scholarly journals Large-scale analysis of redox-sensitive conditionally disordered protein regions reveal their widespread nature and key roles in high-level eukaryotic processes

2018 ◽  
Author(s):  
Gábor Erdős ◽  
Bálint Mészáros ◽  
Dana Reichmann ◽  
Zsuzsanna Dosztányi

AbstractRecently developed quantitative redox proteomic studies enable the direct identification of redox-sensing cysteine residues that regulate the functional behavior of target proteins in response to changing levels of reactive oxygen species (ROS). At the molecular level, redox regulation can directly modify the active sites of enzymes, although a growing number of examples indicate the importance of an additional underlying mechanism that involves conditionally disordered proteins. These proteins alter their functional behavior by undergoing a disorder-to-order transition in response to changing redox conditions. However, the extent to which this mechanism is used in various proteomes is currently unknown. Here, we use a recently developed sequence-based prediction tool incorporated into the IUPred2A web server to estimate redox-sensitive conditionally disordered regions on a large scale. We show that redox-sensitive conditional disorder is fairly widespread in various proteomes and that its presence strongly correlates with the expansion of specific domains in multicellular organisms that largely rely on extra stability provided by disulfide bonds or zinc ion binding. The analyses of yeast redox proteomes and human disease data further underlie the significance of this phenomenon in the regulation of a wide range of biological processes, as well as its biomedical importance.

Aerospace ◽  
2018 ◽  
Vol 5 (4) ◽  
pp. 104 ◽  
Author(s):  
Ilias Lappas ◽  
Michail Bozoudis

The development of a parametric model for the variable portion of the Cost Per Flying Hour (CPFH) of an ‘unknown’ aircraft platform and its application to diverse types of fixed and rotary wing aircraft development programs (F-35A, Su-57, Dassault Rafale, T-X candidates, AW189, Airbus RACER among others) is presented. The novelty of this paper lies in the utilization of a diverse sample of aircraft types, aiming to obtain a ‘universal’ Cost Estimating Relationship (CER) applicable to a wide range of platforms. Moreover, the model does not produce absolute cost figures but rather analogy ratios versus the F-16’s CPFH, broadening the model’s applicability. The model will enable an analyst to carry out timely and reliable Operational and Support (O&S) cost estimates for a wide range of ‘unknown’ aircraft platforms at their early stages of conceptual design, despite the lack of actual data from the utilization and support life cycle stages. The statistical analysis is based on Ordinary Least Squares (OLS) regression, conducted with R software (v5.3.1, released on 2 July 2018). The model’s output is validated against officially published CPFH data of several existing ‘mature’ aircraft platforms, including one of the most prolific fighter jet types all over the world, the F-16C/D, which is also used as a reference to compare CPFH estimates of various next generation aircraft platforms. Actual CPFH data of the Hellenic Air Force (HAF) have been used to develop the parametric model, the application of which is expected to significantly inform high level decision making regarding aircraft procurement, budgeting and future force structure planning, including decisions related to large scale aircraft modifications and upgrades.


2013 ◽  
Vol 21 (1-2) ◽  
pp. 1-16 ◽  
Author(s):  
Marek Blazewicz ◽  
Ian Hinder ◽  
David M. Koppelman ◽  
Steven R. Brandt ◽  
Milosz Ciznicki ◽  
...  

Starting from a high-level problem description in terms of partial differential equations using abstract tensor notation, theChemoraframework discretizes, optimizes, and generates complete high performance codes for a wide range of compute architectures. Chemora extends the capabilities of Cactus, facilitating the usage of large-scale CPU/GPU systems in an efficient manner for complex applications, without low-level code tuning. Chemora achieves parallelism through MPI and multi-threading, combining OpenMP and CUDA. Optimizations include high-level code transformations, efficient loop traversal strategies, dynamically selected data and instruction cache usage strategies, and JIT compilation of GPU code tailored to the problem characteristics. The discretization is based on higher-order finite differences on multi-block domains. Chemora's capabilities are demonstrated by simulations of black hole collisions. This problem provides an acid test of the framework, as the Einstein equations contain hundreds of variables and thousands of terms.


