scholarly journals An Azo Coupling-Based Chemoproteomic Approach to Systematically Profile the Tyrosine Reactivity in the Human Proteome

2021 ◽  
Author(s):  
Fangxu Sun ◽  
Suttipong Suttapitugsakul ◽  
Ronghu Wu
Keyword(s):  
Large Scale ◽  
Diazonium Salt ◽  
Human Proteome ◽  
Binding Property ◽  
Tyrosine Residue ◽  
Azo Coupling ◽  
Mcf7 Cells ◽  
Bioorthogonal Chemistry ◽  
Tyrosine Residues ◽  
Wide Range

<p>The tyrosine residue of proteins participates in a wide range of activities including enzymatic catalysis, protein-protein interaction, and protein-ligand binding. However, the functional annotation of the tyrosine residues on a large scale is still very challenging. Here, we report a novel method integrating azo coupling, bioorthogonal chemistry, and multiplexed proteomics to globally investigate the tyrosine reactivity in the human proteome. Based on the azo-coupling reaction between aryl diazonium salt and the tyrosine residue, the two different probes were evaluated, and the probe with the best performance was employed to specifically target the tyrosine residues. After the reaction, tagged tyrosine containing peptides were selectively enriched using bioorthogonal chemistry, and a small tag on the peptides from the cleavage perfectly fits for site-specific analysis by MS. Coupling with multiplexed proteomics, we quantified over 5,000 tyrosine sites in MCF7 cells and these quantified sites displayed a wide range of reactivity. The tyrosine residues with high reactivity were found on functionally and structurally diverse proteins, including those with the catalytic activity and binding property. This method can be extensively applied to advance our understanding of protein functions and facilitate the development of covalent drugs to regulate protein activity.</p>

scholarly journals An Azo Coupling-Based Chemoproteomic Approach to Systematically Profile the Tyrosine Reactivity in the Human Proteome

2021 ◽  
Author(s):  
Fangxu Sun ◽  
Suttipong Suttapitugsakul ◽  
Ronghu Wu
Keyword(s):  
Large Scale ◽  
Diazonium Salt ◽  
Human Proteome ◽  
Binding Property ◽  
Tyrosine Residue ◽  
Azo Coupling ◽  
Mcf7 Cells ◽  
Bioorthogonal Chemistry ◽  
Tyrosine Residues ◽  
Wide Range

<p>The tyrosine residue of proteins participates in a wide range of activities including enzymatic catalysis, protein-protein interaction, and protein-ligand binding. However, the functional annotation of the tyrosine residues on a large scale is still very challenging. Here, we report a novel method integrating azo coupling, bioorthogonal chemistry, and multiplexed proteomics to globally investigate the tyrosine reactivity in the human proteome. Based on the azo-coupling reaction between aryl diazonium salt and the tyrosine residue, the two different probes were evaluated, and the probe with the best performance was employed to specifically target the tyrosine residues. After the reaction, tagged tyrosine containing peptides were selectively enriched using bioorthogonal chemistry, and a small tag on the peptides from the cleavage perfectly fits for site-specific analysis by MS. Coupling with multiplexed proteomics, we quantified over 5,000 tyrosine sites in MCF7 cells and these quantified sites displayed a wide range of reactivity. The tyrosine residues with high reactivity were found on functionally and structurally diverse proteins, including those with the catalytic activity and binding property. This method can be extensively applied to advance our understanding of protein functions and facilitate the development of covalent drugs to regulate protein activity.</p>

scholarly journals Bioinformatics analysis reveals biophysical and evolutionary insights into the 3-nitrotyrosine post-translational modification in the human proteome

Open Biology ◽  
2013 ◽  
Vol 3 (2) ◽  
pp. 120148 ◽  
Author(s):  
John Y. Ng ◽  
Lies Boelen ◽  
Jason W. H. Wong
Keyword(s):  
Protein Function ◽  
Bioinformatics Analysis ◽  
Proteome Analysis ◽  
Human Proteome ◽  
Prediction Algorithm ◽  
Post Translational Modification ◽  
Tyrosine Residues ◽  
Cellular Processes ◽  
Wide Range ◽  
Human Proteins

