Activation of the HIF pathway in childhood ALL, prognostic implications of VEGF

Hypoxia-inducible factor 1 (HIF-1) controls angiogenesis and glycolysis, two leading characteristics of solid tumor invasion, metastasis, and lethality. Increased angiogenesis is also found in the bone marrow (BM) of leukemias. Less is known in leukemia about the role of HIF-1 and vascular endothelial growth factor (VEGF), the most important proangiogenic target gene of HIF-1. We show by immunohistochemistry that the oxygen-regulated component of HIF-1 (HIF-1alpha) is overexpressed in clusters of leukemic cells in BM specimens of childhood acute lymphoblastic leukemia (ALL) and absent in biopsies of normal BM. Half the HIF-1alpha-positive ALL biopsies exhibited VEGF coexpression. Among 96 children with relapsed ALL, diagnostic BM aspirates with high VEGF mRNA levels were associated with a significantly lower probability of event-free survival at 3 years (0.31±0.08 vs 0.65±0.07, P=0.003). Those with poor molecular response to therapy (evaluated by MRD assessment) had 2.2-fold higher VEGF levels than those responding well to chemotherapy (P=0.005). In conclusion, the data demonstrate activation of the HIF pathway in the BM of ALL patients and indicate that the expression of HIF target genes, such as VEGF, play an important role in leukemia progression, therapy response, and outcome

Hemodynamic Forces, Vascular Oxidative Stress, and Regulation of BMP-2/4 Expression

Changes in the hemodynamic environment (e.g., hypertension, disturbed-flow conditions) are known to promote atherogenesis by inducing proinflammatory phenotypic alterations in endothelial and smooth muscle cells; however, the mechanisms underlying mechanosensitive induction of inflammatory gene expression are not completely understood. Bone morphogenetic protein-2 and -4 (BMP-2/4) are TGF-β superfamily cytokines that are expressed by both endothelial and smooth muscle cells and regulate a number of cellular processes involved in atherogenesis, including vascular calcification and endothelial activation. This review considers how hemodynamic forces regulate BMP-2/4 expression and explores the role of mechanosensitive generation of reactive oxygen species by NAD(P)H oxidases in the control of BMP signaling. Antioxid. Redox Signal. 11, 1683–1697

KOKOGUS. Design of a communication network between Western Europe and the CIS for future joint space projects Executive summary

The KOKOGUS study scrutinizes the capabilities of existing and planned communication networks or services and compares them with the requirements of future joint space projects between Western Europe and the CIS. This comparison is rounded off by an analysis of legal aspects, which have to be considered in the definition of communication concepts. The study comes to the conclusion that the communication requirements of almost all projects under realization are moderate and can be covered either by the incorporation of commercial communication services or by the exploitation of the already existing dedicated infrastructure for space missions. This is demonstrated in several case studies. The study proposes to build the communication network around the existing satellite link between the Russian Mission Control Center in Kaliningrad near Moscow and the German Space Operations Center near Munich. This is the most economic approach since it takes advantage of the enormous capabilities and experiences of both centers. Future projects with extremely complex communication requirements show a strong tendency towards the exploitation of Western systems which are beyond the scope of the present study. (orig.)SIGLEAvailable from TIB Hannover: F95B243+a / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekBundesministerium fuer Forschung und Technologie (BMFT), Bonn (Germany); Deutsche Agentur fuer Raumfahrtangelegenheiten (DARA) GmbH, Bonn (Germany)DEGerman

Operation of HTS dc-SQUID sensors in high magnetic fields

Most visualization techniques have been designed on the assumption that the data to be represented are free from uncertainty. Yet this is rarely the case. Recently the visualization community has risen to the challenge of incorporating an indication of uncertainty into visual representations, and in this article we review their work. We place the work in the context of a reference model for data visualization, that sees data pass through a pipeline of processes. This allows us to distinguish the visualization of uncertainty - which considers how we depict uncertainty specified with the data - and the uncertainty of visualization - which considers how much inaccuracy occurs as we process data through the pipeline. It has taken some time for uncertain visualization methods to be developed, and we explore why uncertainty visualization is hard - one explanation is that we typically need to find another display dimension and we may have used these up already! To organise the material we return to a typology developed by one of us in the early days of visualization, and make use of this to present a catalogue of visualization techniques describing the research that has been done to extend each method to handle uncertainty. Finally we note the responsibility on us all to incorporate any known uncertainty into a visualization, so that integrity of the discipline is maintained