27 research outputs found
Endothelial LRP1 transports amyloid-ÎČ1-42 across the blood-brain barrier
According to the neurovascular hypothesis, impairment of low-density lipoprotein receptor-related protein-1 (LRP1) in brain capillaries of the blood-brain barrier (BBB) contributes to neurotoxic amyloid-beta (A beta) brain accumulation and drives Alzheimer's disease (AD) pathology. However, due to conflicting reports on the involvement of LRP1 in A beta transport and the expression of LRP1 in brain endothelium, the role of LRP1 at the BBB is uncertain. As global Lrp1 deletion in mice is lethal, appropriate models to study the function of LRP1 are lacking. Moreover, the relevance of systemic A beta clearance to AD pathology remains unclear, as no BBB-specific knockout models have been available. Here, we developed transgenic mouse strains that allow for tamoxifen-inducible deletion of Lrp1 specifically within brain endothelial cells (Slo1c1-CreER(Tz) Lrp1(fl/fl) mice) and used these mice to accurately evaluate LRP1-mediated A beta BBB clearance in vivo. Selective deletion of Lrp1 in the brain endothelium of C57BL/6 mice strongly reduced brain efflux of injected [I-125] A beta(1-42). Additionally, in the 5xFAD mouse model of AD, brain endothelial-specific Lrp1 deletion reduced plasma A beta levels and elevated soluble brain A beta, leading to aggravated spatial learning and memory deficits, thus emphasizing the importance of systemic AD elimination via the BBB. Together, our results suggest that receptor-mediated A beta BBB clearance may be a potential target for treatment and prevention of A beta brain accumulation in AD
Detection of argon in the coma of comet 67P/Churyumov-Gerasimenko
Comets have been considered to be representative of icy planetesimals that may have contributed a significant
fraction of the volatile inventory of the terrestrial planets. For example, comets must have brought some water
to Earth. However, the magnitude of their contribution is still debated. We report the detection of argon and its
relation to the water abundance in the Jupiter family comet 67P/Churyumov-Gerasimenko by in situ measurement
of the Rosetta Orbiter Spectrometer for Ion and Neutral Analysis (ROSINA) mass spectrometer aboard the Rosetta
spacecraft. Despite the very low intensity of the signal, argon is clearly identified by the exact determination of the
mass of the isotope 36Ar and by the 36Ar/38Ar ratio. Because of time variability and spatial heterogeneity of the
coma, only a range of the relative abundance of argon to water can be given. Nevertheless, this range confirms that
comets of the type 67P/Churyumov-Gerasimenko cannot be the major source of Earthâs major volatiles
Digitalisierung beruflicher Lern- und Arbeitsprozesse. Impulse aus der Bauwirtschaft und anderen gewerblich-technischen Sektoren
Der Sammelband stellt aktuelle AnsĂ€tze zum digital unterstĂŒtzten beruflichen Lernen dar. Die BeitrĂ€ge geben Einblicke in die dynamische Entwicklung der Schnittstellen von Erwerbsarbeit und beruflicher Aus-, Fort- und Weiterbildung im Kontext der Digitalisierung Arbeits- und Lernmitteln. Der Band schlieĂt damit an die 2019 ebenfalls im UniversitĂ€tsverlag der Technischen UniversitĂ€t Berlin erschienene Publikation âBerufsbildung am Bau digitalâ (hrsg. von Bernd Mahrin und Johannes Meyser) an. Das erste Kapitel erörtert grundsĂ€tzliche didaktische Fragen zu digital unterstĂŒtztem Lernen und Arbeiten einschlieĂlich der Rahmenbedingungen. Im zweiten Kapitel schlieĂen sich BeitrĂ€ge zur KapazitĂ€tsentwicklung, zu Standards und zu digitalen Werkzeugen an. Das dritte Kapitel widmet sich konkreten Einzellösungen mit starkem Praxisbezug und hohem Transferpotenzial zum digitalisierten Arbeiten und Lernen im Bausektor und im Metallbereich. Das abschlieĂende vierte Kapitel prĂ€sentiert ĂŒbergreifend nutzbare und frei zugĂ€ngliche Online-Angebote wie einen Medienpool fĂŒr Bildungszwecke, eine Lernmedien-Datenbank und ein hybrides Lernsystem mit virtuellem 3D-GebĂ€udemodell. Das Buch ist entstanden im Rahmen des durch das Bundesministerium fĂŒr Bildung und Forschung und den EuropĂ€ischen Sozialfonds geförderten Projektes DigiBAU â Digitales Bauberufliches Lernen und Arbeiten. (DIPF/Orig.)The anthology presents current approaches to digitally supported professional learning. The articles provide insights into the dynamic development of the interfaces between gainful employment and vocational training and further education in the context of digitization of work and learning aids. The volume is thus connected to the publication âBerufsbildung am Bau digitalâ (edited by Bernd Mahrin and Johannes Meyser), which was published in 2019 by the University Press of the Technische UniversitĂ€t Berlin. The first chapter discusses fundamental didactic questions about digitally supported learning and working, including the framework conditions. The second chapter picks contributions on capacity development, standards, and digital tools out as central themes. The third chapter is dedicated to concrete specific solutions with strong practical relevance and high transfer potential for digitized work and learning in the construction sector and in the metal sector. The final fourth chapter presents comprehensive and freely accessible online offers such as a media pool for educational purposes, a learning media database and a hybrid learning system with a virtual 3D building model. The book was created as part of the DigiBAU project - digital vocational learning and working in the field of construction - funded by the German Federal Ministry of Education and Research and the European Social Fund. (DIPF/Orig.
Global geomagnetic responses to the IMF <i>B</i><sub>z</sub> fluctuations during the September/October 2003 high-speed stream intervals
Safety and Pharmacokinetics of Escalated Doses of Weekly Intravenous Infusion of CCI-779, a Novel mTOR Inhibitor, in Patients With Cancer
Early Activity of Churyumov-Gerasimenko: ROSINA/RTOF Results
International audienceThe European Space Agencyâs Rosetta spacecraft is now close to the comet 67P/Churyumov-Gerasimenko (67P/C-G). On board is the Rosetta Orbiter Spectrometer for Ion and Neutral Analysis (ROSINA) instrument suite. ROSINA consists of two mass spectrometers, the Double Focusing Mass Spectrometer (DFMS) and the Reflectron-type Time-Of-Flight (RTOF), as well as the COmet Pressure Sensor (COPS).The first signal with ROSINA/RTOF of the gaseous environment of the comet was a significant increase in water density observed on DOY 218.1 of 2014 (at 3.5 AU) by RTOF above the gaseous envelope of the Rosetta spacecraft. A similar density increase is observed by COPS at the same time. A preliminary analysis shows that the water density is nH2O â 1012 mâ3 at 100 km distance from the comet (located at 3.5 AU from the Sun). This gives a density at the surface of nH2O â 6.4·1015 mâ3 and a vertical column density of water of NCH2O â 6.5·1018 mâ2. Assuming an active area of 4% we arrive at a production rate of QH2O â 5.8·1024 mole sâ1. These values are preliminary and will be refined by forthcoming observations. Other than water, no signal related to cometary activity could be observed above the molecular background from the spacecraft at present, e.g. cometary CO and CO2 are not observed in the RTOF data so far. This hints at a possible deficiency of carbon bearing compounds in the comet