A semi-solid route is expected to be a fabrication method that can fabricate aluminum alloy foams with a variety of mechanical properties, but the allowance fluctuation of the fabrication conditions ...of aluminum alloy foams with high reproducibility is not clear. The objective of this study was to reveal the allowance fluctuation between the setting temperature and the actual temperature of the melt to fabricate stable foams, having pores with small pores and high circularity, and the influence of the increasing volume fraction of the solid on the pore morphology. Al-Si alloy foams were fabricated five times by adding a blowing agent into a semi-solid slurry under the same setting fabrication conditions, such as the temperature and concentration of oxygen in the atmosphere. The results of small relative standard deviations of pore diameter and circularity indicated that the conducted fabrication process had high reproducibility, even if the volume fraction of the solid changed in a range of 5%. When the volume fraction of the solid exceeds the minimal fraction of primary crystals for prevention of drainage, the clogging effect works more efficiently because the ratio of clogged cell walls increases. Additionally, the preferred range of the volume fraction of the solid for the fabrication of stable foam was revealed to be around 15% to 35%.
Stress relaxation, which occurs during holding at the bottom dead center in press forming, affects press formability. Because holding at the bottom dead center is completed within several seconds, it ...is important to predict the stress relaxation behavior of the first few seconds after the start of holding. The purpose of this study is to propose a model, the material parameters of which are obtained from tensile tests, to predict the stress decreasing behavior in the early stage of stress relaxation in steel sheets. We constructed the model by modifying the Kocks-Mecking model based on the following assumptions: Stress relaxation at room temperature is due to the slip motion of dislocations, which indicates that the plastic strain rates at the start of stress relaxation are same as those in the previous tensile process. In this study, it was assumed that the change in microstructure during stress relaxation is negligible; hence material parameters remain constant during stress relaxation. The measured and predicted stress relaxation behaviors for various strain rates during the tensile process were compared. It was observed that an increase in the plastic strain rate during the tensile process accelerated stress relaxation. The proposed model was able to predict this phenomenon. However, the relative error between experimental results and the model increased as the stress relaxation progressed mainly owing to dynamic strain aging. Therefore, the proposed model is applicable in the condition when effect of dynamic strain aging is negligible.
Obsessive-compulsive disorder (OCD) and pathological gambling (PG) are accompanied by deficits in behavioural flexibility. In reinforcement learning, this inflexibility can reflect asymmetric ...learning from outcomes above and below expectations. In alternative frameworks, it reflects perseveration independent of learning. Here, we examine evidence for asymmetric reward-learning in OCD and PG by leveraging model-based functional magnetic resonance imaging (fMRI). Compared with healthy controls (HC), OCD patients exhibited a lower learning rate for worse-than-expected outcomes, which was associated with the attenuated encoding of negative reward prediction errors in the dorsomedial prefrontal cortex and the dorsal striatum. PG patients showed higher and lower learning rates for better- and worse-than-expected outcomes, respectively, accompanied by higher encoding of positive reward prediction errors in the anterior insula than HC. Perseveration did not differ considerably between the patient groups and HC. These findings elucidate the neural computations of reward-learning that are altered in OCD and PG, providing a potential account of behavioural inflexibility in those mental disorders.