Edge localized modes (ELMs) in high-confinement mode plasmas were completely suppressed in KSTAR by applying n=1 nonaxisymmetric magnetic perturbations. Initially, the ELMs were intensified with a ...reduction of frequency, but completely suppressed later. The electron density had an initial 10% decrease followed by a gradual increase as ELMs were suppressed. Interesting phenomena such as a saturated evolution of edge T(e) and broadband changes of magnetic fluctuations were observed, suggesting the change of edge transport by the applied magnetic perturbations.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UM
Cytokines of the interleukin-1 (IL-1) family, such as IL-1α/β and IL-18, have pleiotropic activities in innate and adaptive immune responses in host defense and diseases. Insight into their ...biological functions helped develop novel therapeutic approaches to treat human inflammatory diseases. IL-33 is an important member of the IL-1 family of cytokines and is a ligand of the ST2 receptor, a member of the IL-1 receptor family. However, the role of the IL-33/ST2 axis in tumor growth and metastasis of breast cancer remains unclear. Here, we demonstrate that IL-33 is a critical tumor promoter during epithelial cell proliferation and tumorigenesis in the breast. IL-33 dose- and time-dependently increased Cancer Osaka Thyroid (COT) phosphorylation via ST2-COT interaction in normal epithelial and breast cancer cells. The IL-33/ST2/COT cascade induced the activation of the MEK-ERK (MEK-extracellular signal-regulated kinase), JNK-cJun (cJun N-terminal kinase-cJun) and STAT3 (signal transducer and activator of transcription 3) signaling pathways, followed by increased AP-1 and stat3 transcriptional activity. When small interfering RNAs of ST2 and COT were introduced into cells, IL-33-induced AP-1 and stat3 activity were significantly decreased, unlike that in the control cells. The inhibition of COT activity resulted in decreased IL-33-induced epithelial cell transformation, and knockdown of IL-33, ST2 and COT in breast cancer cells attenuated tumorigenicity of breast cancer cells. Consistent with these observations, ST2 levels were positively correlated with COT expression in human breast cancer. These findings provide a novel perspective on the role of the IL-33/ST2/COT signaling pathway in supporting cancer-associated inflammation in the tumor microenvironment. Therapeutic approaches that target this pathway may, therefore, effectively inhibit carcinogenesis in the breast.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Summary
Background
Little is known about factors affecting the quality of life (QoL) of patients with vitiligo, and previous studies have shown conflicting results.
Objectives
To explore the QoL of ...patients with vitiligo and to identify factors affecting QoL.
Methods
A nationwide questionnaire‐based study was conducted with 1123 patients with vitiligo recruited from 21 hospitals in Korea from July 2015 to June 2016. Data were collected using a structured questionnaire for demographic information and the Skindex‐29 instrument. Mild or severely impaired QoL in patients with vitiligo was assessed according to each domain (symptoms, functioning and emotions) of Skindex‐29. Multivariate logistic regression analyses were performed to determine the factors associated with QoL.
Results
Of the enrolled participants, 609 were male and 514 female, with a mean age of 49·8 years (range 20–84). The median duration of disease was 3·0 years (range 0–60). Using multivariate logistic regression modelling, the involvement of visible body parts and a larger affected body surface area were consistently associated with QoL impairment in all three domains of Skindex‐29. Additionally, the QoL of patients aged 20–59 years, who potentially had a more active social life than older patients, was associated with functional impairment. Furthermore, a higher educational background was associated with emotional impairment.
Conclusions
A multitude of factors significantly influence the QoL of patients with vitiligo. A better appreciation of these factors would help the management of these patients.
What's already known about this topic?
Quality of life is highly impaired in patients with vitiligo.
What does this study add?
The involvement of visible body parts and a larger affected body surface area were consistently associated with impaired symptoms, functioning and emotions.
Vitiligo with nonvisible lesions also considerably compromises quality of life; vitiligo should not be regarded as a cosmetic problem.
