The control of Foxp3+ regulatory T cell by interleukin-4 receptor alpha-mediated signaling

T regulatory (Treg) cells play a pivotal role in the maintenance of self-tolerance and immune homeostasis. Forkhead box P3 (Foxp3)+ Treg function is controlled by environmental cues of which cytokine-mediated signaling is a dominant component. Recently, Interleukin (IL)-4 has been shown to play an important role in determining the fate of Foxp3+ Tregs. In vivo, IL-4-mediated signaling via Interleukin-4 receptor alpha (IL4Rα) was convincingly shown to mediate Treg transdifferentiation into ex-Foxp3 Th2 or Th17 cells, suggesting a negative regulation of Foxp3+ Tregs by IL-4Rα-mediated signaling. Puzzlingly, however, IL-4-mediated signaling was also independently found to reinforce the Foxp3+ Tregs, counter-arguing for the positive regulation of Foxp3+ Tregs by IL-4Rα-mediated signaling. In the face of such a conundrum, the present work was set forth as an attempt to unambiguously and conclusively decipher the bases of the regulation of Foxp3+ Treg by IL-4Rα-mediated signaling using transgenic murine models. It was first noted that Foxp3+ Treg cells do express IL-4Rα under steady-state. Furthermore, in vitro, purified CD25+ Tregs were prompted to higher Foxp3 expression and increased survival upon stimulation with IL-4 arguing for a potentiating role of IL-4Rα mediated signaling on Foxp3+ Treg cells. To better address the need for the host Foxp3+ Treg cells to express IL-4Rα as observed, we generated Foxp3-specific IL-4Rα deficient mice where IL-4Rα is specifically deleted from Foxp3+ T cells in the whole organism. Even though naïve Foxp3cre IL-4Rα -/lox mice model at homeostasis did neither reveal any significant alteration of the cellular, tissular and phenotypic profile nor development of spontaneous inflammatory disorder when compared to wild-type mice, under S. mansoni infection impairment IL-4Rα-mediated signaling on Foxp3+ Tregs resulted in heightened activation marker expression and elevated T cell effector functions as indicated by increased cytokines production and greater T cell proliferation rate. This heightened immune responsiveness translated overall into an exacerbated parasitic egg-driven fibrogranulomatous inflammation in the liver and the gut of schistosomiasis-diseased Foxp3cre IL-4Rα-/lox mice. Furthermore, in another model of helminth infection with the parasitic nematode, Nippostrongylus brasiliensis, Foxp3cre IL-4Rα-/lox mice showed a higher level of mucus and exaggerated emphysematous pathology in the lungs. Interestingly, the impairment of IL-4Rα signaling within the Foxp3+ Treg population in Foxp3cre IL-4Rα-/lox mice led to a reduced recruitment of Foxp3+ Tregs and a diminished expression of Foxp3, and other associated Treg suppressive markers (i.e. IRF4 and Helios) during the course of these helminth infections. Taken together, our findings supported a role for IL-4Rα signaling in the positive regulation of Foxp3+ Tregs function and thus, the suppression of inflammatory responses during helminth infections. In conclusion, this work demonstrated a positive role for IL-4Rα mediated signaling in the biology of Foxp3+ Treg cells whereby the latter cells require IL-4Rα signaling to survive and maintain Foxp3 expression and suppressive functions so as to efficiently control tissue inflammatory responses during infection. The data presented do provide insights into the mechanisms of Foxp3+ Treg regulation that are highly relevant for the therapeutic control of inflammation during infectious diseases

