Binding-potential modeling of the structural instability inPrAg1−xCux

1986 ◽  
Vol 34 (1) ◽  
pp. 240-249 ◽  
Author(s):  
I. Abu-Aljarayesh ◽  
J. S. Kouvel ◽  
T. O. Brun
Keyword(s):  
Structural Instability ◽  
Binding Potential

Quantitative accuracy of serotonergic neurotrans-mission imaging with high-resolution 123I SPECT

2004 ◽  
Vol 43 (06) ◽  
pp. 185-189 ◽  
Author(s):  
J. T. Kuikka
Keyword(s):  
High Resolution ◽  
Scatter Correction ◽  
Region Of Interest ◽  
Binding Potential ◽  
Partial Volume ◽  
Therapeutic Drugs ◽  
Quantitative Accuracy ◽  
Critical Error ◽  
Statistical Noise

Summary Aim: Serotonin transporter (SERT) imaging can be used to study the role of regional abnormalities of neurotransmitter release in various mental disorders and to study the mechanism of action of therapeutic drugs or drugs’ abuse. We examine the quantitative accuracy and reproducibility that can be achieved with high-resolution SPECT of serotonergic neurotransmission. Method: Binding potential (BP) of 123I labeled tracer specific for midbrain SERT was assessed in 20 healthy persons. The effects of scatter, attenuation, partial volume, mis-registration and statistical noise were estimated using phantom and human studies. Results: Without any correction, BP was underestimated by 73%. The partial volume error was the major component in this underestimation whereas the most critical error for the reproducibility was misplacement of region of interest (ROI). Conclusion: The proper ROI registration, the use of the multiple head gamma camera with transmission based scatter correction introduce more relevant results. However, due to the small dimensions of the midbrain SERT structures and poor spatial resolution of SPECT, the improvement without the partial volume correction is not great enough to restore the estimate of BP to that of the true one.

A Review on Quantum Dots: Synthesis to In- silico Analysis as Next Generation Antibacterial Agents

2019 ◽  
Vol 20 (3) ◽  
pp. 255-262 ◽  
Author(s):  
Sounik Manna ◽  
Munmun Ghosh ◽  
Ranadhir Chakraborty ◽  
Sudipto Ghosh ◽  
Santi M. Mandal
Keyword(s):  
Quantum Dots ◽  
Pathogenic Bacteria ◽  
Antibacterial Agents ◽  
Antimicrobial Properties ◽  
Binding Potential ◽  
Antibacterial Drug ◽  
Next Generation ◽  
Mechanism Of Reaction ◽  
High Level ◽  
Membrane Components

Succumbing to Multi-Drug Resistant (MDR) bacteria is a great distress to the recent health care system. Out of the several attempts that have been made to kill MDR pathogens, a few gained short-lived success. The failures, of the discovered or innovated antimicrobials, were mostly due to their high level of toxicity to hosts and the phenomenal rate of developing resistance by the pathogens against the new arsenal. Recently, a few quantum dots were tested against the pathogenic bacteria and therefore, justified for potential stockpiling of next-generation antibacterial agents. The key players for antimicrobial properties of quantum dots are considered to be Reactive Oxygen Species (ROS). The mechanism of reaction between bacteria and quantum dots needs to be better understood. They are generally targeted towards the cell wall and membrane components as lipoteichoic acid and phosphatidyl glycerol of bacteria have been documented here. In this paper, we have attempted to simulate ZnS quantum dots and have analysed their mechanism of reaction as well as binding potential to the above bacterial membrane components using CDOCKER. Results have shown a high level of antibacterial activity towards several pathogenic bacteria which specify their potentiality for future generation antibacterial drug development.

scholarly journals An epilepsy-causing mutation leads to co-translational misfolding of the Kv7.2 channel

