeutic options. These factors underscore the need for better anti-T. gondii agents and/or new treatment approach. In the present study, we sought to find out whether preparing and capping nanoparticles (NPs) in amino acids, would enhance specificity toward the parasite versus the host cell. The selection of amino acids was premised on the fact that T. gondii is auxotrophic for some amino acids. The amino acid-nanoparticles (amino-NPs) were synthesized, purified and characterized following established protocols. Next, we tested to determine the anti-T. gondii activity of the amino-NPs using in vitro experimental model of infection. Overall, our data show evidence that supports enhanced and excellent selective action against the parasite versus the host cells by amino-NPs. The findings are promising and provide additional support that warrants exploring the prospects of NPs as alternative anti-parasite agents. In addition, the anti-parasite action by amino-NPs indicates that nutritional requirement of parasite may represent a viable target in the development of better alternative anti-parasite agents. Furthermore, data suggest the anti-parasite mechanism of the amino-NPs involves multiple cellular processes including the production of reactive oxygen species (ROS), modulation of hypoxia-inducing factor-1 alpha (HIF-1α) as well as the activation of kynurenine pathway. Taken together, findings highlight further, the prospects of NPs as alternative source of anti-parasite agents.

Keywords: drug discovery, infectious diseases, mode of action, nanomedicine

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Authors: Maria Francesca Scannone, Martina Bochicchio

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One of the major environmental problems today is hydrocarbon contamination. The promising sustainable technologies for the treatment of these contaminated sites involves the use of biological organisms. In Agri Valley (Basilicata Region) there is a living laboratory (natural oil seeps) where the selective pressure has enriched the environmental matrices with microorganisms, fungi and plant species able to use the hydrocarbons as a source of metabolic energy, to degrade or tolerate hydrocarbons. Observers visiting this area are fascinated by its unspoiled nature, and the condition of the ecosystem does not appear to has been damaged. The amazing resiliency observed in Tramutola site is of key importance to try to bring green remediation technologies, but no research has been done to identify high-performing native species. The aim of this research was to study how natural processes affect the fate of released oil or how individual species or communities of plants and animals are capable of dealing with the burden of otherwise toxic chemicals. The survey of vegetation was carried out, more than 60 species have been identified and divided into tree, shrub and herb layer. Plant data sheets have been completed only for the species that showed the most appropriate properties for phytoremediation. In general, members of the Salicales, Cyperales, Poales, Fagales, Cornales, Equisetales orders were the most commonly identified orders. They are pioneer plants with high adaptive capacity and vegetative propagation. The literature review has highlighted the existence of rhizosphere effect and a green liver model on selected plants. The study provides significant information on the environmental stress adaptation processes of many indigenous plants that are living and growing on a natural leak of crude oil and gas that migrates up through subsurface.

Keywords: green liver, hydrocarbon degradation, oil seeps, phytoremediation

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Authors: Christine Fräulin, Daniela Schurr, Hamed Shahidi Rad, Gerrit Waters, Günter Rinke, Roland Dittmeyer, Michael Nilles

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The reaction mechanisms of many liquid-phase reactions in organic chemistry have not yet been sufficiently clarified. Process conditions of several hundred degrees celsius and pressures to ten megapascals complicate the sampling and the determination of kinetic data. Space resolved in-situ measurements promises new insights. A non-invasive in-situ measurement technique has the advantages that no sample preparation is necessary, there is no change in sample mixture before analysis and the sampling do no lead to interventions in the flow. Thus, the goal of our research was the development of a contact-free spatially resolved measurement technique for kinetic studies of liquid phase reaction under process conditions. Therefore we used laser Raman spectroscopy combined with an optical transparent microchannel reactor. To show the performance of the system we choose the oxidation of cyclohexane as sample reaction. Cyclohexane oxidation is an economically important process. The products are intermediates for caprolactam and adipic acid, which are starting materials for polyamide 6 and 6.6 production. To maintain high selectivities of 70 to 90 %, the reaction is performed in industry at a low conversion of about six percent. As Raman spectroscopy is usually very selective but not very sensitive the detection of the small product concentration in cyclohexane oxidation is quite challenging. To meet these requirements, an optical experimental setup was optimized to determine the concentrations by laser Raman spectroscopy with respect to good detection sensitivity. With this measurement technique space resolved kinetic studies of uncatalysed and homogeneous catalyzed cyclohexane oxidation were carried out to obtain details about the reaction mechanism.

