Abstract Candida albicans is a commensal fungal pathogen that grows in yeast and hyphal forms in the human gut. C. albicans causes mucosal and cutaneous diseases that can result in significant mortality following systematic infections and it also exhibits drug resistance. Zebrafish have been an excellent model to investigate C. albicans infections because of their transparency and the availability of many transgenic lines. However, there is a limitation in using zebrafish as a model because the fish embryos cannot survive at 37°C therefore it is not suitable for studying Candida infections at physiological relevant human body temperature. In this thesis, the normal embryonic development of Arabian killifish (A. dispar) is investigated, revealing that embryogenesis was divided into 32 stages based on diagnostic patterns of development. A. dispar can also found to tolerate a wide range of temperatures and salinities. This suggests that A. dispar could be developed as a novel model to investigate host-pathogen interactions. The tolerance of A. dispar to high temperatures may in part be attributable to brown pigment cells with a highly fluorescent character that may have developed to allow the fish to adapt to live within extreme environmental conditions with strong sunlight and a wide range of temperatures (Chapter 3). In terms of Candida infections, this study examined A. dispar as a model to test C. albicans pathogenicity. The survival of A. dispar embryos following Candida infection showed a dose dependent relationship. We also found that A. dispar can survive longer than zebrafish after infection. Furthermore, C. albicans cells were observed to undergo a transition from yeast to hyphae at 37°C. An investigation of the ability of mutant strains of C. albicans with defects in cell wall mannosylation revealed a significant impact on virulence, host mortality, and the fishes’ immune response. The present study found that although the deletion of O- and N-mannan from the cell wall of C. albicans, affected fungal burden (attenuation), and the survival of the infected embryos per se was significantly decreased in the infections of the mutant strains compared to the WT. This data confirms the importance of the mannosylation state of the cell wall in triggering an immune recognition event (Chapter 4). A. dispar is also shown to be suitable for studying the effectiveness of 3 | P a g e antifungals. Fluconazole treatment of infected embryos and eggs promoted greater rates of survival at high doses, alongside a significant reduction of C. albicans CFUs (Chapter 4). When looking at the Candida-host interaction, we directly observed phagocytosed yeast cells within macrophages. Various detection methods were used to follow macrophages and neutrophils including Western blotting, immunostaining and histological staining (Sudan black and FITC-tyramide) allowing the monitoring of the time course of the immune cells. A biphasic response of macrophages was detected by L-plastin Western blotting, suggesting activation of two different type of macrophage: activated macrophage (M1) and alternative macrophage (M2). We also assayed reactive oxygen species (ROS) within infected embryos using a fluorescent probe (H2DCFDA), revealing the accumulation of the fluorescent probe at the sites of infection. Quantitative and qualitative analyses of the oxidative and immune response using the H2DCFDA and qPCR were also accomplished within A. dispar embryos after infection with both the WT and mutant strains of Candida albicans (WT, pmr1∆, mnt1-mnt2∆, and och1∆). The results confirmed that the mutant strains did not activate a host oxidative stress response nor immune cell accumulation when compared to WT, suggesting that the immune response is less activated against these mutants. Finally, a new transgenic line of A. dispar fish was developed using Betaactin-DsR-LoxP-GFP. The new transgenic A. dispar is suggested to be an ideal model for real time observation of host-pathogen interactions and for investigation of molecular functions of the immune response. Overall these results improve our understanding of the use of a new transparent fish model to study fungal pathogenesis and demonstrates the potential advantages of using this species in future studies of bacterial, fungal and viral pathogens at a physiologically relevant temperature for human infection. Such a model could lead us to investigate in more depth the key interactions between pathogens and their host and permit the screening and development of new antifungal therapies (that might target the pathogens directly or target the host immune system). View full metadata
In this study, we made a comparison between LASSO & SCAD methods, which are two special methods for dealing with models in partial quantile regression. (Nadaraya & Watson Kernel) was used to estimate the non-parametric part ;in addition, the rule of thumb method was used to estimate the smoothing bandwidth (h). Penalty methods proved to be efficient in estimating the regression coefficients, but the SCAD method according to the mean squared error criterion (MSE) was the best after estimating the missing data using the mean imputation method
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the physical paraneters of oxadizole derivaties as donor molecules have been measured the charge transfer and methanol as solvent have been estimated from the electonic spectra
This research was conducted to study the feasibility of using fruit peels as biosorbent for removal of Pb+2, Cu+2 and Zn+2 ions from simulated wastewater. A waste biomass of Pomegranate Peel or Punicagranatum L. (P. granatum L.) was chosen as neutral biosorbent in this study.Fourier transformation infrared (FTIR) was used to characterize the surface of PGP, the results confirm that amino, carboxylic, hydroxyl and carbonyl group on the surface of PGP. Different parameters such as initial concentration range between (25-200) mg/L, pH (3-7), contact time (1-2) hour, amount of sorbent (0.1- 4) gm, agitation speed range (200- 500) rpm and temperature (25- 50oC), influencing the sorp
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The world is confronted with the twin crisis of fossil fuel depletion and environmental degradation caused by fossil fuel usage. Biodiesel produced from renewable feedstocks such as Jatropha seed oil or animal fats by transesterification offers a solution. Although biodiesel has been produced from various vegetable oils such as Jatropha seed oil, the reaction kinetics studies are very few in literature, hence the need for this study. Jatropha curcas seed oil was extracted and analyzed to determine its free fatty acid and fatty acid composition. The oil was transesterified with methanol at a molar ratio of methanol to oil 8:1, using 1% sodium hydroxide catalyst, at different temperature
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The article considers a creolized text as a means of modern communication, describing its key verbal and visual components; the relationship of concepts polycode and creolized text has been shown; the universal basic image features have been called; the following kinds of creolized texts have been distinguished; it has been proved that the effective means of attracting the attention of the addressee is the use of expressive font features, which are divided into two groups: topographics (mechanisms of varying of areal syntagmatic of a text) and supragraphcs (change of typeface of font).
The advertising mail is considered as one of potential tools that followed to transfer the printed messages to the consumers and public customers whom are located at homes or works. This type of advertising is preferable due to the zero expense to receive the announcements of products, which became recently one of the successful procedures to create new customers and keep them in touch with direct communication. It is also possible to send them to specific group of people who can be classified by the advertisers to select even by name their own clients to give the personality to the clients for a long term of communication.
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In this research the a-As flims have been prepared by thermal evaporation with thickness 250 nm and rata of deposition r_d(1.04nm/sec) as function to annealing temperature (373 and 473K), from XRD analysis we can see that the degree of crystalline increase with T_a, and I-V characteristic for dark and illumination shows that forward bias current varieties approximately exponentially with voltage bias. Also we found that the quality factor and saturation current dependence on annealing temperatures.
This study aims to encapsulate atenolol within floating alginate-ethylcellulose beads as an oral controlled-release delivery system using aqueous colloidal polymer dispersion (ACPD) method.To optimize drug entrapment efficiency and dissolution behavior of the prepared beads, different parameters of drug: polymer ratio, polymer mixture ratio, and gelling agent concentration were involved.The prepared beads were investigated with respect to their buoyancy, encapsulation efficiency, and dissolution behavior in the media: 0.1 N HCl (pH 1.2), acetate buffer (pH 4.6) and phosphate buffer (pH 6.8). The release kinetics and mechanism of the drug from the prepared beads was investigated.All prepared atenolol beads remained f
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PKE Sharquie MD, PDPAA Noaimi MD, DDV, FDSM Al-Ogaily MD, IOSR Journal of Dental and Medical Sciences (IOSR-JDMS), 2015