• Title/Summary/Keyword: Mechanisms

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Mechanisms and Physiological Roles of Mitophagy in Yeast

  • Fukuda, Tomoyuki;Kanki, Tomotake
    • Molecules and Cells
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    • v.41 no.1
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    • pp.35-44
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    • 2018
  • Mitochondria are responsible for supplying of most of the cell's energy via oxidative phosphorylation. However, mitochondria also can be deleterious for a cell because they are the primary source of reactive oxygen species, which are generated as a byproduct of respiration. Accumulation of mitochondrial and cellular oxidative damage leads to diverse pathologies. Thus, it is important to maintain a population of healthy and functional mitochondria for normal cellular metabolism. Eukaryotes have developed defense mechanisms to cope with aberrant mitochondria. Mitochondria autophagy (known as mitophagy) is thought to be one such process that selectively sequesters dysfunctional or excess mitochondria within double-membrane autophagosomes and carries them into lysosomes/vacuoles for degradation. The power of genetics and conservation of fundamental cellular processes among eukaryotes make yeast an excellent model for understanding the general mechanisms, regulation, and function of mitophagy. In budding yeast, a mitochondrial surface protein, Atg32, serves as a mitochondrial receptor for selective autophagy that interacts with Atg11, an adaptor protein for selective types of autophagy, and Atg8, a ubiquitin-like protein localized to the isolation membrane. Atg32 is regulated transcriptionally and post-translationally to control mitophagy. Moreover, because Atg32 is a mitophagy-specific protein, analysis of its deficient mutant enables investigation of the physiological roles of mitophagy. Here, we review recent progress in the understanding of the molecular mechanisms and functional importance of mitophagy in yeast at multiple levels.

Analysis of the power augmentation mechanisms of diffuser shrouded micro turbine with computational fluid dynamics simulations

  • Jafari, Seyed A.;Kosasih, Buyung
    • Wind and Structures
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    • v.19 no.2
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    • pp.199-217
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    • 2014
  • Reported experimental and computational fluid dynamic (CFD) studies have demonstrated significant power augmentation of diffuser shrouded horizontal axis micro wind turbine compared to bare turbine. These studies also found the degree of augmentation is strongly dependent on the shape and geometry of the diffuser such as length and expansion angle. However study flow field over the rotor blades in shrouded turbine has not received much attention. In this paper, CFD simulations of an experimental diffuser shrouded micro wind turbine have been carried out with the aim to understand the mechanisms underpinning the power augmentation phenomenon. The simulations provide insight of the flow field over the blades of bare wind turbine and of shrouded one elucidating the augmentation mechanisms. From the analysis, sub-atmospheric back pressure leading to velocity augmentation at the inlet of diffuser and lowering the static pressure on blade suction sides have been identified as th dominant mechanisms driving the power augmentation. And effective augmentation was achieved for ${\lambda}$ above certain value. For the case turbine it is ${\lambda}$ greater than ${\approx}2$.

Antiviral and Tumoricidal Activities of Alginate-Stimulated Macrophages are Mediated by Different Mechanisms

  • Son, Eun-Wha;Rhee, Dong-Kwon;Pyo, Suhk-Neung
    • Archives of Pharmacal Research
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    • v.26 no.11
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    • pp.960-966
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    • 2003
  • Macrophages play an important role in host defenses by killing tumors and virus infections and producing secretory products. High mannuronic acid (HMA) containing alginate was examined to determine the mechanisms by which HMA-activated macrophages resist infection with HSV-1 and inhibit the growth of tumor cells. The ability of macro phages to resist infection with HSV-1 or to inhibit the growth of tumor cells was assessed following treatment with HMA alginate in the presence of either antibodies to various cytokines or inhibitors/scavengers of toxic macrophage products. Only antibodies to IFN-$\alpha$/$\beta$ were able to abrogate the protective effects of HMA alginate in macrophages infected with HSV-1, suggesting that the antiviral activity induced by this immunomodulator was mediated by the production of IFN-$\beta$. In contrast, anti-TNF-$\alpha$, anti-IFN and inhibitors of nitric oxide and reactive oxygen species were all able to partially abrogate HMA-induced cytostatic activity, suggesting that multiple mechanisms are involved in macrophage cytostasis. These results indicate that the HMA-induced intrinsic antiviral and extrinsic cytotoxic activites are mediated by different mechanisms.