Keywords: in-situ laser raman spectroscopy, space resolved kinetic measurements, homogeneous catalysis, chemistry

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Authors: Seyhan Sahan-Firat, Meryem Temiz-Resitoglu, Demet Sinem Guden, Sefika Pinar Kucukkavruk, Bahar Tunctan, Ayse Nihal Sari, Zumrut Kocak

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We hypothesized that mTOR inhibition may prevent the multiple organ failures following severe multiple tissue injury associated with increased NADPH oxidase system activity occur in zymosan-induced systemic inflammation. Therefore, we investigated the role of mTOR in oxidative/nitrosative stress associated with increase in NADPH oxidase activity in zymosan-induced systemic inflammation model in rats. Male Wistar rats received saline (4 ml/kg, i.p.) and zymosan (500 mg/kg, i.p.) at time 0. Saline, or zymosan-treated rats were given rapamycin (1 mg/kg, i.p.) 1 h after saline or zymosan injections. Rats were sacrified 4 h after zymosan challenge and kidney, heart, thoracic aorta, and superior mesenteric artery were collected. NADPH oxidase activity, p22phox, gp91phox, and p47phox protein expression and nitrotyrosine levels were measured in tissue samples. Zymosan administration caused an increase in NADPH oxidase activity, p22phox, gp91phox, and p47phox protein expression and nitrotyrosine levels in kidney, heart, thoracic aorta, and superior mesenteric artery. These changes caused by zymosan reversed by rapamycin, a selective mTOR inhibitor. Rapamycin alone had no effect on the parameters measured. Our results demonstrated that zymosan-induced oxidative/nitrosative stress presumably due to enhanced activity of NADPH oxidase, expression of p22phox, gp91phox, and p47phox and production of peroxynitrite were mediated by mTOR. [This work was financially supported by Research Foundation of Mersin University (2016-2-AP3-1900)].

Keywords: oxidative stress, mTOR, nitrosative stress, zymosan

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Authors: Sidra Shaw, Sarenna Shaw, Chae Joon Lee, Irimpan Mathews, Eric Koehn

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One of the biggest public health concerns of our time is increasing antimicrobial resistance. As of 2019, the CDC has documented more than 2.8 million serious antibiotic resistant infections in the United States. Currently, antibiotic resistant infections are directly implicated in over 750,000 deaths per year globally. On our current trajectory, British economist Jim O’Neill predicts that by 2050, an additional 10 million people (about half the population of New York) will die annually due to drug resistant infections. As a result, new biochemical pathways must be targeted to generate next generation antibiotic drugs that will be effective against drug resistant bacteria. One enticing target is the biosynthesis of DNA within bacteria, as few drugs interrupt this essential life process. Thymidylate synthase enzymes are essential for life as they catalyze the synthesis of a DNA building block, 2′-deoxythymidine-5′-monophosphate (dTMP). In humans, the thymidylate synthase enzyme (TSase) has been shown to be distinct from the flavin-dependent thymidylate synthase (FDTS) produced by many pathogenic bacteria. TSase and FDTS have distinct structures and mechanisms of catalysis, which should allow selective inhibition of FDTS over human TSase. Currently, C. diff is one of the most antibiotic resistant bacteria, and no drugs that target thymine biosynthesis exist for C. diff. Here we present the initial biochemical characterization of FDTS from C. diff. Specifically, we examine enzyme kinetics and binding features of this enzyme to determine the nature of interaction with ligands/inhibitors and understand the molecular mechanism of catalysis. This research will provide more insight into the targetability of the C. diff FDTS enzyme for novel antibiotic drugs.