Nutrients ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 1364 ◽  
Author(s):  
Ludmila V. Puchkova ◽  
Massimo Broggini ◽  
Elena V. Polishchuk ◽  
Ekaterina Y. Ilyechova ◽  
Roman S. Polishchuk

In humans, copper is an important micronutrient because it is a cofactor of ubiquitous and brain-specific cuproenzymes, as well as a secondary messenger. Failure of the mechanisms supporting copper balance leads to the development of neurodegenerative, oncological, and other severe disorders, whose treatment requires a detailed understanding of copper metabolism. In the body, bioavailable copper exists in two stable oxidation states, Cu(I) and Cu(II), both of which are highly toxic. The toxicity of copper ions is usually overcome by coordinating them with a wide range of ligands. These include the active cuproenzyme centers, copper-binding protein motifs to ensure the safe delivery of copper to its physiological location, and participants in the Cu(I) ↔ Cu(II) redox cycle, in which cellular copper is stored. The use of modern experimental approaches has allowed the overall picture of copper turnover in the cells and the organism to be clarified. However, many aspects of this process remain poorly understood. Some of them can be found out using abiogenic silver ions (Ag(I)), which are isoelectronic to Cu(I). This review covers the physicochemical principles of the ability of Ag(I) to substitute for copper ions in transport proteins and cuproenzyme active sites, the effectiveness of using Ag(I) to study copper routes in the cells and the body, and the limitations associated with Ag(I) remaining stable in only one oxidation state. The use of Ag(I) to restrict copper transport to tumors and the consequences of large-scale use of silver nanoparticles for human health are also discussed.


Author(s):  
Rimma Padovano

"Cloud computing" refers to large-scale parallel and distributed systems, which are essentially collections of autonomous. As a result, the “cloud organization” is made up on a wide range of ideas and experiences collected since the first digital computer was used to solve algorithmically complicated problems. Due to the complexity of established parallel and distributed computing ontologies, it is necessary for developers to have a high level of expertise to get the most out of the consolidated computer resources. The directions for future research for parallel and distributed computing are critically presented in this research: technology and application and cross-cutting concerns.


2021 ◽  
Author(s):  
Peixun Xiong ◽  
Yingbo Kang ◽  
Nan Yao ◽  
Xiang Chen ◽  
Lingxing Zeng ◽  
...  

Abstract Aqueous zinc-metal batteries are promising for large-scale energy storage owing to their reasonable energy density, safety and low cost. However, their practical applications are limited by hydrogen evolution, corrosion, and dendrite formation of Zn anode and there is trade-off between efficiency and stability at high and low temperatures. Herein, we propose a solvation chemistry regulation strategy that can adjust the Zn2+-solvation structure and in situ form a robust and Zn2+-conducting Zn5(CO3)2(OH)6 SEI on the Zn surface, using hybrid electrolytes of water and a polar aprotic N, N-dimethylformamide. As verified by experimental characterizations and computational analyses, the unique solvation structure and the newly formed solid electrolyte interface are created by hybrid electrolytes, resulting in highly reversible and dendrite-free Zn plating/stripping process as well as thermal stability and high ionic conductivity from −30 to 70 °C. The Zn||Zn symmetric cells in hybrid electrolytes are very stable over 2500 h at 25 ℃ and 2000 h even at –20 ℃. Thus, the stability and reversibility of the hybrid zinc-ion capacitors with Zn metal anode in hybrid electrolytes are firstly achieved in a wide and extreme temperature range, demonstrating high capacity retentions and Coulombic efficiencies over 14000, 10000, and 600 cycles at 25, −20, and 70 ℃, respectively.


1995 ◽  
Vol 391 ◽  
Author(s):  
R.A. Augur ◽  
R.A.M. Wolters ◽  
W. Schmidt ◽  
S. Kordić

AbstractThis paper presents new results concerning diffusion at the interface between Al and its oxide, due to electromigration in Al interconnects. The results show that the phenomenon is an important and general one. Significant large-scale modification of the surface of Alalloy conductors was observed after electromigration stress under a wide range of different conditions: 1) in a number of different alloys (Al-Si, Al-Cu, Al-Si-V & Al-Si-V-Pd), 2) with and without passivation, 3) over an extended temperature range, 4) over an extended range of current density, and 5) with a number of different underlayers (SiO2, W-Ti (no vacuum-break before Al deposition) and W-Ti (oxidized surface before Al deposition)). After electromigration stressing, the surface showed height variations: at certain locations the original thickness remained, while at adjacent locations the thickness was reduced; as much as 150nm in 2500 hrs, for Al-Si on oxidized W-Ti metallization. Damage by thinning has received little attention in the past. Based on the results presented, a model for the underlying mechanism is proposed. In this model Al atoms diffuse concurrently along the interface between the Al-metal and its oxide, and through the grain boundaries, even at low stress conditions and in non-bamboo lines.


2011 ◽  
Vol 483 ◽  
pp. 281-286
Author(s):  
Zhao Xin Geng ◽  
Wen Liu ◽  
Xuan Ye Wang ◽  
Xiao Dong Wang ◽  
Zhi Hong Li ◽  
...  

