Monitoring phagocytic uptake of amyloid beta into glial cell lysosomes in real time

Phagocytosis by glial cells is essential to regulate brain function during health and disease. Therapies for Alzheimer's disease (AD) have primarily focused on targeting antibodies to amyloid β (Aβ) or inhibitng enzymes that make it, and while removal of Aβ by phagocytosis is protective early in AD it remains poorly understood. Impaired phagocytic function of glial cells during later stages of AD likely contributes to worsened disease outcome, but the underlying mechanisms of how this occurs remain unknown. We have developed a human Aβ_{1-42} analogue (Aβ^{pH}) that exhibits green fluorescence upon internalization into the acidic organelles of cells but is non-fluorescent at physiological pH. This allowed us to image, for the first time, glial uptake of Aβ^{pH} in real time in live animals. We find that microglia phagocytose more AβpH than astrocytes in culture, in brain slices and in vivo. Aβ^{pH} can be used to investigate the phagocytic mechanisms responsible for removing Aβ from the extracellular space, and thus could become a useful tool to study Aβ clearance at different stages of AD

Aiming toWards Evidence baSed inTerpretation of Cardiac biOmarkers in patients pResenting with chest pain using Point of Care Testing (WESTCOR-POC): study design.

OBJECTIVES: Patients presenting with symptoms suggestive of acute coronary syndrome (ACS) contribute to a high workload and overcrowding in the Emergency Department (ED). Accelerated diagnostic protocols for non-ST-elevation myocardial infarction have proved challenging to implement. One obstacle is the turnaround time for analyzing high-sensitivity cardiac troponin (hs-cTn). In the WESTCOR-POC study (Clinical Trials number NCT05354804) we aim to evaluate safety and efficiency of a 0/1 h hs-cTn algorithm utilizing a hs-cTnI point of care (POC) instrument in comparison to central laboratory hs-cTnT measurements. DESIGN: This is a prospective single-center randomized clinical trial aiming to include 1500 patients admitted to the ED with symptoms suggestive of ACS. Patients will receive standard investigations following the European Society of Cardiology 0/1h protocols for centralized hs-cTnT measurements or the intervention using a 0/1h POC hs-cTnI algorithm. Primary end-points are 1) Safety; death, myocardial infarction or acute revascularization within 30 days 2) Efficiency; length of stay in the ED, 3) Cost- effectiveness; total episode cost, 4) Patient satisfaction, 5) Patient symptom burden and 6) Patients quality of life. Secondary outcomes are 12-months death, myocardial infarction or acute revascularization, percentage discharged after 3 and 6 h, total length of hospital stay and all costs related to hospital contact within 12 months. CONCLUSION: Results from this study may facilitate implementation of POC hs-cTn testing assays and accelerated diagnostic protocols in EDs, and may serve as a valuable resource for guiding future investigations for the use of POC high sensitivity troponin assays in outpatient clinics and prehospital settings

Process eco-innovation: assessing meso-level eco-efficiency in industrial water-service systems

Eco-innovation combines economic advantage with lower ecological-resource burdens. Eco-innovation has been generally directed at energy input-substitutes, component recycling, etc. Some companies have made investments reducing resource burdens in the production process. This study investigated options for eco-efficiency improvement in two large manufacturing companies, Volvo and Arla Foods. Their impetus for eco-innovation comes from the companies' environmental policies, as well as from external drivers such as future higher costs and resource scarcity. Relative to their respective industrial sector, these companies represent strong prospects for reducing resource burdens in water-service processes, especially from chemical inputs and wastewater. Such eco-innovations involve more complex interactions beyond the production site, so the options warrant a whole-system comparative assessment. The EcoWater project has analysed the entire water-service value chain through meso-level interactions among heterogeneous actors (process-water users, providers and wastewater treatment companies). The project has developed a methodology to obtain the necessary information, to involve stakeholders in the assessment and to facilitate their discussion on alternative options. Each study stimulated internal company discussions on the need and means to evaluate whole-system effects of investment decisions. Inter-organisational cooperation helped to anticipate how meso-level resource efficiency relates to lower burdens in wastewater treatment. The assessment method can be extended to any water-service system. By comparing options, the method can facilitate better decisions improving meso-level resource efficiency. As wider implications, some improvement options may complicate ‘eco-innovation’ as double-eco benefits: win-win for whom, where and what level

A reference human induced pluripotent stem cell line for large-scale collaborative studies

Human induced pluripotent stem cell (iPSC) lines are a powerful tool for studying development and disease, but the considerable phenotypic variation between lines makes it challenging to replicate key findings and integrate data across research groups. To address this issue, we sub-cloned candidate human iPSC lines and deeply characterized their genetic properties using whole genome sequencing, their genomic stability upon CRISPR-Cas9-based gene editing, and their phenotypic properties including differentiation to commonly used cell types. These studies identified KOLF2.1J as an all-around well-performing iPSC line. We then shared KOLF2.1J with groups around the world who tested its performance in head-to-head comparisons with their own preferred iPSC lines across a diverse range of differentiation protocols and functional assays. On the strength of these findings, we have made KOLF2.1J and its gene-edited derivative clones readily accessible to promote the standardization required for large-scale collaborative science in the stem cell field

Dienstleistung 2000plus: Wettbewerbsfaktor Kreativitaet. Modul 5.2: Kreative Organisationsmodelle zwischen Verwaltung, Wirtschaftsunternehmen und Privathaushalten Abschlussbericht

SIGLEAvailable from TIB Hannover: F99B661 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekBundesministerium fuer Bildung, Wissenschaft, Forschung und Technologie, Bonn (Germany)DEGerman

Reattachment Studies of an Oscillating Airfoil Dynamic Stall Flow Field

The reattaching flow over an oscillating airfoil executing large amplitude sinusoidal motion around a mean angle of attack of 10 degrees has been studied using the techniques of stroboscopic schlieren, two component laser Doppler velocimetry and point diffraction interferometry, for a free stream Mach number of 0.3 and a reduced frequency of 0.05. The results show that the dynamically stalled flow reattaches in a process that begins when the airfoil is very close to the static stall angle on its downward stroke and progresses over the airfoil through a large range of angles of attack as the airfoil angle decreases to about 6 degrees. The airfoil suction peak shows a dramatic rise as the static stall angle is approached and the velocity profiles develop such that the flow near the surface is accelerated. The process completes through the disappearance of a separation bubble that forms over the airfoil.Army Research Office grant (MIPR-ARO-132-90) to the Naval Postgraduate SchoolAFOSR (MIPR-91-0007)NAVAIRArmy Research Office grant (MIPR-ARO-132-90) to the Naval Postgraduate SchoolAFOSR (MIPR-91-0007)NAVAI