Search results for: nitrogen concentration
56 Photobleaching Kinetics and Epithelial Distribution of Hexylaminoleuilinate Induced PpIX in Rat Bladder Cancer
Authors: Sami El Khatib, Agnès Leroux, Jean-Louis Merlin, François Guillemin, Marie-Ange D’Hallewin
Abstract:
Photodynamic therapy (PDT) is a treatment modality based on the cytotoxic effect occurring on the target tissues by interaction of a photosensitizer with light in the presence of oxygen. One of the major advances in PDT can be attributed to the use of topical aminolevulinic (ALA) to induce Protoporphyrin IX (PpIX) for the treatment of early stage cancers as well as diagnosis. ALA is a precursor of the heme synthesis pathway. Locally delivered to the target tissue ALA overcomes the negative feedback exerted by heme and promotes the transient formation of PpIX in situ to reach critical effective levels in cells and tissue. Whereas early steps of the heme pathway occur in the cytosol, PpIX synthesis is shown to be held in the mitochondrial membranes and PpIX fluorescence is expected to accumulate in close vicinity of the initial building site and to progressively diffuse to the neighboring cytoplasmic compartment or other lipophylic organelles. PpIX is known to be highly reactive and will be degraded when irradiated with light. PpIX photobleaching is believed to be governed by a singlet oxygen mediated mechanism in the presence of oxidized amino acids and proteins. PpIX photobleaching and subsequent spectral phototransformation were described widely in tumor cells incubated in vitro with ALA solution, or ex vivo in human and porcine mucosa superfused with hexylaminolevulinate (hALA). PpIX photobleaching was also studied in vivo, using animal models such as normal or tumor mice skin and orthotopic rat bladder model. Hexyl aminolevulinate a more potent lipophilic derivative of ALA was proposed as an adjunct to standard cystoscopy in the fluorescence diagnosis of bladder cancer and other malignancies. We have previously reported the effectiveness of hALA mediated PDT of rat bladder cancer. Although normal and tumor bladder epithelium exhibit similar fluorescence intensities after intravesical instillation of two hALA concentrations (8 and 16 mM), the therapeutic response at 8mM and 20J/cm2 was completely different from the one observed at 16mM irradiated with the same light dose. Where the tumor is destroyed, leaving the underlying submucosa and muscle intact after an 8 mM instillation, 16mM sensitization and subsequent illumination results in the complete destruction of the underlying bladder wall but leaves the tumor undamaged. The object of the current study is to try to unravel the underlying mechanism for this apparent contradiction. PpIX extraction showed identical amounts of photosensitizer in tumor bearing bladders at both concentrations. Photobleaching experiments revealed mono-exponential decay curves in both situations but with a two times faster decay constant in case of 16mM bladders. Fluorescence microscopy shows an identical fluorescence pattern for normal bladders at both concentrations and tumor bladders at 8mM with bright spots. Tumor bladders at 16 mM exhibit a more diffuse cytoplasmic fluorescence distribution. The different response to PDT with regard to the initial pro-drug concentration can thus be attributed to the different cellular localization.Keywords: bladder cancer, hexyl-aminolevulinate, photobleaching, confocal fluorescence microscopy
Procedia PDF Downloads 40055 Metabolic Changes during Reprogramming of Wheat and Triticale Microspores
Authors: Natalia Hordynska, Magdalena Szechynska-Hebda, Miroslaw Sobczak, Elzbieta Rozanska, Joanna Troczynska, Zofia Banaszak, Maria Wedzony
Abstract:
Albinism is a common problem encountered in wheat and triticale breeding programs, which require in vitro culture steps e.g. generation of doubled haploids via androgenesis process. Genetic factor is a major determinant of albinism, however, environmental conditions such as temperature and media composition influence the frequency of albino plant formation. Cold incubation of wheat and triticale spikes induced a switch from gametophytic to sporophytic development. Further, androgenic structures formed from anthers of the genotypes susceptible to androgenesis or treated with cold stress, had a pool of structurally primitive plastids, with small starch granules or swollen thylakoids. High temperature was a factor inducing andro-genesis of wheat and triticale, but at the same time, it was a factor favoring the formation of albino plants. In genotypes susceptible to albinism or after heat stress conditions, cells formed from anthers were vacuolated, and plastids were eliminated. Partial or complete loss of chlorophyll pigments and incomplete differentiation of chloroplast membranes result in formation of tissues or whole plant unable to perform photosynthesis. Indeed, susceptibility to the andro-genesis process was associated with an increase of total concentration of photosynthetic pigments in anthers, spikes and regenerated plants. The proper balance of the synthesis of various pigments, was the starting point for their proper incorporation into photosynthetic membranes. In contrast, genotypes resistant to the androgenesis process and those treated with heat, contained 100 times lower content of photosynthetic pigments. In particular, the synthesis of violaxanthin, zeaxanthin, lutein and chlorophyll b was limited. Furthermore, deregulation of starch and lipids synthesis, which led to the formation of very complex starch granules and an increased number of oleosomes, respectively, correlated with the reduction of the efficiency of androgenesis. The content of other sugars varied depending on the genotype and the type of stress. The highest content of various sugars was found for genotypes susceptible to andro-genesis, and highly reduced for genotypes resistant to androgenesis. The most important sugars seem to be glucose and fructose. They are involved in sugar sensing and signaling pathways, which affect the expression of various genes and regulate plant development. Sucrose, on the other hand, seems to have minor effect at each stage of the androgenesis. The sugar metabolism was related to metabolic activity of microspores. The genotypes susceptible to androgenesis process had much faster mitochondrium- and chloroplast-dependent energy conversion and higher heat production by tissues. Thus, the effectiveness of metabolic processes, their balance and the flexibility under the stress was a factor determining the direction of microspore development, and in the later stages of the androgenesis process, a factor supporting the induction of androgenic structures, chloroplast formation and the regeneration of green plants. The work was financed by Ministry of Agriculture and Rural Development within Program: ‘Biological Progress in Plant Production’, project no HOR.hn.802.15.2018.Keywords: androgenesis, chloroplast, metabolism, temperature stress
Procedia PDF Downloads 25654 Effect of Velocity-Slip in Nanoscale Electroosmotic Flows: Molecular and Continuum Transport Perspectives
Authors: Alper T. Celebi, Ali Beskok
Abstract:
Electroosmotic (EO) slip flows in nanochannels are investigated using non-equilibrium molecular dynamics (MD) simulations, and the results are compared with analytical solution of Poisson-Boltzmann and Stokes (PB-S) equations with slip contribution. The ultimate objective of this study is to show that well-known continuum flow model can accurately predict the EO velocity profiles in nanochannels using the slip lengths and apparent viscosities obtained from force-driven flow simulations performed at various liquid-wall interaction strengths. EO flow of aqueous NaCl solution in silicon nanochannels are simulated under realistic electrochemical conditions within the validity region of Poisson-Boltzmann theory. A physical surface charge density is determined for nanochannels based on dissociations of silanol functional groups on channel surfaces at known salt concentration, temperature and local pH. First, we present results of density profiles and ion distributions by equilibrium MD simulations, ensuring that the desired thermodynamic state and ionic conditions are satisfied. Next, force-driven nanochannel flow simulations are performed to predict the apparent viscosity of ionic solution between charged surfaces and slip lengths. Parabolic velocity profiles obtained from force-driven flow simulations are fitted to a second-order polynomial equation, where viscosity and slip lengths are quantified by comparing the coefficients of the fitted equation with continuum flow model. Presence of charged surface increases the viscosity of ionic solution while the velocity-slip at wall decreases. Afterwards, EO flow simulations are carried out under uniform electric field for different liquid-wall interaction strengths. Velocity profiles present finite slips near walls, followed with a conventional viscous flow profile in the electrical double layer that reaches a bulk flow region in the center of the channel. The EO flow enhances with increased slip at the walls, which depends on wall-liquid interaction strength and the surface charge. MD velocity profiles are compared with the predictions from analytical solutions of the slip modified PB-S equation, where the slip length and apparent viscosity values are obtained from force-driven flow simulations in charged silicon nano-channels. Our MD results show good agreements with the analytical solutions at various slip conditions, verifying the validity of PB-S equation in nanochannels as small as 3.5 nm. In addition, the continuum model normalizes slip length with the Debye length instead of the channel height, which implies that enhancement in EO flows is independent of the channel height. Further MD simulations performed at different channel heights also shows that the flow enhancement due to slip is independent of the channel height. This is important because slip enhanced EO flow is observable even in micro-channels experiments by using a hydrophobic channel with large slip and high conductivity solutions with small Debye length. The present study provides an advanced understanding of EO flows in nanochannels. Correct characterization of nanoscale EO slip flow is crucial to discover the extent of well-known continuum models, which is required for various applications spanning from ion separation to drug delivery and bio-fluidic analysis.Keywords: electroosmotic flow, molecular dynamics, slip length, velocity-slip
Procedia PDF Downloads 15253 Effectiveness of Essential Oils as Inhibitors of Quorum Sensing Activity Using Biomonitor Strain Chromobacterium Violaceum
Authors: Ivana Cabarkapa, Zorica Tomicic, Olivera Duragic
Abstract:
Antimicrobial resistance represents one of the major challenges facing humanity in the last decades. Increasing antibiotic-resistant pathogens indicates the need for the development of alternative antibacterial drugs and new treatment strategies. One of the innovative emerging treatments in overcoming multidrug-resistant pathogens certainly represents the inhibition anti-quorum sensing system. For most of the food-borne pathogens, the expression of the virulence depends on their capability communication with other members of the population by means of quorum sensing (QS). QS represents a specific way of bacterial intercellular communication, which enabled owing to their ability to detect and to respond to cell population density by gene regulation. QS mechanisms are responsible for controls the pathogenesis, virulence luminescence, motility, sporulation and biofilm formation of many organisms by regulating gene expression. Therefore, research in this field is being an attractive target for the development of new natural antibacterial agents. Anti-QS compounds are known to have the ability to prohibit bacterial pathogenicity. Considering the importance of quorum sensing during bacterial pathogenesis, this research has been focused on evaluation anti - QS properties of four essential oils (EOs) Origanum heracleoticum, Origanum vulgare, Thymus vulgare, and Thymus serpyllum, using biomonitor strain of Chromobacterium violaceum CV026. Tests conducted on Luria Bertani agar supplemented with N hexanol DL homoserine lacton (HHL) 10µl/50ml of agar. The anti-QS potential of the EOs was assayed in a range of concentrations of 200 – 0.39 µl/ml using the disc diffusion method. EOs of Th. vulgaris and T. serpyllum were exhibited anti-QS activity indicated by a non- pigmented ring with a dilution-dependent manner. The lowest dilution of EOs T. vulgaris and T. serpyllum in which they exhibited visually detectable inhibition of violacein synthesis was 6.25 µl/ml for both tested EOs. EOs of O. heracleoticum and O. vulgare were displayed different active principles, i.e., antimicrobial activity indicated by the inner clear ring and anti-QS activity indicated by the outer non-pigmented ring, in a concentration-dependent manner. The lowest dilution of EOs of O. heracleoticum and O. vulgare in which exhibited visually detectable inhibition of violacein synthesis was 1.56 and 3.25 µl/ml, respectively. Considering that, the main constituents of the tested EOs represented by monoterpenes (carvacrol, thymol, γ-terpinene, and p-cymene), anti - QS properties of tested EOs can be mainly attributed to their activity. In particular, from the scientific literature, carvacrol and thymol show a sub-inhibitory effect against foodborne pathogens. Previous studies indicated that sub-lethal concentrations of carvacrol reduced the mobility of bacteria due to the ability of interference using QS mechanism between the bacterial cells, and thereby reducing the ability of biofilm formation The precise mechanism by which carvacrol inhibits biofilm formation is still not fully understood. Our results indicated that EOs displayed different active principles, i.e., antimicrobial activity indicated by the inner clear ring and anti-QS activity indicated by an outer non- pigmented ring with visually detectable inhibition of violacein. Preliminary results suggest that EOs represent a promising alternative for effective control of the emergence and spread of resistant pathogens.Keywords: anti-quorum sensing activity, Chromobacterium violaceum, essential oils, violacein
