Reliable low-cost fabrication of low-loss Al2O3:Er3+Al_2O_3:Er^{3+} waveguides with 5.4-dB optical gain

A reliable and reproducible deposition process for the fabrication of $Al_2O_3$ waveguides with losses as low as 0.1 dB/cm has been developed. The thin films are grown at ~ 5 nm/min deposition rate and exhibit excellent thickness uniformity within 1% over 50times50 mm2 area and no detectable $OH^{-}$ incorporation. For applications of the $Al_2O_3$ films in compact, integrated optical devices, a high-quality channel waveguide fabrication process is utilized. Planar and channel propagation losses as low as 0.1 and 0.2 dB/cm, respectively, are demonstrated. For the development of active integrated optical functions, the implementation of rare-earth-ion doping is investigated by cosputtering of erbium during the $Al_2O_3$ layer growth. Dopant levels between 0.2-5times $1020 cm^{-3}$ are studied. At $Er^{3+}$ concentrations of interest for optical amplification, a lifetime of the 4I13/2 level as long as 7 ms is measured. Gain measurements over 6.4-cm propagation length in a 700-nm-thick $Al_2O_3:Er^{3+}$ channel waveguide result in net optical gain over a 41-nm-wide wavelength range between 1526-1567 nm with a maximum of 5.4 dB at 1533 n

CTLA-4 mediates inhibitory function of mesenchymal stem/stromal cells

Mesenchymal stem/stromal cells (MSCs) are stem cells of the connective tissue, possess a plastic phenotype, and are able to differentiate into various tissues. Besides their role in tissue regeneration, MSCs perform additional functions as a modulator or inhibitor of immune responses. Due to their pleiotropic function, MSCs have also gained therapeutic importance for the treatment of autoimmune diseases and for improving fracture healing and cartilage regeneration. However, the therapeutic/immunomodulatory mode of action of MSCs is largely unknown. Here, we describe that MSCs express the inhibitory receptor CTLA-4 (cytotoxic T lymphocyte antigen 4). We show that depending on the environmental conditions, MSCs express different isoforms of CTLA-4 with the secreted isoform (sCTLA-4) being the most abundant under hypoxic conditions. Furthermore, we demonstrate that the immunosuppressive function of MSCs is mediated mainly by the secretion of CTLA-4. These findings open new ways for treatment when tissue regeneration/fracture healing is difficult

Designed Azolopyridinium Salts Block Protective Antigen Pores In Vitro and Protect Cells from Anthrax Toxin

Background:Several intracellular acting bacterial protein toxins of the AB-type, which are known to enter cells by endocytosis, are shown to produce channels. This holds true for protective antigen (PA), the binding component of the tripartite anthrax-toxin of Bacillus anthracis. Evidence has been presented that translocation of the enzymatic components of anthrax-toxin across the endosomal membrane of target cells and channel formation by the heptameric/octameric PA63 binding/translocation component are related phenomena. Chloroquine and some 4-aminoquinolones, known as potent drugs against Plasmodium falciparium infection of humans, block efficiently the PA63-channel in a dose dependent way.Methodology/Principal Findings:Here we demonstrate that related positively charged heterocyclic azolopyridinium salts block the PA63-channel in the μM range, when both, inhibitor and PA63 are added to the same side of the membrane, the cis-side, which corresponds to the lumen of acidified endosomal vesicles of target cells. Noise-analysis allowed the study of the kinetics of the plug formation by the heterocycles. In vivo experiments using J774A.1 macrophages demonstrated that the inhibitors of PA63-channel function also efficiently block intoxication of the cells by the combination lethal factor and PA63 in the same concentration range as they block the channels in vitro.Conclusions/Significance:These results strongly argue in favor of a transport of lethal factor through the PA63-channel and suggest that the heterocycles used in this study could represent attractive candidates for development of novel therapeutic strategies against anthrax. © 2013 Beitzinger et al

Risk Shift of Real Estate Stocks during the COVID-19 Pandemic

The outbreak of the COVID-19 pandemic induces an increase of risk in global equity markets where real estate stocks are often perceived as a ‘safe haven’. Employing the Fama and French’s (2015) five-factor model, we calculate the betas for risk factors and investigate the influence of market crises on excess returns of real estate stocks. The time series used in this study allows for splitting the data into two crisis periods namely the global financial crisis during 2007-2008 and the COVID-19 crisis in 2020. Our empirical evidence underlines that the undifferentiated view of real estate stocks as an overall ‘safe haven’ is not supported: 1) We find the risk factors of Fama and French can be applied to real estate stocks only to some extent, where the investment and profitability factors show opposite signs compared to general stocks; 2) Regional differences exist and Asian real estate markets show stronger diversification benefits during the crises; 3) Differences in business scopes lead to distinct reactions to the crises, where Asian firms focusing on real estate development and diversified activities are proven stronger during the COVID-19 pandemic and thus may offer better diversification value for investors; and 4) European real estate stocks are the worst-performing in terms of annualized return, specifically for firms offering real estate development and diversified activities. During both crisis periods, operating and services firms suffer a significant negative impact in Europe and are less likely to have diversification value