BMC Biology ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Janire Urrutia ◽  
Alejandra Aguado ◽  
Carolina Gomis-Perez ◽  
Arantza Muguruza-Montero ◽  
Oscar R. Ballesteros ◽  
...  
Keyword(s):  
Structural Instability ◽  
Binding Assays ◽  
Iq Motif ◽  
Channel Function ◽  
Human Epilepsy ◽  
Pathogenic Variants ◽  
In Silico Studies ◽  
Nascent Chain

Abstract Background The amino acid sequence of proteins generally carries all the necessary information for acquisition of native conformations, but the vectorial nature of translation can additionally determine the folding outcome. Such consideration is particularly relevant in human diseases associated to inherited mutations leading to structural instability, aggregation, and degradation. Mutations in the KCNQ2 gene associated with human epilepsy have been suggested to cause misfolding of the encoded Kv7.2 channel. Although the effect on folding of mutations in some domains has been studied, little is known of the way pathogenic variants located in the calcium responsive domain (CRD) affect folding. Here, we explore how a Kv7.2 mutation (W344R) located in helix A of the CRD and associated with hereditary epilepsy interferes with channel function. Results We report that the epilepsy W344R mutation within the IQ motif of CRD decreases channel function, but contrary to other mutations at this site, it does not impair the interaction with Calmodulin (CaM) in vitro, as monitored by multiple in vitro binding assays. We find negligible impact of the mutation on the structure of the complex by molecular dynamic computations. In silico studies revealed two orientations of the side chain, which are differentially populated by WT and W344R variants. Binding to CaM is impaired when the mutated protein is produced in cellulo but not in vitro, suggesting that this mutation impedes proper folding during translation within the cell by forcing the nascent chain to follow a folding route that leads to a non-native configuration, and thereby generating non-functional ion channels that fail to traffic to proper neuronal compartments. Conclusions Our data suggest that the key pathogenic mechanism of Kv7.2 W344R mutation involves the failure to adopt a configuration that can be recognized by CaM in vivo but not in vitro.

scholarly journals Free-standing reduced graphene oxide (rGO) membrane for salt-rejecting solar desalination via size effect

Nanophotonics ◽  
2020 ◽  
Vol 9 (15) ◽  
pp. 4601-4608 ◽  
Author(s):  
Pengyu Zhuang ◽  
Hanyu Fu ◽  
Ning Xu ◽  
Bo Li ◽  
Jun Xu ◽  
...  
Keyword(s):  
Graphene Oxide ◽  
Reduced Graphene Oxide ◽  
Conversion Efficiency ◽  
High Salinity ◽  
Interlayer Spacing ◽  
Structural Instability ◽  
Solar Thermal ◽  
Free Standing ◽  
Solar Desalination ◽  
Reduced Graphene

AbstractInterfacial solar vapor generation has revived the solar-thermal-based desalination due to its high conversion efficiency of solar energy. However, most solar evaporators reported so far suffer from severe salt-clogging problems during solar desalination, leading to performance degradation and structural instability. Here, we demonstrate a free-standing salt-rejecting reduced graphene oxide (rGO) membrane serving as an efficient, stable, and antisalt-fouling solar evaporator. The evaporation rate of the membrane reaches up to 1.27 kg m−2 h−1 (solar–thermal conversion efficiency ∼79%) under one sun, out of 3.5 wt% brine. More strikingly, due to the tailored narrow interlayer spacing, the rGO membrane can effectively reject ions, preventing salt accumulation even for high salinity brine (∼8 wt% concentration). With enabled salt-antifouling capability, flexibility, as well as stability, our rGO membrane serves as a promising solar evaporator for high salinity brine treatment.

scholarly journals Treadmilling FtsZ polymers drive the directional movement of sPG-synthesis enzymes via a Brownian ratchet mechanism

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Joshua W. McCausland ◽  
Xinxing Yang ◽  
Georgia R. Squyres ◽  
Zhixin Lyu ◽  
Kevin E. Bruce ◽  
...  
Keyword(s):  
Cell Wall ◽  
Single Molecule ◽  
Theoretical Modelling ◽  
Binding Potential ◽  
Central Component ◽  
Macromolecular Complex ◽  
Bacterial Cells ◽  
Brownian Ratchet ◽  
Ratchet Mechanism ◽  
Directional Movement

AbstractThe FtsZ protein is a central component of the bacterial cell division machinery. It polymerizes at mid-cell and recruits more than 30 proteins to assemble into a macromolecular complex to direct cell wall constriction. FtsZ polymers exhibit treadmilling dynamics, driving the processive movement of enzymes that synthesize septal peptidoglycan (sPG). Here, we combine theoretical modelling with single-molecule imaging of live bacterial cells to show that FtsZ’s treadmilling drives the directional movement of sPG enzymes via a Brownian ratchet mechanism. The processivity of the directional movement depends on the binding potential between FtsZ and the sPG enzyme, and on a balance between the enzyme’s diffusion and FtsZ’s treadmilling speed. We propose that this interplay may provide a mechanism to control the spatiotemporal distribution of active sPG enzymes, explaining the distinct roles of FtsZ treadmilling in modulating cell wall constriction rate observed in different bacteria.

High-Throughput Affinity Selection Mass Spectrometry Using SAMDI-MS to Identify Small-Molecule Binders of the Human Rhinovirus 3C Protease

2021 ◽  
pp. 247255522110232
Author(s):  
Michael D. Scholle ◽  
Doug McLaughlin ◽  
Zachary A. Gurard-Levin
Keyword(s):  
Mass Spectrometry ◽  
Drug Discovery ◽  
High Throughput ◽  
High Throughput Screening ◽  
Human Rhinovirus ◽  
Binding Potential ◽  
Affinity Selection ◽  
Response Curves ◽  
Desorption Ionization ◽  
Self Assembled

Affinity selection mass spectrometry (ASMS) has emerged as a powerful high-throughput screening tool used in drug discovery to identify novel ligands against therapeutic targets. This report describes the first high-throughput screen using a novel self-assembled monolayer desorption ionization (SAMDI)–ASMS methodology to reveal ligands for the human rhinovirus 3C (HRV3C) protease. The approach combines self-assembled monolayers of alkanethiolates on gold with matrix-assisted laser desorption ionization time-of-flight (MALDI TOF) mass spectrometry (MS), a technique termed SAMDI-ASMS. The primary screen of more than 100,000 compounds in pools of 8 compounds per well was completed in less than 8 h, and informs on the binding potential and selectivity of each compound. Initial hits were confirmed in follow-up SAMDI-ASMS experiments in single-concentration and dose–response curves. The ligands identified by SAMDI-ASMS were further validated using differential scanning fluorimetry (DSF) and in functional protease assays against HRV3C and the related SARS-CoV-2 3CLpro enzyme. SAMDI-ASMS offers key benefits for drug discovery over traditional ASMS approaches, including the high-throughput workflow and readout, minimizing compound misbehavior by using smaller compound pools, and up to a 50-fold reduction in reagent consumption. The flexibility of this novel technology opens avenues for high-throughput ASMS assays of any target, thereby accelerating drug discovery for diverse diseases.

scholarly journals Can We Extrapolate SINS Score to Evaluate Instability in Spinal Tuberculosis?

2021 ◽  
pp. 219256822110308
Author(s):  
Yogesh Kishorkant Pithwa ◽  
Vikrant Sinha Roy
Keyword(s):  
Prospective Observational Study ◽  
Surgical Intervention ◽  
Spinal Tuberculosis ◽  
Neurological Status ◽  
Structural Instability ◽  
Stable Group ◽  
Surgical Decision ◽  
Helpful Tool ◽  
Surgical Decision Making

Study Design: Prospective Observational Study. Objectives: To assess the feasibility of utilizing SINS score, originally suggested for neoplastic conditions, to assess structural instability in spinal tuberculosis. Methods: Patients with an established diagnosis of spinal tuberculosis were included in the study. Based on SINS scoring, patients classified as those with “indeterminate stability” were managed with or without surgery based on other parameters including neurological status, severity of pain, medical comorbidities, etc. Results: Eighty [39 males, 41 females] patients prospectively evaluated with mean age 46.74 ± 17.3 years. Classification done into stable [n = 7], indeterminate [n = 45] and unstable [n = 28] groups based on SINS scoring. All the patients in unstable group were treated with surgical stabilization whereas none in the stable group required surgical stabilization. In the indeterminate group, 26 patients underwent surgical stabilization, while 19 treated non-operatively. Major determinants predisposing to surgical intervention in “indeterminate group” were pain [14 of 26 patients] and neurological status [11 of 26 patients]. Mean follow-up 38.5 ± 22.61 months with minimum follow-up being 24 months. Preoperative VAS score for pain improved from median of 9/10 to 1/10 following surgery [ P < .0001]. In the non-operative group, the improvement was from median score of 6/10 to 1/10 [ P < .0001]. Preoperative ODI improved in non-operative and operative group from median of 42% and 70%, respectively to 10% and 12%, respectively in the postoperative period [ P < .0001 for both groups]. Conclusions: SINS scoring can be a helpful tool in surgical decision-making even in spinal tuberculosis. Further refinement of the score can be done with a larger, multicenter study.

scholarly journals Dead-Time Compensation for the First-Order Dead-Time Processes: Towards a Broader Overview

Mathematics ◽  
2021 ◽  
Vol 9 (13) ◽  
pp. 1519
Author(s):  
Mikulas Huba ◽  
Pavol Bistak ◽  
Damir Vrancic ◽  
Katarina Zakova
Keyword(s):  
Degrees Of Freedom ◽  
Dead Time ◽  
Feedforward Control ◽  
Structural Instability ◽  
Smith Predictor ◽  
Actual Process ◽  
Delayed Systems ◽  
First Order ◽  
Plant Modelling ◽  
Dead Time Compensation

The article reviews the results of a number of recent papers dealing with the revision of the simplest approaches to the control of first-order time-delayed systems. The concise introductory review is extended by an analysis of two discrete-time approaches to dead-time compensation control of stable, integrating, and unstable first-order dead-time processes including simple diagnostics of the model used and focusing on the possibility of simplified but reliable plant modelling. The first approach, based on the first historically known dead-time compensator (DTC) with possible dead-beat performance, is based on the reconstruction of the actual process variables and the compensation of input disturbances by an extended state observer (ESO). Such solutions play an important role both in a disturbance observer (DOB) based control and in an active disturbance rejection control (ADRC). The second approach considered comes from the Smith predictor with two degrees of freedom, which combines feedforward control with output disturbance reconstruction and compensation by the parallel plant model. It is shown that these two approaches offer advantageous properties in the case of actuator limitations, in contrast to the commonly used PID controllers. However, when applied to integrating and unstable first-order systems, the unconstrained and possibly unobservable output disturbance signal of the second solution must be eliminated from the control loop, due to the hidden structural instability of the Smith predictor-like solutions. The modified solutions, usually referred to as filtered Smith predictor (FSP), then no longer provide a disturbance signal and thus no longer fully fit into the concept of Industry 4.0, which is focused on further optimization, predictive maintenance in dynamic systems, diagnosis, fault detection and fault identification of dynamic processes and forms the basis for the digitalization of smart production. Nevertheless, the detailed analysis of the elimination of the unstable disturbance response mode is also worth mentioning in terms of other possible solutions. The application of both approaches to the control of a thermal process shows almost equivalent quality, but with different dependencies on the tuning parameters used. It is confirmed that a more detailed identification of the controlled process and the resulting higher complexity of the control algorithms does not necessarily lead to an increase in the resulting quality of the transients, which underlines the importance of the simplified plant modelling for practice.

Sign in / Sign up

Export Citation Format

Share Document