Procedia PDF Downloads 12952 Degradation of Diclofenac in Water Using FeO-Based Catalytic Ozonation in a Modified Flotation Cell
Authors: Miguel A. Figueroa, José A. Lara-Ramos, Miguel A. Mueses
Abstract:
Pharmaceutical residues are a section of emerging contaminants of anthropogenic origin that are present in a myriad of waters with which human beings interact daily and are starting to affect the ecosystem directly. Conventional waste-water treatment systems are not capable of degrading these pharmaceutical effluents because their designs cannot handle the intermediate products and biological effects occurring during its treatment. That is why it is necessary to hybridize conventional waste-water systems with non-conventional processes. In the specific case of an ozonation process, its efficiency highly depends on a perfect dispersion of ozone, long times of interaction of the gas-liquid phases and the size of the ozone bubbles formed through-out the reaction system. In order to increase the efficiency of these parameters, the use of a modified flotation cell has been proposed recently as a reactive system, which is used at an industrial level to facilitate the suspension of particles and spreading gas bubbles through the reactor volume at a high rate. The objective of the present work is the development of a mathematical model that can closely predict the kinetic rates of reactions taking place in the flotation cell at an experimental scale by means of identifying proper reaction mechanisms that take into account the modified chemical and hydrodynamic factors in the FeO-catalyzed Ozonation of Diclofenac aqueous solutions in a flotation cell. The methodology is comprised of three steps: an experimental phase where a modified flotation cell reactor is used to analyze the effects of ozone concentration and loading catalyst over the degradation of Diclofenac aqueous solutions. The performance is evaluated through an index of utilized ozone, which relates the amount of ozone supplied to the system per milligram of degraded pollutant. Next, a theoretical phase where the reaction mechanisms taking place during the experiments must be identified and proposed that details the multiple direct and indirect reactions the system goes through. Finally, a kinetic model is obtained that can mathematically represent the reaction mechanisms with adjustable parameters that can be fitted to the experimental results and give the model a proper physical meaning. The expected results are a robust reaction rate law that can simulate the improved results of Diclofenac mineralization on water using the modified flotation cell reactor. By means of this methodology, the following results were obtained: A robust reaction pathways mechanism showcasing the intermediates, free-radicals and products of the reaction, Optimal values of reaction rate constants that simulated Hatta numbers lower than 3 for the system modeled, degradation percentages of 100%, TOC (Total organic carbon) removal percentage of 69.9 only requiring an optimal value of FeO catalyst of 0.3 g/L. These results showed that a flotation cell could be used as a reactor in ozonation, catalytic ozonation and photocatalytic ozonation processes, since it produces high reaction rate constants and reduces mass transfer limitations (Ha > 3) by producing microbubbles and maintaining a good catalyst distribution.Keywords: advanced oxidation technologies, iron oxide, emergent contaminants, AOTS intensification
Procedia PDF Downloads 10751 Composite Electrospun Aligned PLGA/Curcumin/Heparin Nanofibrous Membranes for Wound Dressing Application
Authors: Jyh-Ping Chen, Yu-Tin Lai
Abstract:
Wound healing is a complicated process involving overlapping hemostasis, inflammation, proliferation, and maturation phases. Ideal wound dressings can replace native skin functions in full thickness skin wounds through faster healing rate and also by reducing scar formation. Poly(lactic-co-glycolic acid) (PLGA) is an U.S. FDA approved biodegradable polymer to be used as ideal wound dressing material. Several in vitro and in vivo studies have demonstrated the effectiveness of curcumin in decreasing the release of inflammatory cytokines, inhibiting enzymes associated with inflammations, and scavenging free radicals that are the major cause of inflammation during wound healing. Heparin has binding affinities to various growth factors. With the unique and beneficial features offered by those molecules toward the complex process of wound healing, we postulate a composite wound dressing constructed from PLGA, curcumin and heparin would be a good candidate to accelerate scarless wound healing. In this work, we use electrospinning to prepare curcumin-loaded aligned PLGA nanofibrous membranes (PC NFMs). PC NFMs were further subject to oxygen plasma modification and surfaced-grafted with heparin through carbodiimide-mediated covalent bond formation to prepare curcumin-loaded PLGA-g-heparin (PCH) NFMs. The nanofibrous membranes could act as three-dimensional scaffolds to attract fibroblast migration, reduce inflammation, and increase wound-healing related growth factors concentrations at wound sites. From scanning electron microscopy analysis, the nanofibers in each NFM are with diameters ranging from 456 to 479 nm and with alignment angles within 0.5°. The NFMs show high tensile strength and good water absorptivity and provide suitable pore size for nutrients/wastes transport. Exposure of human dermal fibroblasts to the extraction medium of PC or PCH NFM showed significant protective effects against hydrogen peroxide than PLGA NFM. In vitro wound healing assays also showed that the extraction medium of PCH NFM showed significantly better migration ability toward fibroblasts than PC NFM, which is further better than PLGA NFM. The in vivo healing efficiency of the NFMs was further evaluated by a full thickness excisional wound healing diabetic rat model. After 14 days, PCH NFMs exhibits 86% wound closure rate, which is significantly different from other groups (79% for PC and 73% for PLGA NFM). Real-time PCR analysis indicated PC and PCH NFMs down regulated anti-oxidative enzymes like glutathione peroxidase (GPx) and superoxide dismutase (SOD), which are well-known transcription factors involved in cellular inflammatory responses to stimuli. From histology, the wound area treated with PCH NFMs showed more vascular lumen formation from immunohistochemistry of α-smooth muscle actin. The wound site also had more collagen type III (65.8%) expression and less collagen type I (3.5%) expression, indicating scar-less wound healing. From Western blot analysis, the PCH NFM showed good affinity toward growth factors from increased concentration of transforming growth factor-β (TGF-β) and fibroblast growth factor-2 (FGF-2) at the wound site to accelerate wound healing. From the results, we suggest PCH NFM as a promising candidate for wound dressing applications.Keywords: Curcumin, heparin, nanofibrous membrane, poly(lactic-co-glycolic acid) (PLGA), wound dressing
Procedia PDF Downloads 15150 Application of Flow Cytometry for Detection of Influence of Abiotic Stress on Plants
Authors: Dace Grauda, Inta Belogrudova, Alexei Katashev, Linda Lancere, Isaak Rashal
Abstract:
The goal of study was the elaboration of easy applicable flow cytometry method for detection of influence of abiotic stress factors on plants, which could be useful for detection of environmental stresses in urban areas. The lime tree Tillia vulgaris H. is a popular tree species used for urban landscaping in Europe and is one of the main species of street greenery in Riga, Latvia. Tree decline and low vitality has observed in the central part of Riga. For this reason lime trees were select as a model object for the investigation. During the period of end of June and beginning of July 12 samples from different urban environment locations as well as plant material from a greenhouse were collected. BD FACSJazz® cell sorter (BD Biosciences, USA) with flow cytometer function was used to test viability of plant cells. The method was based on changes of relative fluorescence intensity of cells in blue laser (488 nm) after influence of stress factors. SpheroTM rainbow calibration particles (3.0–3.4 μm, BD Biosciences, USA) in phosphate buffered saline (PBS) were used for calibration of flow cytometer. BD PharmingenTM PBS (BD Biosciences, USA) was used for flow cytometry assays. The mean fluorescence intensity information from the purified cell suspension samples was recorded. Preliminary, multiple gate sizes and shapes were tested to find one with the lowest CV. It was found that low CV can be obtained if only the densest part of plant cells forward scatter/side scatter profile is analysed because in this case plant cells are most similar in size and shape. The young pollen cells in one nucleus stage were found as the best for detection of influence of abiotic stress. For experiments only fresh plant material was used– the buds of Tillia vulgaris with diameter 2 mm. For the cell suspension (in vitro culture) establishment modified protocol of microspore culture was applied. The cells were suspended in the MS (Murashige and Skoog) medium. For imitation of dust of urban area SiO2 nanoparticles with concentration 0.001 g/ml were dissolved in distilled water. Into 10 ml of cell suspension 1 ml of SiO2 nanoparticles suspension was added, then cells were incubated in speed shaking regime for 1 and 3 hours. As a stress factor the irradiation of cells for 20 min by UV was used (Hamamatsu light source L9566-02A, L10852 lamp, A10014-50-0110), maximum relative intensity (100%) at 365 nm and at ~310 nm (75%). Before UV irradiation the suspension of cells were placed onto a thin layer on a filter paper disk (diameter 45 mm) in a Petri dish with solid MS media. Cells without treatment were used as a control. Experiments were performed at room temperature (23-25 °C). Using flow cytometer BS FACS Software cells plot was created to determine the densest part, which was later gated using oval-shaped gate. Gate included from 95 to 99% of all cells. To determine relative fluorescence of cells logarithmic fluorescence scale in arbitrary fluorescence units were used. 3x103 gated cells were analysed from the each sample. The significant differences were found among relative fluorescence of cells from different trees after treatment with SiO2 nanoparticles and UV irradiation in comparison with the control.Keywords: flow cytometry, fluorescence, SiO2 nanoparticles, UV irradiation
Procedia PDF Downloads 40149 In Vitro Intestine Tissue Model to Study the Impact of Plastic Particles
Authors: Ashleigh Williams
Abstract:
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
Procedia PDF Downloads 8248 Effect of Metarhizium robertsii in Rhipicephalus microplus hemocytes
Authors: Jessica P. Fiorotti, Maria C. Freitas, Caio J. B. Coutinho-Rodrigues, Mariana G. Camargo, Emily S. Mesquita, Amanda R. C. Corval, Ricardo O. B. Bitencourt, Allan F. Marciano, Diva D. Spadacci-Morena, Patricia S. Golo, Isabele C. Angelo, Vania R. E. P. Bittencourt