Surface-enhanced Raman scattering (SERS) with enormous enhancements has shown great potential in single-molecule detection, however, the fabrication of large-scale, controllable and reproducible substrates with high SERS activity is a major limitation. This paper provides method to create wafer level SERS substrate with tunable nanoparticle sizes and interparticle gaps. Silver films with different thicknesses were deposited by electron beam evaporation (EBE) and annealed at 260 °C for 15min in nitrogen gas. When annealed, the thin Ag films break up under surface tension to form isolated nanoparticle. The nanoparticle size, density, and shape are found to be dependent on the thickness of Ag and the condition of annealing. The selective deposition of Ag nanoparticle on the silicon substrate is applied to create SERS active sites before the integration with a PDMS microfluidic chip which functions as a sample delivery device and a transparent optical window for SERS. Detections of Rhodamine 6G SERS spectra are accomplished by using a 633nm laser with 300W excitation power. The results show that the fabrication protocol of such a SERS substrate is low-cost, easy-fabrication and inexpensive. Therefore, this substrate may anticipate a wide range of applications in SERS-based sensors.


2021 ◽  
Author(s):  
Giulia Mazzotti ◽  
Clare Webster ◽  
Richard Essery ◽  
Johanna Malle ◽  
Tobias Jonas

<p>Forest snow cover dynamics affect hydrological regimes, ecosystem processes, and climate feedbacks, and thus need to be captured by model applications that operate across a wide range of spatial scales. At large scales and coarse model resolutions, high spatial variability of the processes shaping forest snow cover evolution creates a major modelling challenge. Variability of canopy-snow interactions is determined by heterogeneous canopy structure and can only be explicitly resolved with hyper-resolution models (<5m).</p><p>Here, we address this challenge with model upscaling experiments with the forest snow model FSM2, using hyper-resolution simulations as intermediary between experimental data and coarse-resolution simulations. When run at 2-m resolution, FSM2 is shown to capture the spatial variability of forest snow dynamics with a high level of detail: Its accurate performance is verified at the level of individual energy balance components based on extensive, spatially distributed sub-canopy measurements of micrometeorological and snow variables, obtained with mobile multi-sensor platforms. Results from hyper-resolution simulations over a 150,000 m<sup>2</sup> domain are then compared to spatially lumped, coarse-resolution runs, where 50m x 50m grid cells are represented by one model run only. For the spatially lumped simulations, we evaluate alternative upscaling strategies, aiming to explore the representation of forest snow processes at model resolutions coarser than the spatial scales at which these processes vary and interact.</p><p>Different upscaling strategies exhibited large discrepancies in simulated (1) distribution of snow water equivalent at peak of winter, and (2) timing of snow disappearance. Our results indicate that detailed canopy structure metrics, as included in hyper-resolution runs, are necessary to capture the spatial variability of forest snow processes even at coarser resolutions. They further demonstrate the relevance of accounting for unresolved sub-grid variability in snowmelt calculations even at relatively small spatial aggregation scales. By identifying important model features, which allow coarse-resolution simulations to approximate spatially averaged results of corresponding hyper-resolution simulations, this work provides recommendations for modelling forest snow processes in medium- to large-scale applications.</p>


Author(s):  
V. C. Kannan ◽  
A. K. Singh ◽  
R. B. Irwin ◽  
S. Chittipeddi ◽  
F. D. Nkansah ◽  
...  

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.


Author(s):  
Georgi Derluguian

The author develops ideas about the origin of social inequality during the evolution of human societies and reflects on the possibilities of its overcoming. What makes human beings different from other primates is a high level of egalitarianism and altruism, which contributed to more successful adaptability of human collectives at early stages of the development of society. The transition to agriculture, coupled with substantially increasing population density, was marked by the emergence and institutionalisation of social inequality based on the inequality of tangible assets and symbolic wealth. Then, new institutions of warfare came into existence, and they were aimed at conquering and enslaving the neighbours engaged in productive labour. While exercising control over nature, people also established and strengthened their power over other people. Chiefdom as a new type of polity came into being. Elementary forms of power (political, economic and ideological) served as a basis for the formation of early states. The societies in those states were characterised by social inequality and cruelties, including slavery, mass violence and numerous victims. Nowadays, the old elementary forms of power that are inherent in personalistic chiefdom are still functioning along with modern institutions of public and private bureaucracy. This constitutes the key contradiction of our time, which is the juxtaposition of individual despotic power and public infrastructural one. However, society is evolving towards an ever more efficient combination of social initiatives with the sustainability and viability of large-scale organisations.


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