Search results for: verb particle constructions

Authors: S. M. Ashikur Elahee, Md. Zahidur Rahman, Md. Shofiqur Rahman

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This study evaluated the impact of different water interventions under WASH program on access of household's to safe drinking water. Following survey method, the study was carried out in two Upazila of South-west coastal region of Bangladesh namely Koyra from Khulna and Shymnagar from Satkhira district. Being an explanatory study, a total of 200 household's selected applying random sampling technique were interviewed using a structured interview schedule. The predicted probability suggests that around 62 percent household's are out of year-round access to safe drinking water whereby, only 25 percent household's have access at SPHERE standard (913 Liters/per person/per year). Besides, majority (78 percent) of the household's have not accessed at both indicators simultaneously. The distance from household residence to the water source varies from 0 to 25 kilometer with an average distance of 2.03 kilometers. The study also reveals that the increase in monthly income around BDT 1,000 leads to additional 11 liters (coefficient 0.01 at p < 0.1) consumption of safe drinking water for a person/year. As expected, lining up time has significant negative relationship with dependent variables i.e., for higher lining up time, the probability of getting access for both SPHERE standard and year round access variables becomes lower. According to ordinary least square (OLS) regression results, water consumption decreases at 93 liters for per person/year of a household if one member is added to that household. Regarding water consumption intensity, ordered logistic regression (OLR) model shows that one-minute increase of lining up time for water collection tends to reduce water consumption intensity. On the other hand, as per OLS regression results, for one-minute increase of lining up time, the water consumption decreases by around 8 liters. Considering access to Deep Tube Well (DTW) as a reference dummy, in OLR, the household under Pond Sand Filter (PSF), Shallow Tube Well (STW), Reverse Osmosis (RO) and Rainwater Harvester System (RWHS) are respectively 37 percent, 29 percent, 61 percent and 27 percent less likely to ensure year round access of water consumption. In line of health impact, different type of water born diseases like diarrhea, cholera, and typhoid are common among the coastal community caused by microbial impurities i.e., Bacteria, Protozoa. High turbidity and TDS in pond water caused by reduction of water depth, presence of suspended particle and inorganic salt stimulate the growth of bacteria, protozoa, and algae causes affecting health hazard. Meanwhile, excessive growth of Algae in pond water caused by excessive nitrate in drinking water adversely effects on child health. In lieu of ensuring access at SPHERE standard, we need to increase the number of water interventions at reasonable distance, preferably a half kilometer away from the dwelling place, ensuring community peoples involved with its installation process where collectively owned water intervention is found more effective than privately owned. In addition, a demand-responsive approach to supply of piped water should be adopted to allow consumer demand to guide investment in domestic water supply in future.

Keywords: access, impact, safe drinking water, Sphere standard, water interventions

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Authors: Raham El-Kahlout, Hadi Yassin, Asmaa Athani, Marwan Abou Madi, Gheyath Nasrallah

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Background: Since its first isolation in September 2012, Middle East respiratory syndrome coronavirus (MERS-CoV) has diffused across 27 countries infecting more than two thousand individuals with a high case fatality rate. MERS-CoV–specific antibodies are widely found in Dromedary camel along with viral shedding of similar viruses detected in human at same region, suggesting that MERS epidemiology may be central role by camel. Interestingly, MERS-CoV has also been also reported to be asymptomatic or to cause influenza-like mild illnesses. Therefore, in a country like Qatar (bordered Saudi Arabia), where camels are widely spread, serological surveys are important to explore the role of camels in MERS-CoV transmission. However, widespread strategic serological surveillances of MERS-CoV among populations, particularly in endemic country, are infrequent. In the absence of clear epidemiological view, cross-sectional MERS antibody surveillances in human populations are of global concern. Method: We performed a comparative serological screening of 4719 healthy blood donors, 135 baseline case contacts (high risk individual), and four MERS confirmed patients (by PCR) for the presence of anti-MERS IgG. Initially, samples were screened using Euroimmune anti- MERS-CoV IgG ELISA kit, the only commercial kit available in the market and recommended by the CDC as a screening kit. To confirm ELISA test results, farther serological testing was performed for all borderline and positive samples using two assays; the anti MERS-CoV IgG and IgM Euroimmune indirect immunofluorescent test (IIFT) and pseudoviral particle neutralizing assay (PPNA). Additionally, to test cross reactivity of anti-MERS-CoV antibody with other family members of coronavirus, borderline and positive samples were tested for the presence of the of IgG antibody of the following viruses; SARS, HCoV-229E, HKU1 using the Euroimmune IIFT for SARS and HCoV-229E and ELISA for HKU1. Results: In all of 4858 screened 15 samples [10 donors (0.21%, 10/4719), 1 case contact (0.77 %, 1/130), 3 patients (75%, 3/4)] anti-MERS IgG reactive/borderline samples were seen in ELISA. However, only 7 (0.14%) of them gave positive with in IIFT and only 3 (0.06%) was confirmed by the specific anti-MERS PPNA. One of the interesting findings was, a donor, who was selected in the control group as a negative anti-MERS IgG ELISA, yield reactive for anti-MERS IgM IIFT and was confirmed with the PPNA. Further, our preliminary results showed that there was a strong cross reactivity between anti- MERS-COV IgG with both HCoV-229E or anti-HKU1 IgG, yet, no cross reactivity of SARS were found. Conclusions: Our findings suggest that MERS-CoV is not heavily circulated among the population of Qatar and this is also indicated by low number of confirmed cases (only 18) since 2012. Additionally, the presence of antibody of other pathogenic human coronavirus may cause false positive results of both ELISA and IIFT, which stress the need for more evaluation studies for the available serological assays. Conclusion: this study provides an insight about the epidemiological view for MERS-CoV in Qatar population. It also provides a performance evaluation for the available serologic tests for MERS-CoV in a view of serologic status to other human coronaviruses.

