Abstract
Here we report on the upgrade of the quasioptical code PAraxial RAy DEscription (2019
Phys. Plasmas
26
072112) to introduce the relativistic effect for electron cyclotron resonance heating ...and current drive on fusion DEMO reactors, e.g. JA-DEMO, where the electron temperature is sufficiently high (almost 35 keV). By fully considering the relativistic effect, it is found that the outside launch used in many tokamaks is not suitable for localized heating in JA-DEMOdue to the contamination of spatially widespread absorption at relativistically down-shifted higher-harmonic resonance. It is proposed to adopt a top launch to avoid this issue, and is shown that top launch can improve the localization of the heating without degrading the current drive efficiency.
Abstract
We report the first applications of the quasioptical (QO) code PARADE (PAraxial RAy DEscription) for modeling the electron cyclotron emission (ECE) diagnostic. Geometrical optics (GO) has ...been exploited to predict the ECE intensity received by an antenna, but is not sufficient since GO drops the information lying on the transverse cross section of the antenna sensitivity. Hence, we studied a QO model of ECE measurement based on the PARADE code. By introducing a weighting operator
W
ˆ
,
induced by the envelope profile of a wave beam virtually injected from an ECE receiving antenna, an integral equation, formally identical to the conventional GO model, is newly derived from the wave-action conservation law. A QO ECE prediction module −E
3
is also newly developed, is applied to the JT-60SA tokamak, and shows that radiation temperature is corrected from conventional GO prediction. The −E
3
module and the PARADE code are applicable to any fusion plasma devices. By using this ECE prediction package, more realistic calculations of radiation temperature are expected by taking the actual structure of an ECE receiving antenna and plasma parameters as well.
Frequency of FGFR2 amplification, its clinicopathological features, and the results of high-throughput screening assays in a large cohort of gastric clinical samples remain largely unclear.
Drug ...sensitivity to a fibroblast growth factor receptor (FGFR) inhibitor was evaluated in vitro. The gene amplification of the FGFRs in formalin-fixed, paraffin-embedded (FFPE) gastric cancer tissues was determined by a real-time PCR-based copy number assay and fluorescence in situ hybridisation (FISH).
FGFR2 amplification confers hypersensitivity to FGFR inhibitor in gastric cancer cell lines. The copy number assay revealed that 4.1% (11 out of 267) of the gastric cancers harboured FGFR2 amplification. No amplification of the three other family members (FGFR1, 3 and 4) was detected. A FISH analysis was performed on 7 cases among 11 FGFR2-amplified cases and showed that 6 of these 7 cases were highly amplified, while the remaining 1 had a relatively low grade of amplification. Although the difference was not significant, patients with FGFR2 amplification tended to exhibit a shorter overall survival period.
FGFR2 amplification was observed in 4.1% of gastric cancers and our established PCR-based copy number assay could be a powerful tool for detecting FGFR2 amplification using FFPE samples. Our results strongly encourage the development of FGFR-targeted therapy for gastric cancers with FGFR2 amplification.
SOX transcription factors are essential for embryonic development and play critical roles in cell fate determination, differentiation and proliferation. We previously reported that the SOX2 protein ...is expressed in normal gastric mucosae but downregulated in some human gastric carcinomas. To clarify the roles of SOX2 in gastric carcinogenesis, we carried out functional characterisation of SOX2 in gastric epithelial cell lines. Exogenous expression of SOX2 suppressed cell proliferation in gastric epithelial cell lines. Flow cytometry analysis revealed that SOX2-overexpressing cells exhibited cell-cycle arrest and apoptosis. We found that SOX2-mediated cell-cycle arrest was associated with decreased levels of cyclin D1 and phosphorylated Rb, and an increased p27(Kip1) level. These cells exhibited further characteristics of apoptosis, such as DNA laddering and caspase-3 activation. SOX2 hypermethylation signals were observed in some cultured and primary gastric cancers with no or weak SOX2 expression. Among the 52 patients with advanced gastric cancers, those with cancers showing SOX2 methylation had a significantly shorter survival time than those without this methylation (P=0.0062). Hence, SOX2 plays important roles in growth inhibition through cell-cycle arrest and apoptosis in gastric epithelial cells, and the loss of SOX2 expression may be related to gastric carcinogenesis and poor prognosis.
In the process of cancer spreading, different modes of invasion exist. One is expansive invasion, in which a group of cancer cells gradually expands along with cancer cell proliferation. Invasion of ...cancer cells is also modified by their interaction with stromal cells including cancer-associated fibroblasts (CAFs). Cancer cells co-invade with CAFs, and invasion by CAFs frequently precede invasion by cancer cells, which indicates CAF-led cancer cell invasion. Here, we show that CAFs induce apoptosis in gastric cancer cells, which prevented expansive invasion by cancer cells and instead facilitated CAF-led invasion. Death receptor 4 and activation of caspase-8 in cancer cells mediated cancer cell apoptosis induced by CAFs, which was dependent on contact between cancer cells and CAFs. Apoptotic cancer cells in turn released apoptotic vesicles and stimulated invasion of CAFs. Accordingly, cancer cells followed the migrating CAFs. Treatment with a caspase inhibitor, ZVAD, or forced expression of a death domain fragment in cancer cells prevented cancer cell apoptosis induced by CAFs and increased expansive invasion by cancer cells in extracellular gel invasion assays, while the rate of cancer cell invasion led by CAFs was decreased. Death domain-fragment expression also prevented intramural invasion by gastric cancer cells in the stomach. Because CAF-led invasion is characterized by the movement of individual cancer cells away from the tumour, adequate cancer cell apoptosis may promote cancer dissemination.
Progressive cognitive deficits that emerge with aging are a result of complex interactions of genetic and environmental factors. Whereas much has been learned about the genetic underpinnings of these ...disorders, the nature of "acquired" contributing factors, and the mechanisms by which they promote progressive learning and memory dysfunction, remain largely unknown. Here, we demonstrate that a period of early-life "psychological" stress causes late-onset, selective deterioration of both complex behavior and synaptic plasticity: two forms of memory involving the hippocampus, were severely but selectively impaired in middle-aged, but not young adult, rats exposed to fragmented maternal care during the early postnatal period. At the cellular level, disturbances to hippocampal long-term potentiation paralleled the behavioral changes and were accompanied by dendritic atrophy and mossy fiber expansion. These findings constitute the first evidence that a short period of stress early in life can lead to delayed, progressive impairments of synaptic and behavioral measures of hippocampal function, with potential implications to the basis of age-related cognitive disorders in humans.
PDF