Abstract:
The bovine tick, Rhipicephalus microplus, is an arthropod of great importance in veterinary medicine leading to anemia, weight loss, animals' leather depreciation and also acting as a vector of many pathogens. In this way, the parasitism causes a loss of 3.24 billion dollars per year in Brazil. Knowingly, entomopathogenic fungi act as natural controller of some arthropods, acting mainly by active penetration through the cuticle. However, it can also act on the hemolymph and through the production of mycotoxins. Hemocytes are responsible for the cellular immune response and participate in the processes of phagocytosis, nodulation and encapsulation and may undergo changes when challenged by pathogens. The aim of the present study was to evaluate changes in R. microplus hemocytes after inoculation of Metarhizium robertsii using transmission electron microscopy. The isolate ARSEF 2575 and 200 engorged R. microplus females were used. The groups were divided into control, in which the females were inoculated with 5 μL of sterile distilled water solution and 0.1% Tween 80, and a group inoculated with 5 μL of fungal suspension at the concentration of 10⁷ conidia mL⁻¹. The experiment was performed in duplicate and each group contained 50 females. Twenty-four hours after fungal inoculation, hemolymph was collected through the cuticle dorsal surface perforation of the tick females. After collection, the hemolymph samples were centrifuged at 500 x g for 3 minutes at 4 °C, the plasma was discarded and the hemocyte pellet was resuspended in 50 μl PBS. The suspension material was fixed in 2% glutaraldehyde in Millonig buffer for three hours. After fixation, the material was centrifuged at 500 x g for 3 minutes, the supernatant was discarded and the cells were resuspended in a wash solution. Subsequently, the cells were post-fixed with 1% osmium tetroxide in phosphate buffer for one hour at room temperature and dehydrated in increasing concentrations of ethanol, and then embedded in Epon resin. The ultrathin sections were examined under the LEO EM 906E transmission electron microscopy at 80kV. The ultrastructural results revealed that.in control group, the cells were considered intact, in which the granulocytes were observed with granules of different electrodensities, intact mitochondria and cytoplasm without vacuolization. In addition, granulocytes showed plasma membrane projections similar to pseudopodia. Plasmatocytes presented as irregularly shaped cells, with the eccentric nucleus, agranular cytoplasm and some cells presented pseudopodia. Nevertheless, in the group exposed to the fungus, most of the cells presented in degeneration. The granulocytes found had fewer granules in the cytoplasm and more vacuoles. Plasmatocytes, after treatment, presented many vacuoles also in the cytoplasm and the lysosomes presented great amount of electrodense material in their interior. Thus, the results suggest that the fungus has a depressant action in the immune system of the tick, not only by the cell degranulation, but also suggesting that this leads to morphological changes in the hemocytes and may even trigger processes such as phagocytosis.Keywords: bovine tick, cellular defense, entomopathogenic fungi, immune response
Procedia PDF Downloads 18547 Modelling Spatial Dynamics of Terrorism
Authors: André Python
Abstract:
To this day, terrorism persists as a worldwide threat, exemplified by the recent deadly attacks in January 2015 in Paris and the ongoing massacres perpetrated by ISIS in Iraq and Syria. In response to this threat, states deploy various counterterrorism measures, the cost of which could be reduced through effective preventive measures. In order to increase the efficiency of preventive measures, policy-makers may benefit from accurate predictive models that are able to capture the complex spatial dynamics of terrorism occurring at a local scale. Despite empirical research carried out at country-level that has confirmed theories explaining the diffusion processes of terrorism across space and time, scholars have failed to assess diffusion’s theories on a local scale. Moreover, since scholars have not made the most of recent statistical modelling approaches, they have been unable to build up predictive models accurate in both space and time. In an effort to address these shortcomings, this research suggests a novel approach to systematically assess the theories of terrorism’s diffusion on a local scale and provide a predictive model of the local spatial dynamics of terrorism worldwide. With a focus on the lethal terrorist events that occurred after 9/11, this paper addresses the following question: why and how does lethal terrorism diffuse in space and time? Based on geolocalised data on worldwide terrorist attacks and covariates gathered from 2002 to 2013, a binomial spatio-temporal point process is used to model the probability of terrorist attacks on a sphere (the world), the surface of which is discretised in the form of Delaunay triangles and refined in areas of specific interest. Within a Bayesian framework, the model is fitted through an integrated nested Laplace approximation - a recent fitting approach that computes fast and accurate estimates of posterior marginals. Hence, for each location in the world, the model provides a probability of encountering a lethal terrorist attack and measures of volatility, which inform on the model’s predictability. Diffusion processes are visualised through interactive maps that highlight space-time variations in the probability and volatility of encountering a lethal attack from 2002 to 2013. Based on the previous twelve years of observation, the location and lethality of terrorist events in 2014 are statistically accurately predicted. Throughout the global scope of this research, local diffusion processes such as escalation and relocation are systematically examined: the former process describes an expansion from high concentration areas of lethal terrorist events (hotspots) to neighbouring areas, while the latter is characterised by changes in the location of hotspots. By controlling for the effect of geographical, economical and demographic variables, the results of the model suggest that the diffusion processes of lethal terrorism are jointly driven by contagious and non-contagious factors that operate on a local scale – as predicted by theories of diffusion. Moreover, by providing a quantitative measure of predictability, the model prevents policy-makers from making decisions based on highly uncertain predictions. Ultimately, this research may provide important complementary tools to enhance the efficiency of policies that aim to prevent and combat terrorism.Keywords: diffusion process, terrorism, spatial dynamics, spatio-temporal modeling
Procedia PDF Downloads 34346 Analysis of Short Counter-Flow Heat Exchanger (SCFHE) Using Non-Circular Micro-Tubes Operated on Water-CuO Nanofluid
Authors: Avdhesh K. Sharma
Abstract:
Key, in the development of energy-efficient micro-scale heat exchanger devices, is to select large heat transfer surface to volume ratio without much expanse on re-circulated pumps. The increased interest in short heat exchanger (SHE) is due to accessibility of advanced technologies for manufacturing of micro-tubes in range of 1 micron m - 1 mm. Such SHE using micro-tubes are highly effective for high flux heat transfer technologies. Nanofluids, are used to enhance the thermal conductivity of re-circulated coolant and thus enhances heat transfer rate further. Higher viscosity associated with nanofluid expands more pumping power. Thus, there is a trade-off between heat transfer rate and pressure drop with geometry of micro-tubes. Herein, a novel design of short counter flow heat exchanger (SCFHE) using non-circular micro-tubes flooded with CuO-water nanofluid is conceptualized by varying the ratio of surface area to cross-sectional area of micro-tubes. A framework for comparative analysis of SCFHE using micro-tubes non-circular shape flooded by CuO-water nanofluid is presented. In SCFHE concept, micro-tubes having various geometrical shapes (viz., triangular, rectangular and trapezoidal) has been arranged row-wise to facilitate two aspects: (1) allowing easy flow distribution for cold and hot stream, and (2) maximizing the thermal interactions with neighboring channels. Adequate distribution of rows for cold and hot flow streams enables above two aspects. For comparative analysis, a specific volume or cross-section area is assigned to each elemental cell (which includes flow area and area corresponds to half wall thickness). A specific volume or cross-section area is assumed to be constant for each elemental cell (which includes flow area and half wall thickness area) and variation in surface area is allowed by selecting different geometry of micro-tubes in SCFHE. Effective thermal conductivity model for CuO-water nanofluid has been adopted, while the viscosity values for water based nanofluids are obtained empirically. Correlations for Nusselt number (Nu) and Poiseuille number (Po) for micro-tubes have been derived or adopted. Entrance effect is accounted for. Thermal and hydrodynamic performances of SCFHE are defined in terms of effectiveness and pressure drop or pumping power, respectively. For defining the overall performance index of SCFHE, two links are employed. First one relates heat transfer between the fluid streams q and pumping power PP as (=qj/PPj); while another link relates effectiveness eff and pressure drop dP as (=effj/dPj). For analysis, the inlet temperatures of hot and cold streams are varied in usual range of 20dC-65dC. Fully turbulent regime is seldom encountered in micro-tubes and transition of flow regime occurs much early (i.e., ~Re=1000). Thus, Re is fixed at 900, however, the uncertainty in Re due to addition of nanoparticles in base fluid is quantified by averaging of Re. Moreover, for minimizing error, volumetric concentration is limited to range 0% to ≤4% only. Such framework may be helpful in utilizing maximum peripheral surface area of SCFHE without any serious severity on pumping power and towards developing advanced short heat exchangers.Keywords: CuO-water nanofluid, non-circular micro-tubes, performance index, short counter flow heat exchanger
Procedia PDF Downloads 20745 Blood Lipid Management: Combined Treatment with Hydrotherapy and Ozone Bubbles Bursting in Water
Authors: M. M. Wickramasinghe
Abstract:
Cholesterol and triglycerides are lipids, mainly essential to maintain the cellular structure of the human body. Cholesterol is also important for hormone production, vitamin D production, proper digestion functions, and strengthening the immune system. Excess fats in the blood circulation, known as hyperlipidemia, become harmful leading to arterial clogging and causing atherosclerosis. Aim of this research is to develop a treatment protocol to efficiently break down and maintain circulatory lipids by improving blood circulation without strenuous physical exercises while immersed in a tub of water. To achieve the target of strong exercise effect, this method involves generating powerful ozone bubbles to spin, collide, and burst in the water. Powerful emission of air into water is capable of transferring locked energy of the water molecules and releasing energy. This method involves water and air-based impact generated by pumping ozone at the speed of 46 lts/sec with a concentration of 0.03-0.05 ppt according to safety standards of The Federal Institute for Drugs and Medical Devices, BfArM, Germany. The direct impact of ozone bubbles on the muscular system and skin becomes the main target and is capable of increasing the heart rate while immersed in water. A total time duration of 20 minutes is adequate to exert a strong exercise effect, improve blood circulation, and stimulate the nervous and endocrine systems. Unstable ozone breakdown into oxygen release onto the surface of the water giving additional benefits and supplying high-quality air rich in oxygen required to maintain efficient metabolic functions. The breathing technique was introduced to improve the efficiency of lung functions and benefit the air exchange mechanism. The temperature of the water is maintained at 39c to 40c to support arterial dilation and enzyme functions and efficiently improve blood circulation to the vital organs. The buoyancy of water and natural hydrostatic pressure release the tension of the body weight and relax the mind and body. Sufficient hydration (3lts of water per day) is an essential requirement to transport nutrients and remove waste byproducts to process through the liver, kidney, and skin. Proper nutritional intake is an added advantage to optimize the efficiency of this method which aids in a fast recovery process. Within 20-30 days of daily treatment, triglycerides, low-density lipoproteins (LDL), and total cholesterol reduction were observed in patients with abnormal levels of lipid profile. Borderline patients were cleared within 10–15 days of treatment. This is a highly efficient system that provides many benefits and is able to achieve a successful reduction of triglycerides, LDL, and total cholesterol within a short period of time. Supported by proper hydration and nutritional balance, this system of natural treatment maintains healthy levels of lipids in the blood and avoids the risk of cerebral stroke, high blood pressure, and heart attacks.Keywords: atherosclerosis, cholesterol, hydrotherapy, hyperlipidemia, lipid management, ozone therapy, triglycerides
