160 research outputs found
An Accurate Graph Generative Model with Tunable Features
A graph is a very common and powerful data structure used for modeling
communication and social networks. Models that generate graphs with arbitrary
features are important basic technologies in repeated simulations of networks
and prediction of topology changes. Although existing generative models for
graphs are useful for providing graphs similar to real-world graphs, graph
generation models with tunable features have been less explored in the field.
Previously, we have proposed GraphTune, a generative model for graphs that
continuously tune specific graph features of generated graphs while maintaining
most of the features of a given graph dataset. However, the tuning accuracy of
graph features in GraphTune has not been sufficient for practical applications.
In this paper, we propose a method to improve the accuracy of GraphTune by
adding a new mechanism to feed back errors of graph features of generated
graphs and by training them alternately and independently. Experiments on a
real-world graph dataset showed that the features in the generated graphs are
accurately tuned compared with conventional models.Comment: This paper was presented at the 32nd International Conference on
Computer Communications and Networks (ICCCN 2023) Poster Trac
Expression of MUC17 is regulated by HIF1α-mediated hypoxic responses and requires a methylation-free hypoxia responsible element in pancreatic cancer.
MUC17 is a type 1 membrane-bound glycoprotein that is mainly expressed in the digestive tract. Recent studies have demonstrated that the aberrant overexpression of MUC17 is correlated with the malignant potential of pancreatic ductal adenocarcinomas (PDACs); however, the exact regulatory mechanism of MUC17 expression has yet to be identified. Here, we provide the first report of the MUC17 regulatory mechanism under hypoxia, an essential feature of the tumor microenvironment and a driving force of cancer progression. Our data revealed that MUC17 was significantly induced by hypoxic stimulation through a hypoxia-inducible factor 1α (HIF1α)-dependent pathway in some pancreatic cancer cells (e.g., AsPC1), whereas other pancreatic cancer cells (e.g., BxPC3) exhibited little response to hypoxia. Interestingly, these low-responsive cells have highly methylated CpG motifs within the hypoxia responsive element (HRE, 5\u27-RCGTG-3\u27), a binding site for HIF1α. Thus, we investigated the demethylation effects of CpG at HRE on the hypoxic induction of MUC17. Treatment of low-responsive cells with 5-aza-2\u27-deoxycytidine followed by additional hypoxic incubation resulted in the restoration of hypoxic MUC17 induction. Furthermore, DNA methylation of HRE in pancreatic tissues from patients with PDACs showed higher hypomethylation status as compared to those from non-cancerous tissues, and hypomethylation was also correlated with MUC17 mRNA expression. Taken together, these findings suggested that the HIF1α-mediated hypoxic signal pathway contributes to MUC17 expression, and DNA methylation of HRE could be a determinant of the hypoxic inducibility of MUC17 in pancreatic cancer cells
MUC4 and MUC1 expression in adenocarcinoma of the stomach correlates with vessel invasion and lymph node metastasis: an immunohistochemical study of early gastric cancer.
We have previously reported that MUC4 expression is a poor prognostic factor in various carcinomas. Our previous study also showed that MUC1 expression in gastric cancers, including the early and advanced stages is a poor prognostic factor. In the present study, the expression profiles of MUC4 and MUC1 were examined by immunohistochemistry (IHC) using two anti-MUC4 monoclonal antibodies (MAbs), 8G7 and 1G8, and anti-MUC1 MAb DF3 in 104 gastrectomy specimens of early gastric adenocarcinoma with submucosal invasion (pT1b2), including 197 histological subtype lesions. Before the IHC study of the human specimens, we evaluated the specificity of the two MAbs by Western blotting and IHC of two MUC4 mRNA expressing gastric cancer cell lines. MAb 8G7 reacted clearly, whereas MAb 1G8 did not show any reactivity, in either Western blotting or IHC. In the IHC of the gastric cancers, the expression rates of MUC4/8G7 detected by MAb 8G7, MUC4/1G8 detected by MAb 1G8 and MUC1/DF3 detected by MAb DF3 in well differentiated types (70%, 38/54; 67%, 36/54; 52%, 28/54) were significantly higher than those in poorly differentiated types (18%, 10/55; 36%, 20/55; 13%, 7/55) (
Phase-dependent Andreev molecules and superconducting gap closing in coherently coupled Josephson junctions
The Josephson junction (JJ) is an essential element of superconducting (SC)
devices for both fundamental and applied physics. The short-range coherent
coupling of two adjacent JJs forms the Andreev molecule states (AMSs), which
will provide a new ingredient to engineer the SC transport in JJs and control
the Andreev qubits. However, no experimental evidence of the AMSs in the
coupled JJs has been reported. Here we provide the tunnel spectroscopic results
of electrically controllable two planar JJs sharing one SC electrode. We
discover that the coupled JJ results are highly modulated from the single JJ
results, due to formation of the phase-dependent AMSs, meaning that the two JJs
are coherently coupled. In addition, the superconducting gap closing due to the
AMS formation is observed. Our results would help in understanding the
microscopic mechanism of the coherent coupling and promoting the AMS physics to
apply for research of the topological superconductivity and quantum information
technology
Potential application of measuring serum infliximab levels in rheumatoid arthritis management: A retrospective study based on KURAMA cohort data
Infliximab (IFX) therapy has considerably improved the treatment of rheumatoid arthritis (RA). However, some patients still do not respond adequately to IFX therapy, or the efficacy of the treatment diminishes over time. Although previous studies have reported a relationship between serum IFX levels and therapeutic efficacy, the potential applications of IFX therapeutic drug monitoring (TDM) in clinical practice remain unclear. The purpose of this study was to investigate the potential applications of IFX TDM by analyzing a Japanese cohort database. Data were collected retrospectively from the Kyoto University Rheumatoid Arthritis Management Alliance cohort between January 1, 2011, and December 31, 2018. Serum IFX levels were measured using a liquid chromatography-tandem mass spectrometer. Out of the 311 RA patients that used IFX, 41 were eligible for the analysis. Serum IFX levels were significantly higher in responders than in non-responders. An optimal cut-off value was determined to be 0.32 μg/mL based on a receiver operating characteristic curve. At the IFX measurement point, a better therapeutic response was observed in the high IFX group (n = 32) than in the low IFX group (n = 9). Conversely, at the maximum effect point, when DAS28-ESR was the lowest between IFX introduction and measurement points, there were no differences in responder proportions between the low and high IFX groups. IFX primary ineffectiveness could be avoided with appropriate dose escalation without blood concentration measurement in clinical practice. In conclusion, IFX TDM could facilitate the identification of secondary non-responders and in turn, proper IFX use
- …