Marine propeller roughness penalties

PhD ThesisThe main objective of the project is to investigate the influence of surface roughness of marine propeller blades on propulsive power. The work has involved studies in the concept and practice of surface roughness measurement and characterisation as well as application of boundary layer theory for the analysis propeller-ship hull flow interaction of propeller flow and propellar-ship hull flow interaction. From extensive measurements of the surface topography of in-service propellers, a standard measurement procedure using different commercially available propeller-surveying instruments is described. A development of turbulent boundary layer procedures has been made to determine sufficiently accurately the increment of drag coefficient of propeller blade sections due to propeller blade surface roughness. The roughness function used for this integral boundary layer analysis is derived using, principally, Musker's experimental data. In addition, an experimental determination of the roughness function of a replicated propeller surface using a rotor apparatus has been carried out and described in detail. The turbulent boundary layer procedures require a knowledge of the surface variation of pressure over the propeller blade. For this purpose a program based on Riegels method has been used to give the velocity distribution for a given propeller section geometry. This is used with the boundary layer procedures for developing a complete program "PROFNESS" to calculate the increment of drag coefficient of the blade section. Results from different propellers analysed indicate that the power penalty is proportional to the relative blade roughness to the 1/3 power. An investigation has been made to compare the increment of frictional coefficient for a flat plate and propeller section profiles. It is shown that a "rough" flat plane calculation is quite adequate for such work.' The use of a flat plate analogue as a reference to calculate the skin friction resistance of both propeller and hull surfaces is considered. It is shown that the proposed solution of flat plate momentum integral equations provides a valid, simple and practical solution to the problem of predicting the hull and propeller roughness drag penalties. It also provides, particularly for ship hull resistance, a strong support for the ITTC Correlation Line, not only, and importantly, in regard to its slope, but also its level. For shipowners and operators who may not wish to access advanced computer programs, a simplified method has been proposed to calculate the propeller roughness penalties. There is a good agreement between the two simplified and detailed propeller analysis methods. The propeller roughness penalties, which can be obtained from either the simplified or the more rigorous method, can be related to the Rubert Propeller Comparator Gauges in order to quantify the benefits and justify the cost of the blade surface roughness. Analytical procedures have been included which can be used to calculate the combined effects on ship performance of propeller blade and ship hull surface roughnesses.Egyptian Government: 1983/84 & 1984/85 ORS Awards from the Vice-Chancellors and Principals of the Universities of the United Kingdom

Fabrication and Modification of Titania Nanotube Arrays for Harvesting Solar Energy and Drug Delivery Applications

The fast diminishing of fossil fuels in the near future, as well as the global warming caused by increasing greenhouse gases have motivated the urgent quest to develop advanced materials as cost-effective photoanodes for solar light harvesting and many other photocatalytic applications. Recently, titania nanotube arrays (TNTAs) fabricated by anodization process has attracted great interest due to their excellent properties such as: high surface area, vertically oriented, highly organized, one-dimensional, nanotubular structure, photoactivity, chemical stability and biocompatibility. This unique combination of excellent properties makes TNTAs an excellent photoanode for solar light harvesting. However, the relatively wide band gap energy of titania limits its photoactivity to the UV spectra which accounts only for 5 % of solar light spectra. The specific objectives of this thesis are to: First, fabricate reproducible well-organized, vertically-oriented TNTAs in different viscous electrolytes and optimize the fabrication parameters. Second, modify the TNTAs by doping nitrogen and carbon and study the effect of modification on optical properties and photoelectrochemical performance. And third, functionalizing the TNTAs surface by monodispersed magnetic ferrite nanoparticles for improved solar light harvesting and drug delivery application in cancer treatment. The effect of each fabrication parameter such as electric potential, pH, water content, anodization time and electrolyte composition was discussed. TNTAs were successfully fabricated in an inexpensive viscous electrolyte composed of 2 wt.% sodium carboxy methylcellulose (CMC). TNTAs were successfully fabricated on both sides of a Ti disc with total tube length of 9.5 µm with a unique structure composed of conducting Ti metal sandwiched between two semiconducting layers of TNTAs on each side with a new potential electronic and photocatalytic applications. A new, facile, low cost, environment-friendly and nanoarchitecture-safe method was introduced to fabricate N- and C-modified TiO2 nanotube arrays. Modified optical properties with narrow band gap energy, Eg, of 2.65 eV was obtained after annealing the modified TNTAs at 550°C. Modified TNTAs showed enhanced photoelectrochemical performance. Photoconversion efficiency (PCE) was increased from 4.35% for pristine (unmodified) TNTAs to 5.18% for modified TNTAs, an increase of 19%. Effect of nanotubes length of modified TNTAs on photoelectrochemical performance was also studied. Photocurrent density and PCE were increased by increasing nanotube length with a maximum PCE of 6.38% for nanotube length of 55 µm. This implies an excellent light penetration up to 55 µm depth into photoanode which is about 3.6 times higher than the maximum penetration depth (15 µm) in the nanoparticulate photoanode. This increasing pattern of photoconversion efficiency with increasing nanotubes length also implied a high charge separation rate and lower charge recombination rate. This high PCE value was attributed to: band gap reduction due to N- and C-modification of TNTAs surface, increased surface area of long TNTAs compared with short TNTAs, investigated in previous studies, and the excellent light penetration and harvesting properties. Ferrite NPs-encapsulated TNTAs were fabricated for the first time using a facile and efficient method. Ferrite nanoparticles of 13 ± 3 nm diameters were successfully distributed all over the top and inner surface of the nanotubes. UV-Vis reflectance spectra showed excellent visible light absorbance up to wave length of 660 nm (Eg = 1.88 eV). The prepared magnetic nanocomposite showed their potential capability to controlling the drug release of an anti-cancer drug (5-fluorouracil). The drug release of 5-fluorouracil by diffusion was sustained with controlled initial burst effect. The suitability of magnetic nanocomposite for cancer drug delivery was confirmed by in vitro cytotoxicity study