Procedia PDF Downloads 8744 Comparative Production of Secondary Metabolites by Prunus africana (Hook. F.) Kalkman Provenances in Cameroon and Some Associated Endophytic Fungi
Authors: Gloria M. Ntuba-Jua, Afui M. Mih, Eneke E. T. Bechem
Abstract:
Prunus africana (Hook. F.) Kalkman, commonly known as Pygeum or African cherry belongs to the Rosaceae family. It is a medium to large, evergreen tree with a spreading crown of 10 to 20 m. It is used by the traditional medical practitioners for the treatment of over 45ailments in Cameroon and sub-Sahara Africa. In modern medicine, it is used in the treatment of benign prostrate hyperplasia (BPH), prostate gland hypertrophy (enlarged prostate glands). This is possible because of its ability to produce some secondary metabolites which are believed to have bioactivity against these ailments. The ready international market for the sale of Prunus bark, uncontrolled exploitation, illegal harvesting using inappropriate techniques and poor timing of harvesting have contributed enormously to making the plant endangered. It is known to harbor a large number of endophytic fungi with the potential to produce similar secondary metabolites as the parent plant. Alternative sourcing of medicinal principles through endophytic fungi requires succinct knowledge of the endophytic fungi. This will serve as a conservation measure for Prunus africana by reducing dependence on Prunus bark for such metabolites. This work thus sought to compare the production of some major secondary metabolites produced by P. africana and some of its associated endophytic fungi. The leaves and stem bark of the plant from different provenances were soaked in methanol for 72 hrs to yield the methanolic crude extract. The phytochemical screening of the methanolic crude extracts using different standard procedures revealed the presence of tannins, flavonoids, terpenoids, saponins, phenolics and steroids. Pure cultures of some predominantly isolated endophyte species from the difference Prunus provenances such as Curvularia sp, and Morphospecies P001 were also grown in Potato Dextrose Broth (PDB) for 21 days and later extracted with Methylene dichloride (MDC) solvent after 24hrs to produce crude culture extracts. Qualitative assessment of crude culture extracts showed the presence of tannins, terpenoids, phenolics and steroids particularly β-Sitosterol, (a major bioactive metabolite) as did the plant tissues. Qualitative analysis by thin layer chromatography (TLC) was done to confirm and compare the production of β-Sitosterol (as marker compounds) in the crude extracts of the plant and endophyte. Samples were loaded on TLC silica gel aluminium barked plate (Kieselgel 60 F254, 0.2 mm, Merck) using acetone/hexane, (3.0:7.0) solvent system. They were visualized under an ultra violet lamp (UV254 and UV360). TLC revealed that leaves had a higher concentration of β-sitosterol in terms of band intensity than stem barks from the different provenances. The intensity of β-sitosterol bands in the culture extracts of endophytes was comparable to the plant extracts except for Curvularia sp (very minute) whose band was very faint. The ability of these fungi to make β-sitosterol was confirmed by TLC analysis with the compound having chromatographic properties (retention factor) similar to those of β-sitosterol standard. The ability of these major endophytes to produce secondary metabolites similar to the host has therefore been demonstrated. There is, therefore, the potential of developing the in vitro production system of Prunus secondary metabolites thereby enhancing its conservation.Keywords: Caneroon, endophytic fungi, Prunus africana, secondary metabolite
Procedia PDF Downloads 22343 Chemopreventive Properties of Cannabis sativa L. var. USO31 in Relation to Its Phenolic and Terpenoid Content
Authors: Antonella Di Sotto, Cinzia Ingallina, Caterina Fraschetti, Simone Circi, Marcello Locatelli, Simone Carradori, Gabriela Mazzanti, Luisa Mannina, Silvia Di Giacomo
Abstract:
Cannabis sativa L. is one of the oldest cultivated plant species known not only for its voluptuous use but also for the wide application in food, textile, and therapeutic industries. Recently, the progress of biotechnologies applied to medicinal plants has allowed to produce different hemp varieties with low content of psychotropic phytoconstituents (tetrahydrocannabinol < 0.2% w/v), thus leading to a renewed industrial and therapeutic interest for this plant. In this context, in order to discover new potential remedies of pharmaceutical and/or nutraceutical interest, the chemopreventive properties of different organic and hydroalcoholic extracts, obtained from the inflorescences of C. sativa L. var. USO31, collected in June and September harvesting, were assessed. Particularly, the antimutagenic activity towards the oxidative DNA-damage induced by tert-butyl hydroperoxide (t-BOOH) was evaluated, and the DPPH (2,2-diphenyl-1-picrylhydrazyl) and ABTS (2,2'-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid) radical scavenging power of the samples were assessed as possible mechanisms of antimutagenicity. Furthermore, the ability of the extracts to inhibit the glucose-6-phosphate dehydrogenase (G6PD), whose overexpression has been found to play a critical role in neoplastic transformation and tumor progression, has been studied as a possible chemopreventive strategy. A careful phytochemical characterization of the extracts for phenolic and terpenoid composition has been obtained by high performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS) methods. Under our experimental condition, all the extracts were found able to interfere with the tBOOH-induced mutagenicity in WP2uvrAR strain, although with different potency and effectiveness. The organic extracts from both the harvesting periods were found to be the main effective antimutagenic samples, reaching about a 55% inhibition of the tBOOH-mutagenicity at the highest concentration tested (250 μg/ml). All the extracts exhibited radical scavenger activity against DPPH and ABTS radicals, with a higher potency of the hydroalcoholic samples. The organic extracts were also able to inhibit the G6PD enzyme, being the samples from September harvesting the highly potent (about 50% inhibition respect to the vehicle). At the phytochemical analysis, all the extracts resulted to contain both polar and apolar phenolic compounds. The HPLC analysis revealed the presence of catechin and rutin as the major constituents of the hydroalcoholic extracts, with lower levels of quercetin and ferulic acid. The monoterpene carvacrol was found to be an ubiquitarian constituent. At GC-MS analysis, different terpenoids, among which caryophyllene sesquiterpenes, were identified. This evidence suggests a possible role of both polyphenols and terpenoids in the chemopreventive properties of the extracts from the inflorescences of C. sativa var. USO31. According to the literature, carvacrol and caryophyllene sesquiterpenes can contribute to the strong antimutagenicity although the role of all the hemp phytocomplex cannot be excluded. In conclusion, present results highlight a possible interest for the inflorescences of C. sativa var. USO31 as source of bioactive molecules and stimulate further studies in order to characterize its possible application for nutraceutical and pharmaceutical purposes.Keywords: antimutagenicity, glucose-6-phosphate dehydrogenase, hemp inflorescences, nutraceuticals, sesquiterpenes
Procedia PDF Downloads 14942 Glucose Uptake Rate of Insulin-Resistant Human Liver Carcinoma Cells (IR/HepG2) by Flavonoids from Enicostema littorale via IR/IRS1/AKT Pathway
Authors: Priyanka Mokashi, Aparna Khanna, Nancy Pandita
Abstract:
Diabetes mellitus is a chronic metabolic disorder which will be the 7th leading cause of death by 2030. The current line of treatment for the diabetes mellitus is oral antidiabetic drugs (biguanides, sulfonylureas, meglitinides, thiazolidinediones and alpha-glycosidase inhibitors) and insulin therapy depending upon the type 1 or type 2 diabetes mellitus. But, these treatments have their disadvantages, ranging from the developing of resistance to the drugs and adverse effects caused by them. Alternative to these synthetic agents, natural products provides a new insight for the development of more efficient and safe drugs due to their therapeutic values. Enicostema littorale blume (A. Raynal) is a traditional Indian plant belongs to the Gentianaceae family. It is widely distributed in Asia, Africa, and South America. There are few reports on Swrtiamarin, major component of this plant for its antidiabetic activity. However, the antidiabetic activity of flavonoids from E. littorale and their mechanism of action have not yet been elucidated. Flavonoids have a positive relationship with disease prevention and can act on various molecular targets and regulate different signaling pathways in pancreatic β-cells, adipocytes, hepatocytes and skeletal myofibers. They may exert beneficial effects in diabetes by (i) improving hyperglycemia through regulation of glucose metabolism in hepatocytes; (ii) enhancing insulin secretion and reducing apoptosis and promoting proliferation of pancreatic β-cells; (iii) increasing glucose uptake in hepatocytes, skeletal muscle and white adipose tissue (iv) reducing insulin resistance, inflammation and oxidative stress. Therefore, we have isolated four flavonoid rich fractions, Fraction A (FA), Fraction B (FB), Fraction C (FC), Fraction D (FD) from crude alcoholic hot (AH) extract from E. littorale, identified by LC/MS. Total eight flavonoids were identified on the basis of fragmentation pattern. Flavonoid FA showed the presence of swertisin, isovitexin, and saponarin; FB showed genkwanin, quercetin, isovitexin, FC showed apigenin, swertisin, quercetin, 5-O-glucosylswertisin and 5-O-glucosylisoswertisin whereas FD showed the presence of swertisin. Further, these fractions were assessed for their antidiabetic activity on stimulating glucose uptake in insulin-resistant HepG2 cell line model (IR/HepG2). The results showed that FD containing C-glycoside Swertisin has significantly increased the glucose uptake rate of IR/HepG2 cells at the concentration of 10 µg/ml as compared to positive control Metformin (0.5mM) which was determined by glucose oxidase- peroxidase method. It has been reported that enhancement of glucose uptake of cells occurs due the translocation of Glut4 vesicles to cell membrane through IR/IRS1/AKT pathway. Therefore, we have studied expressions of three genes IRS1, AKT and Glut4 by real-time PCR to evaluate whether they follow the same pathway or not. It was seen that the glucose uptake rate has increased in FD treated IR/HepG2 cells due to the activation of insulin receptor substrate-1 (IRS1) followed by protein kinase B (AKT) through phosphoinositide 3-kinase (PI3K) leading to translocation of Glut 4 vesicles to cell membrane, thereby enhancing glucose uptake and insulin sensitivity of insulin resistant HepG2 cells. Hence, the up-regulation indicated the mechanism of action through which FD (Swertisin) acts as antidiabetic candidate in the treatment of type 2 diabetes mellitus.Keywords: E. littorale, glucose transporter, glucose uptake rate, insulin resistance
Procedia PDF Downloads 30241 Potential of Hyperion (EO-1) Hyperspectral Remote Sensing for Detection and Mapping Mine-Iron Oxide Pollution
Authors: Abderrazak Bannari
Abstract:
