Kinetic model of the COMPASS tokamak SOL Tskhakaya, D.; Adamek, J.; Dimitrova, M. ...
Nuclear materials and energy,
March 2021, 2021-03-00, 2021-03-01, Letnik:
26
Journal Article
Recenzirano
Odprti dostop
•Kinetic effects are significant in the inner divertor plasma. Parallel heat flux in the entire SOL is strongly non-local.•Normalized power loads to the ID are above the classical values and are ...caused by non-Maxwellian super-thermal electrons.•Different divertor current regimes do not influence overall SOL parameters, except those of the divertor sheath.•Ions in the divertors plasma are colder than the electrons.•Modelling results are in a reasonable agreement with the experimental measurements.
In this work we report on results of full size kinetic modelling of the COMPASS tokamak SOL. Presented simulations indicate, that i. kinetic effects are significant in the inner divertor (ID) plasma; ii. normalized power loads to the ID are above the classical values and are caused by non-Maxwellian super-thermal electrons; iii. different divertor current regimes do not influence overall SOL parameters, except those of the divertor sheath; iv. ions at the divertors plasma are colder than the electrons; v. parallel heat transport is strongly non-local. Modelling results are in a reasonable agreement with the experimental measurements.
•Exogenous TLE1 in A549 cells enhances cell migration and suppresses E-cadherin.•Knockdown of TLE1 in A549 cells reduces cell motility and upregulates E-cadherin.•TLE1 suppresses E-cadherin ...expression at the transcriptional level.•TLE1 recruits HDAC1 to the E-cadherin promoter.•HDAC inhibition attenuates TLE1-induced E-cadherin downregulation and motility.
The Groucho transcriptional corepressor TLE1 protein has recently been shown to be a putative lung specific oncogene, but its underlying oncogenic activity in lung cancer has not been fully elucidated. In this report, we investigated whether TLE1 regulates lung cancer aggressiveness using the human lung adenocarcinoma cell line A549 as a model system. Through a combination of genetic approaches, we found that TLE1 potentiates epithelial-to-mesenchymal transition (EMT) in A549 cells in part through suppression of the tumor suppressor gene E-cadherin. Exogenous expression of TLE1 in A549 cells resulted in heightened EMT phenotypes (enhanced fibroblastoid morphology and increased cell migratory potential) and in molecular alterations characteristic of EMT (downregulation of the epithelial marker E-cadherin and upregulation of the mesenchymal marker Vimentin). Conversely, downregulation of endogenous TLE1 expression in these cells resulted in reversal of basal EMT characterized by a cuboidal-like epithelial cell phenotype, reduced cell motility, and upregulated E-cadherin expression. Mechanistic studies showed that TLE1 suppresses E-cadherin expression at the transcriptional level in part by recruiting histone deacetylase (HDAC) activity to the E-cadherin promoter. Consistently, the HDAC inhibitor TSA partially reversed the TLE1-induced E-cadherin downregulation and cell migration, suggesting a role for HDACs in TLE1-mediated transcriptional repression of E-cadherin and EMT function. These findings uncover a novel role of TLE1 in regulating EMT in A549 cells through its repressive effect on E-cadherin and provide a mechanism for TLE1 oncogenic activity in lung cancer.
Edge localized modes (ELMs)-induced transient heat loads on the divertor targets represent an important threat to target lifetime and can lead to the need to replace them with a frequency that has a ...major impact in the execution of the ITER Research Plan. Predicting the impact of such large transient heat loads through modeling is especially challenging and is often attempted through the use of fluid plasma boundary modeling codes, such as SOLPS-ITER, in which the ELM is crudely approximated as a fixed large, but limited in time, increase in anomalous cross-field transport coefficients for particles and heat to mimic a specified total ELM energy loss. However, one problem with this approach is that the boundary conditions at the target sheath entrance are expected to vary strongly in time through the ELM transient, whilst fixed kinetic target sheath heat transmission factors (SHTF), and more generally, constant heat flux limiters, are typically applied in the fluid codes.
This contribution describes the first results of efforts to address ELMs issues for ITER simulations under high performance conditions using the 1D3V electrostatic parallel Particle-in-Cell (PIC) code BIT1, to study the kinetic effects and to provide time-dependent kinetic target sheath heat transmission factors. In a second step of the work, these are used in the formulation of fluid boundary conditions for calculations of ELM target heat loads using the SOLPS-ITER code.
