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, which can serve as a general probe for PRMTs and a lead for further optimization to increase the selectivity for individual PRMT.
Abstract
The Non - Homogeneous Poisson process is considered as one of the statistical subjects which had an importance in other sciences and a large application in different areas as waiting raws and rectifiable systems method , computer and communication systems and the theory of reliability and many other, also it used in modeling the phenomenon that occurred by unfixed way over time (all events that changed by time).
This research deals with some of the basic concepts that are related to the Non - Homogeneous Poisson process , This research carried out two models of the Non - Homogeneous Poisson process which are the power law model , and Musa –okumto , to estimate th
... Show MoreIn globalization, the world became open area to competition for the attractive of investment, and the abilities of each country to win the confidence of investors depend upon the preparation to optimize circumstances. The competitiveness is an essential means of expanding the capacity of developed to coexist in an international environment characterized by globalization. While competition describes the market structure, the behavior of investors and business, competitiveness is interested in the evaluation of business performance or countries and compare them in the conditions of competition available in these markets. Regarding Malaysia, which is depend on FDI-Export- Led Growth strategy, it has taking on diffe
... Show MoreDetecting protein complexes in protein-protein interaction (PPI) networks is a challenging problem in computational biology. To uncover a PPI network into a complex structure, different meta-heuristic algorithms have been proposed in the literature. Unfortunately, many of such methods, including evolutionary algorithms (EAs), are based solely on the topological information of the network rather than on biological information. Despite the effectiveness of EAs over heuristic methods, more inherent biological properties of proteins are rarely investigated and exploited in these approaches. In this paper, we proposed an EA with a new mutation operator for complex detection problems. The proposed mutation operator is formulate
... Show MoreA fixed firefighting system is a key component of fire safeguarding and reducing fire danger. It is installed as a permanent component in a structure to protect the entire or a portion of the building and its contents. The study aims to review the previous studies that deal with the evaluation of fire safety measures and their use in resolving problems associated with fire threats in buildings. For this reason, a number of previous studies in this field were reviewed compared with the NFPA code. The findings revealed that regulatory developments over the last several decades had created an atmosphere conducive to innovation. This has resulted in a growth in the number of fixed firefighting system types now obtainable. Th
... Show MoreOne of the most popular and legally recognized behavioral biometrics is the individual's signature, which is used for verification and identification in many different industries, including business, law, and finance. The purpose of the signature verification method is to distinguish genuine from forged signatures, a task complicated by cultural and personal variances. Analysis, comparison, and evaluation of handwriting features are performed in forensic handwriting analysis to establish whether or not the writing was produced by a known writer. In contrast to other languages, Arabic makes use of diacritics, ligatures, and overlaps that are unique to it. Due to the absence of dynamic information in the writing of Arabic signatures,
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Asthma is a complex disease defined by chronic airway inflammation and airflow limitation causing variable respiratory symptoms which include shortness of breath (SOB), wheezing, chest tightness and cough. Asthma guidelines advocate adding a second long acting bronchodilator to medium doses of inhaled corticosteroids (ICS) rather using high doses of ICS alone to control moderate to severe persistent asthma. The aim of this study was to evaluate the clinical outcomes of three medication regimens indicated for Iraqi patients suffering from persistent asthma.
This study was interventional randomized clinical study conducted on a sample of adult Iraqi asthm
... Show MoreNumerical study has been conducted to investigate the thermal performance enhancement of flat plate solar water collector by integrating the solar collector with metal foam blocks.The flow is assumed to be steady, incompressible and two dimensional in an inclined channel. The channel is provided with eight foam blocks manufactured form copper. The Brinkman-Forchheimer extended Darcy model is utilized to simulate the flow in the porous medium and the Navier-Stokes equation in the fluid region. The energy equation is used with local thermal equilibrium (LTE) assumption to simulate the thermofield inside the porous medium. The current investigation covers a range of solar radiation intensity at 09:00 AM, 12:00 PM, and 04:00
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