HSP90 inhibitors stimulate DNAJB4 protein expression through a mechanism involving N6-methyladenosine.

Small-molecule inhibitors for the 90-kDa heat shock protein (HSP90) have been extensively exploited in preclinical studies for the therapeutic interventions of human diseases accompanied with proteotoxic stress. By using an unbiased quantitative proteomic method, we uncover that treatment with three HSP90 inhibitors results in elevated expression of a large number of heat shock proteins. We also demonstrate that the HSP90 inhibitor-mediated increase in expression of DNAJB4 protein occurs partly through an epitranscriptomic mechanism, and is substantially modulated by the writer, eraser, and reader proteins of N6-methyladenosine (m6A). Furthermore, exposure to ganetespib leads to elevated modification levels at m6A motif sites in the 5'-UTR of DNAJB4 mRNA, and the methylation at adenosine 114 site in the 5'-UTR promotes the translation of the reporter gene mRNA. This m6A-mediated mechanism is also at play upon heat shock treatment. Cumulatively, we unveil that HSP90 inhibitors stimulate the translation of DNAJB4 through an epitranscriptomic mechanism

On-demand Business Process Integration Based on Intelligent Web Services

This paper proposes to make On-Demand business process integration based on intelligent Web Services. Business processes are modeled with BPEL4WS. They are incorporated into intelligent Web Services as their knowledge. Implementation framework and techniques are presented. A case of online auction is developed to demonstrate these concepts

Heterogeneous Graph Neural Networks for Fraud Detection and Explanation in Supply Chain Finance

It is a critical mission for financial service providers to discover fraudulent borrowers in a supply chain. The borrowers’ transactions in anongoing business are inspected to support the providers’ decision on whether to lend the money. Considering multiple participants in a supply chain business, the borrowers may use sophisticated tricks to cheat, making fraud detection challenging. In this work, we propose a multitask learning framework, MultiFraud, for complex fraud detection with reasonable explanation. The heterogeneous information from multi-view around the entities is leveraged in the detection framework based on heterogeneous graph neural networks. MultiFraud enables multiple domains to share embeddings and enhance modeling capabilities for fraud detection. The developed explainer provides comprehensive explanations across multiple graphs. Experimental results on five datasets demonstrate the framework’s effectiveness in fraud detection and explanation across domains

A Targeted Quantitative Proteomic Method Revealed a Substantial Reprogramming of Kinome during Melanoma Metastasis.

Kinases are involved in numerous critical cell signaling processes, and dysregulation in kinase signaling is implicated in many types of human cancers. In this study, we applied a parallel-reaction monitoring (PRM)-based targeted proteomic method to assess kinome reprogramming during melanoma metastasis in three pairs of matched primary/metastatic human melanoma cell lines. Around 300 kinases were detected in each pair of cell lines, and the results showed that Janus kinase 3 (JAK3) was with reduced expression in the metastatic lines of all three pairs of melanoma cells. Interrogation of The Cancer Genome Atlas (TCGA) data showed that reduced expression of JAK3 is correlated with poorer prognosis in melanoma patients. Additionally, metastatic human melanoma cells/tissues exhibited diminished levels of JAK3 mRNA relative to primary melanoma cells/tissues. Moreover, JAK3 suppresses the migration and invasion of cultured melanoma cells by modulating the activities of matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9). In summary, our targeted kinome profiling method provided by far the most comprehensive dataset for kinome reprogramming associated with melanoma progression, which builds a solid foundation for examining the functions of other kinases in melanoma metastasis. Moreover, our results reveal a role of JAK3 as a potential suppressor for melanoma metastasis

An Integrated Service-Oriented Development Platform for Realization of e-Business Systems

Enterprises need to be responsive to meet dynamic businesses and requirements. Service-oriented architecture can improve e-Business applications in integration and flexibility. Therefore, service-oriented architecture has been envisioned as an appropriate computational paradigm for e-business applications. This paper proposes a multi-model driven collaborative development platform for building service-oriented e-Business systems. The platform supports service-oriented software engineering and application developments. It employs three views, i.e., business view, process view, and service view to support business and technical consultants’ operations. Consultants can collaborate from distributed sites of, e.g., clients and IT vendors to provide their clients’ with rapid system development and demonstration. The proposed platform is service-oriented and driven by three models, i.e., service meta-model, process model and business model. All of these three models are supported by a semantic reasoning engine to facilitate intelligent service discovery, process execution and business-business integration. A simple example has been used to demonstrate its functionality