Keywords: seroprevalence, MERS-CoV, healthy individuals, Qatar

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Authors: Ashleigh Williams

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Micro- and nanoplastics’ (MNLPs) omnipresence and ecological accumulation is evident when surveying recent environmental impact studies. For example, in 2014 it was estimated that at least 52.3 trillion plastic microparticles are floating at sea, and scientists have even found plastics present remote Arctic ice and snow (5,6). Plastics have even found their way into precipitation, with more than 1000 tons of microplastic rain precipitating onto the Western United States in 2020. Even more recent studies evaluating the chemical safety of reusable plastic bottles found that hundreds of chemicals leached into the control liquid in the bottle (ddH2O, ph = 7) during a 24-hour time period. A consequence of the increased abundance in plastic waste in the air, land, and water every year is the bioaccumulation of MNLPs in ecosystems and trophic niches of the animal food chain, which could potentially cause increased direct and indirect exposure of humans to MNLPs via inhalation, ingestion, and dermal contact. Though the detrimental, toxic effects of MNLPs have been established in marine biota, much less is known about the potentially hazardous health effects of chronic MNLP ingestion in humans. Recent data indicate that long-term exposure to MNLPs could cause possible inflammatory and dysbiotic effects. However, toxicity seems to be largely dose-, as well as size-dependent. In addition, the transcytotic uptake of MNLPs through the intestinal epithelia in humans remain relatively unknown. To this point, the goal of the current study was to investigate the mechanisms of micro- and nanoplastic uptake and transcytosis of Polystyrene (PE) in human stem-cell derived, physiologically relevant in vitro intestinal model systems, and to compare the relative effect of particle size (30 nm, 100 nm, 500 nm and 1 µm), and concentration (0 µg/mL, 250 µg/mL, 500 µg/mL, 1000 µg/mL) on polystyrene MNLP uptake, transcytosis and intestinal epithelial model integrity. Observational and quantitative data obtained from confocal microscopy, immunostaining, transepithelial electrical resistance (TEER) measurements, cryosectioning, and ELISA cytokine assays of the proinflammatory cytokines Interleukin-6 and Interleukin-8 were used to evaluate the localization and transcytosis of polystyrene MNPs and its impact on epithelial integrity in human-derived intestinal in vitro model systems. The effect of Microfold (M) cell induction on polystyrene micro- and nanoparticle (MNP) uptake, transcytosis, and potential inflammation was also assessed and compared to samples grown under standard conditions. Microfold (M) cells, link the human intestinal system to the immune system and are the primary cells in the epithelium responsible for sampling and transporting foreign matter of interest from the lumen of the gut to underlying immune cells. Given the uptake capabilities of Microfold cells to interact both specifically and nonspecific to abiotic and biotic materials, it was expected that M- cell induced in vitro samples would have increased binding, localization, and potentially transcytosis of Polystyrene MNLPs across the epithelial barrier. Experimental results of this study would not only help in the evaluation of the plastic toxicity, but would allow for more detailed modeling of gut inflammation and the intestinal immune system.

Keywords: nanoplastics, enteroids, intestinal barrier, tissue engineering, microfold (M) cells

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Authors: Sarah Fitzpatrick, Hossein Zare-Behtash, Konstantinos Kontis

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Traditionally, the focus of horizontal axis wind turbine (HAWT) blade aerodynamic optimisation studies has been the outer working region of the blade. However, recent works seek to better understand, and thus improve upon, the performance of the inboard blade region to enhance power production, maximise load reduction and better control the wake behaviour. This paper presents the design considerations and characterisation of a wind turbine wind tunnel model devised to further the understanding and fundamental definition of horizontal axis wind turbine root vortex shedding and interactions. Additionally, the application of passive and active flow control mechanisms – vortex generators and plasma actuators – to allow for the manipulation and mitigation of unsteady aerodynamic behaviour at the blade inboard section is investigated. A static, modular blade wind turbine model has been developed for use in the University of Glasgow’s de Havilland closed return, low-speed wind tunnel. The model components - which comprise of a half span blade, hub, nacelle and tower - are scaled using the equivalent full span radius, R, for appropriate Mach and Strouhal numbers, and to achieve a Reynolds number in the range of 1.7x105 to 5.1x105 for operational speeds up to 55m/s. The half blade is constructed to be modular and fully dielectric, allowing for the integration of flow control mechanisms with a focus on plasma actuators. Investigations of root vortex shedding and the subsequent wake characteristics using qualitative – smoke visualisation, tufts and china clay flow – and quantitative methods – including particle image velocimetry (PIV), hot wire anemometry (HWA), and laser Doppler anemometry (LDA) – were conducted over a range of blade pitch angles 0 to 15 degrees, and Reynolds numbers. This allowed for the identification of shed vortical structures from the maximum chord position, the transitional region where the blade aerofoil blends into a cylindrical joint, and the blade nacelle connection. Analysis of the trailing vorticity interactions between the wake core and freestream shows the vortex meander and diffusion is notably affected by the Reynold’s number. It is hypothesized that the shed vorticity from the blade root region directly influences and exacerbates the nacelle wake expansion in the downstream direction. As the design of inboard blade region form is, by necessity, driven by function rather than aerodynamic optimisation, a study is undertaken for the application of flow control mechanisms to manipulate the observed vortex phenomenon. The designed model allows for the effective investigation of shed vorticity and wake interactions with a focus on the accurate geometry of a root region which is representative of small to medium power commercial HAWTs. The studies undertaken allow for an enhanced understanding of the interplay of shed vortices and their subsequent effect in the near and far wake. This highlights areas of interest within the inboard blade area for the potential use of passive and active flow control devices which contrive to produce a more desirable wake quality in this region.

