scholarly journals Hierarchy and control of ageing-related methylation networks

2021 ◽  
Vol 17 (9) ◽  
pp. e1009327
Author(s):  
Gergely Palla ◽  
Péter Pollner ◽  
Judit Börcsök ◽  
András Major ◽  
Béla Molnár ◽  
...  

DNA methylation provides one of the most widely studied biomarkers of ageing. Since the methylation of CpG dinucleotides function as switches in cellular mechanisms, it is plausible to assume that by proper adjustment of these switches age may be tuned. Though, adjusting hundreds of CpG methylation levels coherently may never be feasible and changing just a few positions may lead to biologically unstable state. A prominent example of methylation-based age estimators is provided by Horvath’s clock, based on 353 CpG dinucleotides, showing a high correlation (not necessarily causation) with chronological age across multiple tissue types. On this small subset of CpG dinucleotides we demonstrate how the adjustment of one methylation level leads to a cascade of changes at other sites. Among the studied subset, we locate the most important CpGs (and related genes) that may have a large influence on the rest of the sub-system. According to our analysis, the structure of this network is way more hierarchical compared to what one would expect based on ensembles of uncorrelated connections. Therefore, only a handful of CpGs is enough to modify the system towards a desired state. When propagation of the change over the network is taken into account, the resulting modification in the predicted age can be significantly larger compared to the effect of isolated CpG perturbations. By adjusting the most influential single CpG site and following the propagation of methylation level changes we can reach up to 5.74 years in virtual age reduction, significantly larger than without taking into account of the network control. Extending our approach to the whole methylation network may identify key nodes that have controller role in the ageing process.

2012 ◽  
Vol 203 ◽  
pp. 62-66
Author(s):  
Hong Li ◽  
Qiao Zhen Hou

The design uses 32 ARM processor S3C44B0X and Spartan™ -3E500 FPGA chip produced by Xinlinx company for setting up the hardware platform, and integrates the camera, GPS module, MiniGUI interface module. And realized bus vehicle mounted multimedia transmission control network control based on MOST. All of these are in the purpose of achieving a Predigest Project of vehicle-bone multimedia transmission and control network based on FPGA. The experiment indicated that, the transmission and control network system constructed by S3C44B0X and Spartan - 3E500 FPGA is low cast, simple and reliable.


Author(s):  
Kelly O'Neill

This chapter examines the flow of goods across and through Crimea in an attempt to understand the impact of Russian rule on the economic landscape. It focuses on the patterns of exchange and consumption, arguing for the significance of small-scale transactions for understanding the economic geography of the region. While Russian officials were eager to facilitate and control Black Sea trade, farmers and gardeners and craftsmen began participating in the system of overland markets and fairs that connected the southern provinces to merchants and consumers everywhere from Kharkov and Moscow to Nizhnii Novgorod and Kazan. The Crimean economy thus moved southward toward Constantinople and northward toward Moscow, yet the towns of the peninsula remained key nodes of consumption and production, the orchards and vineyards key sites of prosperity.


2009 ◽  
Vol 12 (4) ◽  
pp. 18-29
Author(s):  
Thanh Diep Cong Tu

In recent years, CPM - Continuous Passive Motion has been proved to be one of the most effective therapeutic methods for patients who have problems with motion such as spinal cord injury, ankle and knee injury, parkinson and so on. Many commercial CPM devices are found in market but all of them use motors as the main actuators. The lack of human compliance of electric actuators, which are commonly used in these machines, makes them potentially harmful to patients. An interesting alternative, to electric actuators for medical purposes, particularly promising for rehabilitation, is a pneumatic artificial muscle (PAM) actuator because of its high power/weight ratio and compliance properties. However, the highly nonlinear and hysteresis of PAM make it the challenging for design and control. In this study, a PID compensation using neural network control is studied to improve the control performance of the novel model of Knee CPM device.


2019 ◽  
Vol 22 (07n08) ◽  
pp. 1950021 ◽  
Author(s):  
AMING LI ◽  
YANG-YU LIU

Network science has experienced unprecedented rapid development in the past two decades. The network perspective has also been widely applied to explore various complex systems in great depth. In the first decade, fundamental characteristics of complex network structure, such as the small-worldness, scale-freeness, and modularity, of various complex networked systems were harvested from analyzing big empirical data. The associated dynamical processes on complex networks were also heavily studied. In the second decade, more attention was devoted to investigating the control of complex networked systems, ranging from fundamental theories to practical applications. Here we briefly review the recent progress regarding network dynamics and control, mainly concentrating on research questions proposed in the six papers we collected for this topical issue. This review closes with possible research directions along this line, and several important problems to be solved. We expect that, in the near future, network control will play an even bigger role in more fields, helping us understand and control many complex natural and engineered systems.


