Mobilitätsforschung zur Reichweitenbestimmung in der Deutschen und Schweizer Außenwerbung – Neue Wege mit GPS

Die bestmögliche Positionierung einer Plakatstelle ist seit jeher ein wichtiger Bestandteil in der Außenwerbung. Aus plausiblen Gründen werden Plakatstandorte so gewählt, dass sie häufig von Menschen passiert werden. Während jedoch die Lokalität und das Umfeld bei der Wahl von Plakatstandorten schon immer ein entscheidendes Kriterium gewesen ist, spielen die räumlichen Zusammenhänge bei der Leistungsbewertung und damit bei der Preisbildung von Plakatkampagnen erst in den vergangenen Jahren eine wichtige Rolle. Ziel der Leistungsbewertung ist es festzustellen, wer, wie oft und woher eine Person an einer Plakatkampagne vorbei gekommen ist. Dabei ist die räumliche Verteilung von Plakatstellen von entscheidender Bedeutung. Neue, GPS-basierte Messmethoden der Mobilitätserfassung erlauben die räumlich differenzierte Ausweisung von Leistungswerten für beliebig zusammengestellte Kampagnen sowie soziodemographische und räumlich ausgewählte Zielgruppen. Damit unterscheidet sich dieser GPS-Ansatz von den klassisch eingesetzten Methoden, die bisher versucht haben, über Befragungen von Testpersonen die Mobilität zu rekonstruieren, und nur Durchschnittswerte für Kampagnen anbieten konnten. So wurde z.B. für eine Stadt wie Köln nicht unterschieden, ob es sich bei einer Plakatkampagne um eine stark über die Stadt gestreute oder stark konzentrierte Kampagne handelt. Diese Dissertation widmet sich einer Gesamtschau über neuartige GPS-Verfahren in der Deutschen und Schweizer Außenwerbung und deren Anwendung in der Praxis. Sie ist ein erstmaliger Versuch, eine systematisierte Übersicht über die aktuellen Forschungsergebnisse in der Außenwerbung bzw. Mobilitätsforschung zu erstellen. Die bestehenden Publikationen zur Außenwerbeforschung (Pasquier 1997, Engel und Hofsäss 2003) stammen noch aus der Zeit vor der Mobilitätserfassung mit GPS sowie dem Einsatz von Geographischen Informationssystemen und sind somit veraltet. Zudem betrachten diese Publikationen keine geographischen Aspekte, die mit dem neuen Ansatz in den Fokus der Leistungsbewertung rücken und eine Erfolgsgeschichte für die Geographie bzw. das Geomarketing darstellen. Zur Systematisierung dieser Arbeit zählt, geeignete Lösungswege im Umgang mit zeitlichen und räumlichen Datenlücken zu diskutieren, zu erproben, sowie Validitäts- und Robustheitsanalysen durchzuführen. Es werden geeignete Tests definiert, die z.B. Selektionseffekte in der Rekrutierung von Probanden offen legen. Es wird die Problematik behandelt, wie Leistungswerte auf eine Neuerhebung der Mobilität reagieren und wo die Grenzen einer Leistungswertbestimmung liegen. Dabei sind die Ausgangslage und die Anforderungen in der Schweiz und in Deutschland unterschiedlich. So ist in Deutschland die GPS Stichprobengröße viel geringer als in der Schweiz. Dies hat direkte Konsequenzen auf die Modellierungsschritte und das Ergebnis. Die verwendeten Methoden sind weit über das Gebiet der Außenwerbung und Mediaplanung hinaus für die Modellierung von Mobilität von Interesse

Membrane remodelling triggers maturation of excitation–contraction coupling in 3D-shaped human-induced pluripotent stem cell-derived cardiomyocytes