Keywords: vortex shedding, wake interactions, wind tunnel model, wind turbine

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Authors: Dagmara Malina, Katarzyna Bialik-Wąs, Klaudia Pluta

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The growing significance of transdermal systems, in which skin is a route for systemic drug delivery, has generated a considerable amount of data which has resulted in a deeper understanding of the mechanisms of transport across the skin in the context of the controlled and prolonged release of active substances. One of such solutions may be the use of carrier systems based on intelligent polymers with different physicochemical properties. In these systems, active substances, e.g. drugs, can be conjugated (attached), immobilized, or encapsulated in a polymer matrix that is sensitive to specific environmental conditions (e.g. pH or temperature changes). Intelligent polymers can be divided according to their sensitivity to specific environmental stimuli such as temperature, pH, light, electric, magnetic, sound, or electromagnetic fields. Materials & methods—The first stage of the presented research concerned the synthesis of pH-sensitive polymeric carriers by a radical polymerization reaction. Then, the selected active substance (hydrocortisone) was introduced into polymeric carriers. In a further stage, bio-hybrid sodium alginate/poly(vinyl alcohol) – SA/PVA-based hydrogel matrices modified with various carrier-drug systems were prepared with the chemical cross-linking method. The conducted research included the assessment of physicochemical properties of obtained materials i.e. degree of hydrogel swelling and degradation studies as a function of pH in distilled water and phosphate-buffered saline (PBS) at 37°C in time. The gel fraction represents the insoluble gel fraction as a result of inter-molecule cross-linking formation was also measured. Additionally, the chemical structure of obtained hydrogels was confirmed using FT-IR spectroscopic technique. The dynamic light scattering (DLS) technique was used for the analysis of the average particle size of polymer-carriers and carrier-drug systems. The nanocarriers morphology was observed using SEM microscopy. Results & Discussion—The analysis of the encapsulated polymeric carriers showed that it was possible to obtain the time-stable empty pH-sensitive carrier with an average size 479 nm and the encapsulated system containing hydrocortisone with an average 543 nm, which was introduced into hydrogel structure. Bio-hybrid hydrogel matrices are stable materials, and the presence of an additional component: pH-sensitive carrier – hydrocortisone system, does not reduce the degree of cross-linking of the matrix nor its swelling ability. Moreover, the results of swelling tests indicate that systems containing higher concentrations of the drug have a slightly higher sorption capacity in each of the media used. All analyzed materials show stable and statically changing swelling values in simulated body fluids - there is no sudden fluid uptake and no rapid release from the material. The analysis of FT-IR spectra confirms the chemical structure of the obtained bio-hybrid hydrogel matrices. In the case of modifications with a pH-sensitive carrier, a much more intense band can be observed in the 3200-3500 cm⁻¹ range, which most likely originates from the strong hydrogen interactions that occur between individual components.

Keywords: hydrogels, polymer nanocarriers, sodium alginate/poly(vinyl alcohol) matrices, wound dressings.

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Authors: Niharika Kaushal, Minni Singh

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Citrus fruits fall into the category of those commercially grown fruits that constitute an excellent repository of phytochemicals with health-promoting properties. Fruits belonging to the citrus family, when processed by industries, produce tons of agriculture by-products in the form of peels, pulp, and seeds, which normally have no further usage and are commonly discarded. In spite of this, such residues are of paramount importance due to their richness in valuable compounds; therefore, agro-waste is considered a valuable bioresource for various purposes in the food sector. A range of biological properties, including anti-oxidative, anti-cancerous, anti-inflammatory, anti-allergenicity, and anti-aging activity, have been reported for these bioactive compounds. Taking advantage of these inexpensive residual sources requires special attention to extract bioactive compounds. Mandarin (Citrus nobilis X Citrus deliciosa) is a potential source of bioflavonoids with antioxidant properties, and it is increasingly regarded as a functional food. Despite these benefits, flavonoids suffer from a barrier of pre-systemic metabolism in gastric fluid, which impedes their effectiveness. Therefore, colloidal delivery systems can completely overcome the barrier in question. This study involved the extraction and identification of key flavonoids from mandarin biomass. Using a green chemistry approach, supercritical fluid extraction at 330 bar, temperature 40C, and co-solvent 10% ethanol was employed for extraction, and the identification of flavonoids was made by mass spectrometry. As flavonoids are concerned with a limitation, the obtained extract was encapsulated in polylactic-co-glycolic acid (PLGA) matrix using a solvent evaporation method. Additionally, the antioxidant potential was evaluated by the 2,2-diphenylpicrylhydrazyl (DPPH) assay. A release pattern of flavonoids was observed over time using simulated gastrointestinal fluids. From the results, it was observed that the total flavonoids extracted from the mandarin biomass were estimated to be 47.3 ±1.06 mg/ml rutin equivalents as total flavonoids. In the extract, significantly, polymethoxyflavones (PMFs), tangeretin and nobiletin were identified, followed by hesperetin and naringin. The designed flavonoid-PLGA nanoparticles exhibited a particle size between 200-250nm. In addition, the bioengineered nanoparticles had a high entrapment efficiency of nearly 80.0% and maintained stability for more than a year. Flavonoid nanoparticles showed excellent antioxidant activity with an IC50 of 0.55μg/ml. Morphological studies revealed the smooth and spherical shape of nanoparticles as visualized by Field emission scanning electron microscopy (FE-SEM). Simulated gastrointestinal studies of free extract and nanoencapsulation revealed the degradation of nearly half of the flavonoids under harsh acidic conditions in the case of free extract. After encapsulation, flavonoids exhibited sustained release properties, suggesting that polymeric encapsulates are efficient carriers of flavonoids. Thus, such technology-driven and biomass-derived products form the basis for their use in the development of functional foods with improved therapeutic potential and antioxidant properties. As a result, citrus processing waste can be considered a new resource that has high value and can be used for promoting its utilization.