Keywords: flavin-dependent thymidylate synthase, FDTS, clostridioides difficile, C. diff, antibiotic resistance, DNA synthesis, enzyme kinetics, binding features

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Authors: In-Hwan Baek

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Valsartan is a potent and highly selective antagonist of the angiotensin II type 1 receptor, and is widely used for the treatment of hypertension. The aim of this study was to investigate the pharmacokinetic properties of the valsartan in dogs following oral administration of a single dose using quantitative modeling approaches. Forty beagle dogs were randomly divided into two group. Group A (n=20) was administered a single oral dose of valsartan 80 mg (Diovan® 80 mg), and group B (n=20) was administered a single oral dose of valsartan 160 mg (Diovan® 160 mg) in the morning after an overnight fast. Blood samples were collected into heparinized tubes before and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 and 24 h following oral administration. The plasma concentrations of the valsartan were determined using LC-MS/MS. Non-compartmental pharmacokinetic analyses were performed using WinNonlin Standard Edition software, and modeling approaches were performed using maximum-likelihood estimation via the expectation maximization (MLEM) algorithm with sampling using ADAPT 5 software. After a single dose of valsartan 80 mg, the mean value of maximum concentration (Cmax) was 2.68 ± 1.17 μg/mL at 1.83 ± 1.27 h. The area under the plasma concentration-versus-time curve from time zero to the last measurable concentration (AUC24h) value was 13.21 ± 6.88 μg·h/mL. After dosing with valsartan 160 mg, the mean Cmax was 4.13 ± 1.49 μg/mL at 1.80 ± 1.53 h, the AUC24h was 26.02 ± 12.07 μg·h/mL. The Cmax and AUC values increased in proportion to the increment in valsartan dose, while the pharmacokinetic parameters of elimination rate constant, half-life, apparent of total clearance, and apparent of volume of distribution were not significantly different between the doses. Valsartan pharmacokinetic analysis fits a one-compartment model with first-order absorption and elimination following a single dose of valsartan 80 mg and 160 mg. In addition, high inter-individual variability was identified in the absorption rate constant. In conclusion, valsartan displays the dose-dependent pharmacokinetics in dogs, and Subsequent quantitative modeling approaches provided detailed pharmacokinetic information of valsartan. The current findings provide useful information in dogs that will aid future development of improved formulations or fixed-dose combinations.

Keywords: dose-dependent, modeling, pharmacokinetics, valsartan

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Authors: Nadine Wiesmann, Melanie Viel, Christoph Buhr, Rachel Tanner, Wolfgang Tremel, Juergen Brieger

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Recidivation of tumors and the development of resistances against the classical anti-tumor approaches represent a major challenge we face when treating cancer. In order to master this challenge, we are in desperate need of new treatment options beyond the beaten tracks. Zinc oxide nanoparticles (ZnO NPs) represent such an innovative approach. Zinc oxide is characterized by a high level of biocompatibility, concurrently ZnO NPs are able to exert anti-tumor effects. By concentration of the nanoparticles at the tumor site, tumor cells can specifically be exposed to the nanoparticles while low zinc concentrations at off-target sites are tolerated well and can be excreted easily. We evaluated the toxicity of ZnO NPs in vitro with the help of immortalized tumor cell lines and primary cells stemming from healthy tissue. Additionally, the Chorioallantoic Membrane Assay (CAM Assay) was employed to gain insights into the in vivo behavior of the nanoparticles. We could show that ZnO NPs interact with tumor cells as nanoparticulate matter. Furthermore, the extensive release of zinc ions from the nanoparticles nearby and within the tumor cells results in overload with zinc. Beyond that, ZnO NPs were found to further the generation of reactive oxygen species (ROS). We were able to show that tumor cells were more prone to the toxic effects of ZnO NPs at intermediate concentrations compared to fibroblasts. With the help of ZnO NPs covered by a silica shell in which FITC dye was incorporated, we were able to track ZnO NPs within tumor cells as well as within a whole organism in the CAM assay after injection into the bloodstream. Depending on the applied concentrations, selective tumor cell killing seems feasible. Furthermore, the combinational treatment of tumor cells with radiotherapy and ZnO NPs shows promising results. Still, further investigations are needed to gain a better understanding of the interaction between ZnO NPs and the human body to be able to pave the way for their application as an innovative anti-tumor agent in the clinics.

