2 research outputs found
The metrological aspects of converters based on operational amplifiers used to measure the electrical parameters of oxide coatings
Background. The study is devoted to the issue of improving the accuracy of automated measuring instruments for the electrical parameters of oxide coatings. In measuring instruments, integrating circuits based on an operational amplifier, which is a universal amplifying device, are used to perform linear mathematical operations on analog signals. The disadvantage of the integrating circuit is the use of an operational amplifier, when using which it is necessary to take into account many parameters and factors that can affect the output signal, and hence the accuracy of the measured value. Materials and methods. Methods of indirect measurement of voltage and current on the studied sample with an oxide coating using the proposed structures of measuring channels are presented. It is shown that the parameters of operational amplifiers have a significant influence on the additive and multiplicative errors of measurement results, for the analysis of which a linear model of an operational amplifier is considered. Results. Based on the metrological analysis of the voltage measurement channel on the test sample, formulas for estimating additive, multiplicative and nonlinear error components are obtained. The contribution of multiplicative and additive parameters of the operational amplifier to the error of measurement results is analyzed in detail. Conclusions. Metrological analysis of the equivalent circuit of an operational amplifier with feedback has been performed, which can be used to estimate additive and multiplicative errors of circuits based on operational amplifiers widely used in instruments and measuring systems. It is shown that the total relative error of the developed channels for measuring current and voltage does not exceed 0.5%, which makes it possible to measure these values of the studied oxide coatings with guaranteed accuracy
Functional analysis of androgen receptor mutations that confer anti-androgen resistance identified in circulating cell-free DNA from prostate cancer patients
Background:
The androgen receptor (AR) is a pivotal drug target for the treatment of prostate cancer, including its lethal castration-resistant (CRPC) form. All current non-steroidal AR antagonists, such as hydroxyflutamide, bicalutamide, and enzalutamide, target the androgen binding site of the receptor, competing with endogenous androgenic steroids. Several AR mutations in this binding site have been associated with poor prognosis and resistance to conventional prostate cancer drugs. In order to develop an effective CRPC therapy, it is crucial to understand the effects of these mutations on the functionality of the AR and its ability to interact with endogenous steroids and conventional AR inhibitors.
Results:
We previously utilized circulating cell-free DNA (cfDNA) sequencing technology to examine the AR gene for the presence of mutations in CRPC patients. By modifying our sequencing and data analysis approaches, we identify four additional single AR mutations and five mutation combinations associated with CRPC. Importantly, we conduct experimental functionalization of all the AR mutations identified by the current and previous cfDNA sequencing to reveal novel gain-of-function scenarios. Finally, we evaluate the effect of a novel class of AR inhibitors targeting the binding function 3 (BF3) site on the activity of CRPC-associated AR mutants.
Conclusions:
This work demonstrates the feasibility of a prognostic and/or diagnostic platform combining the direct identification of AR mutants from patients’ serum, and the functional characterization of these mutants in order to provide personalized recommendations regarding the best future therapy.Other UBCNon UBCReviewedFacult