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.
The flexible joint robot manipulators provide various benefits, but also present many control challenges such as nonlinearities, strong coupling, vibration, etc. This paper proposes optimal second order integral sliding mode control (OSOISMC) for a single link flexible joint manipulator to achieve robust and smooth performance. Firstly, the integral sliding mode control is designed, which consists of a linear quadratic regulator (LQR) as a nominal control, and switching control. This control guarantees the system robustness for the entire process. Then, a nonsingularterminal sliding surface is added to give a second order integral sliding mode control (SOISMC), which reduces chartering effect and gives the finite time convergence as well. S
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In this paper, fatigue damage accumulation were studied using many methods i.e.Corton-Dalon (CD),Corton-Dalon-Marsh(CDM), new non-linear model and experimental method. The prediction of fatigue lifetimes based on the two classical methods, Corton-Dalon (CD)andCorton-Dalon-Marsh (CDM), are uneconomic and non-conservative respectively. However satisfactory predictions were obtained by applying the proposed non-linear model (present model) for medium carbon steel compared with experimental work. Many shortcomings of the two classical methods are related to their inability to take into account the surface treatment effect as shot peening. It is clear that the new model shows that a much better and cons
... Show MoreThe advancements in Information and Communication Technology (ICT), within the previous decades, has significantly changed people’s transmit or store their information over the Internet or networks. So, one of the main challenges is to keep these information safe against attacks. Many researchers and institutions realized the importance and benefits of cryptography in achieving the efficiency and effectiveness of various aspects of secure communication.This work adopts a novel technique for secure data cryptosystem based on chaos theory. The proposed algorithm generate 2-Dimensional key matrix having the same dimensions of the original image that includes random numbers obtained from the 1-Dimensional logistic chaotic map for given con
... Show MoreThis paper presents a new algorithm in an important research field which is the semantic word similarity estimation. A new feature-based algorithm is proposed for measuring the word semantic similarity for the Arabic language. It is a highly systematic language where its words exhibit elegant and rigorous logic. The score of sematic similarity between two Arabic words is calculated as a function of their common and total taxonomical features. An Arabic knowledge source is employed for extracting the taxonomical features as a set of all concepts that subsumed the concepts containing the compared words. The previously developed Arabic word benchmark datasets are used for optimizing and evaluating the proposed algorithm. In this paper,
... Show MoreReading is one of the essential components of the English language. Countries that use English as a second language (ESL) sometimes have difficulties in reading and comprehension. According to many researches, mother tongue has proved some interferences with learning a second language. This study investigated the results of reading difficulties of young second language learners in terms of accuracy, comprehension, and rate using the Neale Analysis of Reading Ability test. The study was carried out in one of the High Schools for Boys in Hyderabad, India and included Grade five, aged 10-12 years. In order to understand the reading difficulties of English as a second language, a qualitative approach was employed. Interview, reading tes
... Show MoreIn this study, NAC-capped CdTe/CdS/ZnS core/double shell QDs were synthesized in an aqueous medium to investigate their utility in distinguishing normal DNA from mutated DNA extracted from biological samples. Following the interaction between the synthesized QDs with DNA extracted from leukemia cases (represents damaged DNA) and that of healthy donors (represents undamaged DNA), differential fluorescent emission maxima and intensities were observed. It was found that damaged DNA from leukemic cells DNA-QDs conjugates at 585 nm while intact DNA (from healthy subjects) DNA–QDs conjugates at 574 nm. The obtained results from the optical analyses indicate that the prepared QDs could be utilized as probe for detecting disrupted DNA th
... Show MoreThe Backstepping Sliding Mode Control is a control technique used for controlling nonlinear systems. In this paper, the performance of the backstepping sliding mode controller schemes for the angular velocity control for a rotary actuator of an angular velocity control system that utilizes a novel hydraulic flow control method called inlet throttling was investigated. For the angular velocity dynamic, a linear state feedback with suitable high gain is designed as the virtual controller, where steady state error can be made arbitrarily small according to the gain value. A time varying sliding variable is then selected based on the designed virtual controller. The resulting control design is robust, and the maximum error of the angular veloci
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