The BIT1-SOLPS-ITER coupling allows us to investigate the kinetic effects on the targets, by comparing power and particle fluxes from time-dependent simulations of ITER Type I ELMs.
The mitochondrial Bit1 protein exerts tumor-suppressive function in NSCLC through induction of anoikis and inhibition of EMT. Having this dual tumor suppressive effect, its downregulation in the ...established human lung adenocarcinoma A549 cell line resulted in potentiation of tumorigenicity and metastasis in vivo. However, the exact role of Bit1 in regulating malignant growth and transformation of human lung epithelial cells, which are origin of most forms of human lung cancers, has not been examined. To this end, we have downregulated the endogenous Bit1 expression in the immortalized non-tumorigenic human bronchial epithelial BEAS-2B cells. Knockdown of Bit1 enhanced the growth and anoikis insensitivity of BEAS-2B cells. In line with their acquired anoikis resistance, the Bit1 knockdown BEAS-2B cells exhibited enhanced anchorage-independent growth in vitro but failed to form tumors in vivo. The loss of Bit1-induced transformed phenotypes was in part attributable to the repression of E-cadherin expression since forced exogenous E-cadherin expression attenuated the malignant phenotypes of the Bit1 knockdown cells. Importantly, we show that the loss of Bit1 expression in BEAS-2B cells resulted in increased Erk activation, which functions upstream to promote TLE1-mediated transcriptional repression of E-cadherin. These collective findings indicate that loss of Bit1 expression contributes to the acquisition of malignant phenotype of human lung epithelial cells via Erk activation-induced suppression of E-cadherin expression.
•Downregulation of Bit1 potentiates cell growth, anoikis resistance, and anchorage-independent potential of BEAS-2B cells.•Loss of Bit1 induced E-cadherin repression contributes to enhanced malignant phenotype of Bit1 knockdown cells.•Increased Erk activation in Bit1 knockdown cells promotes TLE1-mediated transcriptional repression of E-cadherin.
The boundary conditions (BCs) involving a plasma-wall transition (PWT) are crucial when estimating the particle and heat fluxes at the wall, and when simulating the edge plasma with fluid, ...gyro-kinetic and gyro-fluid codes. The aim of this work was to derive time-dependent BCs at the PWT for ELM-free, Type-I ELM and post-ELM states based on a kinetic test simulation in the ITER tokamak without neutrals, so as to obtain the steady state. This contribution describes the first results of attempts to address this issue for ITER simulations under high-performance conditions using the 1D3V electrostatic parallel Particle-in-Cell code BIT1 (Tskhakaya in Plasma Phys Control Fusion 59(11401):19pp, 2017). The burning plasma conditions correspond to the ITER Q = 10, 15 MA baseline at
q
95
= 3, for which the poloidal length of the 1D SOL is
∼
20 m from the inner to the outer target, assuming typical upstream separatrix parameters of
n
e
∼
3 to 5
·
10
19
m
-
3
,
T
e
∼
100 to 150 eV and
T
i
∼
200 to 300 eV. Inclined magnetic fields at targets of (
∼
5
∘
) are included, as are the particle collisions, with a total of 3.4
·
10
5
poloidal grid cells, giving shortening factors of 20. The results show that for the ELM-free state the BCs relate to the classic one; in the phase of the Type-I ELM, the BCs are increasing; and in the post-ELM, the BCs are decreasing, reaching the classic values. Taking into account this kind of BC dependence, we can provide realistic ITER plasma profiles for subsequent investigations. As this is a time-consuming process, the simulations are first conducted without neutrals, while in order to obtain realistic values for the BCs, the neutrals are added to the system. At a later stage, these will be used as BCs for the calculations of the ELM target heat loads using the SOLPS-ITER (Bonnin in Plasma Fusion Res 11:1403102, 2016; Wiesen in J Nucl Mater 463:480–484, 2015) code.
Purpose
Posterior capsule opacification (PCO) is a common postoperative complication of cataract surgery. Epithelial–mesenchymal transition (EMT) of lens epithelial cells (LECs) is an important ...initial step of PCO pathogenesis. We have previously shown that Bit1 expresses in rat LECs. In this study, we aim to investigate the role of Bit1 in the EMT of human LECs.
