Orakel der Neuzeit: was leisten Wahlbörsen, Wählerstromanalysen und Wahltagshochrechnungen?

'Wahlbörsen, Wählerstromanalysen und Hochrechnungen werden zwar in der Öffentlichkeit viel beachtet, in der politikwissenschaftlichen Forschung aber nur selten diskutiert, weil die Methodologie jeweils komplex und ungewohnt ist. Alle Verfahren weisen eine Reihe spezifischer Probleme auf, die die Wahlsoziologie nur in Kooperation mit den Experimental Economics, aus denen die Wahlbörsen kommen, und mit der Statistik, aus denen die Wählerstromanalyse kommt, lösen kann. Wahlbörsen haben nach ihren anfänglichen Prognose-Erfolgen eine Größe und eine Öffentlichkeitswirkung erlangt, die die Vorhersagegenauigkeit vermutlich wieder stark beeinträchtigen. In unserem Beitrag fassen wir die jüngste Geschichte der Political Stock Markets zusammen und geben einige Design-Empfehlungen. Wählerstromanalysen, die auch die Basis für Wahltagshochrechnungen liefern, sind mit einer Reihe von methodischen Herausforderungen konfrontiert. Wir belegen mit österreichischen Wahldaten die andernorts geäußerte Vermutung, dass einer adäquaten Gruppierung von Gemeinden zur Vermeidung eines aggregate bias die höchste Aufmerksamkeit geschenkt werden sollte.' (Autorenreferat)'Political stock markets, ecological analysis of electoral data, and election day forecasts based on early returns often achieve high levels of publicity and media coverage; however, they get little attention in political science publications, probably because of their complex and unusual methodology. All three of them deal with specific problems. Electoral research will only be able to solve these problems in cooperation with experimental economics (the origin of political stock markets) and statistics (ecological analysis). Political stock markets, after their quick prognostic success, reached such high user numbers and public attention that this in turn probably reduced their ability to forecast electoral results. In our contribution we summarize the recent history of political stock markets and give recommendations for their future design. Ecological calculation of voting transitions as a basis of election day forecasts is faced with numerous methodological challenges. Earlier research suggests that grouping of communities would help to reduce aggregate bias. We describe evidence from Austrian electoral data that supports this point of view.' (author's abstract

DNA Methylation Levels in Mononuclear Leukocytes from the Mother and Her Child Are Associated with IgE Sensitization to Allergens in Early Life

DNA methylation changes may predispose becoming IgE-sensitized to allergens. We analyzed whether DNA methylation in peripheral blood mononuclear cells (PBMC) is associated with IgE sensitization at 5 years of age (5Y). DNA methylation was measured in 288 PBMC samples from 74 mother/child pairs from the birth cohort ALADDIN (Assessment of Lifestyle and Allergic Disease During INfancy) using the HumanMethylation450BeadChip (Illumina). PBMCs were obtained from the mothers during pregnancy and from their children in cord blood, at 2 years and 5Y. DNA methylation levels at each time point were compared between children with and without IgE sensitization to allergens at 5Y. For replication, CpG sites associated with IgE sensitization in ALADDIN were evaluated in whole blood DNA of 256 children, 4 years old, from the BAMSE (Swedish abbreviation for Children, Allergy, Milieu, Stockholm, Epidemiology) cohort. We found 34 differentially methylated regions (DMRs) associated with IgE sensitization to airborne allergens and 38 DMRs associated with sensitization to food allergens in children at 5Y (Sidak p ≤ 0.05). Genes associated with airborne sensitization were enriched in the pathway of endocytosis, while genes associated with food sensitization were enriched in focal adhesion, the bacterial invasion of epithelial cells, and leukocyte migration. Furthermore, 25 DMRs in maternal PBMCs were associated with IgE sensitization to airborne allergens in their children at 5Y, which were functionally annotated to the mTOR (mammalian Target of Rapamycin) signaling pathway. This study supports that DNA methylation is associated with IgE sensitization early in life and revealed new candidate genes for atopy. Moreover, our study provides evidence that maternal DNA methylation levels are associated with IgE sensitization in the child supporting early in utero effects on atopy predisposition.</p

Global functional association network inference and crosstalk analysis for pathway annotation

