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
Here we present the results of experiments involving cynomolgus macaques, in which a model of traumatic spinal cord injury (TSCI) was created by using a balloon catheter inserted into the epidural space. Prior to the creation of the lesion, we inserted an EMG recording device to facilitate measurement of tail movement and muscle activity before and after TSCI. This model is unique in that the impairment is limited to the tail: the subjects do not experience limb weakness, bladder impairment, or bowel dysfunction. In addition, 4 of the 6 subjects received a combination treatment comprising thyrotropin releasing hormone, selenium, and vitamin E after induction of experimental TSCI. The subjects tolerated the implantation of the recording devi
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Nuclear emission rates for nucleon-induced reactions are theoretically calculated based on the one-component exciton model that uses state density with non-Equidistance Spacing Model (non-ESM). Fair comparison is made from different state density values that assumed various degrees of approximation formulae, beside the zeroth-order formula corresponding to the ESM. Calculations were made for 96Mo nucleus subjected to (N,N) reaction at Emax=50 MeV. The results showed that the non-ESM treatment for the state density will significantly improve the emission rates calculated for various exciton configurations. Three terms might suffice a proper calculation, but the results kept changing even for ten terms. However, five terms is found to give
... Show MoreAerial manipulation of objects has a number of advantages as it is not limited by the morphology of the terrain. One of the main problems of the aerial payload process is the lack of real-time prediction of the interaction between the gripper of the aerial robot and the payload. This paper introduces a digital twin (DT) approach based on impedance control of the aerial payload transmission process. The impedance control technique is implemented to develop the target impedance based on emerging the mass of the payload and the model of the gripper fingers. Tracking the position of the interactional point between the fingers of gripper and payload, inside the impedance control, is achieved using model predictive control (MPD) approach.
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This work is devoted to study the properties of the ground states such as the root-mean square ( ) proton, charge, neutron and matter radii, nuclear density distributions and elastic electron scattering charge form factors for Carbon Isotopes (9C, 12C, 13C, 15C, 16C, 17C, 19C and 22C). The calculations are based on two approaches; the first is by applying the transformed harmonic-oscillator (THO) wavefunctions in local scale transformation (LST) to all nuclear subshells for only 9C, 12C, 13C and 22C. In the second approach, the 9C, 15C, 16C, 17C and 19C isotopes are studied by dividing the whole nuclear system into two parts; the first is the compact core part and the second is the halo part. The core and halo parts are studied using the
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ArcHydro is a model developed for building hydrologic information systems to synthesize geospatial and temporal water resources data that support hydrologic modeling and analysis. Raster-based digital elevation models (DEMs) play an important role in distributed hydrologic modeling supported by geographic information systems (GIS). Digital Elevation Model (DEM) data have been used to derive hydrological features, which serve as inputs to various models. Currently, elevation data are available from several major sources and at different spatial resolutions. Detailed delineation of drainage networks is the first step for many natural resource management studies. Compared with interpretation from aerial photographs or topographic maps, auto
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The logistic regression model of the most important regression models a non-linear which aim getting estimators have a high of efficiency, taking character more advanced in the process of statistical analysis for being a models appropriate form of Binary Data.
Among the problems that appear as a result of the use of some statistical methods I
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The current research aims to investigate the effect of a specimen of Daniel in the acquisition of concepts for the Arabic language curricula material to the students of the third phase of the Faculty of Basic Education Department of Arabic Language. The sample consists of (93) applications and a student of (47) students in the Division (A), which represents the experimental group which studied the use of a specimen of Daniel, and (46) students in the Division (B), which represents the control group, which studied the traditional way. The subject of unified two groups, which subjects the Arabic language curricula which includes six chapters.
The duration of the experiment is a full semester. The researchers also prepared a tool for mea
The developed financial system is essential for increasing economic growth and poverty reduction in the world. The financial development helps in poverty reduction indirectly via intermediate channel which is the economic growth. The financial development enhancing economic development through mobilization of savings and channel them to the most efficient uses with higher economic and social returns. In addition, the economic growth reduces the poverty through two channels. The first is direct by increasing the introduction factors held by poor and improve the situations into the sectors and areas where the poor live. The second is indirect through redistribution the realized incomes from the economic growth as well as the realiz
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