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Nuclear fusion is one of the most attractive alternatives to carbon-dependent energy sources 1 . Harnessing energy from nuclear fusion in a large reactor scale, however, still presents many scientific challenges despite the many years of research and steady advances in magnetic confinement approaches. State-of-the-art magnetic fusion devices cannot yet achieve a sustainable fusion performance, which requires a high temperature above 100 million kelvin and sufficient control of instabilities to ensure steady-state operation on the order of tens of seconds 2 , 3 . Here we report experiments at the Korea Superconducting Tokamak Advanced Research 4 device producing a plasma fusion regime that satisfies most of the above requirements: thanks to abundant fast ions stabilizing the core plasma turbulence, we generate plasmas at a temperature of 100 million kelvin lasting up to 20 seconds without plasma edge instabilities or impurity accumulation. A low plasma density combined with a moderate input power for operation is key to establishing this regime by preserving a high fraction of fast ions. This regime is rarely subject to disruption and can be sustained reliably even without a sophisticated control, and thus represents a promising path towards commercial fusion reactors. A magnetic confinement regime established at the Korea Superconducting Tokamak Advanced Research device enables the generation of plasmas over 10 8  kelvin for 20 seconds with the aid of fast ions without plasma edge instabilities or impurity accumulation.

The path of tokamak fusion and International thermonuclear experimental reactor (ITER) is maintaining high-performance plasma to produce sufficient fusion power. This effort is hindered by the transient energy burst arising from the instabilities at the boundary of plasmas. Conventional 3D magnetic perturbations used to suppress these instabilities often degrade fusion performance and increase the risk of other instabilities. This study presents an innovative 3D field optimization approach that leverages machine learning and real-time adaptability to overcome these challenges. Implemented in the DIII-D and KSTAR tokamaks, this method has consistently achieved reactor-relevant core confinement and the highest fusion performance without triggering damaging bursts. This is enabled by advances in the physics understanding of self-organized transport in the plasma edge and machine learning techniques to optimize the 3D field spectrum. The success of automated, real-time adaptive control of such complex systems paves the way for maximizing fusion efficiency in ITER and beyond while minimizing damage to device components. Damaging energy bursts in a tokamak are a major obstacle to achieving stable high-fusion performance. Here, the authors demonstrate the use of adaptive and machine-learning control to optimize the 3D magnetic field to prevent edge bursts and maximize fusion performance in two different fusion devices, DIII-D and KSTAR.

Nuclear receptors, many of which undergo a major conformational change upon binding specific ligand, belong to a superfamily of proteins that bind to specific DNA sequences and control gene transcription. They regulate the assembly of a transcriptional preinitiation complex at the promoter of target genes and modulate their expression in response to ligand. In particular, nuclear receptors repress or stimulate transcription by recruiting corepressor or coactivator proteins, in addition to directly contacting the basal transcription machinery. In this review, we discuss recent progress in studies of these transcriptional coregulators of nuclear receptors.

Interferon consensus sequence-binding protein (ICSBP) is a transcription factor induced by interferon gamma (IFN- γ ) and a member of the interferon regulatory factor (IRF) family. ICSBP is predominantly expressed in hematopoietic cells and regulates the immune response and cell growth and differentiation. However, little is known about its function in non-hematopoietic cells. Here we show a novel function for ICSBP in epithelial-to-mesenchymal transition (EMT)-like phenomena (ELP), cell motility, and invasion in human osteosarcoma cell lines, including U2OS cells. IFN- γ treatment induced ICSBP expression and EMT-like morphological change in U2OS cells, which were suppressed by ICSBP knockdown. To further investigate the role of ICSBP in ELP, we established a stable U2OS cell line that overexpresses ICSBP. ICSBP expression caused U2OS cells to have a more elongated shape and an increased vimentin and fibronectin expression. ICSBP expression also promoted adhesiveness, motility, and invasiveness of U2OS cells. ICSBP upregulated transforming growth factor (TGF)- β receptors and activated TGF- β signaling cascades, which were responsible for ELP as well as increased cell motility and invasion. In addition, ICSBP-induced TGF- β receptor activation resulted in the upregulation of Snail. Knockdown of Snail attenuated the ICSBP-induced augmentation of cell motility and invasion. Upregulation of Snail, ELP, and increased invasion by ICSBP expression were also observed in other osteosarcoma cell lines, such as Saos-2 and 143B. Furthermore, ICSBP and TGF- β receptor I were expressed in 45/54 (84%) and 47/54 (87%) of human osteosarcoma tissues, respectively, and showed significant correlation ( r =0.47, P =0.0007) with respect to their expression levels. Taken altogether, these data demonstrate a novel function for ICSBP in ELP, cell motility, and invasion through the TGF- β and Snail signaling pathways.

