Die Dorferneuerung in Niederösterreich

Die niederösterreichische Dorferneuerung wurde 1984 gegründet und ist seither ein wichtiger Bestandteil der regionalen Entwicklung geworden. Der Erfolg und das breite Interesse an der Landesaktion haben den Impuls gegeben, die Einflussfaktoren der Dorferneuerung in Niederösterreich zu erforschen. In der vorliegenden Arbeit wird die Projekttätigkeit der Initiative im Zeitraum von 1999 bis 2008 nach gemeindetypischen Merkmalen und deren Einflussnahme auf die Teilnahme an dem Programm hin untersucht. Es werden Umstände und Zusammenhänge erforscht, ob landestypische Siedlungsformen, gemeindetypische Merkmalsausprägungen sowie die Beschreibung bezüglich der geographischen Lage im verkehrsinfrastrukturellen Gefüge die Beteiligung an der Dorferneuerungsinitiative fördern oder der Bereitschaft dazu entgegenwirken können. Die Fragestellungen werden auf der Grundlage statistischer Methoden und der Auswertung geographischer Daten diskutiert. Mit Hilfe ausgewählter Indikatoren wird eine Gemeindetypisierung durchgeführt und mit dem Projektdatensatz verschnitten. Mit der Typisierung wird versucht, Strukturen und Typen herauszuarbeiten, die eine überdurchschnittliche Bereitschaft an der Teilnahme der Dorferneuerung zeigen. In einem weiteren Schritt sollen die Projektorte auf ihre räumlich Lage zum hochrangigen Straßennetz und dem Schienennetz hin erhoben werden. Ziel der Arbeit ist, die geographische Lage von Projektgemeinden zu lokalisieren sowie regionale und raumtypische Zusammenhänge zu entdecken. Im Ergebnis wird deutlich, dass überwiegend Gemeinden mit sinkenden bis stagnierenden Bevölkerungszahlen, einer niedrigen Bevölkerungsdichte, einer hohen Auspendlerintensität, einer hohen Agrarerwerbsquote sowie einer hohen Anzahl an Nebenwohnsitzen eine erhöhte Bereitschaft zur Teilnahme aufweisen. Jene Gemeindetypen finden ihre Verbreitung mehrheitlich in den Randgebieten des Bundeslandes Niederösterreich (nördliches Wald- und Weinviertel sowie der niederösterreichischen Voralpen und Alpen) und bilden dadurch für die Dorferneuerung ein charakteristisches Raummuster

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

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

The MOBI-Kids Study Protocol: Challenges in Assessing Childhood and Adolescent Exposure to Electromagnetic Fields from Wireless Telecommunication Technologies and Possible Association with Brain Tumor Risk

The rapid increase in mobile phone use in young people has generated concern about possible health effects of exposure to radiofrequency (RF) and extremely low frequency (ELF) electromagnetic fields (EMF). MOBI-Kids, a multinational case-control study, investigates the potential effects of childhood and adolescent exposure to EMF from mobile communications technologies on brain tumor risk in 14 countries. The study, which aims to include approximately 1,000 brain tumor cases aged 10-24 years and two individually matched controls for each case, follows a common protocol and builds upon the methodological experience of the INTERPHONE study. The design and conduct of a study on EMF exposure and brain tumor risk in young people in a large number of countries is complex and poses methodological challenges. This manuscript discusses the design of MOBI-Kids and describes the challenges and approaches chosen to address them, including: (1) the choice of controls operated for suspected appendicitis, to reduce potential selection bias related to low response rates among population controls; (2) investigating a young study population spanning a relatively wide age range; (3) conducting a large, multinational epidemiological study, while adhering to increasingly stricter ethics requirements; (4) investigating a rare and potentially fatal disease; and (5) assessing exposure to EMF from communication technologies. Our experience in thus far developing and implementing the study protocol indicates that MOBI-Kids is feasible and will generate results that will contribute to the understanding of potential brain tumor risks associated with use of mobile phones and other wireless communications technologies among young people

Impaired Retromer Function in Niemann-Pick Type C Disease Is Dependent on Intracellular Cholesterol Accumulation

Niemann-Pick type C disease (NPC) is a rare inherited neurodegenerative disorder characterized by an accumulation of intracellular cholesterol within late endosomes and lysosomes due to NPC1 or NPC2 dysfunction. In this work, we tested the hypothesis that retromer impairment may be involved in the pathogenesis of NPC and may contribute to increased amyloidogenic processing of APP and enhanced BACE1-mediated proteolysis observed in NPC disease. Using NPC1-null cells, primary mouse NPC1-deficient neurons and NPC1-deficient mice (BALB/cNctr-Npc1m1N), we show that retromer function is impaired in NPC. This is manifested by altered transport of the retromer core components Vps26, Vps35 and/or retromer receptor sorLA and by retromer accumulation in neuronal processes, such as within axonal swellings. Changes in retromer distribution in NPC1 mouse brains were observed already at the presymptomatic stage (at 4-weeks of age), indicating that the retromer defect occurs early in the course of NPC disease and may contribute to downstream pathological processes. Furthermore, we show that cholesterol depletion in NPC1-null cells and in NPC1 mouse brains reverts retromer dysfunction, suggesting that retromer impairment in NPC is mechanistically dependent on cholesterol accumulation. Thus, we characterized retromer dysfunction in NPC and propose that the rescue of retromer impairment may represent a novel therapeutic approach against NPC