Effect of Propolis as Additive on Some Behavioural Patterns, Performance and Blood Parameters in Muscovy Broiler Ducks

Forty Muscovy ducklings of one day old were used in this study. They were brooded together for 3 weeks and then were randomly divided into two groups, 20 ducklings per each. Each group was housed in a well ventilated, previously cleaned, disinfected and well bedded with saw dust 3 x 3 m pen. Birds were maintained at 33 °C using gas heater and the temperature was gradually reduced by 3 °C / week until 21 °C was reached and then continued to the end of the experiment. Continuous lighting program with 23 hours light to one hour dark was maintained by the natural day light and a 60 watt bulb that placed centrally in each pen at 2 meters height above the heads of birds. Birds were daily fed ad-libitum on a commercial duck broiler starter ration up to 3 weeks of age and on a duck broiler grower finisher ration till 12 weeks old. The first group was fed on these diets without any supplements and used as a control group, however, the second one was fed the finisher rations provided and thoroughly mixed with ethanol extracted propolis at a rate of 2 gm / Kg of diet. Water was freely available allover the experiment. Behaviour, performance and blood parameters of the experimented birds were carried out. Obtained results indicated that use of propolis as a natural feed additive reflected on ducks with a reduction in stress behaviour, increased growth performance, increased immune response and resistance and improved welfare through improving the physical health state

Influence of Some Agricultural Extension Television Elements on Diffusion of Agricultural Information, Rural Knowledge and New Technologies to Tenants in the Gezira Province

Agricultural extension and rural information services provide rural people with information and rural knowledge which they need in order to increase their production, incomes and consequently improve their standard of living. Therefore, rural information systems must involve rural communities and local needs must also be of prime importance. Field surveys were used to collect data from 120 tenants in the Gezira Province in 2003/2004 growing season selected from a total population of 120000 tenants distributed in eight extension areas in the province by using the simple random sampling technique. The collected data were statistically analyzed using percentage and frequency distributions. The results showed unsuitability of some elements of extension television with tenants conditions and preferences in the Gezira Province. It could be concluded that the inconvenient time of broadcasting of extension television programs and their improper presentation negatively influenced diffusion of agricultural information, rural knowledge and new technologies to tenants in the Gezira Province. Thus, more attention should be given to planning, producing and time of transmitting of extension message through effective use of extension television elements

Pilot Experimental Tests on Punching Shear Strength of Flat Plates Reinforced with Stirrups Punching Shear Reinforcement

Flat plates are favor structure systems usually used in parking garages and high-rise buildings due to its simplicity for construction. However, flat plates have some inherent structural problems, due to high shear stress surrounding the supporting columns which cause a catastrophic brittle type of failure called "Punching Shear Failure". Several solutions are used to avoid punching shear failure, including the use of drop panels or punching shear reinforcement. The latter is being a more sophisticated solution from the structural ductility, the architectural and the economical point of view. This study aims at investigating the effect of stirrups as shear reinforcement in enhancing the punching strength of interior slab-column connections. A total of four full-scale interior slab-column connections were tested up to failure. All slabs had a side length of 1700 mm and 160 mm thickness with 200 mm x 200 mm square column. The test parameters were the presence of shear reinforcement and stirrups concentration around the supporting column. The test results showed that the distribution of stirrups over the critical punching shear zone was an efficient solution to enhance not only the punching shear capacity but also the ductility of the connection. Furthermore, the concentrating of stirrups shear reinforcement in the vicinity of the column for the tested slabs increases the punching shear capacity by 13 % compared to the uniform distribution at same amount of shear reinforcement

Productivity of 18F-FDG-PET/CT Diagnostic Tool in the Management of Pediatric Lymphoblastic Lymphoma

