Amplification and overexpression of the ID4 gene at 6p22.3 in bladder cancer

BACKGROUND: Amplifications at 6p22.3 are prevalent in advanced stage bladder cancer (TCC). Previous studies have identified SOX4, CDKAL, and E2F3 as targets of this amplification and therefore potential oncogenes, but the more telomeric DEK gene too has been reported as overexpressed and amplified. We have therefore investigated whether the intermediate region harboring the oncogene candidate ID4 is also part of the amplicon. RESULTS: Expression of E2F3, DEK, and ID4 was investigated by real-time RT-PCR in 28 TCC compared to 6 normal bladder tissues and in 15 TCC cell lines compared to cultured normal urothelial cells. Expression of E2F3 as well as DEK increased on average in tumor vs. normal tissues (3-fold and 2.5-fold, resp.), but only the increase for E2F3 was statistically significant (p = 0.039). ID4 overexpression was observed in selected specimens. Each of the three genes was overexpressed in several cell lines, up to 150-fold (ID4), 30-fold (E2F3), and 9-fold (DEK), but these increases were not correlated to each other. Instead, moderate (DEK) to excellent (ID4) correlations were observed with copy number increases of microsatellites near each gene. Microsatellite copy number increases were highly heterogeneous across the investigated several Mb region revealing at least three subregions of amplification. CONCLUSION: Extending previous reports, our data indicate that the 6p22.3 amplicon in TCC is highly heterogeneous and targets several genes in a variable fashion. Among these, expression of E2F3 and DEK appear to be generally increased in TCC, with additional increases caused by amplifications. In contrast, over-expression of ID4, which is normally predominantly expressed in testes and brain, appears to depend more strictly on gene amplification. Accordingly, the effect of amplifications at 6p22.3 in bladder cancer is expected to be non-uniform, thereby contributing to the highly variable biological and clinical behavior of advanced stage tumors. ID4 is a potential oncogene in a small subset of bladder cancers

Untersuchung zum Marktdesign kooperativer Systeme zur Erhöhung der Verkehrssicherheit