Keywords: citrus, agrowaste, flavonoids, nanoparticles

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Authors: Marian Mihalik, Kornel Csach, Martin Kovalik, Matúš Mihalik, Martina Kubovčíková, Maria Zentková, Martin Vavra, Vladimír Girman, Jaroslav Briančin, Marija Perovic, Marija Boškovic, Magdalena Fitta, Robert Pelka

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Current nanomaterials for use in biomedicine are based mainly on iron oxides and on present knowledge on magnetic nanostructures. Manganites can represent another material which can be used optionally. Manganites and their unique electronic properties have been extensively studied in the last decades not only due to fundamental interest but to possible applications of colossal magnetoresistance, magnetocaloric effect, and ferroelectric properties. It was found that the oxygen-reduction reaction on perovskite oxide is intimately connected with metal ion e.g., orbital occupation. The effect of oxygen deviation from the stoichiometric composition on crystal structure was studied very carefully by many authors on LaMnO₃. Depending on oxygen content, the crystal structure changes from orthorhombic one to rhombohedric for oxygen content 3.1. In the case of hole-doped manganites, the change from the orthorhombic crystal structure, which is typical for La1-xCaxMnO3 based manganites, to the rhombohedric crystal structure (La1-xMxMnO₃ where M = K, Ag, and Sr based materials) results in an enormous increase of the Curie temperature. In our paper, we study the effect of oxygen content on crystal structure, thermal, and magnetic properties (including magnetocaloric effect) of La1-xAgxMnO₃nano particle system. The content of oxygen in samples was tuned by heat treatment in different thermal regimes and in various environment (air, oxygen, argon). Water nanosuspensions based on La0.80Ag0.15MnO₃ magnetic particles with the Curie temperature of about 43oC were prepared by two different approaches. First, by using a laboratory circulation mill for milling of powder in the presence of sodium dodecyl sulphate (SDS) and subsequent centrifugation. Second nanosuspension was prepared using an agate bowl, etching in citric acid and HNO3, ultrasound homogeniser, centrifugation, and dextran 40 kDA or 15 kDA as surfactant. Electrostatic stabilisation obtained by the first approach did not offer long term kinetic and aggregation colloidal stability and was unable to compensate for attractive forces between particles under a magnetic field. By the second approach, we prepared suspension oversaturated by dextran 40 kDA for steric stabilisation, with evidence of the presence of superparamagnetic behaviour. Low concentration of nanoparticles and not ideal coverage of nanoparticles impacting the stability of ferrofluids was the disadvantage of this approach. Strong steric stabilisation was observable at alcaic conditions under pH = ~10. Application of dextran 15 kDA leads to relatively stable ferrofluid with pH around physiological conditions, but desegregation of powder by HNO₃ was not effective enough, and the average size of fragments was to large of about 150 nm, and we did not see any signature of superparamagnetic behaviour. The prepared ferrofluids were characterised by scanning and transition microscope method, thermogravimetry, magnetization, and AC susceptibility measurements. Specific Absorption Rate measurements were undertaken on powder as well on ferrofluids in order to estimate the potential application of La₀.₈₀Ag₀.₁₅MnO₃ magnetic particles based ferrofluid for hyperthermia. Our complex study contains an investigation of biocompatibility and potential biohazard of this material.

Keywords: manganites, magnetic nanoparticles, oxygen content, magnetic phase transition, magnetocaloric effect, ferrofluid, hyperthermia

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Authors: Atabaev I. G., Fayziev Sh. A., Irmatova Sh. K.