Keywords: metal oxide nanoparticles, nanomedicine, overcome resistances against classical treatment options, zinc oxide nanoparticles

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Authors: Rashi Rajput, Manisha Singh

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Escitalopram oxalate (ETP), an FDA approved antidepressant drug from the category of SSRI (selective serotonin reuptake inhibitor) and is used in treatment of general anxiety disorder (GAD), major depressive disorder (MDD).When taken orally, it is metabolized to S-demethylcitalopram (S-DCT) and S-didemethylcitalopram (S-DDCT) in the liver with the help of enzymes CYP2C19, CYP3A4 and CYP2D6. Hence, causing side effects such as dizziness, fast or irregular heartbeat, headache, nausea etc. Therefore, targeted and sustained drug delivery will be a helpful tool for increasing its efficacy and reducing side effects. The present study is designed for formulating mucoadhesive nanoparticle formulation for the same Escitalopram loaded polymeric nanoparticles were prepared by ionic gelation method and characterization of the optimised formulation was done by zeta average particle size (93.63nm), zeta potential (-1.89mV), TEM (range of 60nm to 115nm) analysis also confirms nanometric size range of the drug loaded nanoparticles along with polydispersibility index of 0.117. In this research, we have studied the in vitro drug release profile for ETP nanoparticles, through a semi permeable dialysis membrane. The three important characteristics affecting the drug release behaviour were – particle size, ionic strength and morphology of the optimised nanoparticles. The data showed that on increasing the particle size of the drug loaded nanoparticles, the initial burst was reduced which was comparatively higher in drug. Whereas, the formulation with 1mg/ml chitosan in 1.5mg/ml tripolyphosphate solution showed steady release over the entire period of drug release. Then this data was further validated through mathematical modelling to establish the mechanism of drug release kinetics, which showed a typical linear diffusion profile in optimised ETP loaded nanoparticles.

Keywords: ionic gelation, mucoadhesive nanoparticle, semi-permeable dialysis membrane, zeta potential

Procedia PDF Downloads 268

Authors: Dileep K. Verma, Sunil K. Lal

Abstract:

Influenza still remains one of the most challenging diseases posing significant threat to public health causing seasonal epidemics and pandemics. Previous studies suggest that influenza hemagglutinin is essential for viral attachment to host sialic acid receptors and concentrate in lipid rafts for efficient viral fusion. Studies also reported selective nature of Influenza virus to utilize rafts micro-domain for efficient virus assembly and budding. However, the detailed mechanism of Influenza A Virus (IAV) binding to host cell membrane and entry inside the host remains elusive. In the present study, we investigated if host membrane lipid rafts play any significant role in early life cycle events of influenza A virus. Role of host lipid rafts was studied using raft disruption method by extraction of cholesterol and Methyl-β-Cyclodextrin was used to remove membrane cholesterol. We observed co-localization of Influenza A Virus to lipid rafts by visualization of known lipid raft marker GM1 on host cell membrane. Co-localization suggest direct involvement of these micro-domain in initiation of IAV life cycle. We found significant reduction in influenza A virus adsorption in raft disrupted target host cells indicating poor binding and attachment in absence of coherent membrane rafts. Taken together, the results of present study provide evidence for critical involvement of host lipid rafts and its constituents in adsorption process of Influenza A Virus and suggests crucial involvement in other early events of IAV life cycle. The present study opens a new domain to study influenza virus-host interaction and to combat flu at the very early steps of viral life cycle.

Keywords: lipid raft, adsorption, cholesterol, methyl-β-cyclodextrin, GM1

Procedia PDF Downloads 273

Authors: Sebastien Relave, Christophe Desrayaud, Aurelien Vilani, Alexey Sova

Abstract:

Laser beam melting (LBM) is an additive manufacturing process that enables complex 3D parts to be designed. This process is now commonly employed for various applications such as chemistry or energy, requiring the use of stainless steel grades. LBM can offer comparable and sometimes superior mechanical properties to those of wrought materials. However, we observed an anisotropic microstructure which results from the process, caused by the very high thermal gradients along the building axis. This microstructure can be harmful depending on the application. For this reason, control and prediction of the microstructure are important to ensure the improvement and reproducibility of the mechanical properties. This study is focused on the 316L SS grade and aims at understanding the solidification and transformation mechanisms during process. Experiments to analyse the nucleation and growth of the microstructure obtained by the LBM process according to several conditions. These samples have been designed on different type of support bulk and lattice. Samples are produced on ProX DMP 200 LBM device. For the two conditions the analysis of microstructures, thanks to SEM and EBSD, revealed a single phase Austenite with preferential crystallite growth along the (100) plane. The microstructure was presented a hierarchical structure consisting columnar grains sizes in the range of 20-100 µm and sub grains structure of size 0.5 μm. These sub-grains were found in different shapes (columnar and cellular). This difference can be explained by a variation of the thermal gradient and cooling rate or element segregation while no sign of element segregation was found at the sub-grain boundaries. A high dislocation concentration was observed at sub-grain boundaries. These sub-grains are separated by very low misorientation walls ( < 2°) this causes a lattice of curvature inside large grain. A discussion is proposed on the occurrence of these microstructures formation, in regard of the LBM process conditions.