Objectives: To determine the effect of a single dose of methylphenidate on the cognitive performance of patients with traumatic brain injury (TBI), and particularly on working memory and visuospatial attention. Design: A double-blind placebo-controlled study. The subjects were randomly divided into an experimental group taking methylphenidate and a control group taking a placebo. Setting: The Department of Rehabilitation Medicine of a university hospital. Subjects: Eighteen subjects with TBI (16 male and two female) were enrolled. Interventions: The patients were given 20 mg methylphenidate or a placebo. Cognitive assessments were performed at three times: before the medication as a baseline, 2 h after medication and at follow-up (48 h later). Main measures: Cognitive assessments consisted of working memory tasks and endogenous visuospatial attention tasks designed using SuperLabPro 2.0 software. Response accuracy and reaction time were measured. Results: There were significant improvements in response accuracy in the methylphenidate group compared with the placebo group for both the working memory and visuospatial attention tasks. A significant decrease in the reaction time was also observed in the methylphenidate group only for the working memory task. Conclusions: The administration of single-dose methylphenidate has an effect in improving cognitive functioning following a TBI. The effects were most prominent regarding the reaction time of the working memory.

The kinetics of the formation of the sigma phase in the high strength nickel-based superalloys UDIMET 720 (U720) and UDIMET 720Li (U720Li) have been characterized using a combination of electrolytic extraction and quantitative X-ray diffraction (XRD) involving the Rietveld method. In order to perform the analysis, a database of crystallographic parameters is required and details of this are presented. It is shown that the numerical data generated using this technique are consistent with observations made using conventional optical, scanning, and transmission electron microscopies. The results are presented in the form of temperature-time-transformation (TTT) diagrams. It appears that U720Li is very much less prone to sigma precipitation than U720. The presence of a tensile stress accelerates the reaction, but the kinetics are very slow at temperatures lower than 700 °C. Thermodynamic calculations have been used in order to infer that the formation of sigma is associated predominantly with the dissolution of the γ matrix. Theoretical modeling of sigma formation is carried out using a coupled thermodynamic/kinetic analysis assuming multicomponent diffusion-controlled growth. The numerical results are broadly consistent with the experimental data; in the U720Li alloy, there appears to be an incubation period associated with the onset of reaction, but this is negligible in U720. In principle, the method could be adapted for the quantification of microstructural instabilities in other superalloys. If a maximum tolerable amount of microstructural degradation is defined, the method provides a rational basis for the estimation of the limiting combinations of temperature, time, and stress that any given alloy can withstand.

This study was carried out to evaluate water quality, sediment and plant vegetation in eight tributaries of the Mankyeong River for enhancement of natural purification. Among the tributaries, the Iksancheon water had the highest concentration of BOD, T-N and NH4-N due to inflow of swine wastes from the livestock district. The Yucheon water had the highest level of electrical conductivity and SO4(2-) due to inflow of mis-treated wastewater from industrial districts. The Tabcheon had generally similar concentrations of nitrogen and phosphate to that of the upstream of the Mankyeong River: agricultural activity along the Tabcheon appeared to have little negative influence to the water quality. Among various sediments, concentration of organic matter, nitrogen and phosphate were high in the Iksancheon and the Yucheon due to the livestock wastes and industrial wastes. There were 282 species of plants during summer with 43 aquatic plants, 57 hydrophytes, 178 waterside plants and 4 terrestrial plants. Some plant resources were recommended due to much absorption of nitrogen and phosphate for enhancement of natural purification. C. demersum and H. verticillata were recommended in the submerged aquatic plants, H. dubia, N. indica and N. subinteperrimum in the floating leaf aquatic plants, P. communis, Z. latifolia and T. orientalis in the emerged aquatic plants, C. scutata and P. distichum in the waterside plants.