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In addition to conventional cytology, liquid-based cytology (LBC) is also used for immunocytochemistry and gene analysis. However, an appropriate method to obtain high quality DNA for next-generation ...sequencing (NGS) using LBC specimens remains controversial. We determined the optimal conditions for fixation with an alcohol-based fixative for LBC and DNA extraction using cultured cancer cell lines and clinical specimens. The extracted DNA was processed for NGS after the DNA quality was confirmed based on the DNA concentration and degree of degradation. The optimal conditions for cultured cells to obtain high quality DNA were to fix the cells at a density of 6 × 103 or 2 × 104 cells/mL and to use the magnetic bead-based DNA extraction method. Even after storing the fixed cells for 90 days, DNA extracted using the above and other extraction kits, including membrane-based methods, did not undergo degradation. Furthermore, 5-year-old residual LBC samples demonstrated high DNA quality that was suitable for NGS. Furthermore, a cancer genome panel analysis was successfully performed with DNA extracted from cultured cells fixed at 6 × 103 cells/mL for 90 days, and with DNA from residual LBC samples even after 1 year of storage. Residual LBC samples may be a useful source of DNA for clinical NGS to promote genome-based cancer medicine.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Interferon regulatory factor-5 (IRF5), a transcription factor critical for the induction of innate immune responses, contributes to the pathogenesis of the autoimmune disease systemic lupus ...erythematosus (SLE) in humans and mice. Lyn, a Src family kinase, is also implicated in human SLE, and Lyn-deficient mice develop an SLE-like disease. Here, we found that Lyn physically interacted with IRF5 to inhibit ubiquitination and phosphorylation of IRF5 in the TLR-MyD88 pathway, thereby suppressing the transcriptional activity of IRF5 in a manner independent of Lyn’s kinase activity. Conversely, Lyn did not inhibit NF-κB signaling, another major branch downstream of MyD88. Monoallelic deletion of Irf5 alleviated the hyperproduction of cytokines in TLR-stimulated Lyn–/– dendritic cells and the development of SLE-like symptoms in Lyn–/– mice. Our results reveal a role for Lyn as a specific suppressor of the TLR-MyD88-IRF5 pathway and illustrate the importance of fine-tuning IRF5 activity for the maintenance of immune homeostasis.
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•Lyn binds to and inhibits the activity of IRF5 in the TLR-MyD88 pathway•Lyn inhibits post-translational modifications of IRF5 without Lyn’s kinase activity•Lyn deficiency causes IRF5 hyperactivation in DCs•SLE symptoms in Lyn–/– mice are ameliorated by monoallelic deletion of Irf5
How IRF5 activity is negatively regulated remains largely unknown. Tamura and colleagues identify Lyn as an IRF5-binding protein that suppresses the TLR-MyD88-IRF5 pathway. IRF5 is hyperactivated in Lyn-deficient mice suffering from the autoimmune disease SLE, but reducing the abundance of IRF5 ameliorates the disease development.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Objective:
Despite the use of surgical and chemoradiation therapies, head and neck squamous cell carcinoma (HNSCC) still has a poor prognosis. Immune checkpoint inhibitors have been shown to prolong ...life expectancy but have limited efficacy. Glycoprotein nonmetastatic melanoma protein B (GPNMB) has received significant attention in breast cancer treatment, in which it has been associated with cancer stem cells (CSCs) and epithelial-mesenchymal transition (EMT); however, the function of GPNMB in HNSCC is completely unknown. This study aimed to clarify the characteristics of GPNMB-positive cells
in vitro
and their association with the prognosis by immunostaining clinical specimens.
Methods:
We examined the sphere formation, invasion, and migration ability of GPNMB-positive cells in four HNSCC cell lines
in vitro
. We also immunostained biopsy specimens with GPNMB from 174 patients with HNSCC diagnosed, treated, and followed-up in our institution to evaluate overall survival and progression-free survival.
Results:
GPNMB-positive cells showed enhanced sphere formation, invasion, and migration, suggesting that they could have CSC characteristics and the ability to induce EMT, as reported for breast cancer. Clinical specimens showed that overall survival was 39.4% and 57.8% (
p
= 0.045) and that progression-free survival was 27.6% and 51.6% (
p
= 0.013) for the high-expression and the low-expression groups, respectively, indicating poor prognosis for the high GPNMB group. The high GPNMB group was also more resistant to chemoradiation and bioradiotherapy. GPNMB was more highly expressed in metastatic lymph nodes than in the primary tumor.
Conclusion:
GPNMB-positive cells might have CSC characteristics and induce EMT. Detailed functional analyses of GPNMB in HNSCC and the establishment of therapies targeting GPNMB will lead to improved prognoses.