Von Kooperativen Anwendungen (C-ITS Anwendungen) als integrierter intelligenter Bestandteil sowohl von Fahrzeugen der neuen Generation als auch der zukünftigen verkehrlichen Infrastruktur der öffentlichen Straßenbetreiber wird ein substantieller Beitrag zur Verbesserung der Verkehrssicherheit und der Verkehrseffizienz mit daraus abgeleitet positiven Auswirkungen auf die verkehrsbedingte Umweltbilanz und die gesamtwirtschaftliche Produktivität erwartet. Die vorliegende Untersuchung befasst sich in diesem Kontext mit der Frage, welche auf Bundesfernstraßen zu implementierenden C-ITS Anwendungen aus Sicht des Bundes sinnvoll sind und staatliches Engagement lohnen, welche Rollen dem Bund dabei aus seiner hoheitlichen Verantwortung heraus sowie als Baulastträger und Betreiber von Bundesfernstraßen zufallen und welche der möglichen Kommunikations- und Verbreitungstechnologien sich am besten für eine Implementierung eignen. Dazu werden im ersten Teil der Untersuchung unter Zugrundelegung eines neu entwickelten Nutzen-/Hemmnis-Modells die funktionalen, technischen, organisatorischen und wirtschaftlichen Aspekte von C-ITS Anwendungen durch Expertenbefragung bewertet. Anschließend wird eine Rangliste für solche als "sinnvoll" erachtete C-ITS Anwendungen erstellt, bei deren Einführung und Betrieb dem Bund als für das Bundesfernstraßennetz zuständiger und verantwortlicher Baulastträger und Betreiber eine (pro)aktive Rolle zufällt. In einem weiteren Teil der Untersuchung wird unter Rückgriff auf einen methodischen Ansatz aus der Theorie der Institutionellen Rollenmodelle ebenfalls mittels Expertenbewertung ermittelt, welche der zuvor als sinnvoll erachteten C-ITS Anwendungen durch den Bund gefördert und (pro-)aktiv angestoßen werden sollten und welche nächsten Umsetzungsschritte dazu vorzubereiten sind. Als Ergebnis wird gezeigt, welche C-ITS Anwendungen durch den Bund in den Markt gebracht werden sollten, bei welchen C-ITS Anwendungen er lediglich eine zweitrangige Rolle spielen kann bzw. komplementär tätig sein sollte und letztendlich welche C-ITS Anwendungen nicht in seinem Einflussbereich liegen. Der technologieorientierte Teil der Untersuchung widmet sich der Frage, welche Kommunikations- und Verbreitungstechnologien existieren, damit C-ITS Anwendungen in die Lage versetzt werden, sich ihrem Umfeld mitzuteilen und Informationen über längere Wege zu verschicken und zu empfangen. Dazu werden zu den unterschiedlichen technologischen Möglichkeiten der Realisierung der C-ITS Anwendungen (vor allem ETSI G5, Mobilfunk, (Digital-)Rundfunk, etc.) und zu deren jeweiligen Eignung Vorschläge erarbeitet. As Ergebnis wird für die relevanten C-ITS Anwendungen die Eignung der infrage kommenden Technologien hinsichtlich ihrer Eignung gegenübergestellt. Als Abschluss der Untersuchung werden unter Abstützung auf die dargestellten Ergebnisse Empfehlungen für die räumliche und zeitliche Dimension des Rollouts der am Ende für den Bund relevanten C-ITS Anwendungen abgegeben. In Form einer zusätzlich auf Überlegungen einer praktikablen Vorgehensweise aufbauenden Roadmap werden diese zu einem Gesamtergebnis zusammengeführt mit dem Ziel, dem Bund darüber eine Empfehlung für seine Positionierung und Vorgehensweise bei der Einführung kooperativer Systeme und Dienste zu geben und so einen Beitrag zum Marktdesign für kooperative Systeme zu leisten. Die Untersuchungsergebnisse dienen der umfassenden und koordinierten Erschließung des Verkehrssicherheits- und Verkehrseffizienzpotentials kooperativer Systeme und Dienste in Deutschland, aber auch im europäischen Kontext. Sie tragen zur Umsetzung von Maßnahmen im Rahmen des nationalen IVS-Aktionsplans Straße bei.A substantial contribution to improving road safety and traffic efficiency with consequential positive effects on the traffic-related environmental balance and overall economic productivity is expected from cooperative applications (C-ITS applications) as an integrated, intelligent part of both the latest generation of vehicles as well as the future traffic infrastructure of the public road operator. In this context, the present study addresses the question of which C-ITS applications to be implemented on trunk roads are meaningful and worth state involvement in the opinion of the federal government, which roles the federal government has to assume on account of its sovereign responsibility and as the public road authority and operator of trunk roads, and which of the possible communication and processing technologies are most suited for an implementation. To this end, the first part of this study will assess the functional, technical, organisational and economic aspects of C-ITS applications based on a newly developed benefit-barrier model through an expert survey. A ranking will then be drawn up for those C-ITS applications considered "meaningful" and during whose introduction and operation the federal government has to assume a (pro-)active) role as the public road authority and operator responsible for the trunk road network. In a further part of the study, recourse will be made to a methodical approach from the theory of institutional role models, whereby an expert survey will also determine which of those C-ITS applications previously considered meaningful should be financed and (pro-)actively supported by the federal government and the next implementation steps that have to be prepared. The result will show which C-ITS applications should be launched onto the market by the federal government, in which C-ITS applications they should only play a secondary or complementary role and ultimately which C-ITS applications do not lie within its sphere of influence. The technology-oriented part of the study deals with the question of which communication and processing technologies exist so that C-ITS applications are able to communicate with their environment and send and receive information over long distances. To this end, proposals will be made regarding the different technological possibilities to realise the C-ITS applications (above all ETSI G5, cellular systems, (digital) radio, etc.) and their relevant suitability. The result will be a comparison of the suitability of the technologies in question for the relevant C-ITS applications. The study will conclude with recommendations for the spatial and temporal dimension of the rollout for the C-ITS applications that are ultimately relevant for the federal government based on the results shown. These will be compiled into an overall result in the form of a roadmap based on additional considerations of a practical procedure aimed at providing the federal government with a recommendation about this for its positioning and procedure when introducing cooperative systems and services, thus contributing to the market design of cooperative systems. The results of the study can be used for a comprehensive and coordinated indexing of the road safety and traffic efficiency potential of cooperative systems and services in Germany, though also within a European context. They contribute to the implementation of measures within the scope of the national ITS plan of action "Road"