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Raw materials with high content of Kalium oxide widely used in ceramic technology for prevention or decreasing of deformation of ceramic goods during drying process and under thermal annealing. Becouse to low melting temperature it is also used to decreasing of the temperature of thermal annealing during fabrication of ceramic goods [1,2]. So called “Porceline or China stones” - quartz-sericite (muscovite) minerals is also can be used for prevention of deformation as the content of Kalium oxide in muscovite is rather high (SiO2, + KAl2[AlSi3O10](OH)2). [3] . To estimation of possibility of use of this mineral for ceramic manufacture, in the presented article the influence of thermal processing on phase and a chemical content of this raw material is investigated. As well as to other ceramic raw materials (kaoline, white burning clays) the basic requirements of the industry to quality of "a porcelain stone» are following: small size of particles, relative high uniformity of disrtribution of components and phase, white color after burning, small content of colorant oxides or chromophores (Fe2O3, FeO, TiO2, etc) [4,5]. In the presented work natural minerale from the Boynaksay deposit (Uzbekistan) is investigated. The samples was mechanically polished for investigation by Scanning Electron Microscope. Powder with size of particle up to 63 μm was used to X-ray diffractometry and chemical analysis. The annealing of samples was performed at 900, 1120, 1350oC during 1 hour. Chemical composition of Boynaksay raw material according to chemical analysis presented in the table 1. For comparison the composition of raw materials from Russia and USA are also presented. In the Boynaksay quartz – sericite the average parity of quartz and sericite makes 55-60 and 30-35 % accordingly. The distribution of quartz and sericite phases in raw material was investigated using electron probe scanning electronic microscope «JEOL» JXA-8800R. In the figure 1 the scanning electron microscope (SEM) micrograps of the surface and the distributions of Al, Si and K atoms in the sample are presented. As it seen small granular, white and dense mineral includes quartz, sericite and small content of impurity minerals. Basically, crystals of quartz have the sizes from 80 up to 500 μm. Between quartz crystals the sericite inclusions having a tablet form with radiant structure are located. The size of sericite crystals is ~ 40-250 μm. Using data on interplanar distance [6,7] and ASTM Powder X-ray Diffraction Data it is shown that natural «a porcelain stone» quartz – sericite consists the quartz SiO2, sericite (muscovite type) KAl2[AlSi3O10](OH)2 and kaolinite Al203SiO22Н2О (See Figure 2 and Table 2). As it seen in the figure 3 and table 3a after annealing at 900oC the quartz – sericite contains quartz – SiO2 and muscovite - KAl2[AlSi3O10](OH)2, the peaks related with Kaolinite are absent. After annealing at 1120oC the full disintegration of muscovite and formation of mullite phase Al203 SiO2 is observed (the weak peaks of mullite appears in fig 3b and table 3b). After annealing at 1350oC the samples contains crystal phase of quartz and mullite (figure 3c and table 3с). Well known Mullite gives to ceramics high density, abrasive and chemical stability. Thus the obtained experimental data on formation of various phases during thermal annealing can be used for development of fabrication technology of advanced materials. Conclusion: The influence of thermal annealing in the interval 900-1350oC on phase composition and structure of quartz-sericite minerale is investigated. It is shown that during annealing the phase content of raw material is changed. After annealing at 1350oC the samples contains crystal phase of quartz and mullite (which gives gives to ceramics high density, abrasive and chemical stability).

Keywords: quartz-sericite, kaolinite, mullite, thermal processing

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Authors: Amandeep Thakur, Yi-Hsuan Chu, Chun-Hsu Pan, Kunal Nepali

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The transfer of ADP-ribose residues onto target substrates from nicotinamide adenine dinucleotide (NAD) (PARylation) is catalyzed by Poly (ADP-ribose) polymerases (PARPs). Amongst the PARP family members, the DNA damage response in cancer is majorly regulated by PARP1 and PARP2. The blockade of DNA repair by PARP inhibitors leads to the progression of DNA single-strand breaks (induced by some triggering factors) to double-strand breaks. Notably, PARP inhibitors are remarkably effective in cancers with defective homologous recombination repair (HRR). In particular, cancer cells with BRCA mutations are responsive to therapy with PARP inhibitors. The aforementioned requirement for PARP inhibitors to be effective confers a narrow activity spectrum to PARP inhibitors, which hinders their clinical applicability. Thus, the quest to expand the application horizons of PARP inhibitors beyond BRCA mutations is the need of the hour. Literature precedents reveal that HDAC inhibition induces BRCAness in cancer cells and can broaden the therapeutic scope of PARP inhibitors. Driven by such disclosures, dual inhibitors targeting both PARP and HDAC enzymes were designed by our research group to extend the efficacy of PARP inhibitors beyond BRCA-mutated cancers to cancers with induced BRCAness. The design strategy involved the installation of Veliparib, an investigational PARP inhibitor, as a surface recognition part in the HDAC inhibitor pharmacophore model. The chemical architecture of veliparib was deemed appropriate as a starting point for the generation of dual inhibitors by virtue of its size and structural flexibility. A validatory docking study was conducted at the outset to predict the binding mode of the designed dual modulatory chemical architectures. Subsequently, the designed chemical architectures were synthesized via a multistep synthetic route and evaluated for antitumor efficacy. Delightfully, one compound manifested impressive anti-leukemic effects (HL-60 cell lines) mediated via dual inhibition of PARP and class I HDACs. The outcome of the western blot analysis revealed that the compound could downregulate the expression levels of PARP1 and PARP2 and the HDAC isoforms (HDAC1, 2, and 3). Also, the dual PARP-HDAC inhibitor upregulated the protein expression of the acetyl histone H3, confirming its abrogation potential for class I HDACs. In addition, the dual modulator could arrest the cell cycle at the G0/G1 phase and induce autophagy. Further, polymer-based nanoformulation of the dual inhibitor was furnished to afford targeted delivery of the dual inhibitor at the cancer site. Transmission electron microscopy (TEM) results indicate that the nanoparticles were monodispersed and spherical. Moreover, the polymeric nanoformulation exhibited an appropriate particle size. Delightfully, pH-sensitive behavior was manifested by the polymeric nanoformulation that led to selective antitumor effects towards the HL-60 cell lines. In light of the magnificent anti-leukemic profile of the identified dual PARP-HDAC inhibitor, in-vivo studies (pharmacokinetics and pharmacodynamics) are currently being conducted. Notably, the optimistic findings of the aforementioned study have spurred our research group to initiate several medicinal chemistry campaigns to create bifunctional small molecule inhibitors addressing PARP as the primary target.

Keywords: PARP inhibitors, HDAC inhibitors, BRCA mutations, leukemia

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Authors: Sophio Kobauri, Temur Kantaria, Nina Kulikova, David Tugushi, Ramaz Katsarava

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Polymeric nanoparticles-based drug delivery systems and therapeutics have a great potential in the treatment of a numerous diseases, due to they are characterizing the flexible properties which is giving possibility to modify their structures with a complex definition over their structures, compositions and properties. Important characteristics of the polymeric nanoparticles (PNPs) used as drug carriers are high particle’s stability, high carrier capacity, feasibility of encapsulation of both hydrophilic and hydrophobic drugs, and feasibility of variable routes of administration, including oral application and inhalation; NPs are especially effective for intracellular drug delivery since they penetrate into the cells’ interior though endocytosis. A variety of PNPs based drug delivery systems including charged and neutral, degradable and non-degradable polymers of both natural and synthetic origin have been developed. Among these huge varieties the biodegradable PNPs which can be cleared from the body after the fulfillment of their function could be considered as one of the most promising. For intracellular uptake it is highly desirable to have positively charged PNPs since they can penetrate deep into cell membranes. For long-lasting circulation of PNPs in the body it is important they have so called “stealth coatings” to protect them from the attack of immune system of the organism. One of the effective ways to render the PNPs “invisible” for immune system is their PEGylation which represent the process of pretreatment of polyethylene glycol (PEG) on the surface of PNPs. The present work deals with constructing PNPs from amino acid based biodegradable polymers – regular poly(ester amide) (PEA) composed of sebacic acid, leucine and 1,6-hexandiol (labeled as 8L6), cationic PEA composed of sebacic acid, arginine and 1,6-hexandiol (labeled as 8R6), and comb-like co-PEA composed of sebacic acid, malic acid, leucine and 1,6-hexandiol (labeled as PEG-PEA). The PNPs were fabricated using the polymer deposition/solvent displacement (nanoprecipitation) method. The regular PEA 8L6 form stable negatively charged (zeta-potential within 2-12 mV) PNPs of desired size (within 150-200 nm) in the presence of various surfactants (Tween 20, Tween 80, Brij 010, etc.). Blending the PEAs 8L6 and 8R6 gave the 130-140 nm sized positively charged PNPs having zeta-potential within +20 ÷ +28 mV depending 8L6/8R6 ratio. The PEGylating PEA PEG-PEA was synthesized by interaction of epoxy-co-PEA [8L6]0,5-[tES-L6]0,5 with mPEG-amine-2000 The stable and positively charged PNPs were fabricated using pure PEG-PEA as a surfactant. A firm anchoring of the PEG-PEA with 8L6/8R6 based PNPs (owing to a high afinity of the backbones of all three PEAs) provided good stabilization of the NPs. In vitro biocompatibility study of the new PNPs with four different stable cell lines: A549 (human), U-937 (human), RAW264.7 (murine), Hepa 1-6 (murine) showed they are biocompatible. Considering high stability and cell compatibility of the elaborated PNPs one can conclude that they are promising for subsequent therapeutic applications. This work was supported by the joint grant from the Science and Technology Center in Ukraine and Shota Rustaveli National Science Foundation of Georgia #6298 “New biodegradable cationic polymers composed of arginine and spermine-versatile biomaterials for various biomedical applications”.

Keywords: biodegradable poly(ester amide)s, cationic poly(ester amide), pegylating poly(ester amide), nanoparticles

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Authors: Farideh Namvar, Rosfarizan Mohamed

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In the field of nanotechnology, the use of various biological units instead of toxic chemicals for the reduction and stabilization of nanoparticles, has received extensive attention. This use of biological entities to create nanoparticles has designated as “Green” synthesis and it is considered to be far more beneficial due to being economical, eco-friendly and applicable for large-scale synthesis as it operates on low pressure, less input of energy and low temperatures. The lack of toxic byproducts and consequent decrease in degradation of the product renders this technique more preferable over physical and classical chemical methods. The variety of biomass having reduction properties to produce nanoparticles makes them an ideal candidate for fabrication. Metal oxide nanoparticles have been said to represent a "fundamental cornerstone of nanoscience and nanotechnology" due to their variety of properties and potential applications. However, this also provides evidence of the fact that metal oxides include many diverse types of nanoparticles with large differences in chemical composition and behaviour. In this study, iron oxide nanoparticles (Fe3O4-NPs) were synthesized using a rapid, single step and completely green biosynthetic method by reduction of ferric chloride solution with brown seaweed (Sargassum muticum) water extract containing polysaccharides as a main factor which acts as reducing agent and efficient stabilizer. Antimicrobial activity against six microorganisms was tested using well diffusion method. The resulting S-IONPs are crystalline in nature, with a cubic shape. The average particle diameter, as determined by TEM, was found to be 18.01 nm. The S-IONPs were efficiently inhibited the growth of Listeria monocytogenes, Escherichia coli and Candida species. Our favorable results suggest that S-IONPs could be a promising candidate for development of future antimicrobial therapies. The nature of biosynthesis and the therapeutic potential by S-IONPs could pave the way for further research on design of green synthesis therapeutic agents, particularly nanomedicine, to deal with treatment of infections. Further studies are needed to fully characterize the toxicity and the mechanisms involved with the antimicrobial activity of these particles. Antioxidant activity of S-IONPs synthesized by green method was measured by ABTS (2, 2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) (IC50= 1000µg) radical scavenging activity. Also, with the increasing concentration of S-IONPs, catalase gene expression compared to control gene GAPDH increased. For anti-angiogenesis study the Ross fertilized eggs were divided into four groups; the control and three experimental groups. The gelatin sponges containing albumin were placed on the chorioalantoic membrane and soaked with different concentrations of S-IONPs. All the cases were photographed using a photo stereomicroscope. The number and the lengths of the vessels were measured using Image J software. The crown rump (CR) and weight of the embryo were also recorded. According to the data analysis, the number and length of the blood vessels, as well as the CR and weight of the embryos reduced significantly compared to the control (p < 0.05), dose dependently. The total hemoglobin was quantified as an indicator of the blood vessel formation, and in the treated samples decreased, which showed its inhibitory effect on angiogenesis.