BACKGROUND: Lymphoblastic lymphoma (LL) comprises approximately 20% of childhood non-Hodgkin lymphoma (NHL); however, few studies had investigated the role of 18F-FDG-PET/CT in pediatric LL patients. We aim in this study to assess the role of 18F-FDG-PET/CT in the initial staging of newly diagnosed pediatric patients with LL as well as in the assessment of response after induction chemotherapy. PATIENTS AND METHODS: A prospective study enrolled biopsy proven newly diagnosed pediatric LL patients presenting in the Children Cancer Hospital Egypt (CCHE) during the period from October 2014 to October 2016. 18F-FDG-PET/CT was done initially before therapy and after induction chemotherapy in all patients. The patients were followed until the end of April 2018 (mean 23.5 months). RESULTS: All lymphoma involvement lesions (n = 43) were FDG avid and the intensity of nodal FDG uptake was variable. Two patients (11%) had bone marrow (BM) involvement by < 25% blast cells with corresponding positive BM focal uptake in 18F-FDG-PET/CT (SUVmax = 4 and 4.5). Evaluation post induction phase; CT detected 8 residual lesions in 8 patients (44.4%), while 18F-FDG-PET/CT detected only 3 Deauville-positive residual lesions in 3 patients (16.6%). No intensification of therapy was done in all post-induction positive patients. Repeated 18F-FDG-PET/CT at week 18 for post-induction patients revealed cleared all Deauville-positive residual lesions. On the other hand, repeated CT at week 18 detected regression but still residual in 4/8 (50%) post-induction CT lesions with clearance of the rest (50%). CONCLUSION: In initial staging, 18F-FDG-PET/CT is a useful tool for disease extent evaluation of pediatric LL. Moreover, it could provide a diagnostic hint for BM involvement. 18F-FDG-PET/CT done after induction therapy has a good negative predictive value with higher specificity than CT alone, but is not an indication for treatment intensification due to false positive results. However, larger sample size is required for better conclusion

Pilot Experimental Tests on Punching Shear Strength of Flat Plates Reinforced with Stirrups Punching Shear Reinforcement

Flat plates are favor structure systems usually used in parking garages and high-rise buildings due to its simplicity for construction. However, flat plates have some inherent structural problems, due to high shear stress surrounding the supporting columns which cause a catastrophic brittle type of failure called "Punching Shear Failure". Several solutions are used to avoid punching shear failure, including the use of drop panels or punching shear reinforcement. The latter is being a more sophisticated solution from the structural ductility, the architectural and the economical point of view. This study aims at investigating the effect of stirrups as shear reinforcement in enhancing the punching strength of interior slab-column connections. A total of four full-scale interior slab-column connections were tested up to failure. All slabs had a side length of 1700 mm and 160 mm thickness with 200 mm x 200 mm square column. The test parameters were the presence of shear reinforcement and stirrups concentration around the supporting column. The test results showed that the distribution of stirrups over the critical punching shear zone was an efficient solution to enhance not only the punching shear capacity but also the ductility of the connection. Furthermore, the concentrating of stirrups shear reinforcement in the vicinity of the column for the tested slabs increases the punching shear capacity by 13 % compared to the uniform distribution at same amount of shear reinforcement

Unorthodox synthesis, biological activity and DFT studies of novel and multifunctionalized naphthoxocine derivatives

A new promising protocol has been developed for the synthesis of scarce oxocine derivatives 3a–e and 6 through addition of amine-based nucleophiles such as hydroxylamine hydrochloride, primary amine and hydrazide to chromonylidene benzothiazol-2-ylacetonitrile 2 in refluxing dioxane under metal free reaction conditions in moderate to good yields. Other nitrogen nucleophiles such as piperidine, hydrazine and thiosemicarbazide failed to afford the corresponding oxocinols, and instead pyridine derivatives 7, 8 and 10 were obtained exclusively. Predictive study for the biological activities using PASS (prediction of activity spectra for biologically active substances) online software showed optimistic activities for oxocinols 3a–e in the treatment of cancer, influenza A and microbial infections. Additionally, DFT studies of oxocine derivatives 3a–e and 6 indicated the presence of required thermodynamics parameters for the application in dye-sensitized solar cells (DSSCs)

Prediction of Axial Compressive Strength of Hybrid Reinforced Concrete Columns under Static Loading

Steel corrosion is thought to be one of the primary causes of the inadequate durability of concrete buildings in the maritime environment. Because of this, adopting Fiber-Reinforced Polymer (FRP) bars in harsh settings has attracted a lot of attention for its appealing mechanical properties as well as to prevent corrosion issues. But because there hasn't been much research in this area, we don't fully understand how fiber-reinforced polymer (FRP) bars behave when they are compressed. This work's goal is to assess the expected axial compressive strength of columns when hybrid reinforcement is used in place of steel reinforcement. Hybrid bars are steel bars surrounded by a cover shell of Glass or Carbon FRP (hybrid-steel) for longitudinal reinforcement and/or transverse reinforcement. 17 column specimens were included in an experimental study program that was created.The specimens were tested to failure with an axial loading condition. The parameters studied were the type of fibers, the percentage of steel in the hybrid reinforcement for longitudinal main reinforcement ρL(0.96, 0.44, and 0.25), the ratio of the web reinforcement (internal ties), the proportion of fiber in the hybrid bars, as well as the columns' cross sections' rectangularity. Based on the data, mathematical models were devised and assessed to forecast the load bearing capability of the column. The findings indicate that hybrid reinforced concrete columns have acceptable levels of dependability index in general