Protein 3-nitrotyrosine is a post-translational modification that commonly arises from the nitration of tyrosine residues. This modification has been detected under a wide range of pathological conditions and has been shown to alter protein function. Whether 3-nitrotyrosine is important in normal cellular processes or is likely to affect specific biological pathways remains unclear. Using GPS-YNO2, a recently described 3-nitrotyrosine prediction algorithm, a set of predictions for nitrated residues in the human proteome was generated. In total, 9.27 per cent of the proteome was predicted to be nitratable (27 922/301 091). By matching the predictions against a set of curated and experimentally validated 3-nitrotyrosine sites in human proteins, it was found that GPS-YNO2 is able to predict 73.1 per cent (404/553) of these sites. Furthermore, of these sites, 42 have been shown to be nitrated endogenously, with 85.7 per cent (36/42) of these predicted to be nitrated. This demonstrates the feasibility of using the predicted dataset for a whole proteome analysis. A comprehensive bioinformatics analysis was subsequently performed on predicted and all experimentally validated nitrated tyrosine. This found mild but specific biophysical constraints that affect the susceptibility of tyrosine to nitration, and these may play a role in increasing the likelihood of 3-nitrotyrosine to affect processes, including phosphorylation and DNA binding. Furthermore, examining the evolutionary conservation of predicted 3-nitrotyrosine showed that, relative to non-nitrated tyrosine residues, 3-nitrotyrosine residues are generally less conserved. This suggests that, at least in the majority of cases, 3-nitrotyrosine is likely to have a deleterious effect on protein function and less likely to be important in normal cellular function.

scholarly journals 1H-n.m.r. studies of the isolated activation segment from pig procarboxypeptidase A

1990 ◽  
Vol 267 (1) ◽  
pp. 213-220 ◽  
Author(s):  
J Vendrell ◽  
F X Avilés ◽  
M Vilanova ◽  
C H Turner ◽  
C Crane-Robinson
Keyword(s):  
Solution Structure ◽  
Tyrosine Residue ◽  
Ph Titration ◽  
Tyrosine Residues ◽  
Wide Range ◽  
Activation Segment ◽  
Nuclear Overhauser ◽  
Nuclear Overhauser Effects ◽  
Very High ◽  
Alpha Carbon

The isolated activation segment (asA) from pig pancreatic procarboxypeptidase A was studied by 1H-n.m.r. spectroscopy over a wide range of solution conditions. Isolated asA shows many characteristics of compactly folded globular proteins, such as the observation of perturbed positions for resonances from methyl groups, alpha-carbon atoms, histidine residues and the tyrosine residue. The single tyrosine residue (Tyr-70) exhibits a very high pKa, and both histidine and tyrosine residues show slow chemical modification (deuteration and iodination). In contrast, asA shows rapid NH exchange. Analysis of the spectra by pH titration and nuclear Overhauser effects revealed several residue interactions. Quantitative analysis of deuterium and tritium exchange allowed the assignment of the histidine C-2-H resonances to their respective residues in the sequence. His-66, the closest to the sites of proteolytic attack in the proenzyme, is shown to be the most accessible to solvent in procarboxypeptidase A. It was also shown that asA is thermally very stable [‘melting’ temperature (Tm) 88 degrees C] and requires a high urea concentration for denaturation (6.25 M, at pH 7.5). Evidence is presented for some degree of conformational flexibility in the premelting range, a feature that could be ascribed to the preponderance of helical secondary structure and to the lack of disulphide bridges. The free solution structure of asA is probably unchanged when it binds to carboxypeptidase A.

Electron microscopy study of reactively sputter-deposited Ti/N films on silicon

1992 ◽  
Vol 50 (2) ◽  
pp. 1362-1363
Author(s):  
V. C. Kannan ◽  
A. K. Singh ◽  
R. B. Irwin ◽  
S. Chittipeddi ◽  
F. D. Nkansah ◽  
...  
Keyword(s):  
Integrated Circuits ◽  
Large Scale ◽  
Hexagonal Phase ◽  
Microscopy Study ◽  
Electron Microscopy Study ◽  
Process Conditions ◽  
Tin Films ◽  
Wide Range ◽  
Fcc Phase ◽  
Circuits Vlsi

Titanium nitride (TiN) films have historically been used as diffusion barrier between silicon and aluminum, as an adhesion layer for tungsten deposition and as an interconnect material etc. Recently, the role of TiN films as contact barriers in very large scale silicon integrated circuits (VLSI) has been extensively studied. TiN films have resistivities on the order of 20μ Ω-cm which is much lower than that of titanium (nearly 66μ Ω-cm). Deposited TiN films show resistivities which vary from 20 to 100μ Ω-cm depending upon the type of deposition and process conditions. TiNx is known to have a NaCl type crystal structure for a wide range of compositions. Change in color from metallic luster to gold reflects the stabilization of the TiNx (FCC) phase over the close packed Ti(N) hexagonal phase. It was found that TiN (1:1) ideal composition with the FCC (NaCl-type) structure gives the best electrical property.