Keywords: selective laser melting, stainless steel, microstructure

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Authors: Saeedeh Imani Moqadam, Ilya Bobrov, Jérémy Epp, Nils Ellendt, Lutz Mädler

Abstract:

High entropy alloys (HEAs), having adjustable properties and enhanced stability compared with intermetallic compounds, are solid solution alloys that contain more than five principal elements with almost equal atomic percentage. The concept of producing such alloys pave the way for developing advanced materials with unique properties. However, the synthesis of such alloys may require advanced processes with high cooling rates depending on which alloy elements are used. In this study, the micro spheres of different diameters of HEAs were generated via a drop-on-demand droplet generator and subsequently solidified during free-fall in an argon atmosphere. Such droplet generators can generate individual droplets with high reproducibility regarding droplet diameter, trajectory and cooling while avoiding any interparticle momentum or thermal coupling. Metallography as well as X-ray diffraction investigations for each diameter of the generated metallic droplets where then carried out to obtain information about the microstructural state. To calculate the cooling rate of the droplets, a droplet cooling model was developed and validated using model alloys such as CuSn%6 and AlCu%4.5 for which a correlation of secondary dendrite arm spacing (SDAS) and cooling rate is well-known. Droplets were generated from these alloys and their SDAS was determined using quantitative metallography. The cooling rate was then determined from the SDAS and used to validate the cooling rates obtained from the droplet cooling model. The application of that model on the HEA then leads to the cooling rate dependency and hence to the identification of process windows for the synthesis of these alloys. These process windows were then compared with cooling rates obtained in processes such as powder production, spray forming, selective laser melting and casting to predict if a synthesis is possible with these processes.

Keywords: cooling rate, drop-on-demand, high entropy alloys, microstructure, single droplet generation, X-ray Diffractometry

Procedia PDF Downloads 183

Authors: Maryam Beiranvand, Sajad Yaghoubi

Abstract:

Background: Some microbes can colonize plants’ inner tissues without causing obvious damage and can even produce useful bioactive substances. In the present study, the diversity of the endophytic bacteria associated with medicinal plants from Iran was investigated by culturing techniques, molecular gene identification, as well as measuring them for antibacterial activity. Results: In the spring season from 2013 to 2014, 35 herb pharmacology samples were collected, sterilized, meshed, and then cultured on selective media culture. A total of 199 endophytic bacteria were successfully isolated from 35 tissue cultures of medical plants, and sixty-seven out of 199 bacterial isolates were subjected to identification by the 16S rRNA gene sequence analysis method. Based on the sequence similarity gene and phylogenetic analyses, these isolates were grouped into five classes, fourteen orders, seventeen families, twenty-one genera, and forty strains. The most abundant group of endophytic bacteria was actinobacterial, consisting of thirty-two (47%) out of 67 bacterial isolates. Ten (22.3%) out of 67 bacterial isolates remained unidentified and classified at the genus level. The signature of the 16S rRNA gene formed a distinct line in a phylogenetic tree showing that they might be new species of bacteria. One (5.2%) out of 67 bacterial isolates was still not well categorized. Forty-two out of 67 strains were candidates for antimicrobial activity tests. Nineteen (45%) out of 42 strains showed antimicrobial activity multidrug resistance (MDR); thirteen (68%) out of 19 strains were allocated to classes actinobacteria. Four (21%) out of 19 strains belonged to the Bacillaceae family, one (5.2%) out of 19 strains was the Paenibacillaceae family, and one (5.2%) out of 19 strains belonged to the Pseudomonadaceae family. The other twenty-three strains did not show inhibitory activities. Conclusions: Our research showed a high-level phylogenetic diversity and the intoxicating antibiotic activity of endophytic bacteria in the herb pharmacology of Iran.

