NKIRAS1 and NKIRAS2 (also called as κB-Ras) were identified as members of the atypical RAS family that suppress the transcription factor NF-κB. However, their function in carcinogenesis is still ...controversial. To clarify how NKIRAS acts on cellular transformation, we generated transgenic mice in which NKIRAS2 was forcibly expressed using a cytokeratin 15 (K15) promoter, which is mainly activated in follicle bulge cells. The ectopic expression of NKIRAS2 was mainly detected in follicle bulges of transgenic mice with NKIRAS2 but not in wild type mice. K15 promoter-driven expression of NKIRAS2 failed to affect the development of epidermis, which was evaluated using the expression of K10, K14, K15 and filaggrin. However, K15 promoter-driven expression of NKIRAS2 effectively suppressed the development of skin tumors induced by treatment with 7,12-dimethylbenz(a)anthracene (DMBA)/12-O-tetradecanoylphorbol 13-acetate (TPA). This observation suggested that NKIRAS seemed to function as a tumor suppressor in follicle bulges. However, in the case of oncogenic HRAS-driven cellular transformation of murine fibroblasts, knockdown of NKIRAS2 expression drastically suppressed HRAS-mutant-provoked cellular transformation, suggesting that NKIRAS2 was required for the cellular transformation of murine fibroblasts. Furthermore, moderate enforced expression of NKIRAS2 augmented oncogenic HRAS-provoked cellular transformation, whereas an excess NKIRAS2 expression converted its functional role into a tumor suppressive phenotype, suggesting that NKIRAS seemed to exhibit a biphasic bell-shaped enhancing effect on HRAS-mutant-provoked oncogenic activity. Taken together, the functional role of NKIRAS in carcinogenesis is most likely determined by not only cellular context but also its expression level.
► Equilibrium temperatures of tetrabutylammonium bromide and tetrabutylammonium chloride hydrates are measured. ► Mass fraction of tetrabutylammonium bromide aqueous solution from 0.10 to 0.55. ► The ...highest equilibrium temperature of tetrabutylammonium bromide hydrate was 285.9K at 0.35<wTBAB<0.37. ► Mass fraction of tetrabutylammonium chloride aqueous solution from 0.10 to 0.55. ► The highest equilibrium temperature of tetrabutylammonium chloride hydrate was 288.2K at wTBAC=0.35.
This paper reports the accurate phase equilibrium measurements of two ionic semiclathrate hydrates with tetrabutylammonium bromide (TBAB) and tetrabutylammonium chloride (TBAC). These ionic semiclathrate hydrates are suggested as cool energy storage media for air-conditioning system since their dissociation heats of phase transitions are as large as 200–500kJ/kg and they form at 278–293K under atmospheric pressure. Tetrabutylammonium bromide and tetrabutylammonium chloride form ionic semiclathrate hydrates and there are several previous reports of the equilibrium temperatures of these hydrates in the literature. However, there is inconsistency in the literature data of equilibrium temperatures. Also, there are no clear notifications of experimental procedures and uncertainty of measurements in some of the previous reports. Therefore, we have performed accurate measurements of the phase equilibrium of tetrabutylammonium bromide and tetrabutylammonium chloride hydrates and the comparison with the literature data is also made in this paper. The highest equilibrium temperature for tetrabutylammonium bromide system was 285.9K at 0.35<wTBAB<0.37, where wTBAB denotes the mass fraction of tetrabutylammonium bromide (or the mole fraction of tetrabutylammonium bromide, 0.029<xTBAB<0.032), under atmospheric pressure. That for tetrabutylammonium chloride system was 288.2K at wTBAC=0.35, where wTBAC is the mass fraction of tetrabutylammonium chloride (or the mole fraction of tetrabutylammonium chloride, xTBAC=0.034), under atmospheric pressure.
Objectives. Various autoantibodies are detected in the sera of PM/DM patients. Some of them are specific to PM/DM patients and closely associated with clinical manifestations of the diseases. ...Recently, the anti-CADM-140 antibody was reported to be found specifically in clinically amyopathic DM (C-ADM) patients and to be associated with acute interstitial lung disease (ILD). We assessed the clinical significance of the anti-CADM-140 antibody and then investigated the autoantigen recognized by the anti-CADM-140 antibody. Methods. Autoantibodies were screened in 192 patients with various CTDs and 21 healthy controls using immunoprecipitation with 35Smethionine-labelled HeLa cells. Immunoabsorbent column chromatography was used to purify an autoantigen that was subsequently subjected to peptide mass fingerprinting. Results. The anti-CADM-140 antibody was revealed to be specific to DM. Most of the anti-CADM-140-positive patients were C-ADM although some of them showed apparent myositis. The anti-CADM-140-positive patients frequently showed hyperferritinaemia and acute progressive ILD with poor prognosis. The anti-CADM-140 antibody was shown to recognize IFN induced with helicase C domain protein 1 (IFIH1), also known as the melanoma differentiation-associated gene 5 (MDA5), which is one of the RIG-I-like receptors and plays a role in innate immune responses. Conclusion. The anti-CADM-140 antibody was a marker of DM and intractable ILD and recognized IFIH1/MDA5, which is involved in innate immunity. These findings may give a new insight into the pathogenesis of DM.
•Four-phase (H2 + CO2) + water + THP + hydrate equilibrium conditions was measured.•THP acts as the hydrate thermodynamic promoter in this system.•The equilibrium conditions in this system can be ...estimated from CO2 partial pressure.•H2 might scarcely influences the stability of the hydrate with H2 + CO2 + THP.•The structure of the hydrate in this system was identified to be structure II.
This paper reports the thermodynamic and crystallographic characterization of the clathrate hydrate formed in H2 + CO2 + tetrahydropyran (THP) + water system by phase equilibrium measurements and powder X-ray diffraction measurements with a goal of developing a hydrate-based carbon capture technology in an integrated coal gasification combined cycle. The four-phase (H2 + CO2) gas + water liquid + THP liquid + hydrate equilibrium conditions were measured with two series of gas compositions (around H2:CO2 = 0.7:0.3 and 0.9:0.1 in mole fractions) in the range of 2.64 MPa to 7.51 MPa. At around H2:CO2 = 0.7:0.3 in gas phase, the equilibrium temperatures in (H2 + CO2) gas + THP + water system are always higher by approximately 9 to 10 K compared to the equilibrium temperatures of H2 + CO2 + water system. This means that THP acts as the hydrate thermodynamic promoter. The equilibrium conditions in (H2 + CO2) gas + THP + water system, which is only considered with CO2 partial pressure, greatly agree with those in CO2 + THP + water system. Therefore, the equilibrium conditions in (H2 + CO2) gas + THP + water system would only depend on the partial pressure of CO2. Moreover, the crystallographic structure of the hydrate formed in H2 + CO2 + THP + water system was identified to be structure II, which is the same structure as the hydrate formed in H2 + CO2 + water system. These results can contribute to the study of a hydrate-based gas separation and carbon capture.
Higher impulsivity is thought to be a risk factor for drug addiction, criminal involvement, and suicide. Excessive levels of impulsivity are often observed in several psychiatric disorders including ...attention-deficit/hyperactivity disorder and schizophrenia. Previous studies have demonstrated that nicotinic acetylcholine receptors (nAChRs) are involved in impulsive behavior. Here, we introduce recent advances in this field and describe the role of the following nAChR-related brain mechanisms in modulating impulsive behavior: dopamine release in the ventral striatum; α4β2 nAChRs in the infralimbic cortex, which is a ventral part of the medial prefrontal cortex (mPFC); and dopamine release in the mPFC. We also suggest several potential therapeutic drugs to address these mechanisms in impulsivity-related disorders and explore future directions to further elucidate the roles of central nAChRs in impulsive behavior.
Self-crack-healing by oxidation of a pre-incorporated healing agent is an essential property of high-temperature structural ceramics for components with stringent safety requirements, such as turbine ...blades in aircraft engines. Here, we report a new approach for a self-healing design containing a 3D network of a healing activator, based on insight gained by clarifying the healing mechanism. We demonstrate that addition of a small amount of an activator, typically doped MnO localised on the fracture path, selected by appropriate thermodynamic calculation significantly accelerates healing by >6,000 times and significantly lowers the required reaction temperature. The activator on the fracture path exhibits rapid fracture-gap filling by generation of mobile supercooled melts, thus enabling efficient oxygen delivery to the healing agent. Furthermore, the activator promotes crystallisation of the melts and forms a mechanically strong healing oxide. We also clarified that the healing mechanism could be divided to the initial oxidation and additional two stages. Based on bone healing, we here named these stages as inflammation, repair, and remodelling stages, respectively. Our design strategy can be applied to develop new lightweight, self-healing ceramics suitable for use in high- or low-pressure turbine blades in aircraft engines.
We performed in situ compression of interstitial-free steel nanoblades using transmission electron microscopy (TEM) in order to determine the relation between the evolution of the dislocation ...structures and the flow stress during deformation. In the early stage of deformation, the sample deforms elastically with a few dislocation motions. The dislocation multiplication processes have been discussed. Remarkable plastic softening with increasing dislocation density is observed after the maximum stress is reached, which can be understood as a situation in which the dislocation density is the dominant factor affecting the softening based on the Johnston–Gilman model.
High resolution transmission electron microscopy (HRTEM) with nanometer-scaled energy-dispersive X-ray (EDX) was employed to investigate the transformation mechanisms of the GP zone → η′ → η ...precipitation sequence of AA7050, an Al-Zn-Mg-Cu alloy. Serial in-situ HRTEM frames revealed that separated nucleation of an η′ precipitate occurred elsewhere as the adjacent GPII zone dissolved. Evidence from HRTEM coupled with EDX showed that in-situ nucleation of a new η2 precipitate (one form of η) took place, wherein it gradually developed from the original η′ precipitate via a similar hexagonal structure with different compositions. The in-situ transition product was composed of two distinctive regions; one was identified as η′, and the other, as η.
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The surface solar radiation (SSR) is an important factor influencing the local and global energy budget. However, information on the spatial and temporal variation of SSR is limited. A more commonly ...available measure, which may provide such information, is the diurnal temperature range (DTR). In this study we analyze the relationship between DTR and SSR in Europe between 1970 and 2005 on seasonal and decadal scale. When comparing the mean anomalies time series composed of 31 pairs of sites with long‐term SSR and DTR measurements, we found a correlation coefficient of 0.87 in the annual mean and between 0.61 and 0.92 in the seasonal mean anomalies. When investigating the individual pairs of SSR and DTR individually, we found that local correlations are mostly lower than the European mean and that they decrease rapidly in seasons and latitudes with low incident angles and at high alpine altitude. The highest correlation on local and seasonal scales seems to be connected with the variability of the large‐scale circulation in Europe. The output of 11 simulations of current generation regional climate models over Europe confirms the strong relationship between SSR and DTR. The seasonal dependence of the relationship is well reproduced, but the absolute values of DTR and SSR are mostly too low. The pattern of decrease (dimming) and increase (brightening) in SSR and DTR was not reproduced in the modeled time series. There is still strong evidence from both models and observations that DTR is a reliable representative of SSR.
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