The prospective use of human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) for cardiac regenerative medicine strongly depends on the electro-mechanical properties of these cells, especially regarding the Ca$^{2+}$-dependent excitation–contraction (EC) coupling mechanism. Currently, the immature structural and functional features of hiPSC-CM limit the progression towards clinical applications. Here, we show that a specific microarchitecture is essential for functional maturation of hiPSC-CM. Structural remodelling towards a cuboid cell shape and induction of BIN1, a facilitator of membrane invaginations, lead to transverse (t)-tubule-like structures. This transformation brings two Ca$^{2+}$ channels critical for EC coupling in close proximity, the L-type Ca$^{2+}$ channel at the sarcolemma and the ryanodine receptor at the sarcoplasmic reticulum. Consequently, the Ca$^{2+}$-dependent functional interaction of these channels becomes more efficient, leading to improved spatio-temporal synchronisation of Ca$^{2+}$ transients and higher EC coupling gain. Thus, functional maturation of hiPSC-cardiomyocytes by optimised cell microarchitecture needs to be considered for future cardiac regenerative approaches

Reassessment of Blood Gene Expression Markers for the Prognosis of Relapsing-Remitting Multiple Sclerosis

Despite considerable advances in the treatment of multiple sclerosis, current drugs are only partially effective. Most patients show reduced disease activity with therapy, but still experience relapses, increasing disability, and new brain lesions. Since there are no reliable clinical or biological markers of disease progression, long-term prognosis is difficult to predict for individual patients. We identified 18 studies that suggested genes expressed in blood as predictive biomarkers. We validated the prognostic value of those genes with three different microarray data sets comprising 148 patients in total. Using these data, we tested whether the genes were significantly differentially expressed between patients with good and poor courses of the disease. Poor progression was defined by relapses and/or increase of disability during a two-year follow-up, independent of the administered therapy. Of 110 genes that have been proposed as predictive biomarkers, most could not be confirmed in our analysis. However, the G protein-coupled membrane receptor GPR3 was expressed at significantly lower levels in patients with poor disease progression in all data sets. GPR3 has therefore a high potential to be a biomarker for predicting future disease activity. In addition, we examined the IL17 cytokines and receptors in more detail and propose IL17RC as a new, promising, transcript-based biomarker candidate. Further studies are needed to better understand the roles of these receptors in multiple sclerosis and its treatment and to clarify the utility of GPR3 and IL17RC expression levels in the blood as markers of long-term prognosis

Approaching the uncultured endosymbiont of Riftia pachyptila by physiological proteomics

Author Posting. © The Authors, 2006. This is the author's version of the work. It is posted here by permission of AAAS for personal use, not for redistribution. The definitive version was published in Science 315 (2007): 247-250, doi:10.1126/science.1132913.The bacterial endosymbiont of the deep-sea tube worm Riftia pachyptila has never been successfully cultivated outside its host. In the absence of cultivation data we have taken a proteomic approach based on the metagenome sequence to study the metabolism of this peculiar microorganism in detail. As one result, we found that three major sulfide oxidation proteins constitute ~12% of the total cytosolic proteome, highlighting the essential role of these enzymes for the symbiont’s energy metabolism. Unexpectedly, the symbiont uses the reductive tricarboxylic acid (TCA) cycle in addition to the previously identified Calvin cycle for CO2 fixation.This work was supported by the DFG, grant Schw595/3-1. Other funding sources were: NSF (OCE 04-52333) and NASA Astrobiology Institute (NNA04CC04A) for SMS, MH: postdoctoral scholarship from WHOI, HF: Academic Senate (RF811S and RE518S)

Guideline for Trustworthy Artificial Intelligence -- AI Assessment Catalog

Artificial Intelligence (AI) has made impressive progress in recent years and represents a key technology that has a crucial impact on the economy and society. However, it is clear that AI and business models based on it can only reach their full potential if AI applications are developed according to high quality standards and are effectively protected against new AI risks. For instance, AI bears the risk of unfair treatment of individuals when processing personal data e.g., to support credit lending or staff recruitment decisions. The emergence of these new risks is closely linked to the fact that the behavior of AI applications, particularly those based on Machine Learning (ML), is essentially learned from large volumes of data and is not predetermined by fixed programmed rules. Thus, the issue of the trustworthiness of AI applications is crucial and is the subject of numerous major publications by stakeholders in politics, business and society. In addition, there is mutual agreement that the requirements for trustworthy AI, which are often described in an abstract way, must now be made clear and tangible. One challenge to overcome here relates to the fact that the specific quality criteria for an AI application depend heavily on the application context and possible measures to fulfill them in turn depend heavily on the AI technology used. Lastly, practical assessment procedures are needed to evaluate whether specific AI applications have been developed according to adequate quality standards. This AI assessment catalog addresses exactly this point and is intended for two target groups: Firstly, it provides developers with a guideline for systematically making their AI applications trustworthy. Secondly, it guides assessors and auditors on how to examine AI applications for trustworthiness in a structured way

