Protein arginine methyltransferases (PRMTs) play important roles in transcription, splicing, DNA damage repair, RNA biology, and cellular metabolism. Thus, PRMTs have been attractive targets for various diseases. In this study, we reported the design and synthesis of a potent pan-inhibitor for PRMTs that tethers a thioadenosine and various substituted guanidino groups through a propyl linker. Compound II757 exhibits a half-maximal inhibition concentration (IC50) value of 5 to 555 nM for eight tested PRMTs, with the highest inhibition for PRMT4 (IC50 = 5 nM). The kinetic study demonstrated that II757 competitively binds at the SAM binding site of PRMT1. Notably, II757 is selective for PRMTs over a panel of other methyltransferases, w

Presentation of urinary calculus ranges from painful urination to acute retention. Diagnosed by x-ray pelvis and non-contrast CT and removal of stone by various methods is the management. Variety in symptoms, sometimes make clinical diagnosis difficult until radiological investigations confirm it. In this case presentation, initial diagnosis was made of Urethrocutaneous fistula may be due to distal stricture, but on investigating, he was diagnosed as urethral calculus in urethral diverticulum , as the reason for his symptoms

The evaluation of subsurface formations as applied to oil well drilling started around 50 years ago. Generally, the curent review articule includes all methods for coring, logging, testing, and sampling. Also the methods for deciphering logs and laboratory tests that are relevant to assessing formations beneath the surface, including a look at the fluids they contain are discussed. Casing is occasionally set in order to more precisely evaluate the formations; as a result, this procedure is also taken into account while evaluating the formations. The petrophysics of reservoir rocks is the branch of science interested in studying chemical and physical properties of permeable media and the components of reservoir rocks which are associated

This study examines the structural performance of concrete-encased pultruded Glass Fiber Reinforced Polymer (GFRP) I-sections with shear connections. It specifically focuses on how different parameters affect the latter’s ductility, flexural strength, and load-carrying capacity. The key variables studied include various shear connector types, spacing, and geometries, as well as the compressive strength of concrete and the properties of GFRP. The finite element modeling and experimental validation show that the shear connectors significantly improve the ductility, ultimate capacity, and load transmission efficiency. The present review emphasizes that the shear connectors greatly enhance the structural performance when they are prop

     In this paper, the botnet detection problem is defined as a feature selection problem and the genetic algorithm (GA) is used to search for the best significant combination of features from the entire search space of set of features. Furthermore, the Decision Tree (DT) classifier is used as an objective function to direct the ability of the proposed GA to locate the combination of features that can correctly classify the activities into normal traffics and botnet attacks. Two datasets  namely the UNSW-NB15 and the Canadian Institute for Cybersecurity Intrusion Detection System 2017 (CICIDS2017), are used as evaluation datasets. The results reveal that the proposed DT-aware GA can effectively find the relevant features from

In this paper two ranking functions are employed to treat the fuzzy multiple objective (FMO) programming model, then using two kinds of membership function, the first one is trapezoidal fuzzy (TF) ordinary membership function, the second one is trapezoidal fuzzy weighted membership function. When the objective function is fuzzy, then should transform and shrinkage the fuzzy model to traditional model, finally solving these models to know which one is better