Review and Prospects of PEM Water Electrolysis at Elevated Temperature Operation

Polymer electrolyte membrane water electrolyzers (PEMWE) are currently restricted to an operating temperature range between 50 to 80 °C. This review shows that elevated temperature (ET) above 90 °C can be advantageous with respect to i) reduced cell voltages, ii) a reduction of catalyst loading or possibly the employment of less noble electrocatalysts, and iii) a greater potential for waste heat utilization when the electrolyzer is operated in exothermal mode (when the cell voltage is higher than the thermoneutral voltage). Together with presenting an overview of the materials and components utilized in elevated temperature PEMWE under liquid and steam operation, this article summarizes the experimental and modeling performances reported to date, highlights the challenges ahead, and suggests aspects, which will need to be considered to improve the performance at elevated temperature. Key points, which arise from this work are the extensive need of re‐assessing the material selection both for the cell components and also at a system level, the effects and optimization of working with steam operation, and in the long run, the need for techno‐economic analyses to ultimately assess whether efficiency gains will truly translate to a cost‐effective technology alternative

Prediction of Short and Long Survival after Surgery for Breast Cancer Brain Metastases

Background: Brain metastases requiring surgical treatment determine the prognosis of patients with breast cancer. We aimed to develop the scores for the prediction of short (n = 95), 18 (18.9%) and 22 (23.2%) patients experienced short and long postoperative survival, respectively. Breast-preserving surgery, presence of multiple brain metastases and age ≥ 65 years at breast cancer diagnosis were identified as independent predictors of short postoperative survival. In turn, positive HER2 receptor status in brain metastases, time interval ≥ 3 years between breast cancer and brain metastases diagnosis and KPS ≥ 90% independently predicted long survival. The appropriate short and long survival scores showed higher diagnostic accuracy for the prediction of short (AUC = 0.773) and long (AUC = 0.775) survival than the breast Graded Prognostic Assessment score (AUC = 0.498/0.615). A cumulative survival score (total score) showed significant association with overall survival (p = 0.001). Conclusion: We identified predictors independently impacting the prognosis after BCBM surgery. After external validation, the presented scores might become useful tools for the selection of proper candidates for BCBM surgery

Promotion of Glioblastoma Cell Motility by Enhancer of Zeste Homolog 2 (EZH2) Is Mediated by AXL Receptor Kinase

<div><p>Enhancer of zeste homolog 2 (EZH2) is the catalytic subunit of the Polycomb-repressive complex 2 (PRC2) that epigenetically silences gene transcription through histone H3 lysine trimethylation (H3K27me3). EZH2 has been implicated in stem cell maintenance and is overexpressed in hematological and solid malignancie`s including malignant glioma. EZH2 is thought to promote tumor progression by silencing tumor suppressor genes. Hence pharmacological disruption of the PRC2 is an attractive therapeutic strategy for cancer treatment. Here we show that EZH2 is expressed in human glioma and correlates with malignancy. Silencing of EZH2 reduced glioma cell proliferation and invasiveness. While we did not observe induction of cell cycle-associated tumor suppressor genes by silencing or pharmacological inhibition of EZH2, microarray analyses demonstrated a strong transcriptional reduction of the AXL receptor kinase. Neither histone nor DNA methylation appeared to be involved in the positive regulation of AXL by EZH2. Silencing AXL mimicked the antiinvasive effects of EZH2 knockdown. Finally, AXL expression is found in human gliomas with high EZH2 expression. Collectively these data suggest that EZH2 drives glioma invasiveness via transcriptional control of AXL independent of histone or DNA methylation.</p> </div

EZH2-knockdown inhibits proliferation and invasion of human malignant glioma cells.

<p><b>A </b><i>EZH2</i> transcript expression was decreased 24 h after si<i>EZH2</i> treatment (left). Western blot showing EZH2 protein expression, 120 h after knockdown by siRNA (right). Tubulin served as loading control. <b>B</b> Cell cycle analysis of U87MG glioma cells 120 h after specific knockdown of <i>EZH2</i> (si<i>EZH2</i>, right) or scrambled control (siC, left). <b>C</b> Invasion of U87MG glioma cells with transient <i>EZH2</i> knockdown (lower panel, black bar) through a matrigel-coated boyden chamber in comparison to control (upper panel, white bar). <b>D</b> Representative dot plots and corresponding analysis of Annexin-V-FITC/DAPI co-staining of U87MG glioma cells untreated or treated for 120 h with 10 µM DZNep. The lower left quadrants represent the living cells (low Annexin-V-FITC-/DAPI-signal), the lower right quadrants represents early apoptosis (low DAPI- and strong Annexin-V-FITC-signal) and the upper right late apoptotic/necrotic cells (double-stained cells). <b>E</b> H3K27me3 methylation was strongly decreased in whole cell lysates of U87MG glioma cells after treatment with 5 µM DZNep or after specific knockdown of <i>EZH2</i> for 120 h. Tubulin served as loading control. <b>F</b> Cell cycle analysis of U87MG glioma cells untreated or treated for 120 h with 500 nM and 5 µM DZNep. <b>G</b> Analysis of nestin expression in S24 glioma-initiating cells untreated (left) or treated with 5 µM DZNep for 120 h (right) by flow cytometry. <b>H</b> Matrigel boyden chamber assay of U87MG glioma cells untreated (upper panel, white bar) and treated (lower panel, black bar) with 5 µM DZNep. Asterisk indicates * (p<0.05). Error bars indicate s.e.m.</p

Methylation independent regulation of AXL.

<p><b>A </b><i>AXL</i> mRNA expression of U87MG human glioma cells treated with 5 µM DZNep for 120 h in comparison to control. <b>B</b> Analysis of AXL protein expression in U87MG glioma cells untreated (solid line) or treated with 5 µM DZNep for 120 h (dashed line) stained with an AXL specific antibody (blue) or an isotype control antibody (red). <b>C</b> Comparison of genes with decreased (upper Venn-diagram) or increased (lower Venn diagram) expression after 120 h of <i>EZH2</i> knockdown (purple) or DZNep treatment (blue) of U87MG glioma cells. Cutoff: 1.5 fold change. <b>D </b><i>AXL</i> mRNA expression of U87MG human malignant glioma cells after 96 h treatment with the DNA methylation inhibitor 5-aza-2′-deoxycytidine (5-aza) (black bars) or DMSO (white bar). <b>E </b><i>EZH2</i> and <i>AXL</i> mRNA expression of U87MG glioma cells after the stimulation with indicated concentrations of the histone deacetylase inhibitors suberoylanilide hydroxamic acid (SAHA) or trichostatin A (TSA) (black bars) or DMSO (white bars) for 24 h. Asterisk indicates * (p<0.05). Error bars indicate s.e.m.</p