The novel, small-molecule DNA methylation inhibitor SGI-110 as an ovarian cancer chemosensitizer

PURPOSE: To investigate SGI-110 as a "chemosensitizer" in ovarian cancer and to assess its effects on tumor suppressor genes (TSG) and chemoresponsiveness-associated genes silenced by DNA methylation in ovarian cancer. EXPERIMENTAL DESIGN: Several ovarian cancer cell lines were used for in vitro and in vivo platinum resensitization studies. Changes in DNA methylation and expression levels of TSG and other cancer-related genes in response to SGI-110 were measured by pyrosequencing and RT-PCR. RESULTS: We demonstrate in vitro that SGI-110 resensitized a range of platinum-resistant ovarian cancer cells to cisplatin (CDDP) and induced significant demethylation and reexpression of TSG, differentiation-associated genes, and putative drivers of ovarian cancer cisplatin resistance. In vivo, SGI-110 alone or in combination with CDDP was well tolerated and induced antitumor effects in ovarian cancer xenografts. Pyrosequencing analyses confirmed that SGI-110 caused both global (LINE1) and gene-specific hypomethylation in vivo, including TSGs (RASSF1A), proposed drivers of ovarian cancer cisplatin resistance (MLH1 and ZIC1), differentiation-associated genes (HOXA10 and HOXA11), and transcription factors (STAT5B). Furthermore, DNA damage induced by CDDP in ovarian cancer cells was increased by SGI-110, as measured by inductively coupled plasma-mass spectrometry analysis of DNA adduct formation and repair of cisplatin-induced DNA damage. CONCLUSIONS: These results strongly support further investigation of hypomethylating strategies in platinum-resistant ovarian cancer. Specifically, SGI-110 in combination with conventional and/or targeted therapeutics warrants further development in this setting

Platinum-Induced Ubiquitination of Phosphorylated H2AX by RING1A is Mediated by Replication Protein A in Ovarian Cancer

Platinum resistance is a common occurrence in high-grade serous ovarian cancer and a major cause of ovarian cancer deaths. Platinum agents form DNA cross-links, which activate nucleotide excision repair (NER), Fanconi anemia, and homologous recombination repair (HRR) pathways. Chromatin modifications occur in the vicinity of DNA damage and play an integral role in the DNA damage response (DDR). Chromatin modifiers, including polycomb repressive complex 1 (PRC1) members, and chromatin structure are frequently dysregulated in ovarian cancer and can potentially contribute to platinum resistance. However, the role of chromatin modifiers in the repair of platinum DNA damage in ovarian cancer is not well understood. We demonstrate that the PRC1 complex member RING1A mediates monoubiquitination of lysine 119 of phosphorylated H2AX (γH2AXub1) at sites of platinum DNA damage in ovarian cancer cells. After platinum treatment, our results reveal that NER and HRR both contribute to RING1A localization and γH2AX monoubiquitination. Importantly, replication protein A, involved in both NER and HRR, mediates RING1A localization to sites of damage. Furthermore, RING1A deficiency impairs the activation of the G2-M DNA damage checkpoint, reduces the ability of ovarian cancer cells to repair platinum DNA damage, and increases sensitivity to platinum. IMPLICATIONS: Elucidating the role of RING1A in the DDR to platinum agents will allow for the identification of therapeutic targets to improve the response of ovarian cancer to standard chemotherapy regimens

Isoscaling in dissipative projectile breakup

Dynamical breakup of projectile-like fragments (PLF) following dissipative reactions of Ca-48 projectiles with Sn-112 and Sn-124 is shown to exhibit "isoscaling" regularities that can be understood in terms of phase space governed by ground state masses. Ambiguities in isoscaling parameters obscure information on nuclear symmetry energy at subnormal densities

Opportunistic Spectrum Access: Designing Link and Transport layer

TelecommunicationsElectrical Engineering, Mathematics and Computer Scienc

On distributed sensor fusion in batteryless intermittent networks

###EgeUn###Distributed and collaborative computation has never been considered before in networks of batteryless sensors. This can bring many advantages for applications (e.g. longer transmission ranges, lower network costs), however introducing new research challenges. In this paper, we focus on the well-known distributed sensor fusion but in an intermittently-powered batteryless sensor network. The goal is to estimate a parameter collaboratively by considering individual sensor measurements. We show that, even though the nodes stop operation with high probability due to random power failures and they neither communicate with their neighbors nor perform computation most of the time, the simplest implementation of the fully-distributed sensor fusion based on average consensus improves the overall estimation quality of the network considerably. In the light of this, we anticipate that if harvested energy is used efficiently so that nodes have more opportunity to receive and send packets, existing fully-distributed protocols can be implemented with tiny modifications in networks of batteryless sensors. © 2019 IEEE

Self Adaptive Safe Provisioning of Wireless Power Using DCOPs

Wireless Power Transfer (WPT) technologies aim at getting rid of cables used by consumer devices for energy provision. As long distance WPT is becoming mature, the health impact of WPT becomes increasingly important to consider. In this paper we look at how to maximize the wireless power transfer to remote devices, while maintaining a safe level of electromagnetic radiation (EMR) for humans that are in the vicinity of the energy transmitters. Classically, this problem can be described as a centralized optimization problem of finding the optimal set of safe power levels at locations of human presence. Instead, we advocate to formulate this problem as an agent-based Distributed Constraint Optimization Problem (DCOP). As a solution to this problem we introduce CoCoA-WPT, a variant of the DCOP solver CoCoA. CoCoA-WPT provides a solution of similar quality to centralized solver even for a large scale network involving over a thousand nodes. Based on CoCoA-WPT, we propose a self-adaptive charging system: Transferring Energy Safely by Self-Adaptation (TESSA). TESSA keeps the charging network safe even when it is perturbed by environmental dynamics. We show that TESSA can reach on average up to 85% of the theoretical optimal maximum total transmitted power (calculated using centralized solution) while satisfying the EMR safety constraints. © 2017 IEEE. Axon AI; Dynamic Object Language Labs (DOLL); et al.; IEEE; IEEE Computer Society; NS