Author(s):  
Andrew C. Hyder ◽  
J. Lane Thames ◽  
Dirk Schaefer

The use of remotely operated laboratory experiments is gaining credibility to substitute traditional experimentation practices for distance learning students. Universities have been exploring this option to cater to the growing number of nontraditional students who are only able to participate in education remotely. In this paper the authors discuss how recent advances in robotic and network control have laid the foundation for which remote labs can be built and used as a novel educational tool. Models of how to implement remote laboratory experiments demonstrate the important considerations and best practices which would be addressed when developing an experiment. The consideration of network navigation is essential to foster the smooth connection between remote users and local equipment without inhibiting existing system functionality. Firewall communication through static and dynamic IP addresses must be delegated carefully while network and security administrators open channels for communication. Command and control interfaces can substantially reduce this complex orchestrate by serving as a dedicated web server. With the proper pedagogical and technical developments, remote laboratories will become a viable means to provide realistic experiences to anyone throughout the world.


2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Xiaodong Li ◽  
Shufang Bu ◽  
Ran Ran Pan ◽  
Cong Zhou ◽  
Kun Qu ◽  
...  

Abstract Background The goal of our study is to investigate whether the methylation levels of AHCY and CBS promoters are related to the risk of cerebral infarction by detecting the methylation level of AHCY and CBS genes. Methods We extracted peripheral venous blood from 152 patients with cerebral infarction and 152 gender- and age-matched healthy controls, and determined methylation levels of AHCY and CBS promoters using quantitative methylation-specific polymerase chain reaction. We used the percentage of methylation reference (PMR) to indicate gene methylation level. Results We compared the promoter methylation levels of two genes (AHCY and CBS) in peripheral blood DNA between the cerebral infarction case group and the control group. Our study showed no significant difference in AHCY promoter methylation between case and control. Subgroup analysis by gender showed that the methylation level of AHCY in males in the case group was lower than that in the control group, but the difference was not statistically significant in females. In a subgroup analysis by age, there was no significant difference in the AHCY methylation level between the case and control in the young group (≤44 years old). However, the level of AHCY gene methylation in the middle-aged group (45–59 years old) was significantly higher and the aged group (≥60 years old) was significantly lower than that in the control groups. However, CBS promoter methylation levels were significantly lower in the case group than in the control group (median PMR: 70.20% vs 104.10%, P = 3.71E-10). In addition, the CBS methylation levels of males and females in the case group were significantly lower than those in the control group (male: 64.33% vs 105%, P = 2.667E-08; female: 78.05% vs 102.8%, P = 0.003). We also found that the CBS levels in the young (23–44), middle-aged (45–59), and older (60–90) groups were significantly lower than those in the control group (young group: 69.97% vs 114.71%; P = 0.015; middle-aged group: 56.04% vs 91.71%; P = 6.744E-06; older group: 81.6% vs 119.35%; P = 2.644E-04). Our ROC curve analysis of CBS hypomethylation showed an area under the curve of 0.713, a sensitivity of 67.4%, and a specificity of 74.0%. Conclusion Our study suggests that hypomethylation of the CBS promoter may be closely related to the risk of cerebral infarction and may be used as a non-invasive diagnostic biomarker for cerebral infarction.


Algorithms ◽  
2019 ◽  
Vol 12 (5) ◽  
pp. 97
Author(s):  
Song Zheng ◽  
Chao Bi ◽  
Yilin Song

This paper presents a novel diagonal recurrent neural network hybrid controller based on the shared memory of real-time database structure. The controller uses Data Engine (DE) technology, through the establishment of a unified and standardized software architecture and real-time database in different control stations, effectively solves many problems caused by technical standard, communication protocol, and programming language in actual industrial application: the advanced control algorithm and control system co-debugging difficulties, algorithm implementation and update inefficiency, and high development and operation and maintenance costs effectively fill the current technical gap. More importantly, the control algorithm development uses a unified visual graphics configuration programming environment, effectively solving the problem of integrated control of heterogeneous devices; and has the advantages of intuitive configuration and transparent data processing process, reducing the difficulty of the advanced control algorithms debugging in engineering applications. In this paper, the application of a neural network hybrid controller based on DE in motor speed measurement and control system shows that the system has excellent control characteristics and anti-disturbance ability, and provides an integrated method for neural network control algorithm in a practical industrial control system, which is the major contribution of this article.