Keywords: anti-angiogenesis, antimicrobial, antioxidant, biosynthesis, iron oxide (fe3o4) nanoparticles, sargassum muticum, seaweed

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Authors: Juergen Orasche, Vesta Kohlmeier, George C. Dragan, Gert Jakobi, Patricia Forbes, Ralf Zimmermann

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Underground mining poses a difficult environment for both man and machines. At more than 1000 meters underneath the surface of the earth, ores and other mineral resources are still gained by conventional and motorised mining. Adding to the hazards caused by blasting and stone-chipping, the working conditions are best described by the high temperatures of 35-40°C and high humidity, at low air exchange rates. Separate ventilation shafts lead fresh air into a mine and others lead expended air back to the surface. This is essential for humans and machines working deep underground. Nevertheless, mines are widely ramified. Thus the air flow rate at the far end of a tunnel is sensed to be close to zero. In recent years, conventional mining was supplemented by mining with heavy diesel machines. These very flat machines called Load Haul Dump (LHD) vehicles accelerate and ease work in areas favourable for heavy machines. On the other hand, they emit non-filtered diesel exhaust, which constitutes an occupational hazard for the miners. Combined with a low air exchange, high humidity and inorganic dust from the mining it leads to 'black smog' underneath the earth. This work focuses on the air quality in mines employing LHDs. Therefore we performed personal sampling (samplers worn by miners during their work), stationary sampling and aethalometer (Microaeth MA200, Aethlabs) measurements in a platinum mine in around 1000 meters under the earth’s surface. We compared areas of high diesel exhaust emission with areas of conventional mining where no diesel machines were operated. For a better assessment of health risks caused by air pollution we applied a separated gas-/particle-sampling tool (or system), with first denuder section collecting intermediate VOCs. These multi-channel silicone rubber denuders are able to trap IVOCs while allowing particles ranged from 10 nm to 1 µm in diameter to be transmitted with an efficiency of nearly 100%. The second section is represented by a quartz fibre filter collecting particles and adsorbed semi-volatile organic compounds (SVOC). The third part is a graphitized carbon black adsorber – collecting the SVOCs that evaporate from the filter. The compounds collected on these three sections were analyzed in our labs with different thermal desorption techniques coupled with gas chromatography and mass spectrometry (GC-MS). VOCs and IVOCs were measured with a Shimadzu Thermal Desorption Unit (TD20, Shimadzu, Japan) coupled to a GCMS-System QP 2010 Ultra with a quadrupole mass spectrometer (Shimadzu). The GC was equipped with a 30m, BP-20 wax column (0.25mm ID, 0.25µm film) from SGE (Australia). Filters were analyzed with In-situ derivatization thermal desorption gas chromatography time-of-flight-mass spectrometry (IDTD-GC-TOF-MS). The IDTD unit is a modified GL sciences Optic 3 system (GL Sciences, Netherlands). The results showed black carbon concentrations measured with the portable aethalometers up to several mg per m³. The organic chemistry was dominated by very high concentrations of alkanes. Typical diesel engine exhaust markers like alkylated polycyclic aromatic hydrocarbons were detected as well as typical lubrication oil markers like hopanes.

Keywords: diesel emission, personal sampling, aethalometer, mining

Procedia PDF Downloads 157

Authors: Nino Kupatadze, Tamar Memanishvili, Natia Ochkhikidze, David Tugushi, Zaal Kokaia, Ramaz Katsarava