Review of Sarcoplasmic Reticulum Ca$^{2+}$ Releasing Mechanisms in Skeletal Muscle Contraction (골격근 수축에 있어서 근장그물로부터의 Ca$^{2+}$ 유리 기전에 대한 고찰)

  • Koo, Hyun-Mo;Kim, Jin-Sang
    • The Journal of Korean Physical Therapy
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    • v.13 no.1
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    • pp.237-243
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    • 2001
  • Skeletal muscle cells are activated by ${\alpha}$-motorneurons which release acetylcholine at the neuromuscular junction. This results in a local depolarization of surface membrane which triggers an action potential. The action potential propagates along the surface membrane and also into the T-tubule system. In the triads T-tubules are in close connection with the terminal cisternae of the sarcoplasmic reticulum(SR). The action potential activaies T-tubule voltage sensors(DHP receptors). which activates SR Ca$^{2+}$ release channels(ryanodinc receptors). Ca$^{2+}$ have a key role in skeletal muscle in that an increase of free myoplasmic Ca$^{2+}$ concentration. The process of coupling chemical and electrical signals at the cell surface to the intracellular release of Ca$^{2+}$and ultimate contraction of muscle fibers is termed excitation-contraction coupling(ECC). Coupling of cel1 surface signals to intracellular Ca$^{2+}$ release proceeds by several mechanisms in skeletal muscle cells. This review focus on sarcopiasmic reticulum(SR) Ca$^{2+}$ releasing mechanisms from sarcoplasmic reticulum in the skeletal muscle. The mechanisms include DCCR, CICR, and HCR.

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Dysregulation of NRF2 in Cancer: from Molecular Mechanisms to Therapeutic Opportunities

  • Jung, Byung-Jin;Yoo, Hwan-Sic;Shin, Sooyoung;Park, Young-Joon;Jeon, Sang-Min
    • Biomolecules & Therapeutics
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    • v.26 no.1
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    • pp.57-68
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    • 2018
  • Nuclear factor E2-related factor 2 (NRF2) plays an important role in redox metabolism and antioxidant defense. Under normal conditions, NRF2 proteins are maintained at very low levels because of their ubiquitination and proteasomal degradation via binding to the kelch-like ECH associated protein 1 (KEAP1)-E3 ubiquitin ligase complex. However, oxidative and/or electrophilic stresses disrupt the KEAP1-NRF2 interaction, which leads to the accumulation and transactivation of NRF2. During recent decades, a growing body of evidence suggests that NRF2 is frequently activated in many types of cancer by multiple mechanisms, including the genetic mutations in the KEAP1-NRF2 pathway. This suggested that NRF2 inhibition is a promising strategy for cancer therapy. Recently, several NRF2 inhibitors have been reported with anti-tumor efficacy. Here, we review the mechanisms whereby NRF2 is dysregulated in cancer and its contribution to the tumor development and radiochemoresistance. In addition, among the NRF2 inhibitors reported so far, we summarize and discuss repurposed NRF2 inhibitors with their potential mechanisms and provide new insights to develop selective NRF2 inhibitors.

Epigenetics: Linking Nutrition to Molecular Mechanisms in Aging

  • Park, Joo Hyun;Yoo, Yeongran;Park, Yoon Jung
    • Preventive Nutrition and Food Science
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    • v.22 no.2
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    • pp.81-89
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    • 2017
  • Healthy aging has become a major goal of public health. Many studies have provided evidence and theories to explain molecular mechanisms of the aging process. Recent studies suggest that epigenetic mechanisms are responsible for life span and the progression of aging. Epigenetics is a fascinating field of molecular biology, which studies heritable modifications of DNA and histones that regulate gene expression without altering the DNA sequence. DNA methylation is a major epigenetic mark that shows progressive changes during aging. Recent studies have investigated aging-related DNA methylation as a biomarker that predicts cellular age. Interestingly, growing evidence proposes that nutrients play a crucial role in the regulation of epigenetic modifiers. Because various nutrients and their metabolites function as substrates or cofactors for epigenetic modifiers, nutrition can modulate or reverse epigenetic marks in the genome as well as expression patterns. Here, we will review the results on aging-associated epigenetic modifications and the possible mechanisms by which nutrition, including nutrient availability and bioactive compounds, regulate epigenetic changes and affect aging physiology.

Coordination of Anti-Spoofing Mechanisms in Partial Deployments

  • An, Hyok;Lee, Heejo;Perrig, Adrian
    • Journal of Communications and Networks
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    • v.18 no.6
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    • pp.948-961
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    • 2016
  • Internet protocol (IP) spoofing is a serious problem on the Internet. It is an attractive technique for adversaries who wish to amplify their network attacks and retain anonymity. Many approaches have been proposed to prevent IP spoofing attacks; however, they do not address a significant deployment issue, i.e., filtering inefficiency caused by a lack of deployment incentives for adopters. To defeat attacks effectively, one mechanism must be widely deployed on the network; however, the majority of the anti-spoofing mechanisms are unsuitable to solve the deployment issue by themselves. Each mechanism can work separately; however, their defensive power is considerably weak when insufficiently deployed. If we coordinate partially deployed mechanisms such that they work together, they demonstrate considerably superior performance by creating a synergy effect that overcomes their limited deployment. Therefore, we propose a universal anti-spoofing (UAS) mechanism that incorporates existing mechanisms to thwart IP spoofing attacks. In the proposed mechanism, intermediate routers utilize any existing anti-spoofing mechanism that can ascertain if a packet is spoofed and records this decision in the packet header. The edge routers of a victim network can estimate the forgery of a packet based on this information sent by the upstream routers. The results of experiments conducted with real Internet topologies indicate that UAS reduces false alarms up to 84.5% compared to the case where each mechanism operates individually.

OSEK PS Kernel Mechanisms for Reducing Dynamic Memory Usage (동적 메모리 사용 감소를 위한 OSEK OS 커널 구현 메커니즘)

  • Lim, Jin-Tack;Keum, Han-Hong;Park, Ji-Yong;Hong, Seong-Soo
    • Transactions of the Korean Society of Automotive Engineers
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    • v.17 no.3
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    • pp.127-141
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    • 2009
  • While the ever-increasing complexity of automotive software systems can be effectively managed through the adoption of a reliable real-time operating system (RTOS), it may incur additional resource usage to a resultant system. Due to the mass production nature of the automotive industry, reducing physical resources used by automotive software is of the utmost importance for cost reduction. OSEK OS is an automotive real-time kernel standard specifically defined to address this issue. Thus, it is very important to develop and exploit kernel mechanisms such that they can achieve minimal resource usage in the OSEK OS implementation. In this paper, we analyze the task subsystem, resource subsystem, application mode and conformance classes of OSEK OS as well as the OSEK Implementation Language (OIL). Based on our analysis, we in turn devise and implement kernel mechanisms to minimize the dynamic memory usage of the OSEK OS implementation. Finally, we show that our mechanisms effectively reduce the memory usage of OSEK OS and applications.

Clustering of extreme winds in the mixed climate of South Africa

  • Kruger, A.C.;Goliger, A.M.;Retief, J.V.;Sekele, S.S.
    • Wind and Structures
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    • v.15 no.2
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    • pp.87-109
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    • 2012
  • A substantial part of South Africa is subject to more than one strong wind source. The effect of that on extreme winds is that higher quantiles are usually estimated with a mixed strong wind climate estimation method, compared to the traditional Gumbel approach based on a single population. The differences in the estimated quantiles between the two methods depend on the values of the Gumbel distribution parameters for the different strong wind mechanisms involved. Cluster analysis of the distribution parameters provides a characterization of the effect of the relative differences in their values, and therefore the dominance of the different strong wind mechanisms. For gusts, cold fronts tend to dominate over the coastal and high-lying areas, while other mechanisms, especially thunderstorms, are dominant over the lower-lying areas in the interior. For the hourly mean wind speeds cold fronts are dominant in the south-west, south and east of the country. On the West Coast the ridging of the Atlantic Ocean high-pressure system dominate in the south, while the presence of a deep trough or coastal low pressure system is the main strong wind mechanism in the north. In the central interior cold fronts tend to share their influence almost equally with other synoptic-scale mechanisms.

Fault-tolerance Performance Evaluation of Fieldbus for NPCS Network of KNGR

  • Jung, Hyun-Gi;Seong, Poong-Hyun
    • Nuclear Engineering and Technology
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    • v.33 no.1
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    • pp.1-11
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    • 2001
  • In contrast with conventional fieldbus researches which are focused merely on real-time performance, this study aims to evaluate the real-time performance of the communication system including fault-tolerant mechanisms Maintaining performance in presence of recoverable faults is very important in case that the communication network is applied to a highly reliable system such as next generation Nuclear. Power. Plant (NPP). If the tie characteristics meet the requirements of the system, the faults will be recovered by fieldbus recovery mechanisms and the system will be safe. If the time characteristics can not meet the requirements, the faults in the fieldbus can propagate to the system failure. In this study, for the purpose of investigating the time characteristics of fieldbus, the recoverable faults are classified and then the formulas that represent delays including recovery mechanisms are developed. In order to validate the proposed approach, we have developed a simulation model that represents the Korea Next Generation Reactor (KNGR) NSSS Process Control System (NPCS). The results of the simulation show us the reasonable delay characteristics of the fault cases with recovery mechanisms. Using the simulation results and the system requirements, we also can calculate the failure propagation probability from fieldbus to outer system.

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