This study aims to establish predictive formulas for the temperature dependence of impurity diffusion coefficient based on a hard-sphere (HS) model and the measurement results. The impurity diffusion ...coefficients of Sb, Bi, and In in liquid Sn were measured using the shear cell technique and stable density layering at 773 K and 973 K (500 °C and 700 °C, respectively) with suppression of natural convection. The temperature dependence of the impurity diffusion coefficient can be predicted by multiplying the ratio of the solvent to the solute of the following three factors by the self-diffusion coefficient of the solvent as the slope: (i) the square of mean atomic diameter, (ii) the first peak of the pair distribution function calculated by the HS model, and (iii) the square root of the converted atomic weight. If the ratio of the atomic diameter is close to one, the temperature dependence of the impurity diffusion coefficient can also be predicted with an accuracy similar to the abovementioned relationship by multiplying the following two factors by the self-diffusion coefficient of the solvent as the slope: (i) the atomic diameter ratio of the solvent to the solute and (ii) the thermodynamic factor. The predictive formulas based on the HS model showed an accuracy of approximately ±10 pct for the experimental values from 573 K to 973 K (300 °C to 700 °C).
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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
The crystal orientation of a drawn high carbon steel wire was analyzed through electron backscatter diffraction analysis under the assumption that the wire consists of a mesoscale structure ...characterized by the fiber texture. The microstructure forming the mesoscale structure and the mechanical properties depending on the mesoscale structure were explained by the results of transmission electron microscopy observation, measurement of the electrical resistivity, differential scanning calorimetry thermal analysis, and tensile testing. In the beginning of the wire drawing, the wire has only {100} −{111} (the primary fiber texture). Then, the wire has this orientation at the outer side and {110} −{111} (the secondary fiber texture) at the inner side. At a drawing strain larger than approximately 2.7, the subprimary fiber texture ({100} −{111} ) is formed at the outer side and will occupy the volume of the wire. The results indicate that with the increase of the drawing strain, the lamellar spacing decreased, and the amount of lattice defects increased. The tensile strength, uniform elongation, and reduction of area were typically uniform in the radial direction of the wire. On the other hand, the wire with only the primary fiber texture had lamellae whose angle with respect to the drawing direction decreased during wire drawing, as well as a surface layer with low longitudinal ductility. The wire with the subprimary fiber texture contained decomposed cementite. The wire also had a large variation of reduction of area. Increasing the back stress ratio shifts the transition of the mesoscale structure to a lower drawing strain.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Adolescence is a period of life in which social influences-particularly if they come from peers-play a critical role in shaping learning and decision preferences. Recent studies in adults show ...evidence of a risk contagion effect; that is, individual risk preferences are modulated by observing and learning from others' risk-related decisions. In this study, using choice data and computational modeling, we demonstrate stronger risk contagion in male adolescents when observing peers compared to nonpeers. This effect was only present when the observed peer showed risk-seeking preferences. Moreover, adolescents represented the peers' decisions better than those of adults. Intriguingly, the degree of peer-biased risk contagion in adolescents was positively associated with real-life social integration. Contrary to previous accounts, our data suggest that peer conformity during risky decision-making in adolescence is a socially motivated, deliberative process. Susceptibility to peer influence in adolescence might be adaptive, associated with higher degrees of social functioning.
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CEKLJ, FFLJ, NUK, ODKLJ, PEFLJ, UPUK
The detection of object movement that is contingent on one's own actions (i.e., movements with action contingency) influences social perception of the object; such interactive objects tend to create ...a good impression. However, it remains unclear whether neural representation of action contingency is associated with subsequent socio-cognitive evaluation of "contacting agents", or whether the appearance of agents (e.g., face- or non-face-like avatars) is essential for this effect. In this study, we conducted a functional magnetic resonance imaging (fMRI) task with two phases: contact (contact with face- or non-face-like avatars moving contingently or non-contingently) and recognition (rating a static image of each avatar). Deactivation of the frontoparietal self-agency network and activation of the reward network were the main effects of action contingency during the contact phase, consistent with previous findings. During the recognition phase, static avatars that had previously moved in a contingent manner deactivated the frontal component of the frontoparietal network (bilateral insula and inferior-middle frontal gyri), regardless of person-like appearance. Our results imply that frontal deactivation may underlie the effect of action contingency on subsequent social perception, independent of person-like appearance.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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