Keywords: Antibacterial activity, endophytic bacteria, multidrug-resistant bacteria, whole genom sequencing

Procedia PDF Downloads 59

Authors: Chung Danbi, Linton Oliver, Whang Yoon-Jae

Abstract:

Supermodularity, or complementarity, is a popular concept in economics which can characterize many objective functions such as utility, social welfare, and production functions. Further, supermodular dominance captures a preference for greater interdependence among inputs of those functions, and it can be applied to examine which input set would produce higher expected utility, social welfare, or production. Therefore, we propose and justify a consistent testing for a useful implication of supermodular dominance. We also conduct Monte Carlo simulations to explore the finite sample performance of our test, with critical values obtained from the recentered bootstrap method, with and without the selective recentering, and the subsampling method. Under various parameter settings, we confirmed that our test has reasonably good size and power performance. Finally, we apply our test to compare the geographic and distant knowledge spillover in terms of their effects on social welfare using the National Bureau of Economic Research (NBER) patent data. We expect localized citing to supermodularly dominate distant citing if the geographic knowledge spillover engenders greater social welfare than distant knowledge spillover. Taking subgroups based on firm and patent characteristics, we found that there is industry-wise and patent subclass-wise difference in the pattern of supermodular dominance between localized and distant citing. We also compare the results from analyzing different time periods to see if the development of Internet and communication technology has changed the pattern of the dominance. In addition, to appropriately deal with the sparse nature of the data, we apply high-dimensional methods to efficiently select relevant data.

Keywords: supermodularity, supermodular dominance, stochastic dominance, Monte Carlo simulation, bootstrap, subsampling

Procedia PDF Downloads 95

Authors: John Onolame Unuofin, Uchechukuw U. Nwodo, Anthony I. Okoh

Abstract:

Laccase is constantly gaining status as important biocatalyst in biotechnology. The illimitable potential of its industrial applications and the corresponding aggressive need for phenomenal volumes of extracellularly secreted laccases have called for its interminable production from sources which are able to meet this demand within a relatively short period of time, preferably bacteria. In response to this call, this study was designed to source for laccase-producing bacteria from different environmental matrices. Three sampling environments were chosen such as wastewater treatment plants, University of Fort Hare vicinity and the Hogback woodland, all within the Eastern Cape, South Africa. Samples such as effluents, sediments, leaf litters, degrading wood and rock scrapings were selectively enriched with some model aromatic compounds and were further screened qualitatively and quantitatively on five phenolic substrates ABTS (2,2’-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid), Guaiacol, 1-Naphthol, Potassium Ferric Cyanide and Syringaldazine). Basis for selection was their ability to elicit a colour change on at least three of the above mentioned agar based assay substrates. The choice isolates were further identified based on 16S rRNA molecular identification techniques. 33 isolates were screened out of the 40 representative distinct colonies during the qualitative plate screens, while quantitative screens selected out 11 bacterial isolates. They were, based on molecular identification, desginated as members of the genera Pseudomonas, Stenotrophomonas and Citrobacter of the gammaproteobacteria and Bordetalla and Achromobacter of the betaproteobacteria respectively. We therefore conclude based on our outcomes that we may have isolated efficient laccase-producing bacteria, which might be of beneficial significance in catalysis and biotechnology.

Keywords: beta proteobacteria, catalysis, gammaproteobacteria, laccase

Procedia PDF Downloads 148

Authors: Vinod Kumar Gupta, Narendrakumar M. Chaudhari, Suchismitha Iskepalli, Chitra Dutta

Abstract:

Background-The community composition of the human microbiome is known to vary at distinct anatomical niches. But little is known about the nature of variations if any, at the genome/sub-genome levels of a specific microbial community across different niches. The present report aims to explore, as a case study, the variations in gene repertoire of 28 Prevotella reference draft genomes derived from different body-sites of human, as reported earlier by the Human Microbiome Consortium. Results-The analysis reveals the exclusive presence of 11798, 3673, 3348 and 934 gene families and exclusive absence of 17, 221, 115 and 645 gene families in Prevotella genomes derived from the human oral cavity, gastro-intestinal tracts (GIT), urogenital tract (UGT) and skin, respectively. The pan-genome for Prevotella remains “open”. Distribution of various functional COG categories differs appreciably among the habitat-specific genes, within Prevotella pan-genome and between the GIT-derived Bacteroides and Prevotella. The skin and GIT isolates of Prevotella are enriched in singletons involved in Signal transduction mechanisms, while the UGT and oral isolates show higher representation of the Defense mechanisms category. No niche-specific variations could be observed in the distribution of KEGG pathways. Conclusion-Prevotella may have developed distinct genetic strategies for adaptation to different anatomical habitats through selective, niche-specific acquisition and elimination of suitable gene-families. In addition, individual microorganisms tend to develop their own distinctive adaptive stratagems through large repertoires of singletons. Such in situ, habitat-driven refurbishment of the genetic makeup can impart substantial intra-lineage genome diversity within the microbes without perturbing their general taxonomic heritage.

Keywords: body niche adaptation, human microbiome, pangenome, Prevotella

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Authors: Himanshu Lal, Bipasha Ghosh, Arun Srivastava

Abstract:

A pilot study of indoor air quality in terms of bioaerosol (fungus and bacteria) and few selective microbial volatile organic compounds (MVOCs) was carried out in different indoor sections of a library for two seasons, namely monsoon and post monsoon. Bioaerosol sampling was carried out using Anderson six stage viable sampler at a flow rate of 28.3 L/min while MVOCs were collected on activated charcoal tubes ORBOTM 90 Carboxen 564.Collected MVOCs were desorbed using carbon disulphide (CS2) and analysed by GC-FID. Microscopic identification for fungus was only carried out. Surface dust was collected by sterilised buds and cultured to identify fungal contaminants. Unlike bacterial size distribution, fungal bioaerosol concentration was found to be highest in the fourth stage in different sections of the library. In post monsoon season both fungal bioaerosol (710 to 3292cfu/m3) and bacterial bioaerosol (298 to 1475cfu/m3) were fund at much greater concentration than in monsoon. In monsoon season unlike post monsoon, I/O ratio for both the bioaerosol fractions was more than one. Rain washout could be the reason of lower outdoor concentration in monsoon season. On the contrary most of the MVOCs namely 1-hexene, 1-pentanol and 1-octen-3-ol were found in the monsoon season instead of post monsoon season with the highest being 1-hexene with 7.09µg/m3 concentration. Among the six identified fungal bioaerosol Aspergillus, Cladosporium and Penicillium were found in maximum concentration while Aspergillus niger, Curvuleria lunata, Cladosporium cladosporioides and Penicillium sp., was indentified in surface dust samples. According to regression analysis apart from environmental factors other factors also played an important role. Thus apart from outdoor infiltration and human sources, accumulated surface dust mostly on organic materials like books, wooden furniture and racks can be attributed to being one of the major sources of both fungal bioaerosols as well as MVOCs found in the library.

Keywords: bacteria, Fungi, indoor air, MVOCs

Procedia PDF Downloads 281

Authors: Maryam Beiranvand, Sajad Yaghoubi

Abstract:

Background: Some microbes can colonize plants’ inner tissues without causing obvious damage and can even produce useful bioactive substances. In the present study, the diversity of the endophytic bacteria associated with medicinal plants from Iran was investigated by culturing techniques, molecular gene identification, as well as measuring them for antibacterial activity. Results: In the spring season from 2013 to 2014, 35 herb pharmacology samples were collected, sterilized, meshed, and then cultured on selective media culture. A total of 199 endophytic bacteria were successfully isolated from 35 tissue cultures of medical plants, and sixty-seven out of 199 bacterial isolates were subjected to identification by the 16S rRNA gene sequence analysis method. Based on the sequence similarity gene and phylogenetic analyses, these isolates were grouped into five classes, fourteen orders, seventeen families, twenty-one genera, and forty strains. The most abundant group of endophytic bacteria was actinobacterial, consisting of thirty-two (47%) out of 67 bacterial isolates. Ten (22.3%) out of 67 bacterial isolates remained unidentified and classified at the genus level. The signature of the 16S rRNA gene formed a distinct line in a phylogenetic tree showing that they might be new species of bacteria. One (5.2%) out of 67 bacterial isolates was still not well categorized. Forty-two out of 67 strains were candidates for antimicrobial activity tests. Nineteen (45%) out of 42 strains showed antimicrobial activity multidrug-resistance (MDR); thirteen (68%) out of 19 strains were allocated to classes actinobacteria. Four (21%) out of 19 strains belonged to the Bacillaceae family, one (5.2%) out of 19 strains was the Paenibacillaceae family, and one (5.2%) out of 19 strains belonged to the Pseudomonadaceae family. The other twenty-three strains did not show inhibitory activities. Conclusions: Our research showed a high-level phylogenetic diversity and the intoxicating antibiotic activity of endophytic bacteria in the herb pharmacology of Iran.