Cell functions are steered by complex interactions of gene products, like forming a temporary or stable complex, altering gene expression or catalyzing a reaction. Mapping these interactions is the key in understanding biological processes and therefore is the focus of numerous experiments and studies. Small-scale experiments deliver high quality data but lack coverage whereas high-throughput techniques cover thousands of interactions but can be error-prone. Unfortunately all of these approaches can only focus on one type of interaction at the time. This makes experimental mapping of the genome-wide network a cost and time intensive procedure. However, to overcome these problems, different computational approaches have been suggested that integrate multiple data sets and/or different evidence types. This widens the stringent definition of an interaction and introduces a more general term - functional association.  FunCoup is a database for genome-wide functional association networks of Homo sapiens and 16 model organisms. FunCoup distinguishes between five different functional associations: co-membership in a protein complex, physical interaction, participation in the same signaling cascade, participation in the same metabolic process and for prokaryotic species, co-occurrence in the same operon. For each class, FunCoup applies naive Bayesian integration of ten different evidence types of data, to predict novel interactions. It further uses orthologs to transfer interaction evidence between species. This considerably increases coverage, and allows inference of comprehensive networks even for not well studied organisms.  BinoX is a novel method for pathway analysis and determining the relation between gene sets, using functional association networks. Traditionally, pathway annotation has been done using gene overlap only, but these methods only get a small part of the whole picture. Placing the gene sets in context of a network provides additional evidence for pathway analysis, revealing a global picture based on the whole genome. PathwAX is a web server based on the BinoX algorithm. A user can input a gene set and get online network crosstalk based pathway annotation. PathwAX uses the FunCoup networks and 280 pre-defined pathways. Most runs take just a few seconds and the results are summarized in an interactive chart the user can manipulate to gain further insights of the gene set's pathway associations.At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 2: Manuscript.</p

Das Match ums Parlament: Drei Beiträge zur österreichischen Nationalratswahl vom 17. Dezember 1995

aus dem Inhaltsverzeichnis: Denn erstens kommt es anders ... Die Gründe für das Überraschungsergebnis der Nationalratswahlen vom 17. Dezember 1995; Achtung, gender gap! Geschlecht und Wahlverhalten 1979-1995; Wählerwanderungen: Ein Vergleich fünf verschiedener Wählerstromanalysen anläßlich der Nationalratswahl 1995

Einwanderung und Niederlassung II: Soziale Kontakte, Diskriminierungserfahrung, Sprachkenntnisse, Bleibeabsichten, Arbeitsmarktintegration und Armutsgefährdung der ausländischen Wohnbevölkerung in Wien - Endbericht ; Studie im Auftrag des Wiener Integrationsfonds

aus dem Inhaltsverzeichnis: Zusammenfassung und Schlußfolgerungen; Soziale Kontakte; Diskriminierung und Problemsicht; Sprachkenntnisse und Sprachkurse; Bleibeabsichten - Bindungen zum Herkunftsland; Der Arbeitsmarkt für Ausländerinnen; Armutsgefährdung; Der legale Status von Einwanderern und das Einkommen im Kontext mit anderen Faktore

Tuning Nanoparticle Uptake: Live-Cell Imaging Reveals Two Distinct Endocytosis Mechanisms Mediated by Natural and Artificial EGFR Targeting Ligand

Therapeutic nanoparticles can be directed to cancer cells by incorporating selective targeting ligands. Here, we investigate the epidermal growth factor receptor (EGFR)-mediated endocytosis of gene carriers (polyplexes) either targeted with natural EGF or GE11, a short synthetic EGFR-binding peptide. Highly sensitive live-cell fluorescence microcopy with single particle resolution unraveled the existence of two different uptake mechanisms; EGF triggers accelerated nanoparticle endocytosis due to its dual active role in receptor binding and signaling activation. For GE11, an alternative EGFR signaling independent, actin-driven pathway is presented

Lck mediates signal transmission from CD59 to the TCR/CD3 pathway in Jurkat T cells.

The glycosylphosphatidylinositol (GPI)-anchored molecule CD59 has been implicated in the modulation of T cell responses, but the underlying molecular mechanism of CD59 influencing T cell signaling remained unclear. Here we analyzed Jurkat T cells stimulated via anti-CD3ε- or anti-CD59-coated surfaces, using time-resolved single-cell Ca(2+) imaging as a read-out for stimulation. This analysis revealed a heterogeneous Ca(2+) response of the cell population in a stimulus-dependent manner. Further analysis of T cell receptor (TCR)/CD3 deficient or overexpressing cells showed that CD59-mediated signaling is strongly dependent on TCR/CD3 surface expression. In protein co-patterning and fluorescence recovery after photobleaching experiments no direct physical interaction was observed between CD59 and CD3 at the plasma membrane upon anti-CD59 stimulation. However, siRNA-mediated protein knock-downs of downstream signaling molecules revealed that the Src family kinase Lck and the adaptor molecule linker of activated T cells (LAT) are essential for both signaling pathways. Furthermore, flow cytometry measurements showed that knock-down of Lck accelerates CD3 re-expression at the cell surface after anti-CD59 stimulation similar to what has been observed upon direct TCR/CD3 stimulation. Finally, physically linking Lck to CD3ζ completely abolished CD59-triggered Ca(2+) signaling, while signaling was still functional upon direct TCR/CD3 stimulation. Altogether, we demonstrate that Lck mediates signal transmission from CD59 to the TCR/CD3 pathway in Jurkat T cells, and propose that CD59 may act via Lck to modulate T cell responses