Acid Mine Drainage (AMD) from mine wastes and contaminations of soils and water with metals are considered as a major environmental problem in mining areas. It is produced by interactions of water, air, and sulphidic mine wastes. This environment problem results from a series of chemical and biochemical oxidation reactions of sulfide minerals e.g. pyrite and pyrrhotite. These reactions lead to acidity as well as the dissolution of toxic and heavy metals (Fe, Mn, Cu, etc.) from tailings waste rock piles, and open pits. Soil and aquatic ecosystems could be contaminated and, consequently, human health and wildlife will be affected. Furthermore, secondary minerals, typically formed during weathering of mine waste storage areas when the concentration of soluble constituents exceeds the corresponding solubility product, are also important. The most common secondary mineral compositions are hydrous iron oxide (goethite, etc.) and hydrated iron sulfate (jarosite, etc.). The objectives of this study focus on the detection and mapping of MIOP in the soil using Hyperion EO-1 (Earth Observing - 1) hyperspectral data and constrained linear spectral mixture analysis (CLSMA) algorithm. The abandoned Kettara mine, located approximately 35 km northwest of Marrakech city (Morocco) was chosen as study area. During 44 years (from 1938 to 1981) this mine was exploited for iron oxide and iron sulphide minerals. Previous studies have shown that Kettara surrounding soils are contaminated by heavy metals (Fe, Cu, etc.) as well as by secondary minerals. To achieve our objectives, several soil samples representing different MIOP classes have been resampled and located using accurate GPS ( ≤ ± 30 cm). Then, endmembers spectra were acquired over each sample using an Analytical Spectral Device (ASD) covering the spectral domain from 350 to 2500 nm. Considering each soil sample separately, the average of forty spectra was resampled and convolved using Gaussian response profiles to match the bandwidths and the band centers of the Hyperion sensor. Moreover, the MIOP content in each sample was estimated by geochemical analyses in the laboratory, and a ground truth map was generated using simple Kriging in GIS environment for validation purposes. The acquired and used Hyperion data were corrected for a spatial shift between the VNIR and SWIR detectors, striping, dead column, noise, and gain and offset errors. Then, atmospherically corrected using the MODTRAN 4.2 radiative transfer code, and transformed to surface reflectance, corrected for sensor smile (1-3 nm shift in VNIR and SWIR), and post-processed to remove residual errors. Finally, geometric distortions and relief displacement effects were corrected using a digital elevation model. The MIOP fraction map was extracted using CLSMA considering the entire spectral range (427-2355 nm), and validated by reference to the ground truth map generated by Kriging. The obtained results show the promising potential of the proposed methodology for the detection and mapping of mine iron oxide pollution in the soil.Keywords: hyperion eo-1, hyperspectral, mine iron oxide pollution, environmental impact, unmixing
Procedia PDF Downloads 22340 Modeling and Simulation of the Structural, Electronic and Magnetic Properties of Fe-Ni Based Nanoalloys
Authors: Ece A. Irmak, Amdulla O. Mekhrabov, M. Vedat Akdeniz
Abstract:
There is a growing interest in the modeling and simulation of magnetic nanoalloys by various computational methods. Magnetic crystalline/amorphous nanoparticles (NP) are interesting materials from both the applied and fundamental points of view, as their properties differ from those of bulk materials and are essential for advanced applications such as high-performance permanent magnets, high-density magnetic recording media, drug carriers, sensors in biomedical technology, etc. As an important magnetic material, Fe-Ni based nanoalloys have promising applications in the chemical industry (catalysis, battery), aerospace and stealth industry (radar absorbing material, jet engine alloys), magnetic biomedical applications (drug delivery, magnetic resonance imaging, biosensor) and computer hardware industry (data storage). The physical and chemical properties of the nanoalloys depend not only on the particle or crystallite size but also on composition and atomic ordering. Therefore, computer modeling is an essential tool to predict structural, electronic, magnetic and optical behavior at atomistic levels and consequently reduce the time for designing and development of new materials with novel/enhanced properties. Although first-principles quantum mechanical methods provide the most accurate results, they require huge computational effort to solve the Schrodinger equation for only a few tens of atoms. On the other hand, molecular dynamics method with appropriate empirical or semi-empirical inter-atomic potentials can give accurate results for the static and dynamic properties of larger systems in a short span of time. In this study, structural evolutions, magnetic and electronic properties of Fe-Ni based nanoalloys have been studied by using molecular dynamics (MD) method in Large-scale Atomic/Molecular Massively Parallel Simulator (LAMMPS) and Density Functional Theory (DFT) in the Vienna Ab initio Simulation Package (VASP). The effects of particle size (in 2-10 nm particle size range) and temperature (300-1500 K) on stability and structural evolutions of amorphous and crystalline Fe-Ni bulk/nanoalloys have been investigated by combining molecular dynamic (MD) simulation method with Embedded Atom Model (EAM). EAM is applicable for the Fe-Ni based bimetallic systems because it considers both the pairwise interatomic interaction potentials and electron densities. Structural evolution of Fe-Ni bulk and nanoparticles (NPs) have been studied by calculation of radial distribution functions (RDF), interatomic distances, coordination number, core-to-surface concentration profiles as well as Voronoi analysis and surface energy dependences on temperature and particle size. Moreover, spin-polarized DFT calculations were performed by using a plane-wave basis set with generalized gradient approximation (GGA) exchange and correlation effects in the VASP-MedeA package to predict magnetic and electronic properties of the Fe-Ni based alloys in bulk and nanostructured phases. The result of theoretical modeling and simulations for the structural evolutions, magnetic and electronic properties of Fe-Ni based nanostructured alloys were compared with experimental and other theoretical results published in the literature.Keywords: density functional theory, embedded atom model, Fe-Ni systems, molecular dynamics, nanoalloys
Procedia PDF Downloads 23739 Magnesium Nanoparticles for Photothermal Therapy
Authors: E. Locatelli, I. Monaco, R. C. Martin, Y. Li, R. Pini, M. Chiariello, M. Comes Franchini
Abstract:
Despite the many advantages of application of nanomaterials in the field of nanomedicine, increasing concerns have been expressed on their potential adverse effects on human health. There is urgency for novel green strategies toward novel materials with enhanced biocompatibility using safe reagents. Photothermal ablation therapy, which exploits localized heat increase of a few degrees to kill cancer cells, has appeared recently as a non-invasive and highly efficient therapy against various cancer types; anyway new agents able to generate hyperthermia when irradiated are needed and must have precise biocompatibility in order to avoid damage to healthy tissues and prevent toxicity. Recently, there has been increasing interest in magnesium as a biomaterial: it is the fourth most abundant cation in the human body, and it is essential for human metabolism. However magnesium nanoparticles (Mg NPs) have had limited diffusion due to the high reduction potential of magnesium cations, which makes NPs synthesis challenging. Herein, we report the synthesis of Mg NPs and their surface functionalization for the obtainment of a stable and biocompatible nanomaterial suitable for photothermal ablation therapy against cancer. We synthesized the Mg crystals by reducing MgCl2 with metallic lithium and exploiting naphthalene as an electron carrier: the lithium–naphthalene complex acts as the real reducing agent. Firstly, the nanocrystal particles were coated with the ligand 12-ethoxy ester dodecanehydroxamic acid, and then entrapped into water-dispersible polymeric micelles (PMs) made of the FDA-approved PLGA-b-PEG-COOH copolymer using the oil-in-water emulsion technique. Lately, we developed a more straightforward methodology by introducing chitosan, a highly biocompatible natural product, at the beginning of the process, simultaneously using lithium–naphthalene complex, thus having a one-pot procedure for the formation and surface modification of MgNPs. The obtained MgNPs were purified and fully characterized, showing diameters in the range of 50-300 nm. Notably, when coated with chitosan the particles remained stable as dry powder for more than 10 months. We proved the possibility of generating a temperature rise of a few to several degrees once MgNPs were illuminated using a 810 nm diode laser operating in continuous wave mode: the temperature rise resulted significant (0-15 °C) and concentration dependent. We then investigated potential cytotoxicity of the MgNPs: we used HN13 epithelial cells, derived from a head and neck squamous cell carcinoma and the hepa1-6 cell line, derived from hepatocellular carcinoma and very low toxicity was observed for both nanosystems. Finally, in vivo photothermal therapy was performed on xenograft hepa1-6 tumor bearing mice: the animals were treated with MgNPs coated with chitosan and showed no sign of suffering after the injection. After 12 hours the tumor was exposed to near-infrared laser light. The results clearly showed an extensive damage to tumor tissue after only 2 minutes of laser irradiation at 3Wcm-1, while no damage was reported when the tumor was treated with the laser and saline alone in control group. Despite the lower photothermal efficiency of Mg with respect to Au NPs, we consider MgNPs a promising, safe and green candidate for future clinical translations.Keywords: chitosan, magnesium nanoparticles, nanomedicine, photothermal therapy
Procedia PDF Downloads 26438 The Optimization of Topical Antineoplastic Therapy Using Controlled Release Systems Based on Amino-functionalized Mesoporous Silica
Authors: Lacramioara Ochiuz, Aurelia Vasile, Iulian Stoleriu, Cristina Ghiciuc, Maria Ignat
Abstract:
Topical administration of chemotherapeutic agents (eg. carmustine, bexarotene, mechlorethamine etc.) in local treatment of cutaneous T-cell lymphoma (CTCL) is accompanied by multiple side effects, such as contact hypersensitivity, pruritus, skin atrophy or even secondary malignancies. A known method of reducing the side effects of anticancer agent is the development of modified drug release systems using drug incapsulation in biocompatible nanoporous inorganic matrices, such as mesoporous MCM-41 silica. Mesoporous MCM-41 silica is characterized by large specific surface, high pore volume, uniform porosity, and stable dispersion in aqueous medium, excellent biocompatibility, in vivo biodegradability and capacity to be functionalized with different organic groups. Therefore, MCM-41 is an attractive candidate for a wide range of biomedical applications, such as controlled drug release, bone regeneration, protein immobilization, enzymes, etc. The main advantage of this material lies in its ability to host a large amount of the active substance in uniform pore system with adjustable size in a mesoscopic range. Silanol groups allow surface controlled functionalization leading to control of drug loading and release. This study shows (I) the amino-grafting optimization of mesoporous MCM-41 silica matrix by means of co-condensation during synthesis and post-synthesis using APTES (3-aminopropyltriethoxysilane); (ii) loading the therapeutic agent (carmustine) obtaining a modified drug release systems; (iii) determining the profile of in vitro carmustine release from these systems; (iv) assessment of carmustine release kinetics by fitting on four mathematical models. Obtained powders have been described in terms of structure, texture, morphology thermogravimetric analysis. The concentration of the therapeutic agent in the dissolution medium has been determined by HPLC method. In vitro dissolution tests have been done using cell Enhancer in a 12 hours interval. Analysis of carmustine release kinetics from mesoporous systems was made by fitting to zero-order model, first-order model Higuchi model and Korsmeyer-Peppas model, respectively. Results showed that both types of highly ordered mesoporous silica (amino grafted by co-condensation process or post-synthesis) are thermally stable in aqueous medium. In what regards the degree of loading and efficiency of loading with the therapeutic agent, there has been noticed an increase of around 10% in case of co-condensation method application. This result shows that direct co-condensation leads to even distribution of amino groups on the pore walls while in case of post-synthesis grafting many amino groups are concentrated near the pore opening and/or on external surface. In vitro dissolution tests showed an extended carmustine release (more than 86% m/m) both from systems based on silica functionalized directly by co-condensation and after synthesis. Assessment of carmustine release kinetics revealed a release through diffusion from all studied systems as a result of fitting to Higuchi model. The results of this study proved that amino-functionalized mesoporous silica may be used as a matrix for optimizing the anti-cancer topical therapy by loading carmustine and developing prolonged-release systems.Keywords: carmustine, silica, controlled, release