Patients aged 20–59 years experienced significant functional impairment, and those with a higher educational background had more impairment in their emotions.
Linked Comment: Ezzedine and Eleftheriadou. Br J Dermatol 2018; 178:28–29.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The influence of a galaxy's environment on its evolution has been studied and compared extensively in the literature, although differing techniques are often used to define environment. Most methods ...fall into two broad groups: those that use nearest neighbours to probe the underlying density field and those that use fixed apertures. The differences between the two inhibit a clean comparison between analyses and leave open the possibility that, even with the same data, different properties are actually being measured. In this work, we apply 20 published environment definitions to a common mock galaxy catalogue constrained to look like the local Universe. We find that nearest-neighbour-based measures best probe the internal densities of high-mass haloes, while at low masses the interhalo separation dominates and acts to smooth out local density variations. The resulting correlation also shows that nearest-neighbour galaxy environment is largely independent of dark matter halo mass. Conversely, aperture-based methods that probe superhalo scales accurately identify high-density regions corresponding to high-mass haloes. Both methods show how galaxies in dense environments tend to be redder, with the exception of the largest apertures, but these are the strongest at recovering the background dark matter environment. We also warn against using photometric redshifts to define environment in all but the densest regions. When considering environment, there are two regimes: the 'local environment' internal to a halo best measured with nearest neighbour and 'large-scale environment' external to a halo best measured with apertures. This leads to the conclusion that there is no universal environment measure and the most suitable method depends on the scale being probed.
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BFBNIB, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Hearing and balance depend upon the precise morphogenesis and mechanosensory function of stereocilia, the specialized structures on the apical surface of sensory hair cells in the inner ear. Previous ...studies of Grxcr1 mutant mice indicated a critical role for this gene in control of stereocilia dimensions during development. In this study, we analyzed expression of the paralog Grxcr2 in the mouse and evaluated auditory and vestibular function of strains carrying targeted mutations of the gene. Peak expression of Grxcr2 occurs during early postnatal development of the inner ear and GRXCR2 is localized to stereocilia in both the cochlea and in vestibular organs. Homozygous Grxcr2 deletion mutants exhibit significant hearing loss by 3 weeks of age that is associated with developmental defects in stereocilia bundle orientation and organization. Despite these bundle defects, the mechanotransduction apparatus assembles in relatively normal fashion as determined by whole cell electrophysiological evaluation and FM1-43 uptake. Although Grxcr2 mutants do not exhibit overt vestibular dysfunction, evaluation of vestibular evoked potentials revealed subtle defects of the mutants in response to linear accelerations. In addition, reduced Grxcr2 expression in a hypomorphic mutant strain is associated with progressive hearing loss and bundle defects. The stereocilia localization of GRXCR2, together with the bundle pathologies observed in the mutants, indicate that GRXCR2 plays an intrinsic role in bundle orientation, organization, and sensory function in the inner ear during development and at maturity.