Risk Shift of Real Estate Stocks during the COVID-19 Pandemic

The outbreak of the COVID-19 pandemic induces an increase of risk in global equity markets where real estate stocks are often perceived as a ‘safe haven’. Employing the Fama and French’s (2015) five-factor model, we calculate the betas for risk factors and investigate the influence of market crises on excess returns of real estate stocks. The time series used in this study allows for splitting the data into two crisis periods namely the global financial crisis during 2007-2008 and the COVID-19 crisis in 2020. Our empirical evidence underlines that the undifferentiated view of real estate stocks as an overall ‘safe haven’ is not supported: 1) We find the risk factors of Fama and French can be applied to real estate stocks only to some extent, where the investment and profitability factors show opposite signs compared to general stocks; 2) Regional differences exist and Asian real estate markets show stronger diversification benefits during the crises; 3) Differences in business scopes lead to distinct reactions to the crises, where Asian firms focusing on real estate development and diversified activities are proven stronger during the COVID-19 pandemic and thus may offer better diversification value for investors; and 4) European real estate stocks are the worst-performing in terms of annualized return, specifically for firms offering real estate development and diversified activities. During both crisis periods, operating and services firms suffer a significant negative impact in Europe and are less likely to have diversification value

Was kann eLib? : Kommunikationsstrategie zur Einführung von Discovery-System, Linkresolver und Bibliothekssystem in den Fraunhofer-Bibliotheken

Jedes Forschungsvorhaben beginnt mit einer Recherche. Um ihre Mitarbeiter bei diesem Vorgang besser als bisher zu unterstützen, führt die Fraunhofer-Gesellschaft ab Januar 2013 eine neue Fachinformations-Infrastruktur unter dem Namen eLib ein. eLib steht für enhanced Library Services und kombiniert drei Elemente zu einem wirkungsmächtigen System. Neben einem Discovery-System, das eine zentrale Suche über verschiedene Quellen ermöglicht, sorgt zukünftig ein Linkresolver (Delivery-System) für eine direkte Weiterleitung zum Volltext, und als dritte Komponente wird das bisherige Bibliothekssystem durch ein neues ersetzt. Die drei Elemente werden ab Januar 2013 sukzessive in etwa 60 Fraunhofer-Bibliotheken eingeführt. Im vorliegenden Artikel wird das Ergebnis der Kommunikationsstrategieentwicklung für die Einführung von eLib beschrieben, welches u. a. die heterogene Bibliothekslandschaft der Fraunhofer-Gesellschaft berücksichtigt. Die Autorinnen unterstützen mit ihren Überlegungen das eLib-Projektteam, die Kommunikationsstrategie zur Einführung von eLib zu entwickeln. Dabei wird insbesondere die Perspektive der Fachinformationsmanager der Fraunhofer-Bibliotheken berücksichtigt. Primäres Ziel ist, ihnen eine Toolbox mit einzelnen Kommunikationsinstrumenten zur Verfügung zur stellen, welche sie jeweils an die individuelle Situation vor Ort anpassen können. Langfristig soll die Strategie zu einer Image-Steigerung der Fraunhofer-Bibliotheken führen.The starting point of every scientific project is thorough research. Since January 2013 the Fraunhofer-Gesellschaft has been offering their employees a new search engine. It is called eLib and was introduced in order to support the crucial process of researching. eLib (Enhanced Library Services) combines three components to a powerful tool: A discovery system enables a centralized search different sources. A linkresolver allows to switch directly to the full text and the previous library management system was replaced by a new one. These three components will be introduced step by step in about 60 Fraunhofer libraries. This article outlines the communication strategy for the introduction of eLib, which – among others – takes into account the heterogeneous library landscape of the Fraunhofer-Gesellschaft. With their reflections the authors support the eLib project team in developping a communication strategy for the introduction of eLib. In particular, the perspective of the Fraunhofer librarians is considered. An important element of the strategy is therefore to provide the librarians with a toolbox containing various communication tools, which they can adapt to their individual situation. In the long term, the strategy is contributing to an improved image of the Fraunhofer libraries

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN