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In the present work, the evolution of the boundary layer over a low-pressure turbine blade is studied using direct numerical simulations, with the aim of investigating the unsteady flow field induced by the rotor-stator interaction. The freestream flow is characterized by the high level of freestream turbulence and periodically impinging wakes. As in the experiments, the wakes are shed by moving bars modeling the rotor blades and placed upstream of the turbine blades. To include the presence of the wake without employing an ad-hoc model, we simulate both the moving bars and the stationary blades in their respective frames of reference and the coupling of the two domains is done through appropriate boundary conditions. The presence of the wake mainly affects the development of the boundary layer on the suction side of the blade. In particular, the flow separation in the rear part of the blade is suppressed. Moreover, the presence of the wake introduces alternating regions in the streamwise direction of high- and low-velocity fluctuations inside the boundary layer. These fluctuations are responsible for significant variations of the shear stress. The analysis of the velocity fields allows the characterization of the streaky structures forced in the boundary layer by turbulence carried by upstream wakes. The breakdown events are observed once positive streamwise velocity fluctuations reach the end of the blade. Both the fluctuations induced by the migration of the wake in the blade passage and the presence of the streaks contribute to high values of the disturbance velocity inside the boundary layer with respect to a steady inflow case. The amplification of the boundary layer disturbances associated with different spanwise wavenumbers has been computed. It was found that the migration of the wake in the blade passage stands for the most part of the perturbations with zero spanwise wavenumber. The non-zero wavenumbers are found to be amplified in the rear part of the blade at the boundary between the low- and high-speed regions associated with the wakes.

BackgroundIgG4 is associated with two emerging groups of rare diseases: 1) IgG4 autoimmune diseases (IgG4-AID) and 2) IgG4-related diseases (IgG4-RLD). Anti-neuronal IgG4-AID include MuSK myasthenia gravis, LGI1- and Caspr2-encephalitis and autoimmune nodo-/paranodopathies (CNTN1 or NF155 antibodies). IgG4-RLD is a multiorgan disease hallmarked by tissue-destructive fibrotic lesions with lymphocyte and IgG4 plasma cell infiltrates and increased serum IgG4 concentrations. It is unclear, whether IgG4-AID and IgG4-RLD share relevant clinical and immunopathological features.MethodsWe collected and analysed serological, clinical, and histopathological data in 50 patients with anti-neuronal IgG4-AID and 16 patients with IgG4-RLD.ResultsA significantly higher proportion of IgG4-RLD patients had serum IgG4 elevation when compared to IgG4-AID patients (50% vs. 16%, p = .015). Moreover, those IgG4-AID patients with elevated IgG4 did not meet the diagnostic criteria of IgG4-RLD, and their autoantibody titres did not correlate with their serum IgG4 concentrations. In addition, patients with IgG4-RLD were negative for anti-neuronal/neuromuscular autoantibodies and among these patients, men showed a significantly higher propensity for IgG4 elevation, when compared to women (p = .041). Last, a kidney biopsy from a patient with autoimmune paranodopathy due to CNTN1/Caspr1-complex IgG4 autoantibodies and concomitant nephrotic syndrome did not show fibrosis or IgG4+ plasma cells, which are diagnostic hallmarks of IgG4-RLD.ConclusionOur observations suggest that anti-neuronal IgG4-AID and IgG4-RLD are most likely distinct disease entities.

A field measurement campaign was conducted from June to October 2009 in a 20 km2 catchment of the Swiss Alps with a wireless network of 12 weather stations and river discharge monitoring. The objective was to investigate the spatial variability of meteorological forcing and to assess its impact on streamflow generation. The analysis of the runoff dynamics highlighted the important contribution of snowmelt from spring to early summer. During the entire experimental period the streamflow discharge was dominated by base flow contributions with temporal variations due to occasional rainfallrunoff events and a regular contribution from glacier melt. Given the importance of snow and ice melt runoff in this catchment patterns of near surface air temperatures were studied in detail. Statistical data analyses revealed that meteorological variables inside the watershed exhibit spatial variability. Air temperatures were influenced by topographic effects such as slope aspect and elevation. Rainfall was found to be spatially variable inside the catchment. The impact of this variability on streamflow generation was assessed using a lumped degree day model. Despite the variability within the watershed the streamflow discharge could be described using the lumped model. The novelty of this work mainly consists in quantifying spatial variability for a small watershed and showing to which extent this is important. When the focus is on aggregated outputs such as streamflow discharge average values of meteorological forcing can be adequately used. On the contrary when the focus is on distributed fields such as evaporation or soil moisture their estimate can benefit from distributed measurements.

