168 research outputs found

    A Novel Design to Minimise the Energy Consumption and Node Traversing in Blockchain Over Cloud Using Ensemble Cuckoo Model

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    The article outlines the Blockchain’s behavioral model for services. Their reliability is proven through the use of experimental evidence. The authors highlight the major technical aspects and characteristics that are associated with the transmission of data through the network. The authors define the scheme for the network, which works with blockchain transactions, and the relationship between network characteristics on parameters used by the application. They examine the use of this model to identification of the blockchain service and also the likelihood of existing security mechanisms that are based on the technology being bypassed. Additionally, the article provides guidelines to conceal the Blockchain's traffic profile to make it more difficult for its detection in the information network. This study offers a thorough analysis of blockchain-based trust models applied to cloud computing. The paper highlights the challenges that remain unsolved and offers suggestions for future studies in the area based on new cloud-edge trust management system and double-blockchain structure, which is a cloud-based transaction model. The paper also identifies the existing challenges and offers suggestions for future studies in the area based on new cloud-edge trust management system and double-blockchain structure, which is a cloud-based transaction model. The flow of the network will be supported by models that are enhanced by cuckoo to frame the perfect network transform of data from one point to cluster, or alternatively

    Synthesis, spectral characterization and anti-diabetic activity evaluation of phosphoramidate derivatives

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    60-68In the present work, a series of new phosphoramidate derivatives have been conveniently synthesized by using 4- chlorobenzene-sulfonyl chloride as preliminary material via substituted sulfonamides as intermediates with high yields in a short period by conventional and microwave irradiation techniques. All the synthesized compound have been characterized by spectral and elemental analyses. An in silico molecular docking study has been performed to find potent anti-diabetic drugs. In vitro anti-diabetic activity of the title compounds have also been screened by standard α-amylase inhibition assay. Some of the tested compounds have been proven to possess promising activity when compared with reference drug

    Critical depinning force and vortex lattice order in disordered superconductors

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    We simulate the ordering of vortices and its effects on the critical current in superconductors with varied vortex-vortex interaction strength and varied pinning strengths for a two-dimensional system. For strong pinning the vortex lattice is always disordered and the critical depinning force only weakly increases with decreasing vortex-vortex interactions. For weak pinning the vortex lattice is defect free until the vortex-vortex interactions have been reduced to a low value, when defects begin to appear with a simultaneous rapid increase in the critical depinning force. In each case the depinning force shows a maximum for non-interacting vortices. The relative height of the peak increases and the peak width decreases for decreasing pinning strength in excellent agreement with experimental trends associated with the peak effect. We show that scaling relations exist between the distance between defects in the vortex lattice and the critical depinning force.Comment: 5 pages, 6 figure

    GADD34 keeps the mTOR pathway inactivated in endoplasmic reticulum stress related autophagy

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    The balance of protein synthesis and proteolysis (i.e. proteostasis) is maintained by a complex regulatory network in which mTOR (mechanistic target of rapamycin serine/threonine kinase) pathway and unfolded protein response are prominent positive and negative actors. The interplay between the two systems has been revealed; however the mechanistic details of this crosstalk are largely unknown. The aim of the present study was to investigate the elements of crosstalk during endoplasmic reticulum stress and to verify the key role of GADD34 in the connection with the mTOR pathway. Here, we demonstrate that a transient activation of autophagy is present in endoplasmic reticulum stress provoked by thapsigargin or tunicamycin, which is turned into apoptotic cell death. The transient phase can be characterized by the elevation of the autophagic marker LC3II/I, by mTOR inactivation, AMP-activated protein kinase activation and increased GADD34 level. The switch from autophagy to apoptosis is accompanied with the appearance of apoptotic markers, mTOR reactivation, AMP-activated protein kinase inactivation and a decrease in GADD34. Inhibition of autophagy by 3-methyladenine shortens the transient phase, while inhibition of mTOR by rapamycin or resveratrol prolongs it. Inhibition of GADD34 by guanabenz or transfection of the cells with siGADD34 results in down-regulation of autophagy-dependent survival and a quick activation of mTOR, followed by apoptotic cell death. The negative effect of GADD34 inhibition is diminished when guanabenz or siGADD34 treatment is combined with rapamycin or resveratrol addition. These data confirm that GADD34 constitutes a mechanistic link between endoplasmic reticulum stress and mTOR inactivation, therefore promotes cell survival during endoplasmic reticulum stress. © 2016 Holczer et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

    Neuregulin Promotes Incomplete Autophagy of Prostate Cancer Cells That Is Independent of mTOR Pathway Inhibition

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    Growth factors activating the ErbB receptors have been described in prostate tumors. The androgen dependent prostate cancer cell line, LNCaP, expresses the ErbB-1, ErbB-2 and ErbB-3 receptor tyrosine kinases. Previously, it was demonstrated that NRG activates ErbB-2/ErbB-3 heterodimers to induce LNCaP cell death, whereas, EGF activates ErbB-1/ErbB-1 or ErbB-1/ErbB-2 dimers to induce cell growth and survival. It was also demonstrated that PI3K inhibitors repressed this cell death suggesting that in androgen deprived LNCaP cells, NRG activates a PI3K-dependent pathway associated with cell death.In the present study we demonstrate that NRG induces autophagy in LNCaP cells, using LC3 as a marker. However, the autophagy induced by NRG may be incomplete since p62 levels elevate. We also demonstrated that NRG- induced autophagy is independent of mammalian target of rapamycin (mTOR) inhibition since NRG induces Akt and S6K activation. Interestingly, inhibition of reactive oxygen species (ROS) by N-acetylcysteine (NAC), inhibited NRG-induced autophagy and cell death. Our study also identified JNK and Beclin 1 as important components in NRG-induced autophagy and cell death. NRG induced elevation in JNK phosphorylation that was inhibited by NAC. Moreover, inhibitor of JNK inhibited NRG-induced autophagy and cell death. Also, in cells overexpressing Bcl-2 or cells expressing sh-RNA against Beclin 1, the effects of NRG, namely induction of autophagy and cell death, were inhibited.Thus, in LNCaP cells, NRG-induces incomplete autophagy and cell death that depend on ROS levels. These effects of NRG are mediated by signaling pathway that activates JNK and Beclin 1, but is independent of mTOR inhibition

    Attenuation of Skeletal Muscle and Renal Injury to the Lower Limb following Ischemia-Reperfusion Using mPTP Inhibitor NIM-811.

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    INTRODUCTION: Operation on the infrarenal aorta and large arteries of the lower extremities may cause rhabdomyolysis of the skeletal muscle, which in turn may induce remote kidney injury. NIM-811 (N-metyl-4-isoleucine-cyclosporine) is a mitochondria specific drug, which can prevent ischemic-reperfusion (IR) injury, by inhibiting mitochondrial permeability transition pores (mPTP). OBJECTIVES: Our aim was to reduce damages in the skeletal muscle and the kidney after IR of the lower limb with NIM-811. MATERIALS AND METHODS: Wistar rats underwent 180 minutes of bilateral lower limb ischemia and 240 minutes of reperfusion. Four animal groups were formed called Sham (receiving vehicle and sham surgery), NIM-Sham (receiving NIM-811 and sham surgery), IR (receiving vehicle and surgery), and NIM-IR (receiving NIM-811 and surgery). Serum, urine and histological samples were taken at the end of reperfusion. NADH-tetrazolium staining, muscle Wet/Dry (W/D) ratio calculations, laser Doppler-flowmetry (LDF) and mean arterial pressure (MAP) monitoring were performed. Renal peroxynitrite concentration, serum TNF-alpha and IL-6 levels were measured. RESULTS: Less significant histopathological changes were observable in the NIM-IR group as compared with the IR group. Serum K+ and necroenzyme levels were significantly lower in the NIM-IR group than in the IR group (LDH: p<0.001; CK: p<0.001; K+: p = 0.017). Muscle mitochondrial viability proved to be significantly higher (p = 0.001) and renal function parameters were significantly better (creatinine: p = 0.016; FENa: p<0.001) in the NIM-IR group in comparison to the IR group. Serum TNF-alpha and IL-6 levels were significantly lower (TNF-alpha: p = 0.003, IL-6: p = 0.040) as well as W/D ratio and peroxynitrite concentration were significantly lower (p = 0.014; p<0.001) in the NIM-IR group than in the IR group. CONCLUSION: NIM-811 could have the potential of reducing rhabdomyolysis and impairment of the kidney after lower limb IR injury

    Autophagy: Regulation and role in disease

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    Crosstalk Between Macroautophagy and Chaperone-Mediated Autophagy: Implications for the Treatment of Neurological Diseases

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