Methods
The expression of Bit1 was firstly detected in human PCO-attached LECs and human lens cell line SRA01/04 by real-time PCR and immunofluorescence staining. The proliferation and migration of Bit1 knockdown SRA01/04 cells were evaluated by cell counting, wound-healing assay, and transwell migration assay. The EMT of LECs was triggered by TGF-β2, and then the effect of Bit1 on EMT with a key biomarker of α-smooth muscle actin (α-SMA) was analyzed by siRNA knockdown assay, and the reversal of EMT was validated by real-time PCR and western blot.
Results
Bit1 was obviously augmented in LECs derived from PCO tissues and Bit1 expressed with high levels in the cytoplasm of cultured SRA01/04 cells. Cell proliferation, invasion, and migration, as well as α-SMA expression, were significantly decreased in Bit1 knockdown SRA01/04 cells. While TGF-β2 elevated Bit1 and α-SMA expression levels in a dose-dependent manner, with peak levels at 10 ng/ml of TGF-β2 treatment, suppression of Bit1 in SRA01/04 cells reversed the EMT process. TGF-β2 induced elevation of α-SMA expression level, as well as migration, and invasion abilities were all suppressed by Bit1 deficiency.
Conclusions
These findings reveal that Bit1 promotes TGF-β2 induced α-SMA expression and acts as an positive regulator of EMT. Suppressing Bit1 inhibits the proliferation, migration, and EMT of LECs. Bit1 may be a potential novel therapeutic target for the prevention and treatment of PCO.
Summary
Cryptochromes (CRY) are one of the two major classes of photoreceptors that perceive light stimuli in the UV‐A to blue light region and they are involved in multiple aspects of plant growth ...and development. However, knowledge regarding their signaling transduction components and mechanisms remains limited. Here, we report that a MYB transcription factor Blue Insensitive Trait 1 (BIT1), plays an important role in controlling blue light responses. Hypocotyl growth responses indicate that BIT1 functions as a positive element in blue light signaling, since BIT1 antisense and knock‐out lines show a reduced light response in blue light. BIT1 controls blue light‐dependent expression of various genes such as PsbS, a member of the light‐harvesting complex gene family. A transactivation assay showed that BIT1 regulates promoter activity of PsbS in a blue light‐dependent manner and that it requires CRY1 for activation of the PsbS promoter. BIT1 undergoes degradation in darkness and CRY1 functions to stabilize BIT1 in a blue light‐dependent manner. In contrast, COP1 binds to BIT1 and mediates its degradation. We propose that the PsbS promoter is activated in blue light via the blue light‐dependent stabilization of BIT1 by CRY1, while in darkness BIT1 is degraded by COP1‐mediated proteolysis.
The endoplasmic reticulum (ER) is an essential organelle whose major functions are to ensure proper secretory protein folding and trafficking. These mechanisms involve the activation of specific ...ER-resident molecular machines, which might be regulated by their membranous environments. Based on this observation, we aimed to characterize the proteome of ER-membrane microdomains to identify new components of the ER that have a role in secretory pathway-associated functions. Using this approach with dog pancreatic rough microsomes, we found that mitochondrial Bcl-2 inhibitor of transcription (BIT1) localized in the early secretory pathway and accumulated in the Golgi complex. Using both a chimeric protein of the luminal and transmembrane domains of ER-resident TRAPα and the cytosolic domain of BIT1, and silencing of BIT1 expression, we perturbed endogenous BIT1 oligomerization and localization to the Golgi. This led to enhanced ERK signaling from the Golgi complex, which resulted in improved stress resistance. This work provides the first evidence for the existence of ER microdomains that are involved in the regulation of BIT1 structure and trafficking, and identifies BIT1 as a negative regulator of the ERK-MAPK signaling pathway in the Golgi.
The Bit-1 protein appears to be a part of the integrin-specific signaling pathway involved into anoikis. When Bit1 is released from the mitochondria into the cytoplasm it can elicit ...caspase-independent apoptosis. The expression of Bit1 in 78 serous papillary adenocarcinomas and 78 normal epithelial ovarian tissue specimens was analyzed by immunohistochemistry. We also investigate Bit1 function by transfection. Bit1 was expressed in 100% and 33.3% of ovarian cancers and normal epithelial tissues, respectively, and its expression was significantly correlated with histologic grade and overall survival. However, Bit1 expression was not associated with age. We also confirmed that Bit1 overexpression in cytosol of Caov-3 cells induced apoptosis. Bit1 may be a useful pathological marker and a prognostic marker for serous papillary adenocarcinomas outcome. Its pro-apoptotic property also makes it a potential gene medicine for ovarian cancers therapy.
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