Small guanosine triphosphatases, typified by the mammalian Ras proteins, play major roles in the regulation of numerous cellular pathways. A subclass of evolutionarily conserved Ras-like proteins was identified, members of which differ from other Ras proteins in containing amino acids at positions 12 and 61 that are similar to those present in the oncogenic forms of Ras. These proteins, κB-Ras1 and κB-Ras2, interact with the PEST domains of IκBα and IκBβ [inhibitors of the transcription factor nuclear factor kappa B (NF-κB)] and decrease their rate of degradation. In cells, κB-Ras proteins are associated only with NF-κB: IκBβ complexes and therefore may provide an explanation for the slower rate of degradation of IκBβ compared with IκBα.

BackgroundWe compared the efficacy, tolerability, and safety of oral sulfate tablets (OST, which contains simethicone) and 2 L-polyethylene glycol/ascorbate (2 L-PEG/Asc) with a split-dosing regimen in older individuals aged ≥ 70 years who underwent scheduled colonoscopy.MethodsThis prospective, randomized, investigator-blinded, multicenter study was conducted between June 2022 and October 2023. Participants aged ≥ 70 years were randomized at a ratio of 1:1 to the OST or 2 L-PEG/Asc groups.ResultsIn total, 254 patients were evaluated using a modified full analysis set. Successful overall bowel preparation was excellent and similar between the OST and 2 L-PEG/Asc groups for the Boston Bowel Preparation Scale (BBPS) (96.5% vs. 96.6%) and Harefield Cleansing Scale (HCS) (96.5% vs. 97.4%). The overall high-quality preparation rate was higher in the OST group than in the 2 L-PEG/Asc group (BBPS: 55.7% vs. 28.4%, P < 0.001; HCS: 66.1% vs. 38.8%, P < 0.001). The overall adenoma detection rate (54.8% vs. 35.3, P = 0.003) was superior in the OST group compared to the 2 L-PEG/Asc group. Tolerability scores, including overall satisfaction, were generally higher in the OST group than in the 2 L-PEG/Asc group. The incidence of major solicited adverse events was comparable between the two groups (55.7% vs. 68.1, P = 0.051), and there were no clinically significant changes in the serum laboratory profiles on the day of or 7 days after colonoscopy.ConclusionsOST is an effective and safe low-volume agent for colonoscopy, with better tolerance than 2 L-PEG/Asc, in older individuals aged ≥ 70 years.

BackgroundCold snare polypectomy (CSP) is recommended for the resection of small colorectal polyps. However, few studies have investigated the efficacy of cold endoscopic mucosal resection (cold EMR) for small polyps. Thus, the aim of this study was to investigate the efficacy and safety of cold EMR compared with CSP for small colorectal polyps.MethodsThis was a multicenter, randomized trial conducted in three tertiary centers from January 2018 to February 2021. Patients with polyps sized 6–10 mm were randomized to CSP or cold EMR group. After polypectomy, two additional biopsies were performed to assess the completeness of resection. The primary outcome was complete polyp resection rate. Secondary outcomes were total procedure time and rate of adverse events such as immediate bleeding, delayed bleeding, and perforation.ResultsA total of 444 polyps in 327 patients were assessed and randomly assigned to each group. Of those, 425 polyps were finally analyzed based on pathology results. The complete resection rate was not significantly different between cold EMR and CSP groups (91.9% vs 89.8%, p = 0.24). However, the total procedure time was significantly increased in cold EMR (87.6 s vs. 45.8 s, p < 0.001). The rate of polypectomy adverse events was not significantly different between the two groups. No patient had massive bleeding or perforation.ConclusionsThere was no difference in complete resection rate or adverse events between CSP and cold EMR. However, CSP reduced the total procedure time.