NRF2 regulates HER1 signaling pathway to modulate the sensitivity of ovarian cancer cells to lapatinib and erlotinib

NF-E2-related factor 2 (NRF2) regulates the transcription of a battery of metabolic and cytoprotective genes. NRF2 and epidermal growth factor receptors (EGFRs/HERs) are regulators of cellular proliferation and determinants of cancer initiation and progression. NRF2 and HERs confer cancers with resistance to several therapeutic agents. Nevertheless, there is limited understanding of the regulation of HER expression and activation and the link between NRF2 and HER signalling pathways. We show that NRF2 regulates both basal and inducible expression of HER1, as treatment of ovarian cancer cells (PEO1, OVCAR3, and SKOV3) with NRF2 activator tBHQ inducing HER1, while inhibition of NRF2 by siRNA knockdown or with retinoid represses HER1. Furthermore, treatment of cells with tBHQ increased total and phosphorylated NRF2, HER1, and AKT levels and compromised the cytotoxic effect of lapatinib or erlotinib. Treatment with siRNA or retinoid antagonised the effect of tBHQ on NRF2 and HER1 levels and enhanced the sensitivity of ovarian cancer cells to lapatinib or erlotinib. Pharmacological or genetic inhibition of NRF2 and/or treatment with lapatinib or erlotinib elevated cellular ROS and depleted glutathione. This extends the understanding of NRF2 and its regulation of HER family receptors and opens a strategic target for improving cancer therapy

Intelligent Tutoring Systems for Generation Z's Addiction

As generation Z's big data is flooding the Internet through social nets, neural network based data processing is turning an important cornerstone, showing significant potential for fast extraction of data patterns. Online course delivery and associated tutoring are transforming into customizable, on-demand services driven by the learner. Besides automated grading, strong potential exists for the development and deployment of next generation intelligent tutoring software agents. Self-adaptive, online tutoring agents exhibiting "intelligent-like" behavior, being capable "to learn" from the learner, will become the next educational superstars. Over the past decade, computer-based tutoring agents were deployed in a variety of extended reality environments, from patient rehabilitation to psychological trauma healing. Most of these agents are driven by a set of conditional control statements and a large answers/questions pairs dataset. This article provides a brief introduction on Generation Z's addiction to digital information, highlights important efforts for the development of intelligent dialogue systems, and explains the main components and important design decisions for Intelligent Tutoring System.Comment: 4 page

A Magma Accretion Model for the Formation of Oceanic Lithosphere: Implications for Global Heat Loss

A simple magma accretion model of the oceanic lithosphere is proposed and its implications for understanding the thermal field of oceanic lithosphere examined. The new model (designated VBA) assumes existence of lateral variations in magma accretion rates and temperatures at the boundary zone between the lithosphere and the asthenosphere. Heat flow and bathymetry variations calculated on the basis of the VBA model provide vastly improved fits to respective observational datasets. The improved fits have been achieved for the entire age range and without the need to invoke the ad-hoc hypothesis of large-scale hydrothermal circulation in stable ocean crust. The results suggest that estimates of global heat loss need to be downsized by at least 25%.Comment: 45 pages, 11 figure

Modeling and Experimental Investigation of Laminar Ceiling Air Distribution System for Operating Room in Merjan Teaching Hospital

Room air distribution in operating rooms is critical to successful surgical treatment. The present study investigated the effects of the location of the air supply and exhaust grills on the air movement and air parameters inside an operating room. This paper presents an experimental and numerical analysis of air distribution in the operating room. The experimental work was conducted in an operating room in Merjan Teaching Hospital in the city of Babylon. Air was supplied from one square plenum box located in the middle of the ceiling, while air was exhausted through eight grills: large exhaust grills in the four upper corners and small exhaust grills in the four lower corners. In the theoretical work, a model of the operating room was developed and two cases were analyzed using the FLUEN 6.3.26 software program. The first case included all eight exhaust grills, while the second case included only the four lower exhaust grills. The ceiling system gave good ventilation for air distribution inside the operating room. There was no clear effect of the small exhaust grills located in the upper corners of the operating room. The height of the ceiling room is an effective factor in air distribution

Wireless Communication in Data Centers: A Survey

Data centers (DCs) is becoming increasingly an integral part of the computing infrastructures of most enterprises. Therefore, the concept of DC networks (DCNs) is receiving an increased attention in the network research community. Most DCNs deployed today can be classified as wired DCNs as copper and optical fiber cables are used for intra- and inter-rack connections in the network. Despite recent advances, wired DCNs face two inevitable problems; cabling complexity and hotspots. To address these problems, recent research works suggest the incorporation of wireless communication technology into DCNs. Wireless links can be used to either augment conventional wired DCNs, or to realize a pure wireless DCN. As the design spectrum of DCs broadens, so does the need for a clear classification to differentiate various design options. In this paper, we analyze the free space optical (FSO) communication and the 60 GHz radio frequency (RF), the two key candidate technologies for implementing wireless links in DCNs. We present a generic classification scheme that can be used to classify current and future DCNs based on the communication technology used in the network. The proposed classification is then used to review and summarize major research in this area. We also discuss open questions and future research directions in the area of wireless DCs

Limit theorems and ergodicity for general bootstrap random walks

Given the increments of a simple symmetric random walk $(X_n)_{n\ge0}$, we characterize all possible ways of recycling these increments into a simple symmetric random walk $(Y_n)_{n\ge0}$ adapted to the filtration of $(X_n)_{n\ge0}$. We study the long term behavior of a suitably normalized two-dimensional process $((X_n,Y_n))_{n\ge0}$. In particular, we provide necessary and sufficient conditions for the process to converge to a two-dimensional Brownian motion (possibly degenerate). We also discuss cases in which the limit is not Gaussian. Finally, we provide a simple necessary and sufficient condition for the ergodicity of the recycling transformation, thus generalizing results from Dubins and Smorodinsky (1992) and Fujita (2008), and solving the discrete version of the open problem of the ergodicity of the general L\'evy transformation (see Mansuy and Yor, 2006).Comment: 22 pages, 2 figure