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Tumor-associated macrophages (TAMs), especially the M2-like phenotype, promote tumor progression, making them candidate targets for anti-tumor therapy. We previously discovered a cyclic sulfur compound, Onionin A (ONA), which suppresses tumor progression by inhibiting the M2-polarization of TAMs. In the present study, we sought to find new candidate compounds possessing a stronger effect compared to ONA by exploring compounds with structures similar to those of ONA among several cyclic sulfur compounds. A total of 81 cyclic sulfur compounds were screened, and their effects on macrophage polarization toward an M2-like phenotype were tested using human monocyte-derived macrophages (HMDMs). The anti-tumor effects of the identified candidate compounds were examined in a tumor-bearing mouse model. Three candidate compounds inhibited both IL-10- and tumor culture supernatant (TCS)-induced M2-polarization of HMDMs. These compounds also suppressed STAT3 activation in HMDMs stimulated by IL-10 and TCS, whereas these compounds had no effect on STAT3 activation in tumor cells. Furthermore, these compounds inhibited tumor cell proliferation under co-culture conditions with HMDMs, indicating that the three candidate compounds suppress tumor proliferation by regulating cell–cell interactions between tumor cells and macrophages. In addition, two of these candidate compounds had inhibitory effects on tumor growth and lung metastasis in the LM8 tumor-bearing mouse model. Our study identified new candidate cyclic sulfur compounds for anti-tumor therapy targeting the M2-polarization of TAMs. [ABSTRACT FROM AUTHOR]

Objectives: Septic (or endotoxin) shock is a severe systemic inflammatory disease caused by bacteraemia or endotoxaemia. Although it is known that increased serum levels of CD163 are observed in septic/endotoxin shock patients, the exact function and significance of CD163 in macrophage activation remain unclear. Therefore, in the current study, we tested whether CD163 contributes to the pathogenesis of endotoxin shock in mice. Methods and results: In samples obtained from autopsy, the number of CD163‐positive macrophages was increased in the kidney, liver, heart, bone marrow and spleen of patients who had died from septic/endotoxin shock when compared to patients who had died from other causes. The animal study revealed a significantly lower survival rate in CD163‐deficient mice after lipopolysaccharide (LPS) injection. Several cytokines and oxidative stress‐related molecules were significantly elevated in the sera of LPS‐induced endotoxin shock mice models. Higher concentrations of IL‐6, TNF‐α, IL‐1β, nitrite (NO2‐) and nitrate (NO3‐) and a lower concentration of IL‐10 were observed in CD163‐deficient mice treated with LPS. Similar results were observed in CD163‐deficient LPS‐stimulated macrophages. Furthermore, in an antitype II collagen antibody‐induced arthritis (CAIA), rheumatoid arthritis model, inflammation and bone erosion scores as well as the expression of IL‐6 and IL‐1β were significantly increased in CD163‐deficient mice. Conclusions: CD163 was suggested to be involved in the regulation of inflammatory cytokine expression in septic/endotoxin shock and CAIA. [ABSTRACT FROM AUTHOR]

M2-like tumor-associated macrophages (TAMs) in the tumor tissues promote tumor progression by various mechanisms and represent possible targets of antitumor therapy. In the present study, we tested whether compounds from Epimedii Herba inhibit macrophage polarization to the M2/protumorigenic phenotype and prevent tumor progression, using human monocyte-derived macrophages (HMDMs) and an animal sarcoma model. Four Epimedii Herba -derived flavonoid compounds, namely, limonianin, epimedokoreanin B, icaritin, and desmethylicaritin, inhibited CD163 expression and interleukin (IL)-10 production, which are known M2 markers, suggesting that these compounds inhibit M2 polarization. Among these compounds, epimedokoreanin B and limonianin suppressed STAT3 activation in HMDMs. Notably, epimedokoreanin B also suppressed cell proliferation by blocking STAT3 activation in Saos-2 human sarcoma and LM8 mouse sarcoma cell lines. Furthermore, oral administration of epimedokoreanin B inhibited tumor growth in an LM8 tumor-bearing murine model. These results indicate that Epimedii Herba and Epimedii Herba- derived compounds, such as epimedokoreanin B, may be potentially new agents that can be used for the treatment and prevention of various malignant tumors. They may also be promising compounds for targeting the tumor microenvironment by inhibiting M2 polarization of the TAMs. [ABSTRACT FROM AUTHOR]

In the semiconductor, an advanced process control (APC) system using virtual metrology (VM) for plasma etching is required to achieve further device miniaturization. VM is a method to predict process outputs such as the critical dimension (CD) from equipment data indicating the etcher condition. The prediction model for VM is called VM model. Although a highly accurate VM model is necessary to realize the APC system, the prediction accuracy can be worse when the correlations between the CD and equipment data change because of changes in etcher conditions. To solve the problem, we propose a multiple VM model selection APC system. The proposed APC builds: 1) multiple local VM models that are built using a series of lot data to cope with the correlation change and 2) a global VM model that is built using all of the lot data to improve the robustness of CD prediction. When APC is applied, the proposed APC selects the optimal VM model among the multiple VM models that have been built. This paper shows that the proposed system contributes to improving prediction accuracy even though the correlation change occurs by simulation based on actual etcher experimental data. [ABSTRACT FROM AUTHOR]