A Proteomic View of an Important Human Pathogen – Towards the Quantification of the Entire Staphylococcus aureus Proteome

The genome sequence is the “blue-print of life,” but proteomics provides the link to the actual physiology of living cells. Because of their low complexity bacteria are excellent model systems to identify the entire protein assembly of a living organism. Here we show that the majority of proteins expressed in growing and non-growing cells of the human pathogen Staphylococcus aureus can be identified and even quantified by a metabolic labeling proteomic approach. S. aureus has been selected as model for this proteomic study, because it poses a major risk to our health care system by combining high pathogenicity with an increasing frequency of multiple antibiotic resistance, thus requiring the development of new anti-staphylococcal therapy strategies. Since such strategies will likely have to target extracellular and surface-exposed virulence factors as well as staphylococcal survival and adaptation capabilities, we decided to combine four subproteomic fractions: cytosolic proteins, membrane-bound proteins, cell surface-associated and extracellular proteins, to comprehensively cover the entire proteome of S. aureus. This quantitative proteomics approach integrating data ranging from gene expression to subcellular localization in growing and non-growing cells is a proof of principle for whole-cell physiological proteomics that can now be extended to address physiological questions in infection-relevant settings. Importantly, with more than 1700 identified proteins (and 1450 quantified proteins) corresponding to a coverage of about three-quarters of the expressed proteins, our model study represents the most comprehensive quantification of a bacterial proteome reported to date. It thus paves the way towards a new level in understanding of cell physiology and pathophysiology of S. aureus and related pathogenic bacteria, opening new avenues for infection-related research on this crucial pathogen

Association of candidate pharmacogenetic markers with platinum-induced ototoxicity:PanCareLIFE dataset

Genetic association studies suggest a genetic predisposi- tion for cisplatin-induced ototoxicity. Among other candidate genes, thiopurine methyltransferase ( TPMT ) is considered a critical gene for susceptibility to cisplatin-induced hearing loss in a pharmacogenetic guideline. The PanCareLIFE cross- sectional cohort study evaluated the genetic associations in a large pan-European population and assessed the diagnos- tic accuracy of the genetic markers. 1,112 pediatric cancer survivors who had provided biomaterial for genotyping were screened for participation in the pharmacogenetic association study. 900 participants qualified for inclusion. Based on the assessment of original audiograms, patients were assigned to three phenotype categories: no, minor, and clinically relevant hearing loss. Fourteen variants in eleven candidate genes ( ABCC3, OTOS, TPMT, SLC22A2, NFE2L2, SLC16A5, LRP2, GSTP1, SOD2, WFS1, and ACYP2 ) were genotyped. The genotype and phenotype data represent a resource for conducting meta- analyses to derive a more precise pooled estimate of the ef- fects of genes on the risk of hearing loss due to platinum treatment

Association of candidate pharmacogenetic markers with platinum-induced ototoxicity: PanCareLIFE dataset

Genetic association studies suggest a genetic predisposition for cisplatin-induced ototoxicity. Among other candidate genes, thiopurine methyltransferase (TPMT) is considered a critical gene for susceptibility to cisplatin-induced hearing loss in a pharmacogenetic guideline. The PanCareLIFE cross-sectional cohort study evaluated the genetic associations in a large pan-European population and assessed the diagnostic accuracy of the genetic markers. 1,112 pediatric cancer survivors who had provided biomaterial for genotyping were screened for participation in the pharmacogenetic association study. 900 participants qualified for inclusion. Based on the assessment of original audiograms, patients were assigned to three phenotype categories: no, minor, and clinically relevant hearing loss. Fourteen variants in eleven candidate genes (ABCC3, OTOS, TPMT, SLC22A2, NFE2L2, SLC16A5, LRP2, GSTP1, SOD2, WFS1, and ACYP2) were genotyped. The genotype and phenotype data represent a resource for conducting meta-analyses to derive a more precise pooled estimate of the effects of genes on the risk of hearing loss due to platinum treatment