Search

ABSTRACTIntroduction: Proteolysis – targeting chimeras (PROTACs) have emerged as a new modality with the potential to revolutionize drug discovery. PROTACs are heterobifunctional molecules comprising of a ligand targeting a protein of interest, a ligand targeting an E3 ligase and a connecting linker. The aim is instead of inhibiting the target to induce its proteasomal degradation.Areas covered: PROTACs, due to their bifunctional design, possess properties that differentiate them from classical inhibitors. A structural analysis, based on published crystal aspects, kinetic features and aspects of selectivity are discussed. Specific types such as homoPROTACs, PROTACs targeting Tau protein and the first PROTACs recently entering clinical trials are examined.Expert opinion: PROTACs have shown remarkable biological responses in challenging targets, including an unprecedented selectivity over protein family members and even efficacy starting from weak or unspecific binders. Moreover, PROTACs are standing out from classical pharmacology by inducing the degradation of the target protein and not merely its inhibition. However, there are also challenges in the field, such as the rational structure optimization, the evolution of computational tools, limited structural data and the greatly anticipated clinical data. Despite the remaining hurdles, PROTACs are expected to soon become a new therapeutic category of drugs.

AbstractIn this work, the advection-diffusion equation was solved in two dimensions to calculate the normalized crosswind integrated concentration by Laplace technique. Considering that the wind speed is constant and we have two models of the vertical eddy diffusivity, one depends on downwind distance and the other model depends on vertical distance. A comparison between our proposed two models, Gaussian, previous work and observed data measured at Copenhagen, Denmark, have been carried out. One finds that there is a good agreement between predicted (2) model and the observed concentrations than predicted (1), Gaussian and previous work.From the statistical technique, one finds that all models are inside a factor of two with observed data. Regarding to Normalized mean square error (NMSE) and Fraction Bais (FB), proposed model (2) is performance well with observed data than the predicted (1), Gaussian and previous work in unstable condition.

In this  report, we solved the advection–diffusion equation under pollutants deposition on the ground surface, taking wind speed and vertical diffusion depend on the vertical height. Also, we estimated a simple diffusion model from point source in an urban atmosphere and the conservative material with downwind was evaluated. Then, we calculated the extreme ground-level concentration as a function of stack height and plume rise in two cases. Comparison between the proposed models and the emission from the Egyptian Atomic Research Reactor at Inshas had been done. Lastly, we discussed the results in this report.

Die vertikale Diffusion eines inerten Spurenstoffs, der aus einer Quelle in eine instabil geschichtete atmosphärische Grenzschicht freigesetzt wird, wird mit einem analytischen Modell und Feldversuchen untersucht. Die erhaltene analytische Lösung für die Ausbreitungsgleichung basiert auf der Annahme, dass die vertikalen Profile der mittleren Windgeschwindigkeit und des turbulenten vertikalen Diffusionskoeffizienten Potenzgesetzen gehorchen. Die Lösung führt für die vertikale Spurenstoffverteilung auf der Mittellinie der sich ausbreitenden Spurenstoffwolke zu einer nicht gaussförmigen Verteilung. Das analytische Modell wird mit Daten von neun Versuchen verglichen, die in Inshas, Kairo, in Ägypten durchgeführt wurden. Das Modell zeigt eine gute Übereinstimmung mit den gemessenen Daten.

Nearly 5 years of meteorological data were analysed from 18 stations throughout Egypt, classified as located in Mediterranean, Inland, and Red Sea zones. The national annual average wind speed was 5.8 m/s at 10 m height. The Hurguda station (Red Sea coast) has 5.8 m/s mean annual wind speed and the largest peak wind speed there was 13.8 m/s, with 98% of wind-speed records being in the range of 3 to 10 m/s. Dekhala station (Inland) has the least annual average wind speed of 2.3 m/s, with 98.5% of wind speed records in the range of 1 to 5 m/s. For Mediterranean stations, Port Said has the largest mean wind speed of 4.9 m/s. A general wind energy potential considering both wind speed and air density was derived. Comparison are made between Weibull, Rayleigh, and actual data distributions of wind speed and wind power of two years (2003 and 2004). A Weibull distribution is the best match to the actual probability distribution of wind speed data for most stations. The maximum wind energy potential was 373 W/m2in June at El-Tor (Red Sea coast) where the annual mean value was 207 W/m2.

The wind speed at Inshas, Egypt in 2003 is considered as a case study. A statistical analysis gave the annual average wind speed as 3.80 m/s, in the range of 3.0 to 5.0 m/s for 89% of the time. Comparison among Weibull, Rayleigh, and actual data distributions of wind speed and wind power indicates that the Weibull distribution is the better fit. The mean monthly wind speed had its maximum in December and its minimum in February. The maximum wind energy potential was 63.6 W/m2in December and, the annual mean value was 34.4 W/m2.

Wind energy potential is proportional to both air density and the third power of the wind speed averaged over a suitable time period. The wind speed and air density are random variables depending on both time and location. The main objective of this paper is to derive a general wind energy potential formulation, considering the time dependence of both wind speed and air density. A correction factor is derived explicitly in terms of the cross-correlation and the coefficients of variation. The application is performed for environmental and wind speed measurements at the Radiation Protection Department, Nuclear Research Center at Inshas, Egypt.