Procedia PDF Downloads 25637 Optimizing Solids Control and Cuttings Dewatering for Water-Powered Percussive Drilling in Mineral Exploration
Authors: S. J. Addinell, A. F. Grabsch, P. D. Fawell, B. Evans
Abstract:
The Deep Exploration Technologies Cooperative Research Centre (DET CRC) is researching and developing a new coiled tubing based greenfields mineral exploration drilling system utilising down-hole water-powered percussive drill tooling. This new drilling system is aimed at significantly reducing the costs associated with identifying mineral resource deposits beneath deep, barren cover. This system has shown superior rates of penetration in water-rich, hard rock formations at depths exceeding 500 metres. With fluid flow rates of up to 120 litres per minute at 200 bar operating pressure to energise the bottom hole tooling, excessive quantities of high quality drilling fluid (water) would be required for a prolonged drilling campaign. As a result, drilling fluid recovery and recycling has been identified as a necessary option to minimise costs and logistical effort. While the majority of the cuttings report as coarse particles, a significant fines fraction will typically also be present. To maximise tool life longevity, the percussive bottom hole assembly requires high quality fluid with minimal solids loading and any recycled fluid needs to have a solids cut point below 40 microns and a concentration less than 400 ppm before it can be used to reenergise the system. This paper presents experimental results obtained from the research program during laboratory and field testing of the prototype drilling system. A study of the morphological aspects of the cuttings generated during the percussive drilling process shows a strong power law relationship for particle size distributions. This data is critical in optimising solids control strategies and cuttings dewatering techniques. Optimisation of deployable solids control equipment is discussed and how the required centrate clarity was achieved in the presence of pyrite-rich metasediment cuttings. Key results were the successful pre-aggregation of fines through the selection and use of high molecular weight anionic polyacrylamide flocculants and the techniques developed for optimal dosing prior to scroll decanter centrifugation, thus keeping sub 40 micron solids loading within prescribed limits. Experiments on maximising fines capture in the presence of thixotropic drilling fluid additives (e.g. Xanthan gum and other biopolymers) are also discussed. As no core is produced during the drilling process, it is intended that the particle laden returned drilling fluid is used for top-of-hole geochemical and mineralogical assessment. A discussion is therefore presented on the biasing and latency of cuttings representivity by dewatering techniques, as well as the resulting detrimental effects on depth fidelity and accuracy. Data pertaining to the sample biasing with respect to geochemical signatures due to particle size distributions is presented and shows that, depending on the solids control and dewatering techniques used, it can have unwanted influence on top-of-hole analysis. Strategies are proposed to overcome these effects, improving sample quality. Successful solids control and cuttings dewatering for water-powered percussive drilling is presented, contributing towards the successful advancement of coiled tubing based greenfields mineral exploration.Keywords: cuttings, dewatering, flocculation, percussive drilling, solids control
Procedia PDF Downloads 24336 Development of Peptide Inhibitors against Dengue Virus Infection by in Silico Design
Authors: Aussara Panya, Nunghathai Sawasdee, Mutita Junking, Chatchawan Srisawat, Kiattawee Choowongkomon, Pa-Thai Yenchitsomanus
Abstract:
Dengue virus (DENV) infection is a global public health problem with approximately 100 million infected cases a year. Presently, there is no approved vaccine or effective drug available; therefore, the development of anti-DENV drug is urgently needed. The clinical reports revealing the positive association between the disease severity and viral titer has been reported previously suggesting that the anti-DENV drug therapy can possibly ameliorate the disease severity. Although several anti-DENV agents showed inhibitory activities against DENV infection, to date none of them accomplishes clinical use in the patients. The surface envelope (E) protein of DENV is critical for the viral entry step, which includes attachment and membrane fusion; thus, the blocking of envelope protein is an attractive strategy for anti-DENV drug development. To search the safe anti-DENV agent, this study aimed to search for novel peptide inhibitors to counter DENV infection through the targeting of E protein using a structure-based in silico design. Two selected strategies has been used including to identify the peptide inhibitor which interfere the membrane fusion process whereby the hydrophobic pocket on the E protein was the target, the destabilization of virion structure organization through the disruption of the interaction between the envelope and membrane proteins, respectively. The molecular docking technique has been used in the first strategy to search for the peptide inhibitors that specifically bind to the hydrophobic pocket. The second strategy, the peptide inhibitor has been designed to mimic the ectodomain portion of membrane protein to disrupt the protein-protein interaction. The designed peptides were tested for the effects on cell viability to measure the toxic to peptide to the cells and their inhibitory assay to inhibit the DENV infection in Vero cells. Furthermore, their antiviral effects on viral replication, intracellular protein level and viral production have been observed by using the qPCR, cell-based flavivirus immunodetection and immunofluorescence assay. None of tested peptides showed the significant effect on cell viability. The small peptide inhibitors achieved from molecular docking, Glu-Phe (EF), effectively inhibited DENV infection in cell culture system. Its most potential effect was observed for DENV2 with a half maximal inhibition concentration (IC50) of 96 μM, but it partially inhibited other serotypes. Treatment of EF at 200 µM on infected cells also significantly reduced the viral genome and protein to 83.47% and 84.15%, respectively, corresponding to the reduction of infected cell numbers. An additional approach was carried out by using peptide mimicking membrane (M) protein, namely MLH40. Treatment of MLH40 caused the reduction of foci formation in four individual DENV serotype (DENV1-4) with IC50 of 24-31 μM. Further characterization suggested that the MLH40 specifically blocked viral attachment to host membrane, and treatment with 100 μM could diminish 80% of viral attachment. In summary, targeting the hydrophobic pocket and M-binding site on the E protein by using the peptide inhibitors could inhibit DENV infection. The results provide proof of-concept for the development of antiviral therapeutic peptide inhibitors to counter DENV infection through the use of a structure-based design targeting conserved viral protein.Keywords: dengue virus, dengue virus infection, drug design, peptide inhibitor
Procedia PDF Downloads 35135 Accumulation of Trace Metals in Leaf Vegetables Cultivated in High Traffic Areas in Ghent, Belgium
Authors: Veronique Troch, Wouter Van der Borght, Véronique De Bleeker, Bram Marynissen, Nathan Van der Eecken, Gijs Du Laing
Abstract:
Among the challenges associated with increased urban food production are health risks from food contamination, due to the higher pollution loads in urban areas, compared to rural sites. Therefore, the risks posed by industrial or traffic pollution of locally grown food, was defined as one of five high-priority issues of urban agriculture requiring further investigation. The impact of air pollution on urban horticulture is the subject of this study. More particular, this study focuses on the atmospheric deposition of trace metals on leaf vegetables cultivated in the city of Ghent, Belgium. Ghent is a particularly interesting study site as it actively promotes urban agriculture. Plants accumulate heavy metals by absorption from contaminated soils and through deposition on parts exposed to polluted air. Accumulation of trace metals in vegetation grown near roads has been shown to be significantly higher than those grown in rural areas due to traffic-related contaminants in the air. Studies of vegetables demonstrated, that the uptake and accumulation of trace metals differed among crop type, species, and among plant parts. Studies on vegetables and fruit trees in Berlin, Germany, revealed significant differences in trace metal concentrations depending on local traffic, crop species, planting style and parameters related to barriers between sampling site and neighboring roads. This study aims to supplement this scarce research on heavy metal accumulation in urban horticulture. Samples from leaf vegetables were collected from different sites, including allotment gardens, in Ghent. Trace metal contents on these leaf vegetables were analyzed by ICP-MS (inductively coupled plasma mass spectrometry). In addition, precipitation on each sampling site was collected by NILU-type bulk collectors and similarly analyzed for trace metals. On one sampling site, different parameters which might influence trace metal content in leaf vegetables were analyzed in detail. These parameters are distance of planting site to the nearest road, barriers between planting site and nearest road, and type of leaf vegetable. For comparison, a rural site, located farther from city traffic and industrial pollution, was included in this study. Preliminary results show that there is a high correlation between trace metal content in the atmospheric deposition and trace metal content in leaf vegetables. Moreover, a significant higher Pb, Cu and Fe concentration was found on spinach collected from Ghent, compared to spinach collected from a rural site. The distance of planting site to the nearest road significantly affected the accumulation of Pb, Cu, Mo and Fe on spinach. Concentrations of those elements on spinach increased with decreasing distance between planting site and the nearest road. Preliminary results did not show a significant effect of barriers between planting site and the nearest road on accumulation of trace metals on leaf vegetables. The overall goal of this study is to complete and refine existing guidelines for urban gardening to exclude potential health risks from food contamination. Accordingly, this information can help city governments and civil society in the professionalization and sustainable development of urban agriculture.Keywords: atmospheric deposition, leaf vegetables, trace metals, traffic pollution, urban agriculture
Procedia PDF Downloads 22834 Effects of Combined Lewis Acid and Ultrasonic Pretreatment on the Physicochemical Properties of Heat-Treated Moso Bamboo
Authors: Tianfang Zhang, Luxi He, Zhengbin He, Songlin Yi
Abstract:
Moso bamboo is a common non-wood forest resource in Asia that is widely used in construction, furniture, and other fields. Influenced by the heterogeneous structure and various hygroscopic groups of bamboo, the deformation occurs as moisture absorption and desorption when the environment temperature and humidity conditions change. Thermal modification is a well-established commercial technology for improving the dimensional stability of bamboo. However, the higher energy consumption and carbon emissions limit its further development. Previous studies have indicated that inorganic salt-assisted thermal modification could lead to significant reductions in moisture absorption and energy consumption. Represented by metal chlorides, it could show Lewis acid properties when dissolved in water, generating metal ion ligand complexes. In addition, ultrasonic treatment, as an efficient and environmentally friendly physical treatment method, improved the accessibility of pretreatment chemical impregnation agents and intensified mass and heat transfer during reactions. To save energy and reduce deformation, this study elucidates the influence of zinc chloride-ultrasonic treatment on the physicochemical properties of heat-treated bamboo, and the details of the bamboo deformation mechanism with Lewis acid are explained. Three sets of parameters (inorganic salt concentration, ultrasonic frequency and heat treatment temperature) were designed, and an optimized process was proposed to clarify this scientific question, that is: 5% (w/w) zinc chloride solution, 40 kHz ultrasonic waves and heat treatment at 160 °C. The samples were characterized by different means to analyze changes in their macroscopic features, pore structure, chemical structure and chemical composition. The results suggested that the maximum weight loss rate was reduced by at least 19.75%. The maximum thermal degradation peak of hemicellulose was significantly shifted forward. The hygroscopicity was reduced by 10.15%, the relative crystallinity was increased by 4.4%, the surface contact angle was increased by 25.2%, and the color change was increased by 23.60 in the optimal condition. From the electron microscope observation, the treated surface became rougher, and cracks appeared in some weaker areas, accelerating starch loss and removing granular attachments around the pits. By ion diffusion, zinc ions diffused into hemicellulose and a partial amorphous region of cellulose. Parts of the cell wall structure were subjected to swelling and degradation, leading to the broken state of parenchyma cells. From the Raman spectrum, compared to conventional thermal modifications, hemicellulose thermal degradation and lignin migration is promoted by Lewis acid under dilute acid-thermal condition. As shown in this work, the combined Lewis acid and ultrasonic pretreatment as an environmentally friendly, safe, and efficient physic-chemical combined pretreatment method improved the dimensional stability of Moso bamboo and lowered the thermal degradation conditions. This method has great potential for development in the field of bamboo heat treatment, and it might provide some guidance for making dark bamboo flooring.Keywords: Moso bamboo, Lewis acid, ultrasound, heat treatment
Procedia PDF Downloads 7133 EGF Serum Level in Diagnosis and Prediction of Mood Disorder in Adolescents and Young Adults
Authors: Monika Dmitrzak-Weglarz, Aleksandra Rajewska-Rager, Maria Skibinska, Natalia Lepczynska, Piotr Sibilski, Joanna Pawlak, Pawel Kapelski, Joanna Hauser
Abstract:
Epidermal growth factor (EGF) is a well-known neurotrophic factor that involves in neuronal growth and synaptic plasticity. The proteomic research provided in order to identify novel candidate biological markers for mood disorders focused on elevated EGF serum level in patients during depression episode. However, the EGF association with mood disorder spectrum among adolescents and young adults has not been studied extensively. In this study, we aim to investigate the serum levels of EGF in adolescents and young adults during hypo/manic, depressive episodes and in remission compared to healthy control group. In our study, we involved 80 patients aged 12-24 years in 2-year follow-up study with a primary diagnosis of mood disorder spectrum, and 35 healthy volunteers matched by age and gender. Diagnoses were established according to DSM-IV-TR criteria using structured clinical interviews: K-SADS for child and adolescents, and SCID for young adults. Clinical and biological evaluations were made at baseline and euthymic mood (at 3th or 6th month of treatment and after 1 and 2 years). The Young Mania Rating Scale and Hamilton Rating Scale for Depression were used for assessment. The study protocols were approved by the relevant ethics committee. Serum protein concentration was determined by Enzyme-Linked Immunosorbent Assays (ELISA) method. Human EGF (cat. no DY 236) DuoSet ELISA kit was used (R&D Systems). Serum EGF levels were analysed with following variables: age, age under 18 and above 18 years old, sex, family history of affective disorders, drug-free vs. medicated. Shapiro-Wilk test was used to test the normality of the data. The homogeneity of variance was calculated with Levene’s test. EGF levels showed non-normal distribution and the homogeneity of variance was violated. Non-parametric tests: Mann-Whitney U test, Kruskall-Wallis ANOVA, Friedman’s ANOVA, Wilcoxon signed rank test, Spearman correlation coefficient was applied in the analyses The statistical significance level was set at p<0.05. Elevated EGF level at baseline (p=0.001) and at month 24 (p=0.02) was detected in study subjects compared with controls. Increased EGF level in women at month 12 (p=0.02) compared to men in study group have been observed. Using Wilcoxon signed rank test differences in EGF levels were detected: decrease from baseline to month 3 (p=0.014) and increase comparing: month 3 vs. 24 (p=0.013); month 6 vs. 12 (p=0.021) and vs. 24 (p=0.008). EGF level at baseline was negatively correlated with depression and mania occurrence at 24 months. EGF level at 24 months was positively correlated with depression and mania occurrence at 12 months. No other correlations of EGF levels with clinical and demographical variables have been detected. The findings of the present study indicate that EGF serum level is significantly elevated in the study group of patients compared to the controls. We also observed fluctuations in EGF levels during two years of disease observation. EGF seems to be useful as an early marker for prediction of diagnosis, course of illness and treatment response in young patients during first episode od mood disorders, which requires further investigation. Grant was founded by National Science Center in Poland no 2011/03/D/NZ5/06146.Keywords: biological marker, epidermal growth factor, mood disorders, prediction
Procedia PDF Downloads 18332 Integrated Mathematical Modeling and Advance Visualization of Magnetic Nanoparticle for Drug Delivery, Drug Release and Effects to Cancer Cell Treatment
Authors: Norma Binti Alias, Che Rahim Che The, Norfarizan Mohd Said, Sakinah Abdul Hanan, Akhtar Ali
Abstract:
This paper discusses on the transportation of magnetic drug targeting through blood within vessels, tissues and cells. There are three integrated mathematical models to be discussed and analyze the concentration of drug and blood flow through magnetic nanoparticles. The cell therapy brought advancement in the field of nanotechnology to fight against the tumors. The systematic therapeutic effect of Single Cells can reduce the growth of cancer tissue. The process of this nanoscale phenomena system is able to measure and to model, by identifying some parameters and applying fundamental principles of mathematical modeling and simulation. The mathematical modeling of single cell growth depends on three types of cell densities such as proliferative, quiescent and necrotic cells. The aim of this paper is to enhance the simulation of three types of models. The first model represents the transport of drugs by coupled partial differential equations (PDEs) with 3D parabolic type in a cylindrical coordinate system. This model is integrated by Non-Newtonian flow equations, leading to blood liquid flow as the medium for transportation system and the magnetic force on the magnetic nanoparticles. The interaction between the magnetic force on drug with magnetic properties produces induced currents and the applied magnetic field yields forces with tend to move slowly the movement of blood and bring the drug to the cancer cells. The devices of nanoscale allow the drug to discharge the blood vessels and even spread out through the tissue and access to the cancer cells. The second model is the transport of drug nanoparticles from the vascular system to a single cell. The treatment of the vascular system encounters some parameter identification such as magnetic nanoparticle targeted delivery, blood flow, momentum transport, density and viscosity for drug and blood medium, intensity of magnetic fields and the radius of the capillary. Based on two discretization techniques, finite difference method (FDM) and finite element method (FEM), the set of integrated models are transformed into a series of grid points to get a large system of equations. The third model is a single cell density model involving the three sets of first order PDEs equations for proliferating, quiescent and necrotic cells change over time and space in Cartesian coordinate which regulates under different rates of nutrients consumptions. The model presents the proliferative and quiescent cell growth depends on some parameter changes and the necrotic cells emerged as the tumor core. Some numerical schemes for solving the system of equations are compared and analyzed. Simulation and computation of the discretized model are supported by Matlab and C programming languages on a single processing unit. Some numerical results and analysis of the algorithms are presented in terms of informative presentation of tables, multiple graph and multidimensional visualization. As a conclusion, the integrated of three types mathematical modeling and the comparison of numerical performance indicates that the superior tool and analysis for solving the complete set of magnetic drug delivery system which give significant effects on the growth of the targeted cancer cell.Keywords: mathematical modeling, visualization, PDE models, magnetic nanoparticle drug delivery model, drug release model, single cell effects, avascular tumor growth, numerical analysis
Procedia PDF Downloads 42631 La0.80Ag0.15MnO3 Magnetic Nanoparticles for Self-Controlled Magnetic Fluid Hyperthermia
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
Abstract:
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
Procedia PDF Downloads 8330 Pharmacokinetics of First-Line Tuberculosis Drugs in South African Patients from Kwazulu-Natal: Effects of Pharmacogenetic Variation on Rifampicin and Isoniazid Concentrations
Authors: Anushka Naidoo, Veron Ramsuran, Maxwell Chirehwa, Paolo Denti, Kogieleum Naidoo, Helen McIlleron, Nonhlanhla Yende-Zuma, Ravesh Singh, Sinaye Ngcapu, Nesri Padayatachi
Abstract:
Background: Despite efforts to introduce new drugs and shorter drug regimens for drug-susceptible tuberculosis (TB), the standard first-line treatment has not changed in over 50 years. Rifampicin, isoniazid, and pyrazinamide are critical components of the current standard treatment regimens. Some studies suggest that microbiologic failure and acquired drug resistance are primarily driven by low drug concentrations that result from pharmacokinetic (PK) variability independent of adherence to treatment. Wide between-patient pharmacokinetic variability for rifampin, isoniazid, and pyrazinamide has been reported in prior studies. There may be several reasons for this variability. However, genetic variability in genes coding for drug metabolizing and transporter enzymes have been shown to be a contributing factor for variable tuberculosis drug exposures. Objective: We describe the pharmacokinetics of first-line TB drugs rifampicin, isoniazid, and pyrazinamide and assess the effect of genetic variability in relevant selected drug metabolizing and transporter enzymes on pharmacokinetic parameters of isoniazid and rifampicin. Methods: We conducted the randomized-controlled Improving retreatment success TB trial in Durban, South Africa. The drug regimen included rifampicin, isoniazid, and pyrazinamide. Drug concentrations were measured in plasma, and concentration-time data were analysed using nonlinear-mixed-effects models to quantify the effects of relevant covariates and single nucleotide polymorphisms (SNP’s) of drug metabolizing and transporter genes on rifampicin, isoniazid and pyrazinamide exposure. A total of 25 SNP’s: four NAT2 (used to determine acetylator status), four SLCO1B1, three Pregnane X receptor (NR1), six ABCB1 and eight UGT1A, were selected for analysis in this study. Genotypes were determined for each of the SNP’s using a TaqMan® Genotyping OpenArray™. Results: Among fifty-eight patients studied; 41 (70.7%) were male, 97% black African, 42 (72.4%) HIV co-infected and 40 (95%) on efavirenz-based ART. Median weight, fat-free mass (FFM), and age at baseline were 56.9 kg (interquartile range, IQR: 51.1-65.2), 46.8 kg (IQR: 42.5-50.3) and 37 years (IQR: 31-42), respectively. The pharmacokinetics of rifampicin and pyrazinamide was best described using one-compartment models with first-order absorption and elimination, while for isoniazid two-compartment disposition was used. The median (interquartile range: IQR) AUC (h·mg/L) and Cmax (mg/L) for rifampicin, isoniazid, and pyrazinamide were; 25.62 (23.01-28.53) and 4.85 (4.36-5.40), 10.62 (9.20-12.25) and 2.79 (2.61-2.97), 345.74 (312.03-383.10) and 28.06 (25.01-31.52), respectively. Eighteen percent of patients were classified as rapid acetylators, and 34% and 43% as slow and intermediate acetylators, respectively. Rapid and intermediate acetylator status based on NAT 2 genotype resulted in 2.3 and 1.6 times higher isoniazid clearance than slow acetylators. We found no effects of the SLCO1B1 genotypes on rifampicin pharmacokinetics. Conclusion: Plasma concentrations of rifampicin, isoniazid, and pyrazinamide were low overall in our patients. Isoniazid clearance was high overall and as expected higher in rapid and intermediate acetylators resulting in lower drug exposures. In contrast to reports from previous South African or Ugandan studies, we did not find any effects of the SLCO1B1 or other genotypes tested on rifampicin PK. However, our findings are in keeping with more recent studies from Malawi and India emphasizing the need for geographically diverse and adequately powered studies. The clinical relevance of the low tuberculosis drug concentrations warrants further investigation.Keywords: rifampicin, isoniazid pharmacokinetics, genetics, NAT2, SLCO1B1, tuberculosis