We provide a decomposition of the trace of the Brownian motion into a simple path and an independent Brownian soup of loops that intersect the simple path. More precisely, we prove that any subsequential scaling limit of the loop erased random walk is a simple path (a new result in three dimensions), which can be taken as the simple path of the decomposition. In three dimensions, we also prove that the Hausdorff dimension of any such subsequential scaling limit lies in (1,53]. We conjecture that our decomposition characterizes uniquely the law of the simple path. If so, our results would give a new strategy to the existence of the scaling limit of the loop erased random walk and its rotational invariance. [ABSTRACT FROM AUTHOR]

We previously reported that allergic responses to nickel (Ni) were minimal in mice deficient in the histamine-forming enzyme histidine decarboxylase ( HDC- KO), suggesting an involvement of histamine in allergic responses to Ni. However, it remains unclear how histamine is involved in the process of Ni allergy. Here, we examined the role of histamine in Ni allergy using a murine model previously established by us. Mice were sensitized to Ni by intraperitoneal injection of a NiCl2-lipopolysaccharide ( LPS) mixture. Ten days later, allergic inflammation was elicited by challenging ear-pinnas intradermally with NiCl2. Then, ear-swelling was measured. Pyrilamine (histamine H1-receptor antagonist) or cromoglicate (mast cell stabilizer) was intravenously injected 1 h before the sensitization or the challenge. In cell-transfer experiments, spleen cells from Ni-sensitized donor mice were intravenously transferred into non-sensitized recipient mice. In both sensitized and non-sensitized mice, 1 m m or more NiCl2 (injected into ear-pinnas) induced transient non-allergic inflammation (Ni- TI) with accompanying mast cell degranulation. LPS did not affect the magnitude of this Ni- TI. Pyrilamine and cromoglicate reduced either the Ni- TI or the ensuing allergic inflammation when administered before Ni- TI (at either the sensitization or elicitation step), but not if administered when the Ni- TI had subsided. Experiments on HDC- KO and H1-receptor- KO mice, and also cell-transfer experiments using these mice, demonstrated histamine's involvement in both the sensitization and elicitation steps. These results suggest that mast cell histamine-mediated Ni- TI promotes subsequent allergic inflammatory responses to Ni, raising the possibility that control of Ni- TI by drugs may be effective at preventing or reducing Ni allergy. [ABSTRACT FROM AUTHOR]

The correlation between the change in the etching rate of SiN and the change in the monitored plasma impedance was investigated to estimate the capability of critical dimension (CD) prediction with a plasma impedance monitor (PIM). The results obtained with the PIM were compared with those of optical emission spectroscopy (OES), which was performed using the emission intensity ratio of C2/H, and showed that the SiN etching rate is strongly correlated with several values obtained with the PIM. We conclude that the PIM has the potential to predict CDs with the same accuracy as that of OES. [ABSTRACT FROM AUTHOR]

Let S be a simple random walk starting at the origin in $${\mathbb{Z}^{4}}$$. We consider $${{\mathcal G}=S[0,\infty)}$$ to be a random subgraph of the integer lattice and assume that a resistance of unit 1 is put on each edge of the graph $${{\mathcal G}}$$. Let $${R_{{\mathcal G}}(0,S_{n})}$$ be the effective resistance between the origin and S. We derive the exact value of the resistance exponent; more precisely, we prove that $${n^{-1}E(R_{{\mathcal G}}(0,S_{n}))\approx (\log n)^{-\frac{1}{2}}}$$. As an application, we obtain sharp heat kernel estimates for random walk on $${\mathcal G}$$ at the quenched level. These results give the answer to the problem raised by Burdzy and Lawler (J Phys A Math Gen 23:L23-L28, ) in four dimensions. [ABSTRACT FROM AUTHOR]

This study was a preliminary investigation of non-verbal communication in Japanese subjects. Sixteen males and sixteen females were interviewed by one of two male confederates. The confederates were described and dressed as either high or equal status persons. They assumed either a forward lean or a backward lean during the four minute interview. Tape and video recordings were analyzed across a wide spectrum of non-verbal behaviors emitted by the subjects during the interview. Both status and body lean variables affected a variety of dependent measures, particularly for female subjects. A factor analysis of the non-verbal behaviors produced some unexpected results which have implications for similar studies done in other cultures. [ABSTRACT FROM PUBLISHER]

Dimensions of Japanese person perception were assessed using Norman's (1963) method and stimulus materials. These dimensions were then compared statistically with results from similar studies involving subjects from the United States and from the Philippines. Students from Japan and the United States grouped the same behaviors into the five factors of extroversion, good-naturedness, conscientiousness, emotional stability, and culture. For all three subject populations, the same behavior descriptions were grouped together to form the high variance dimensions of extroversion, good-naturedness, and conscientiousness. The factors of emotional stability and culture, however, appear to be construed in culturally specific ways. Differences in the relative strength of the first three factors across the three cultures were discussed with the prominence of the extroversion factor in Japan being related to the importance of relative status in Japanese society. [ABSTRACT FROM PUBLISHER]