Neutralization of LINGO-1 during In Vitro Differentiation of Neural Stem Cells Results in Proliferation of Immature Neurons

Identifying external factors that can be used to control neural stem cells division and their differentiation to neurons, astrocytes and oligodendrocytes is of high scientific and clinical interest. Here we show that the Nogo-66 receptor interacting protein LINGO-1 is a potent regulator of neural stem cell maturation to neurons. LINGO-1 is expressed by cortical neural stem cells from E14 mouse embryos and inhibition of LINGO-1 during the first days of neural stem cell differentiation results in decreased neuronal maturation. Compared to neurons in control cultures, which after 6 days of differentiation have long extending neurites, neurons in cultures treated with anti-LINGO-1 antibodies retain an immature, round phenotype with only very short processes. Furthermore, neutralization of LINGO-1 results in a threefold increase in βIII tubulin-positive cells compared to untreated control cultures. By using BrdU incorporation assays we show that the immature neurons in LINGO-1 neutralized cultures are dividing neuroblasts. In contrast to control cultures, in which no cells were double positive for βIII tubulin and BrdU, 36% of the neurons in cultures treated with anti-LINGO-1 antibodies were proliferating after three days of differentiation. TUNEL assays revealed that the amount of cells going through apoptosis during the early phase of differentiation was significantly decreased in cultures treated with anti-LINGO-1 antibodies compared to untreated control cultures. Taken together, our results demonstrate a novel role for LINGO-1 in neural stem cell differentiation to neurons and suggest a possibility to use LINGO-1 inhibitors to compensate for neuronal cell loss in the injured brain

Evaluation of a new 10 mA DC current reference standard

A new DC current reference standard has been developed as a component in a Current calibration hierarchy in the LHC project at CERN. The standard provides 10 mA DC current with an accuracy less than 0.5 ppm, drift less than 2 ppm/year and compliance error less than 0.1 ppm for 0-10 V. The paper gives the results from two years evaluation of a series of 5 units

Design and evaluation of a 10-mA DC current reference standard

A new DC current reference standard has been developed for high- current power converter calibration in the large hadron collider (LHC) project at the European Organization for Nuclear Research (CERN). This standard provides a near ideal 10-mA DC current with long-term drift of one part in 10/sup 6/ per year. The paper describes the requirements and the detailed design and evaluation of the unit. Since similar 10-V standards are commercially available, the paper concentrates on the unique current output capability of this device. (4 refs)

The impact of new technologies on mode shift towards sustainable travel: findings from the STTRIDE project

STTRIDE is funded by the Conference of European Directors of Roads. It is addressing how best to use"br" technological advances to deliver positive modal shift towards sustainable travel, with emphasis on the interurban"br" network managed by National Road Authorities. This paper summarises the results of the part of the"br" project that is concerned with assessing the potential impact of a selection of ten new technologies on mode shift."br" It is based on an extensive review of literature and consultation with experts. The analysis identified three"br" different types of mode shift, to which the technologies contribute in varying ways and with different roles for"br" road authorities in implementation. The conclusions relate to the contribution of each technology towards mode"br" shift but also identify several key uncertainties around the impacts of new technologies on mode shift