Abstract. Immersion freezing is the most relevant heterogeneous ice nucleation mechanism through which ice crystals are formed in mixed-phase clouds. In recent years, an increasing number of laboratory experiments utilizing a variety of instruments have examined immersion freezing activity of atmospherically relevant ice-nucleating particles. However, an intercomparison of these laboratory results is a difficult task because investigators have used different ice nucleation (IN) measurement methods to produce these results. A remaining challenge is to explore the sensitivity and accuracy of these techniques and to understand how the IN results are potentially influenced or biased by experimental parameters associated with these techniques.Within the framework of INUIT (Ice Nuclei Research Unit), we distributed an illite-rich sample (illite NX) as a representative surrogate for atmospheric mineral dust particles to investigators to perform immersion freezing experiments using different IN measurement methods and to obtain Published by Copernicus Publications on behalf of the European Geosciences Union. N. Hiranuma et al.: A comparison of 17 IN measurement techniquesIN data as a function of particle concentration, temperature (T ), cooling rate and nucleation time. A total of 17 measurement methods were involved in the data intercomparison. Experiments with seven instruments started with the test sample pre-suspended in water before cooling, while 10 other instruments employed water vapor condensation onto drydispersed particles followed by immersion freezing. The resulting comprehensive immersion freezing data set was evaluated using the ice nucleation active surface-site density, n s , to develop a representative n s (T ) spectrum that spans a wide temperature range (−37 • C < T < −11 • C) and covers 9 orders of magnitude in n s .In general, the 17 immersion freezing measurement techniques deviate, within a range of about 8 • C in terms of temperature, by 3 orders of magnitude with respect to n s . In addition, we show evidence that the immersion freezing efficiency expressed in n s of illite NX particles is relatively independent of droplet size, particle mass in suspension, particle size and cooling rate during freezing. A strong temperature dependence and weak time and size dependence of the immersion freezing efficiency of illite-rich clay mineral particles enabled the n s parameterization solely as a function of temperature. We also characterized the n s (T ) spectra and identified a section with a steep slope between −20 and −27 • C, where a large fraction of active sites of our test dust may trigger immersion freezing. This slope was followed by a region with a gentler slope at temperatures below −27 • C. While the agreement between different instruments was reasonable below ∼ −27 • C, there seemed to be a different trend in the temperature-dependent ice nucleation activity from the suspension and dry-dispersed particle measurements for this mineral dust, in particular at higher temperatures. For instance,...

Tauopathies are widespread neurodegenerative disorders characterised by the intracellular accumulation of hyperphosphorylated tau. Especially in Alzheimer's disease, pathological alterations in the retina are discussed as potential biomarkers to improve early diagnosis of the disease. Using mice expressing human mutant P301S tau, we demonstrate for the first time a straightforward optical approach for the in vivo detection of fibrillar tau in the retina. Longitudinal examinations of individual animals revealed the fate of single cells containing fibrillar tau and the progression of tau pathology over several months. This technique is most suitable to monitor therapeutic interventions aimed at reducing the accumulation of fibrillar tau. In order to evaluate if this approach can be translated to human diagnosis, we tried to detect fibrillar protein aggregates in the post-mortem retinas of patients that had suffered from Alzheimer's disease or Progressive Supranuclear Palsy. Even though we could detect hyperphosphorylated tau, we did not observe any fibrillar tau or Aß aggregates. In contradiction to previous studies, our observations do not support the notion that Aβ or tau in the retina are of diagnostic value in Alzheimer's disease.

The consequences of O-acetylated alginate-producing Pseudomonas aeruginosa biofilms in the lungs of chronically infected cystic fibrosis (CF) patients are tolerance to both antibiotic treatments and effects on the innate and the adaptive defense mechanisms. In clinical trials, azithromycin (AZM) has been shown to improve the lung function of CF patients. The present study was conducted in accordance with previous in vitro studies suggesting that the effect of AZM may be the inhibition of alginate production, blockage of quorum sensing (QS), and increased sensitivity to hydrogen peroxide and the complement system. Moreover, we show that AZM may affect the polymerization of P. aeruginosa alginate by the incomplete precipitation of polymerized alginate and high levels of readily dialyzable uronic acids. In addition, we find that mucoid bacteria in the stationary growth phase became sensitive to AZM, whereas cells in the exponential phase did not. Interestingly, AZM-treated P. aeruginosa lasI mutants appeared to be particularly resistant to serum, whereas bacteria with a functional QS system did not. We show in a CF mouse model of chronic P. aeruginosa lung infection that AZM treatment results in the suppression of QS-regulated virulence factors, significantly improves the clearance of P. aeruginosa alginate biofilms, and reduces the severity of the lung pathology compared to that in control mice. We conclude that AZM attenuates the virulence of P. aeruginosa, impairs its ability to form fully polymerized alginate biofilms, and increases its sensitivity to complement and stationary-phase killing, which may explain the clinical efficacy of AZM.Mucoid Pseudomonas aeruginosa plays an important role in chronic lung infections among patients with CF due to its ability to form alginate-producing biofilms, which enable the bacteria to resist treatments with antibiotics and which affect the actions of the cells of the immune system (23). Macrolides such as azithromycin (AZM) are normally used against grampositive bacteria, whereas many gram-negative rods, such as Pseudomonas spp., are inherently resistant to macrolides (56). However, several clinical studies from Japan (36, 39, 65) have highlighted the beneficial effects of different macrolides, including AZM, in the treatment of patients with diffuse panbronchiolitis, a disease which is very similar to CF. The first indication that AZM therapy could also benefit the lung function in CF patients was given by Jaffe et al. (27) and was subsequently confirmed by other investigators (9,16,58,74). The mechanisms of action macrolides are multiple and may include an anti-inflammatory effect (36, 40), inhibition of a key enzyme in the alginate synthesis pathway (47), modulation of the production of quorum-sensing (QS) bacterial virulence factors (33,44,69), and/or inhibition of protein synthesis after prolonged exposure (67, 68).In P. aeruginosa, the production of several virulence factors is regulated by cell-to-cell communication, based on the lasand rhl-encoded QS systems (6), w...