Procedia PDF Downloads 17829 Charcoal Traditional Production in Portugal: Contribution to the Quantification of Air Pollutant Emissions
Authors: Cátia Gonçalves, Teresa Nunes, Inês Pina, Ana Vicente, C. Alves, Felix Charvet, Daniel Neves, A. Matos
Abstract:
The production of charcoal relies on rudimentary technologies using traditional brick kilns. Charcoal is produced under pyrolysis conditions: breaking down the chemical structure of biomass under high temperature in the absence of air. The amount of the pyrolysis products (charcoal, pyroligneous extract, and flue gas) depends on various parameters, including temperature, time, pressure, kiln design, and wood characteristics like the moisture content. This activity is recognized for its inefficiency and high pollution levels, but it is poorly characterized. This activity is widely distributed and is a vital economic activity in certain regions of Portugal, playing a relevant role in the management of woody residues. The location of the units establishes the biomass used for charcoal production. The Portalegre district, in the Alto Alentejo region (Portugal), is a good example, essentially with rural characteristics, with a predominant farming, agricultural, and forestry profile, and with a significant charcoal production activity. In this district, a recent inventory identifies almost 50 charcoal production units, equivalent to more than 450 kilns, of which 80% appear to be in operation. A field campaign was designed with the objective of determining the composition of the emissions released during a charcoal production cycle. A total of 30 samples of particulate matter and 20 gas samples in Tedlar bags were collected. Particulate and gas samplings were performed in parallel, 2 in the morning and 2 in the afternoon, alternating the inlet heads (PM₁₀ and PM₂.₅), in the particulate sampler. The gas and particulate samples were collected in the plume as close as the emission chimney point. The biomass (dry basis) used in the carbonization process was a mixture of cork oak (77 wt.%), holm oak (7 wt.%), stumps (11 wt.%), and charred wood (5 wt.%) from previous carbonization processes. A cylindrical batch kiln (80 m³) with 4.5 m diameter and 5 m of height was used in this study. The composition of the gases was determined by gas chromatography, while the particulate samples (PM₁₀, PM₂.₅) were subjected to different analytical techniques (thermo-optical transmission technique, ion chromatography, HPAE-PAD, and GC-MS after solvent extraction) after prior gravimetric determination, to study their organic and inorganic constituents. The charcoal production cycle presents widely varying operating conditions, which will be reflected in the composition of gases and particles produced and emitted throughout the process. The concentration of PM₁₀ and PM₂.₅ in the plume was calculated, ranging between 0.003 and 0.293 g m⁻³, and 0.004 and 0.292 g m⁻³, respectively. Total carbon, inorganic ions, and sugars account, in average, for PM10 and PM₂.₅, 65 % and 56 %, 2.8 % and 2.3 %, 1.27 %, and 1.21 %, respectively. The organic fraction studied until now includes more than 30 aliphatic compounds and 20 PAHs. The emission factors of particulate matter to produce charcoal in the traditional kiln were 33 g/kg (wooddb) and 27 g/kg (wooddb) for PM₁₀ and PM₂.₅, respectively. With the data obtained in this study, it is possible to fill the lack of information about the environmental impact of the traditional charcoal production in Portugal. Acknowledgment: Authors thanks to FCT – Portuguese Science Foundation, I.P. and to Ministry of Science, Technology and Higher Education of Portugal for financial support within the scope of the project CHARCLEAN (PCIF/GVB/0179/2017) and CESAM (UIDP/50017/2020 + UIDB/50017/2020).Keywords: brick kilns, charcoal, emission factors, PAHs, total carbon
Procedia PDF Downloads 13428 Flood Risk Assessment for Agricultural Production in a Tropical River Delta Considering Climate Change
Authors: Chandranath Chatterjee, Amina Khatun, Bhabagrahi Sahoo
Abstract:
With the changing climate, precipitation events are intensified in the tropical river basins. Since these river basins are significantly influenced by the monsoonal rainfall pattern, critical impacts are observed on the agricultural practices in the downstream river reaches. This study analyses the crop damage and associated flood risk in terms of net benefit in the paddy-dominated tropical Indian delta of the Mahanadi River. The Mahanadi River basin lies in eastern part of the Indian sub-continent and is greatly affected by the southwest monsoon rainfall extending from the month of June to September. This river delta is highly flood-prone and has suffered from recurring high floods, especially after the 2000s. In this study, the lumped conceptual model, Nedbør Afstrømnings Model (NAM) from the suite of MIKE models, is used for rainfall-runoff modeling. The NAM model is laterally integrated with the MIKE11-Hydrodynamic (HD) model to route the runoffs up to the head of the delta region. To obtain the precipitation-derived future projected discharges at the head of the delta, nine Global Climate Models (GCMs), namely, BCC-CSM1.1(m), GFDL-CM3, GFDL-ESM2G, HadGEM2-AO, IPSL-CM5A-LR, IPSL-CM5A-MR, MIROC5, MIROC-ESM-CHEM and NorESM1-M, available in the Coupled Model Intercomparison Project-Phase 5 (CMIP5) archive are considered. These nine GCMs are previously found to best-capture the Indian Summer Monsoon rainfall. Based on the performance of the nine GCMs in reproducing the historical discharge pattern, three GCMs (HadGEM2-AO, IPSL-CM5A-MR and MIROC-ESM-CHEM) are selected. A higher Taylor Skill Score is considered as the GCM selection criteria. Thereafter, the 10-year return period design flood is estimated using L-moments based flood frequency analysis for the historical and three future projected periods (2010-2039, 2040-2069 and 2070-2099) under Representative Concentration Pathways (RCP) 4.5 and 8.5. A non-dimensional hydrograph analysis is performed to obtain the hydrographs for the historical/projected 10-year return period design floods. These hydrographs are forced into the calibrated and validated coupled 1D-2D hydrodynamic model, MIKE FLOOD, to simulate the flood inundation in the delta region. Historical and projected flood risk is defined based on the information about the flood inundation simulated by the MIKE FLOOD model and the inundation depth-damage-duration relationship of a normal rice variety cultivated in the river delta. In general, flood risk is expected to increase in all the future projected time periods as compared to the historical episode. Further, in comparison to the 2010s (2010-2039), an increased flood risk in the 2040s (2040-2069) is shown by all the three selected GCMs. However, the flood risk then declines in the 2070s as we move towards the end of the century (2070-2099). The methodology adopted herein for flood risk assessment is one of its kind and may be implemented in any world-river basin. The results obtained from this study can help in future flood preparedness by implementing suitable flood adaptation strategies.Keywords: flood frequency analysis, flood risk, global climate models (GCMs), paddy cultivation
Procedia PDF Downloads 6427 Photosynthesis Metabolism Affects Yield Potentials in Jatropha curcas L.: A Transcriptomic and Physiological Data Analysis
Authors: Nisha Govender, Siju Senan, Zeti-Azura Hussein, Wickneswari Ratnam
Abstract:
Jatropha curcas, a well-described bioenergy crop has been extensively accepted as future fuel need especially in tropical regions. Ideal planting material required for large-scale plantation is still lacking. Breeding programmes for improved J. curcas varieties are rendered difficult due to limitations in genetic diversity. Using a combined transcriptome and physiological data, we investigated the molecular and physiological differences in high and low yielding Jatropha curcas to address plausible heritable variations underpinning these differences, in regard to photosynthesis, a key metabolism affecting yield potentials. A total of 6 individual Jatropha plant from 4 accessions described as high and low yielding planting materials were selected from the Experimental Plot A, Universiti Kebangsaan Malaysia (UKM), Bangi. The inflorescence and shoots were collected for transcriptome study. For the physiological study, each individual plant (n=10) from the high and low yielding populations were screened for agronomic traits, chlorophyll content and stomatal patterning. The J. curcas transcriptomes are available under BioProject PRJNA338924 and BioSample SAMN05827448-65, respectively Each transcriptome was subjected to functional annotation analysis of sequence datasets using the BLAST2Go suite; BLASTing, mapping, annotation, statistical analysis and visualization Large-scale phenotyping of the number of fruits per plant (NFPP) and fruits per inflorescence (FPI) classified the high yielding Jatropha accessions with average NFPP =60 and FPI > 10, whereas the low yielding accessions yielded an average NFPP=10 and FPI < 5. Next generation sequencing revealed genes with differential expressions in the high yielding Jatropha relative to the low yielding plants. Distinct differences were observed in transcript level associated to photosynthesis metabolism. DEGs collection in the low yielding population showed comparable CAM photosynthetic metabolism and photorespiration, evident as followings: phosphoenolpyruvate phosphate translocator chloroplastic like isoform with 2.5 fold change (FC) and malate dehydrogenase (2.03 FC). Green leaves have the most pronounced photosynthetic activity in a plant body due to significant accumulation of chloroplast. In most plants, the leaf is always the dominant photosynthesizing heart of the plant body. Large number of the DEGS in the high-yielding population were found attributable to chloroplast and chloroplast associated events; STAY-GREEN chloroplastic, Chlorophyllase-1-like (5.08 FC), beta-amylase (3.66 FC), chlorophyllase-chloroplastic-like (3.1 FC), thiamine thiazole chloroplastic like (2.8 FC), 1-4, alpha glucan branching enzyme chloroplastic amyliplastic (2.6FC), photosynthetic NDH subunit (2.1 FC) and protochlorophyllide chloroplastic (2 FC). The results were parallel to a significant increase in chlorophyll a content in the high yielding population. In addition to the chloroplast associated transcript abundance, the TOO MANY MOUTHS (TMM) at 2.9 FC, which code for distant stomatal distribution and patterning in the high-yielding population may explain high concentration of CO2. The results were in agreement with the role of TMM. Clustered stomata causes back diffusion in the presence of gaps localized closely to one another. We conclude that high yielding Jatropha population corresponds to a collective function of C3 metabolism with a low degree of CAM photosynthetic fixation. From the physiological descriptions, high chlorophyll a content and even distribution of stomata in the leaf contribute to better photosynthetic efficiency in the high yielding Jatropha compared to the low yielding population.Keywords: chlorophyll, gene expression, genetic variation, stomata
Procedia PDF Downloads 234