Tumor metastasis to bone is a common event in multiple forms of malignancy. Inflammation holds essential functions in homeostasis as a defense mechanism against infections and is a strategy to repair injured tissue and to adapt to stress conditions. However, exaggerated and/or persistent (chronic) inflammation may eventually become maladaptive and evoke diseases such as autoimmunity, diabetes, inflammatory tissue damage, fibrosis, and cancer. In fact, inflammation is now considered a hallmark of malignancy with prognostic relevance. Emerging studies have revealed a central involvement of inflammation in several steps of the metastatic cascade of bone-homing tumor cells through supporting their survival, migration, invasion, and growth. The mechanisms by which inflammation favors these steps involve activation of epithelial-to-mesenchymal transition (EMT), chemokine-mediated homing of tumor cells, local activation of osteoclastogenesis, and a positive feedback amplification of the protumorigenic inflammation loop between tumor and resident cells. In this review, we summarize established and evolving concepts of inflammation-driven tumorigenesis, with a special focus on bone metastasis.

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Aims Physical activity is one of the most potent strategies to prevent endothelial dysfunction. Recent evidence suggests vaso-protective properties of hydrogen peroxide (H2O2) produced by main endothelial NADPH oxidase isoform 4 (Nox4) in the vasculature. Therefore, we hypothesized that Nox4 connects physical activity with vaso-protective effects. Methods and results Analysis of the endothelial function using Mulvany Myograph showed endothelial dysfunction in wild-type (WT) as well as in C57BL/6J/ Nox4−/− (Nox4−/−) mice after 20 weeks on high-fat diet (HFD). Access to running wheels during the HFD prevented endothelial dysfunction in WT but not in Nox4−/− mice. Mechanistically, exercise led to an increased H2O2 release in the aorta of WT mice with increased phosphorylation of eNOS pathway member AKT serine/threonine kinase 1 (AKT1). Both H2O2 release and phosphorylation of AKT1 were diminished in aortas of Nox4−/− mice. Deletion of Nox4 also resulted in lower intracellular calcium release proven by reduced phenylephrine-mediated contraction, whilst potassium-induced contraction was not affected. H2O2 scavenger catalase reduced phenylephrine-induced contraction in WT mice. Supplementing H2O2 increased phenylephrine-induced contraction in Nox4−/− mice. Exercise-induced peroxisome proliferative-activated receptor gamma, coactivator 1 alpha (Ppargc1a), as key regulator of mitochondria biogenesis in WT but not Nox4−/− mice. Furthermore, exercise-induced citrate synthase activity and mitochondria mass were reduced in the absence of Nox4. Thus, Nox4−/− mice became less active and ran less compared with WT mice. Conclusions Nox4 derived H2O2 plays a key role in exercise-induced adaptations of eNOS and Ppargc1a pathway and intracellular calcium release. Hence, loss of Nox4 diminished physical activity performance and vascular protective effects of exercise.

This survey paper is based on the evolution of TPUs from first generation TPUs to edge TPUs and their architectures. This paper compares CPUs, GPUs, FPGAs and TPUs, their hardware architectures, their similarities and differences will be discussed. Modern neural networks are immensely used these days but they require more time, computation and energy. Due to the greater demand and attractive options for architects to explore, companies are continuously working to reduce training and inference response time. Due to the demands and cost factors different kinds of ASICs (application specific integrated circuits) are developed and research is increased in this area. Many models of CPUs, GPUs and TPUs have been developed to support these networks and to improve training and inference phase. Intel developed CPUs for this purpose, NVIDIA developed GPUs and Google developed cloud TPUs. The hardware of CPUs and GPUs can be sold to businesses while Google offers TPU processing for everyone from the cloud. When the data is away from the computational source, it increases the overall cost and to reduce this cost companies implements memory management and caching techniques close to ALUs.