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Although a great deal is known biochemically about peroxiredoxins (Prxs), little is known about their real physiological function. We show here that two cytosolic yeast Prxs, cPrxI and II, which ...display diversity in structure and apparent molecular weights (MW), can act alternatively as peroxidases and molecular chaperones. The peroxidase function predominates in the lower MW forms, whereas the chaperone function predominates in the higher MW complexes. Oxidative stress and heat shock exposure of yeasts causes the protein structures of cPrxI and II to shift from low MW species to high MW complexes. This triggers a peroxidase-to-chaperone functional switch. These in vivo changes are primarily guided by the active peroxidase site residue, Cys
47, which serves as an efficient “H
2O
2-sensor” in the cells. The chaperone function of these proteins enhances yeast resistance to heat shock.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract We have comprehensively studied the multiscale physical properties of the massive infrared dark cloud G28.34 (the Dragon cloud) with dust polarization and molecular line data from Planck, ...FCRAO-14 m, James Clerk Maxwell Telescope, and Atacama Large Millimeter/submillimeter Array. We find that the averaged magnetic fields of clumps tend to be either parallel with or perpendicular to the cloud-scale magnetic fields, while the cores in clump MM4 tend to have magnetic fields aligned with the clump fields. Implementing the relative orientation analysis (for magnetic fields, column density gradients, and local gravity), velocity gradient technique, and modified Davis–Chandrasekhar–Fermi analysis, we find that G28.34 is located in a trans-to-sub-Alfvénic environment; the magnetic field is effectively resisting gravitational collapse in large-scale diffuse gas, but is distorted by gravity within the cloud and affected by star formation activities in high-density regions, and the normalized mass-to-flux ratio tends to increase with increasing density and decreasing radius. Considering the thermal, magnetic, and turbulent supports, we find that the environmental gas of G28.34 is in a supervirial (supported) state, the infrared dark clumps may be in a near-equilibrium state, and core MM4-core4 is in a subvirial (gravity-dominant) state. In summary, we suggest that magnetic fields dominate gravity and turbulence in the cloud environment at large scales, resulting in relatively slow cloud formation and evolution processes. Within the cloud, gravity could overwhelm both magnetic fields and turbulence, allowing local dynamical star formation to happen.
Despite remarkable progress in cutaneous melanoma genomic profiling, the mutational landscape of primary mucosal melanomas (PMM) remains unclear. Forty-six PMMs underwent targeted exome sequencing of ...111 cancer-associated genes. Seventy-six somatic nonsynonymous mutations in 42 genes were observed, and recurrent mutations were noted on eight genes, including TP53 (13%), NRAS (13%), SNX31 (9%), NF1 (9%), KIT (7%) and APC (7%). Mitogen-activated protein kinase (MAPK; 37%), cell cycle (20%) and phosphatidylinositol 3-kinase (PI3K)-mTOR (15%) pathways were frequently mutated. We biologically characterized a novel ZNF767-BRAF fusion found in a vemurafenib-refractory respiratory tract PMM, from which cell line harboring ZNF767-BRAF fusion were established for further molecular analyses. In an independent data set, NFIC-BRAF fusion was identified in an oral PMM case and TMEM178B-BRAF fusion and DGKI-BRAF fusion were identified in two malignant melanomas with a low mutational burden (number of mutation per megabase, 0.8 and 4, respectively). Subsequent analyses revealed that the ZNF767-BRAF fusion protein promotes RAF dimerization and activation of the MAPK pathway. We next tested the in vitro and in vivo efficacy of vemurafenib, trametinib, BKM120 or LEE011 alone and in combination. Trametinib effectively inhibited tumor cell growth in vitro, but the combination of trametinib and BKM120 or LEE011 yielded more than additive anti-tumor effects both in vitro and in vivo in a melanoma cells harboring the BRAF fusion. In conclusion, BRAF fusions define a new molecular subset of PMM that can be targeted therapeutically by the combination of a MEK inhibitor with PI3K or cyclin-dependent kinase 4/6 inhibitors.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Experimental observations assisted by 2-D imaging diagnostics on the KSTAR tokamak show that a solitary perturbation (SP) emerges prior to a boundary burst of magnetized toroidal plasmas, which puts ...forward SP as a potential candidate for the burst trigger. We have constructed a machine learning (ML) model based on a convolutional deep neural network architecture for a statistical study to identify the SP as a boundary burst trigger. The ML model takes sequential signals detected from 19 toroidal Mirnov coils as input and predicts whether each temporal frame corresponds to an SP. We trained the network in a supervised manner on a training set consisting of real signals with manually annotated SP locations and synthetic burst signals. The trained model achieves high performances in various metrics on a test data set. We also demonstrated the reliability of the model by visualizing the discriminative parts of the input signals that the model recognizes. Finally, we applied the trained model to new data from KSTAR experiments, which were never seen during training, and confirmed that the large burst at the plasma boundary that can fatally damage the fusion device always involves the emergence of SP. This result suggests that the SP is a key to understanding and controlling of the boundary burst in magnetized toroidal plasmas.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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