TCR/CD3- and CD59-mediated Ca²⁺ signaling are dependent on Lck and LAT.

<p>Cluster distribution of Ca²⁺ time traces in differently treated cells upon anti-CD3 and anti-CD59 stimulation. Each color represents the percentage of a certain Ca²⁺ time trace cluster in the cell population. (A) Ca²⁺ measurements were performed with WT cells transiently transfected with negative control siRNA (siNeg), Lck-specific siRNA (siLck), WT cells treated with 10 µM PP2 (PP2), and Lck-deficient J.CaM1.6 cells. Clusters representing Ca²⁺ release patterns are framed in black (89.4±10.1%, 76.5±10.4%, 28.3±39.1%, and 23.4±9.9% upon anti-CD3 stimulation, 36.9±13.2%, 12.7±6.1%, 2.6±2.0%, and 1.2±1.2% upon anti-CD59 stimulation for siNeg, siLck, PP2-treated, and J.CaM1.6 cells, respectively). Mean values from at least two independent experiments, each with three technical replicates, are shown (n ≥ 204 per cell type and condition). (B) Cluster analysis of Ca²⁺ time traces in WT cells transiently transfected with negative control siRNA (siNeg), LAT-specific siRNA (siLAT), and LAT-deficient J.CaM2.5 cells. Clusters representing Ca²⁺ release patterns are framed in black (89.4±10.1%, 73.5±5.8%, and 3.0±2.3% upon anti-CD3 stimulation, 36.9±13.2%, 13.0±6.6%, and 1.7±1.6% upon anti-CD59 stimulation for siNeg, siLAT, and J.CaM2.5 cells, respectively). Mean values from at least three independent experiments, each with three technical replicates, are shown (n ≥ 208 per cell type and condition). Multiple comparison tests for the fractions showing Ca²⁺ release patterns in (A) and (B) were assessed by one-way ANOVA, significances are shown where applicable, ** p < 0.01, *** p < 0.001. (C) Knock-down of target proteins was tested by Western blotting. 48 h after transfection cell lysates from siRNA treated cells were probed with anti-Lck, anti-LAT, and anti-β-actin. J.CaM1.6 cells, J.CaM2.5 cells, and WT cells served as controls.</p

CD59-mediated Ca²⁺ signaling requires CD3ζ expression.

<p>(A) Cluster distribution of Ca²⁺ time traces in WT and TCR^high cells is shown upon anti-CD3 and anti-CD59 stimulation. Each color represents the percentage of a certain Ca²⁺ time trace cluster in the cell population. Clusters representing Ca²⁺ release patterns are framed in black (91.4±2.1% and 92.9±3.9% upon anti-CD3 stimulation, 34.4±16.3% and 72.0±16.6% upon anti-CD59 stimulation in WT and TCR^high cells, respectively). Mean values from two independent experiments, each with three technical replicates are shown (n ≥ 167 per cell type and condition). (B) Cluster distribution of Ca²⁺ time traces in WT, TCR^-, and cells expressing CD8-ζ fusion protein is shown upon anti-CD3 and anti-CD59 stimulation. Each color represents the percentage of a certain Ca²⁺ time trace cluster in the cell population. Clusters representing Ca²⁺ release patterns are framed in black (90.1±1.4%, 1.9±0.7% and 7.4±2.3% upon anti-CD3 stimulation, 25.2±6.8%, 1.6±0.4% and 13.4±1.6% upon anti-CD59 stimulation for WT, TCR^-, and CD8-ζ cells, respectively). Mean values from four independent experiments, each with three technical replicates, are shown (n ≥ 343 per cell type and condition). Multiple comparison tests for the fractions showing Ca²⁺ release patterns in (A) and (B) were assessed by one-way ANOVA, significances are shown where applicable, * p < 0.05, ** p < 0.01, *** p < 0.001.</p