THE SOME QUESTIONS OF AUTONOMOUS MOTION AND MANAGEMENT OF LAND-MOBILE ROBOTIC COMPLEXES FOR UKRAINIAN GROUND FORCESE

2019 ◽  
pp. 53-58
Author(s):  
О. Кravchuk ◽  
V. Symonenkov ◽  
I. Symonenkova ◽  
O. Hryhorev
Keyword(s):  
Large Scale ◽  
Armed Forces ◽  
Distributed Information ◽  
Wide Range ◽  
Highly Effective ◽  
Information Management Systems ◽  
Robotic Devices ◽  
Principles And Standards ◽  
And Control ◽  
The Eu

Today, more than forty countries of the world are engaged in the development of military-purpose robots. A number of unique mobile robots with a wide range of capabilities are already being used by combat and intelligence units of the Armed forces of the developed world countries to conduct battlefield intelligence and support tactical groups. At present, the issue of using the latest information technology in the field of military robotics is thoroughly investigated, and the creation of highly effective information management systems in the land-mobile robotic complexes has acquired a new phase associated with the use of distributed information and sensory systems and consists in the transition from application of separate sensors and devices to the construction of modular information subsystems, which provide the availability of various data sources and complex methods of information processing. The purpose of the article is to investigate the ways to increase the autonomy of the land-mobile robotic complexes using in a non-deterministic conditions of modern combat. Relevance of researches is connected with the necessity of creation of highly effective information and control systems in the perspective robotic means for the needs of Land Forces of Ukraine. The development of the Armed Forces of Ukraine management system based on the criteria adopted by the EU and NATO member states is one of the main directions of increasing the effectiveness of the use of forces (forces), which involves achieving the principles and standards necessary for Ukraine to become a member of the EU and NATO. The inherent features of achieving these criteria will be the transition to a reduction of tasks of the combined-arms units and the large-scale use of high-precision weapons and land remote-controlled robotic devices. According to the views of the leading specialists in the field of robotics, the automation of information subsystems and components of the land-mobile robotic complexes can increase safety, reliability, error-tolerance and the effectiveness of the use of robotic means by standardizing the necessary actions with minimal human intervention, that is, a significant increase in the autonomy of the land-mobile robotic complexes for the needs of Land Forces of Ukraine.

Stirring and aeration system for the upgrading of small waste water treatment plants

1994 ◽  
Vol 29 (12) ◽  
pp. 149-156 ◽  
Author(s):  
Marcus Höfken ◽  
Katharina Zähringer ◽  
Franz Bischof
Keyword(s):  
Waste Water ◽  
Water Treatment ◽  
Large Scale ◽  
Waste Water Treatment ◽  
Water Treatment Plants ◽  
Waste Water Treatment Plants ◽  
Basic Fluid ◽  
Aeration System ◽  
Technical Realization ◽  
Wide Range

A novel agitating system has been developed which allows for individual or combined operation of stirring and aeration processes. Basic fluid mechanical considerations led to the innovative hyperboloid design of the stirrer body, which ensures high efficiencies in the stirring and the aeration mode, gentle circulation with low shear forces, excellent controllability, and a wide range of applications. This paper presents the basic considerations which led to the operating principle, the technical realization of the system and experimental results in a large-scale plant. The characteristics of the system and the differences to other stirring and aeration systems are illustrated. Details of the technical realization are shown, which conform to the specific demands of applications in the biological treatment of waste water. Special regard is given to applications in the upgrading of small compact waste water treatment plants.

Thin structure of heterogeneous and multiphase fluid flows

2012 ◽  
Vol 9 (1) ◽  
pp. 175-180
Author(s):  
Yu.D. Chashechkin
Keyword(s):  
Large Scale ◽  
Fundamental System ◽  
Fluid Flows ◽  
Regular Solutions ◽  
Flow Models ◽  
Group Methods ◽  
Wide Range ◽  
Thin Structure ◽  
Multiphase Fluid ◽  
Complete Solutions

According to the results of visualization of streams, the existence of structures in a wide range of scales is noted: from galactic to micron. The use of a fundamental system of equations is substantiated based on the results of comparing symmetries of various flow models with the usage of theoretical group methods. Complete solutions of the system are found by the methods of the singular perturbations theory with a condition of compatibility, which determines the characteristic equation. A comparison of complete solutions with experimental data shows that regular solutions characterize large-scale components of the flow, a rich family of singular solutions describes formation of the thin media structure. Examples of calculations and observations of stratified, rotating and multiphase media are given. The requirements for the technique of an adequate experiment are discussed.

Integrative Data Analysis from a Unifying Research Synthesis Perspective

2018 ◽  
Author(s):  
Eun-Young Mun ◽  
Anne E. Ray
Keyword(s):  
Data Analysis ◽  
Large Scale ◽  
Research Synthesis ◽  
Alcohol Intervention ◽  
Data Set ◽  
Integrative Data Analysis ◽  
Level Data ◽  
Model Complex ◽  
Wide Range ◽  
Individual Participant

Integrative data analysis (IDA) is a promising new approach in psychological research and has been well received in the field of alcohol research. This chapter provides a larger unifying research synthesis framework for IDA. Major advantages of IDA of individual participant-level data include better and more flexible ways to examine subgroups, model complex relationships, deal with methodological and clinical heterogeneity, and examine infrequently occurring behaviors. However, between-study heterogeneity in measures, designs, and samples and systematic study-level missing data are significant barriers to IDA and, more broadly, to large-scale research synthesis. Based on the authors’ experience working on the Project INTEGRATE data set, which combined individual participant-level data from 24 independent college brief alcohol intervention studies, it is also recognized that IDA investigations require a wide range of expertise and considerable resources and that some minimum standards for reporting IDA studies may be needed to improve transparency and quality of evidence.

Quantum Optomechanics and Nanomechanics

2020 ◽  
Keyword(s):  
Gravitational Wave ◽  
Summer School ◽  
Large Scale ◽  
Quantum Noise ◽  
Foundations Of Quantum Mechanics ◽  
Wide Range ◽  
Measurement Laser ◽  
Quantum Limits ◽  
Quantum Optomechanics ◽  
Quantum Ground State

The Les Houches Summer School 2015 covered the emerging fields of cavity optomechanics and quantum nanomechanics. Optomechanics is flourishing and its concepts and techniques are now applied to a wide range of topics. Modern quantum optomechanics was born in the late 70s in the framework of gravitational wave interferometry, initially focusing on the quantum limits of displacement measurements. Carlton Caves, Vladimir Braginsky, and others realized that the sensitivity of the anticipated large-scale gravitational-wave interferometers (GWI) was fundamentally limited by the quantum fluctuations of the measurement laser beam. After tremendous experimental progress, the sensitivity of the upcoming next generation of GWI will effectively be limited by quantum noise. In this way, quantum-optomechanical effects will directly affect the operation of what is arguably the world’s most impressive precision experiment. However, optomechanics has also gained a life of its own with a focus on the quantum aspects of moving mirrors. Laser light can be used to cool mechanical resonators well below the temperature of their environment. After proof-of-principle demonstrations of this cooling in 2006, a number of systems were used as the field gradually merged with its condensed matter cousin (nanomechanical systems) to try to reach the mechanical quantum ground state, eventually demonstrated in 2010 by pure cryogenic techniques and a year later by a combination of cryogenic and radiation-pressure cooling. The book covers all aspects—historical, theoretical, experimental—of the field, with its applications to quantum measurement, foundations of quantum mechanics and quantum information. Essential reading for any researcher in the field.

scholarly journals Current Wildland Fire Patterns and Challenges in Europe: A Synthesis of National Perspectives

2021 ◽  
Vol 14 ◽  
pp. 117862212110281
Author(s):  
Nieves Fernandez-Anez ◽  
Andrey Krasovskiy ◽  
Mortimer Müller ◽  
Harald Vacik ◽  
Jan Baetens ◽  
...  
Keyword(s):  
Land Use ◽  
Large Scale ◽  
Wildland Fire ◽  
Human Life ◽  
Local Analysis ◽  
Wildland Fires ◽  
Fire Statistics ◽  
Quantitative Evidence ◽  
Wide Range ◽  
Fire Patterns

Changes in climate, land use, and land management impact the occurrence and severity of wildland fires in many parts of the world. This is particularly evident in Europe, where ongoing changes in land use have strongly modified fire patterns over the last decades. Although satellite data by the European Forest Fire Information System provide large-scale wildland fire statistics across European countries, there is still a crucial need to collect and summarize in-depth local analysis and understanding of the wildland fire condition and associated challenges across Europe. This article aims to provide a general overview of the current wildland fire patterns and challenges as perceived by national representatives, supplemented by national fire statistics (2009–2018) across Europe. For each of the 31 countries included, we present a perspective authored by scientists or practitioners from each respective country, representing a wide range of disciplines and cultural backgrounds. The authors were selected from members of the COST Action “Fire and the Earth System: Science & Society” funded by the European Commission with the aim to share knowledge and improve communication about wildland fire. Where relevant, a brief overview of key studies, particular wildland fire challenges a country is facing, and an overview of notable recent fire events are also presented. Key perceived challenges included (1) the lack of consistent and detailed records for wildland fire events, within and across countries, (2) an increase in wildland fires that pose a risk to properties and human life due to high population densities and sprawl into forested regions, and (3) the view that, irrespective of changes in management, climate change is likely to increase the frequency and impact of wildland fires in the coming decades. Addressing challenge (1) will not only be valuable in advancing national and pan-European wildland fire management strategies, but also in evaluating perceptions (2) and (3) against more robust quantitative evidence.

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