Keywords: medical plant, endophytic bacteria, antimicrobial activity, whole genome sequencing analysis

Procedia PDF Downloads 86

Authors: Brigitta Bodnár, Lajos Kovács, Zoltán Kupihár

Abstract:

The cancer cells require higher amount of nucleoside building blocks for their proliferation, therefore they have significantly higher uptake of nucleosides by the different nucleoside transporters. Therefore, the conjugation with nucleosides may significantly increase the efficiency and selectivity of potential active pharmaceutical ingredients. On the other hand, the advantage of using a nucleoside could be either the higher activity on targeted enzymes overrepresented in cancer cells or an enhanced cellular uptake of the bioconjugates in these cells compared to the healthy ones. This fact can be used to make the nucleosides, as targeting moieties covalently bound to anti-cancer drug molecules which can selectively accumulate in cancer cells. However, in order to form the nucleoside-drug conjugates, such nucleoside building blocks are needed, which can selectively be coupled to the drug molecules containing even a high number of diverse functional groups. One of the most selective conjugation techniques is the copper-catalyzed azide-alkyne click reaction that requires the presence of an alkyl group on one of the conjugated molecules and an azide group on the other. In case of nucleosides, the development of azide group is simpler for which the replacement of the 5'-hydroxy group is the most suitable. This transformation generally involves many side reactions and result in very low yields. In addition, during our experiments, the transformation of the 2'-deoxyguanosine to the corresponding 5'-deoxy-5’-azido-2’-deoxyguanosine could not be performed with any of the methods described in the literature. Therefore, we have tried to overcome these difficulties with not only using the traditional process based on the 2 step exchange of tosyl to azide, but also using the Mitsunobu reaction which requires only one step. However, this path proved to be unsuccessful in spite of the optimizing the reaction conditions. Finally, a method has been developed whereby the azide groups were incorporated into the 5’-position resulting in significantly better yields compared to all other previous methods, and we were able to produce all the four nucleoside derivatives.

Keywords: 5'-azidonucleosides, bioconjugate, click reaction, proliferation

Procedia PDF Downloads 218

Authors: Iori Hamada

Abstract:

Australia's skilled migrant selection system is constantly changing its target skills and criteria according to the labour market demands. The government's intention to employ this highly selective market-driven selection system is to better target the skills needed in the economy, enable skilled migrants to be employed in industries that have the highest need, and consequently boost the economy and population. However, migration scholars have called this intention into question, arguing that the system is not making the best use of skilled migrants. This paper investigates the impact of recent reforms in Australian skilled migration system on skilled migrants' employment and related life conditions. Drawing on semi-structured qualitative interviews with Japanese skilled migrants in Australia, it argues that Australia’s skilled migrant selection system guarantees neither skilled migrants' employment nor successful transfer of their skills to the labour market. The findings show that Japanese skilled migrants are often unemployed or under-employed, although they intend to achieve upward occupational mobility. The interview data also reveal that male unemployment or under-employment status prompts some Japanese men to leave Australia and find a job that better matches their skills and qualifications in a new destination. Further, it finds that Japanese male skilled migrants who experience downward occupational mobility tend to continue to take a primary breadwinner role, which affects the distribution of paid and unpaid work within their families. There is a growing body of research investigating skilled migrants’ downward career mobility. However, little has been written on skilled Japanese migrants. Further, the work-family intersection is a 'hot public policy topic' in Australia and elsewhere. Yet, the existing studies focus almost exclusively on non-migrant families. This calls attention to the urgency of assessing the work-family lives of skilled migrants. This study fills these gaps, presenting additional insight into Japanese skilled migrants’ work and family in and beyond Australia.

Keywords: Australia, employment, family, Japanese skilled migrants

Procedia PDF Downloads 90