2014 ◽  
Vol 701-702 ◽  
pp. 807-811 ◽  
Author(s):  
Xin Lai ◽  
Xin Bo Chen ◽  
Xiao Jun Wu ◽  
Dong Liang

The structure and principle of four-wheels independent driving and steering (4WIS-4WID) electric vehicle are presented firstly, and on this basis the structure of network control system base on CAN bus is built. Kinematics and dynamics models of typical steering modes (such as all wheel steering, front (rear) wheel steering, parallel steering, zero-radius steering) are built, and the control strategy is presented. The experimental results show that the control system structure and control algorithm are effective.


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1863-1863
Author(s):  
Supachai Ekwattanakit ◽  
Suchada Riolueang ◽  
Vip Viprakasit

Abstract Hemoglobin (Hb) switching is described as temporal, tissue- and stage-specific patterns of globin gene expression; from embryonic to fetal and adult Hb in parallel to developmental stages of erythropoiesis. DNA methylation, one of the epigenetic mechanisms, was associated with inactivated chromatin domain and repressive transcription. To study the role of the DNA methylation on the beta (β)-globin genes, we analyzed CpG dinucleotides in 87 kb regions around β-globin gene cluster, including 5’upstream locus control regions (LCR; DNAse I Hypersensitive site (HS) 1–5), 3’HS1, the promoter regions of the G-and A-gamma (Gγ and Aγ), and β-globin genes, in several representative cells. These cells were primary adult erythroid cells culture (three different stages: early, intermediate, and late), fetal cord blood DNA, and neutrophil cell line (non-erythroid). Using bisulphite modification, followed by nested PCR and in vitro translation, the cleavage products were analysed by MALDI-TOF Mass Spectrometry to quantify the DNA methylation level. The results were consistent with bisulphite sequencing. We found that the promoters of Gγ and Aγ-globin genes were significantly hypomethylated in fetal cells (44% and 47% global methylation), when γ-globin genes were fully expressed, while they were heavily methylated in non-erythroid (86% and 95%). There was also a decreasing trend of the DNA methylation level at Gγ and Aγ-globin genes during adult erythroid differentiation from 80% and 82%, in early stage, to 67% and 66% in late stage (p=0.12 and 0.04). At β-globin promoter, the global methylation level changed from 90% in non-erythroid to 81%, 42%, and 26% in fetal, early and late adult erythroid cells, respectively. Moreover, we found the significant changes at 5’HS4, 3, and 1 as all erythroid cells were hypomethylated compare to non-erythroid. While at the insulators, 5’HS5 and 3’HS1, all tested CpG dinucleotides were heavily methylated in all cells. This is the first report that demonstrates the differences in DNA methylation at β-globin LCR between erythroid and non-erythroid cells. These epigenetic marks were associated with globin genes expression and might be useful to predict clinical severity in patients with β-thalassemia intermedia.


2016 ◽  
Vol 229 (3) ◽  
pp. 259-266 ◽  
Author(s):  
Ewa Ocłoń ◽  
Anna Latacz ◽  
Joanna Zubel–Łojek ◽  
Krystyna Pierzchała–Koziec

MicroRNAs (miRNAs) are a class of molecular posttranscriptional regulators found to participate in numerous biological mechanisms, such as adipogenesis, fat deposition, or glucose metabolism. Additionally, a detailed analysis on the molecular and cellular mechanisms of miRNA-related effects on metabolism leads to developing novel diagnostic markers and therapeutic approaches. To identify miRNA whose activity changed in epicardial adipose tissue in piglets during hyperglycemia, we analyzed the different miRNA expression patterns between control and hyperglycemia groups. The microarray analysis selected three differentially expressed microRNAs as potential biomarkers: hsa-miR-675-5p, ssc-miR-193a-3p, and hsa-miR-144-3p. The validation of miRNA expression with real-time PCR indicated an increased expression levels of ssc-miR-193a-3p and miR-675-5p, whereas the expression level of hsa-miR-144-3p was lower in epicardial adipose tissue in response to hyperglycemia (P<0.01). The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses suggested that these miRNAs differentially expressed between hyperglycemic and control piglets are involved in insulin, adipocytokine, and phosphatidylinositol 3-kinase–Akt signaling pathways, and development of type 2 diabetes as well. The results suggested that hyperglycemia can significantly affect the expression patterns of miRNA in porcine adipose tissue.


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