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.
In this article, a numerical method integrated with statistical data simulation technique is introduced to solve a nonlinear system of ordinary differential equations with multiple random variable coefficients. The utilization of Monte Carlo simulation with central divided difference formula of finite difference (FD) method is repeated n times to simulate values of the variable coefficients as random sampling instead being limited as real values with respect to time. The mean of the n final solutions via this integrated technique, named in short as mean Monte Carlo finite difference (MMCFD) method, represents the final solution of the system. This method is proposed for the first time to calculate the numerical solution obtained fo
... Show MoreThis work presents the construction of a test apparatus for air-conditioning application that is flexible in changing a scaled down adsorbent bed modules. To improve the heat and mass transfer performance of the adsorbent bed, a finned-tube of the adsorbent bed heat exchanger was used. The results show that the specific cooling power (SCP) and the coefficient of performance (COP) are 163 W/kg and 0.16, respectively, when the cycle time is 40 min, the hot water temperature is 90oC, the cooling water temperature is 30oC and the evaporative water temperature is 11.4oC.
The main objective of resources management is to supply and support the site operation with necessary resources in a way to achieve the required timing in handing over the work as well as to achieve the cost-realism within the budget estimated. The research aims to know the advantage of using GIS in management of resources as one of the new tools that keep pace with the evolution in various countries around the world also collect the vast amount of spatial data resources in one environment easily to handled and accessed quickly and this help to make the right decision regarding management of resources in various construction projects. The process of using GIS in the management and identification of resources is of extreme importance in t
... Show MoreA simple and accurate method to determinate furosemide (FUR) based on converting the secondary amine to primary amine with acidic hydrolysis then azotization by nitrous acid and coupled with resorcinol as a coupling agent in aqueous medium at pH 13. The optical characteristic like beers law limit found to be (0.25-2.5) μg.ml−1, detection and quantification limits (0.0196) (0.0654) μg.ml−1respectivly and Sandel sensitivity was 0.006738 μg.cm−2. The least-square method was used to evaluate the regression equation and the correlation coefficient. The resulted azo dye has a maximum absorbance at 430 nm with light oran
This paper proposes a new approach to model and analyze erect posture, based on a spherical inverted pendulum which is used to mimic the body posture. The pendulum oscillates in two directions, [Formula: see text] and [Formula: see text], from which the mathematical model was derived and two torque components in oscillation directions were introduced. They are estimated using stabilometric data acquired by a foot pressure mapping system. The model was quantitatively investigated using data from 19 participants, who were first were classified into three groups, according to the foot arch-index. Stabilometric data were then collected and fed into the model to estimate the torque’s components. The components were statistically proce
... Show MoreCancer disease has a complicated pathophysiology and is one of the major causes of death and morbidity. Classical cancer therapies include chemotherapy, radiation therapy, and immunotherapy. A typical treatment is chemotherapy, which delivers cytotoxic medications to patients to suppress the uncontrolled growth of cancerous cells. Conventional oral medication has a number of drawbacks, including a lack of selectivity, cytotoxicity, and multi-drug resistance, all of which offer significant obstacles to effective cancer treatment. Multidrug resistance (MDR) remains a major challenge for effective cancer chemotherapeutic interventions. The advent of nanotechnology approach has developed the field of tumor diagnosis and treatment. Cancer nanote
... Show MoreIn addition to being a novel medication in treating obesity and type 2 diabetes mellitus, tirzepatide is currently being studied to assess its effectiveness and safety on various health parameters, specifically with an emphasis on the neurological field, including sleep medicine and neurodegenerative conditions. In this perspective, we highlight the recent FDA approval of tirzepatide’s use for the treatment of obstructive sleep apnea, with recommendations for future research to extend use in children and adolescents.
Toxic substances have been released into water supplies in recent decades because of fast industrialization and population growth. Fenton electrochemical process has been addressed to treat wastewater which is very popular because of its high efficiency and straightforward design. One of the advanced oxidation processes (AOPs) is electro-Fenton (EF) process, and electrode material significantly affects its performance. Nickel foam was chosen as the source of electro-generated hydrogen peroxide (H2O2) due to its good characteristics. In the present study, the main goals were to explore the effects of operation parameters (FeSO4 concentration, current density, and electrolysis time) on the catalytic performance that was optimized by r
... Show MoreBackground :Evening preparation for colonoscopy is often unsatisfactory and inconvenient. This study was performed to compare the efficacy of bowel preparation at two different timings: night before and morning of endoscopy and to compare the cecal intubation rate and disturbance of sleep hours between these two groups.
Methods: In this prospective randomized endoscopist- blinded trial, 150 patients were enrolled between March 2010 and August 2011. Patients aged between 18 to 80 years needing colonoscopy were included. Patients with prior bowel surgery, suspected bowel obstruction or those who didn't completely fulfill the preparation instructions were excluded. Patients received polyethyelen glycol electrolyte preparation in a mornin