On the AC spectrum of one-dimensional random Schroedinger operators with matrix-valued potentials

We consider discrete one-dimensional random Schroedinger operators with decaying matrix-valued, independent potentials. We show that if the l^2-norm of this potential has finite expectation value with respect to the product measure then almost surely the Schroedinger operator has an interval of purely absolutely continuous (ac) spectrum. We apply this result to Schroedinger operators on a strip. This work provides a new proof and generalizes a result obtained by Delyon, Simon, and Souillard.Comment: (1 figure

Rashba precession in quantum wires with interaction

Rashba precession of spins moving along a one-dimensional quantum channel is calculated, accounting for Coulomb interactions. The Tomonaga--Luttinger model is formulated in the presence of spin-orbit scattering and solved by Bosonization. Increasing interaction strength at decreasing carrier density is found to {\sl enhance} spin precession and the nominal Rashba parameter due to the decreasing spin velocity compared with the Fermi velocity. This result can elucidate the observed pronounced changes of the spin splitting on applied gate voltages which are estimated to influence the interface electric field in heterostructures only little.Comment: now replaced by published versio

Of Mice, Cattle, and Humans: The Immunology and Treatment of River Blindness

River blindness is a seriously debilitating disease caused by the filarial parasite Onchocerca volvulus, which infects millions in Africa as well as in South and Central America. Research has been hampered by a lack of good animal models, as the parasite can only develop fully in humans and some primates. This review highlights the development of two animal model systems that have allowed significant advances in recent years and hold promise for the future. Experimental findings with Litomosoides sigmodontis in mice and Onchocerca ochengi in cattle are placed in the context of how these models can advance our ability to control the human disease

Nonstationary Collisional Dynamics in Determining Nitric Oxide Laser-Induced Flourescence Spectra

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/77237/1/AIAA-8783-947.pd

Hourly Exposure to Ultrafine Particle Metrics and the Onset of Myocardial Infarction in Augsburg, Germany

BACKGROUND: Epidemiological evidence on the health effects of ultrafine particles (UFP) remains insufficient to infer a causal relationship that is largely due to different size ranges and exposure metrics examined across studies. Moreover, evidence regarding the association between UFP and cardiovascular disease at a sub-daily timescale is lacking. OBJECTIVE: We investigated the relationship between different particle metrics, including particle number (PNC), length (PLC), and surface area (PSC) concentrations, and myocardial infarction (MI) at an hourly timescale. METHODS: We collected hourly air pollution and meteorological data from fixed urban Background: monitoring sites and hourly nonfatal MI cases from a MI registry in Augsburg, Germany, during 2005-2015. We conducted a time-stratified case-crossover analysis with conditional logistic regression to estimate the association between hourly particle metrics and MI cases, adjusted for air temperature and relative humidity. We also examined the independent effects of a certain particle metric in two-pollutant models by adjusting for copollutants, including particulate matter (PM) with an aerodynamic diameter of >= 10 mu m or 2.5 mu m (PM10 and PM2.5, respectively), nitrogen dioxide, ozone, and black carbon. RESULTS: Overall, a total of 5,898 cases of nonfatal MI cases were recorded. Exploratory analyses showed similar associations across particle metrics in the first 6-12 h. For example, interquartile range increases in PNC within the size range of 10-100 nm, PLC, and PSC were associated with an increase of MI 6 h later by 3.27% [95% confidence interval (CI): 0.27, 6.37], 5.71% (95% CI: 1.79, 9.77), and 5.84% (95% CI: 1.04, 10.87), respectively. Positive, albeit imprecise, associations were observed for PNC within the size range of 10-30 nm and 100-500 nm. Effect estimates for PLC and PSC remained similar after adjustment for PM and gaseous pollutants. CONCLUSIONS: Transient exposure to particle number, length, and surface area concentrations or other potentially related exposures may trigger the onset of nonfatal myocardial infraction