RAB25 expression is epigenetically downregulated in oral and oropharyngeal squamous cell carcinoma with lymph node metastasis

Oral and oropharyngeal squamous cell carcinoma (OOSCC) have a low survival rate, mainly due to metastasis to the regional lymph nodes. For optimal treatment of these metastases, a neck dissection is required; however, inaccurate detection methods results in under- and over-treatment. New DNA prognostic methylation biomarkers might improve lymph node metastases detection. To identify epigenetically regulated genes associated with lymph node metastases, genome-wide methylation analysis was performed on 6 OOSCC with (pN+) and 6 OOSCC without (pN0) lymph node metastases and combined with a gene expression signature predictive for pN+ status in OOSCC. Selected genes were validated using an independent OOSCC cohort by immunohistochemistry and pyrosequencing, and on data retrieved from The Cancer Genome Atlas. A two-step statistical selection of differentially methylated sequences revealed 14 genes with increased methylation status and mRNA downregulation in pN+ OOSCC. RAB25, a known tumor suppressor gene, was the highest-ranking gene in the discovery set. In the validation sets, both RAB25 mRNA (P = 0.015) and protein levels (P = 0.012) were lower in pN+ OOSCC. RAB25 mRNA levels were negatively correlated with RAB25 methylation levels (P < 0.001) but RAB25 protein expression was not. Our data revealed that promoter methylation is a mechanism resulting in downregulation of RAB25 expression in pN+ OOSCC and decreased expression is associated with lymph node metastasis. Detection of RAB25 methylation might contribute to lymph node metastasis diagnosis and serve as a potential new therapeutic target in OOSCC

Platform-specific Modeling for RIOT based IoT Systems

ACM SIGSOFT;Association for Computing Machinery (ACM);IEEE Computer Society;IEEE Technical Council on Software Engineering (TCSE);Korean Institute of Information Scientists and Engineers42nd IEEE/ACM International Conference on Software Engineering Workshops, ICSEW 2020 -- 27 June 2020 through 19 July 2020 -- -- 163291The variety of smart devices and their communication models increase the development complexity of embedded software for IoT. Thus, the development of these systems becomes more error-prone, complex, and costly. To tackle this problem, in this study, a model-driven approach is proposed for the development of RIOT-OS based IoT systems. To this end, a meta-model is designed for RIOT-OS. Based on this meta-model, a Domain-specific Modeling Language (DSML) is developed to graphically represent the domain models. To gain more functionality for the language, domain rules are defined as constraints. Also, system codes are generated partially from the instance models. In this way, the development is supported by code synthesis and the number of bugs is reduced. Finally, a smart irrigation system and a smart lighting system are implemented to evaluate the proposed DSML. The results show that about 83.5% of the final code is generated automatically on average. © 2020 ACM.Ege ÜniversitesiThis study is partially funded by the Scientific Research Project No 17-UBE-002 at EGE University, Izmir, Turkey. Some of the ideas in this work were developed during Short Term Scientific Missions (STSM Nos. 41940 and 41967) by two of the authors, within the IC1404 Multi-Paradigm Modelling for Cyber-Physical Systems (MPM4CPS) COST Action

Analyzing wsn-based iot systems using mde techniques and petri-net models?

4th Workshop on Model-Driven Engineering for the Internet-of-Things, 1st International Workshop on Modeling Smart Cities, and 5th International Workshop on Open and Original Problems in Software Language Engineering, STAF-WS 2020 -- 22 June 2020 through 26 June 2020 -- -- 1642832-s2.0-85095588831There are various computation components, operating systems, and firmware used in the development of the Internet of Things (IoT). This variety increases the structural complexity and development cost and effort of the IoT systems. Besides, analyzing and troubleshooting these systems are time-consuming, costly, and cumbersome. To address these problems, this study aims to provide a higher level of abstraction for analyzing and developing IoT systems using Model-driven Engineering techniques and Petri-net models. To this end, a Domain-specific modeling Language (DSML), called DSML4Contiki, was presented in our previous study for the development of Wireless Sensor Systems (WSN) based IoT systems. The current study extends DSML4Contiki by providing an automated mechanism to analyze the IoT system at the early design phase, resulting in a reduction of the number of errors in the system and iterations in the development process. This is achieved using model transformation rules to transform the domain models at a high level to both the target platform artifacts as well as Petri-net models. By applying k-boundedness property checking on the Petri-net models, different analyses (such as power consumption, bottlenecks, and first crashing node) are realized for WSN based IoT systems. To evaluate the proposed approach, the engineering of a smart fire detection system is considered as a case study. © 2020 CEUR-WS. All rights reserved

RAB25 expression is epigenetically downregulated in oral and oropharyngeal squamous cell carcinoma with lymph node metastasis

Oral and oropharyngeal squamous cell carcinoma (OOSCC) have a low survival rate, mainly due to metastasis to the regional lymph nodes. For optimal treatment of these metastases, a neck dissection is required; however, inaccurate detection methods results in under- and over-treatment. New DNA prognostic methylation biomarkers might improve lymph node metastases detection. To identify epigenetically regulated genes associated with lymph node metastases, genome-wide methylation analysis was performed on 6 OOSCC with (pN+) and 6 OOSCC without (pN0) lymph node metastases and combined with a gene expression signature predictive for pN+ status in OOSCC. Selected genes were validated using an independent OOSCC cohort by immunohistochemistry and pyrosequencing, and on data retrieved from The Cancer Genome Atlas. A two-step statistical selection of differentially methylated sequences revealed 14 genes with increased methylation status and mRNA downregulation in pN+ OOSCC. RAB25, a known tumor suppressor gene, was the highest-ranking gene in the discovery set. In the validation sets, both RAB25 mRNA (P = 0.015) and protein levels (P = 0.012) were lower in pN+ OOSCC. RAB25 mRNA levels were negatively correlated with RAB25 methylation levels (P <0.001) but RAB25 protein expression was not. Our data revealed that promoter methylation is a mechanism resulting in downregulation of RAB25 expression in pN+ OOSCC and decreased expression is associated with lymph node metastasis. Detection of RAB25 methylation might contribute to lymph node metastasis diagnosis and serve as a potential new therapeutic target in OOSCC