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Amino acid-based Biodegradable poly(ester-amide)s (PEAs) have gained considerable interest as a promising materials for numerous biomedical applications. These polymers reveal a high biocompatibility and easily form small particles suitable for delivery various biological, as well as elastic bio-erodible films serving as matrices for constructing antibacterial coatings. In the present work we have demonstrated a potential of the PEAs for two applications: 1. cell therapy for stroke as vehicles for delivery and sustained release of growth factors, 2. bactericidal coating as prevention biofilm and applicable in infected wound management. Stroke remains the main cause of adult disability with limited treatment options. Although stem cell therapy is a promising strategy, it still requires improvement of cell survival, differentiation and tissue modulation. .Recently, microspheres (MPs) made of biodegradable polymers have gained significant attention for providing necessary support of transplanted cells. To investigate this strategy in the cell therapy of stroke, MPs loaded with transcription factors Wnt3A/BMP4 were prepared. These proteins have been shown to mediate the maturation of the cortical neurons. We have suggested that implantation of these materials could create a suitable microenvironment for implanted cells. Particles with spherical shape, porous surface, and 5-40 m in size (monitored by scanning electron microscopy) were made on the basis of the original PEA composed of adipic acid, L-phenylalanine and 1,4-butanediol. After 4 months transplantation of MPs in rodent brain, no inflammation was observed. Additionally, factors were successfully released from MPs and affected neuronal cell differentiation in in vitro. The in vivo study using loaded MPs is in progress. Another severe problem in biomedicine is prevention of surgical devices from biofilm formation. Antimicrobial polymeric coatings are most effective “shields” to protect surfaces/devices from biofilm formation. Among matrices for constructing the coatings preference should be given to bio-erodible polymers. Such types of coatings will play a role of “unstable seating” that will not allow bacteria to occupy the surface. In other words, bio-erodible coatings would be discomfort shelter for bacteria that along with releasing “killers of bacteria” should prevent the formation of biofilm. For this purpose, we selected an original biodegradable PEA composed of L-leucine, 1,6-hexanediol and sebacic acid as a bio-erodible matrix, and nanosilver (AgNPs) as a bactericidal agent (“killer of bacteria”). Such nanocomposite material is also promising in treatment of superficial wound and ulcer. The solubility of the PEA in ethanol allows to reduce AgNO3 to NPs directly in the solution, where the solvent served as a reductive agent, and the PEA served as NPs stabilizer. The photochemical reduction was selected as a basic method to form NPs. The obtained AgNPs were characterized by UV-spectroscopy, transmission electron microscope (TEM), and dynamic light scattering (DLS). According to the UV-data and TEM data the photochemical reduction resulted in spherical AgNPs with wide particle size distribution with a high contribution of the particles below 10 nm that are known as responsible for bactericidal activity of AgNPs. DLS study showed that average size of nanoparticles formed after photo-reduction in ethanol solution ranged within ca. 50 nm.

Keywords: biodegradable polymers, microparticles, nanocomposites, stem cell therapy, stroke

Procedia PDF Downloads 395

Authors: Sireetorn Kuharat, Anwar Beg

Abstract:

Motivation- Solar energy constitutes the most promising renewable energy source on earth. Nanofluids are a very successful family of engineered fluids, which contain well-dispersed nanoparticles suspended in a stable base fluid. The presence of metallic nanoparticles (e.g. gold, silver, copper, aluminum etc) significantly improves the thermo-physical properties of the host fluid and generally results in a considerable boost in thermal conductivity, density, and viscosity of nanofluid compared with the original base (host) fluid. This modification in fundamental thermal properties has profound implications in influencing the convective heat transfer process in solar collectors. The potential for improving solar collector direct absorber efficiency is immense and to gain a deeper insight into the impact of different metallic nanoparticles on efficiency and temperature enhancement, in the present work, we describe recent computational fluid dynamics simulations of an annular solar collector system. The present work studies several different metallic nano-particles and compares their performance. Methodologies- A numerical study of convective heat transfer in an annular pipe solar collector system is conducted. The inner tube contains pure water and the annular region contains nanofluid. Three-dimensional steady-state incompressible laminar flow comprising water- (and other) based nanofluid containing a variety of metallic nanoparticles (copper oxide, aluminum oxide, and titanium oxide nanoparticles) is examined. The Tiwari-Das model is deployed for which thermal conductivity, specific heat capacity and viscosity of the nanofluid suspensions is evaluated as a function of solid nano-particle volume fraction. Radiative heat transfer is also incorporated using the ANSYS solar flux and Rosseland radiative models. The ANSYS FLUENT finite volume code (version 18.1) is employed to simulate the thermo-fluid characteristics via the SIMPLE algorithm. Mesh-independence tests are conducted. Validation of the simulations is also performed with a computational Harlow-Welch MAC (Marker and Cell) finite difference method and excellent correlation achieved. The influence of volume fraction on temperature, velocity, pressure contours is computed and visualized. Main findings- The best overall performance is achieved with copper oxide nanoparticles. Thermal enhancement is generally maximized when water is utilized as the base fluid, although in certain cases ethylene glycol also performs very efficiently. Increasing nanoparticle solid volume fraction elevates temperatures although the effects are less prominent in aluminum and titanium oxide nanofluids. Significant improvement in temperature distributions is achieved with copper oxide nanofluid and this is attributed to the superior thermal conductivity of copper compared to other metallic nano-particles studied. Important fluid dynamic characteristics are also visualized including circulation and temperature shoots near the upper region of the annulus. Radiative flux is observed to enhance temperatures significantly via energization of the nanofluid although again the best elevation in performance is attained consistently with copper oxide. Conclusions-The current study generalizes previous investigations by considering multiple metallic nano-particles and furthermore provides a good benchmark against which to calibrate experimental tests on a new solar collector configuration currently being designed at Salford University. Important insights into the thermal conductivity and viscosity with metallic nano-particles is also provided in detail. The analysis is also extendable to other metallic nano-particles including gold and zinc.

Keywords: heat transfer, annular nanofluid solar collector, ANSYS FLUENT, metallic nanoparticles

Procedia PDF Downloads 143