The model repository (MREP) is a relational database management system (RDBMS) developed under the auspices of models of infectious disease agent study (MIDAS). The purpose of the MREP is to organize and catalog the models, results, and suggestions for using the MIDAS and to store them in a way to allow users to run models from an access-controlled disease MREP. The MREP contains source and object code of disease models developed by infectious disease modelers and tested in a production environment. Different versions of models used to describe various aspects of the same disease are housed in the repository. Models are linked to their developers and different versions of the codes are tied to Subversion, a version control tool. An additional element of the MREP will be to house, manage, and control access to a disease model results warehouse, which consists of output generated by the models contained in the MREP. The result tables and files are linked to the version of the model and the input parameters that collectively generated the results. The result tables are warehoused in a relational database that permits them to be easily identified, categorized, and downloaded.

Nine retinoid analogues were synthesized and their effects on cell proliferation and differentiation of tumor cell lines were analysed and compared with those of natural retinoids (retinoic acid, retinol, retinal). Our results demonstrate differential inhibitory effects of the synthetic retinoids on cell growth. This inhibitory activity of the synthetic retinoids was, in some cases, higher than that of retinoic acid and retinol. Natural and synthetic retinoids were found to be able to induce to a different extent erythroid differentiation of murine erythroleukemia cells and adipogenic conversion of Chinese Hamster FHO6N1-1 cells. Our data suggest that studies on the relationship between structure and biological activity could be approached by using the analysed synthetic retinoids.

To further explore the SAR of resveratrol-related trans-stilbene derivatives, here we describe the synthesis of (a) a series of 3,5-dimethoxy analogues in which a variety of substituents were introduced at positions 2', 3', 4', and 5' of the stilbene scaffold and (b) a second group of derivatives (2-phenylnaphthalenes and terphenyls) that incorporate a phenyl ring as a bioisosteric replacement of the stilbene alkenyl bridge. We thoroughly characterized all of the new compounds with respect to their apoptosis-inducing activity and their effects on the cell cycle. One of the new derivatives, 13g, behaved differently from the others, as it was able to block the cell cycle in the G(0)-G(1) phase and also to induce differentiation in acute myelogenous leukemia HL60 cells. Compared to resveratrol, the synthetic terphenyl 13g showed a more potent apoptotic and differentiating activity. Moreover, it was active on both multidrug resistance and Bcr-Abl-expressing cells that were resistant to resveratrol.

Pterostilbene and 3,5-hydroxypterostilbene are the natural 3,5-dimethoxy analogs of trans-resveratrol and piceatannol, two compounds which can induce apoptosis in tumor cells. In previous studies we demonstrated the importance of a 3,5-dimethoxy motif in conferring pro-apoptotic activity to stilbene based compounds so we now wanted to evaluate the ability of pterostilbene and 3,5-hydroxypterostilbene in inducing apoptosis in sensitive and resistant leukemia cells. When tested in sensitive cell lines, HL60 and HUT78, 3'-hydroxypterostilbene was 50-97 times more potent than trans-resveratrol in inducing apoptosis, while pterostilbene appeared barely active. However, both compounds, but not trans-resveratrol and piceatannol, were able to induce apoptosis in the two Fas-ligand resistant lymphoma cell lines, HUT78B1 and HUT78B3, and the multi drug-resistant leukemia cell lines HL60-R and K562-ADR (a Bcr-Abl-expressing cell line resistant to imatinib mesylate). Of note, pterostilbene-induced apoptosis was not inhibited by the pancaspase-inhibitor Z-VAD-fmk, suggesting that this compound acts through a caspase-independent pathway. On the contrary, 3'-hydroxypterostilbene seemed to trigger apoptosis through the intrinsic apoptotic pathway: indeed, it caused a marked disruption of the mitochondrial membrane potential delta psi and its apoptotic effects were inhibited by Z-VAD-fmk and the caspase-9-inhibitor Z-LEHD-fmk. Moreover, pterostilbene and 3'-hydroxypterostilbene, when used at concentrations that elicit significant apoptotic effects in tumor cell lines, did not show any cytotoxicity in normal hemopoietic stem cells. In conclusion, our data show that pterostilbene and particularly 3'-hydroxypterostilbene are interesting antitumor natural compounds that may be useful in the treatment of resistant hematological malignancies, including imatinib, non-responsive neoplasms.