Condition number estimates for combined potential integral operators in acoustics and their boundary element discretisation

We consider the classical coupled, combined-field integral equation formulations for time-harmonic acoustic scattering by a sound soft bounded obstacle. In recent work, we have proved lower and upper bounds on the $L^2$ condition numbers for these formulations, and also on the norms of the classical acoustic single- and double-layer potential operators. These bounds to some extent make explicit the dependence of condition numbers on the wave number $k$, the geometry of the scatterer, and the coupling parameter. For example, with the usual choice of coupling parameter they show that, while the condition number grows like $k^{1/3}$ as $k\to\infty$, when the scatterer is a circle or sphere, it can grow as fast as $k^{7/5}$ for a class of `trapping' obstacles. In this paper we prove further bounds, sharpening and extending our previous results. In particular we show that there exist trapping obstacles for which the condition numbers grow as fast as $\exp(\gamma k)$, for some $\gamma>0$, as $k\to\infty$ through some sequence. This result depends on exponential localisation bounds on Laplace eigenfunctions in an ellipse that we prove in the appendix. We also clarify the correct choice of coupling parameter in 2D for low $k$. In the second part of the paper we focus on the boundary element discretisation of these operators. We discuss the extent to which the bounds on the continuous operators are also satisfied by their discrete counterparts and, via numerical experiments, we provide supporting evidence for some of the theoretical results, both quantitative and asymptotic, indicating further which of the upper and lower bounds may be sharper.

Sustainable urban metabolism as a link between bio-physical sciences and urban planning: the BRIDGE project

Urban metabolism considers a city as a system with flows of energy and material between it and the environment. Recent advances in bio-physical sciences provide methods and models to estimate local scale energy, water, carbon and pollutant fluxes. However, good communication is required to provide this new knowledge and its implications to endusers (such as urban planners, architects and engineers). The FP7 project BRIDGE (sustainaBle uRban plannIng Decision support accountinG for urban mEtabolism) aimed to address this gap by illustrating the advantages of considering these issues in urban planning. The BRIDGE Decision Support System (DSS) aids the evaluation of the sustainability of urban planning interventions. The Multi Criteria Analysis approach adopted provides a method to cope with the complexity of urban metabolism. In consultation with targeted end-users, objectives were defined in relation to the interactions between the environmental elements (fluxes of energy, water, carbon and pollutants) and socioeconomic components (investment costs, housing, employment, etc.) of urban sustainability. The tool was tested in five case study cities: Helsinki, Athens, London, Florence and Gliwice; and sub-models were evaluated using flux data selected. This overview of the BRIDGE project covers the methods and tools used to measure and model the physical flows, the selected set of sustainability indicators, the methodological framework for evaluating urban planning alternatives and the resulting DSS prototype.

Six new loci associated with body mass index highlight a neuronal influence on body weight regulation

Common variants at only two loci, FTO and MC4R, have been reproducibly associated with body mass index (BMI) in humans. To identify additional loci, we conducted meta-analysis of 15 genome-wide association studies for BMI (n > 32,000) and followed up top signals in 14 additional cohorts (n > 59,000). We strongly confirm FTO and MC4R and identify six additional loci (P < 5 x 10(-8)): TMEM18, KCTD15, GNPDA2, SH2B1, MTCH2 and NEGR1 (where a 45-kb deletion polymorphism is a candidate causal variant). Several of the likely causal genes are highly expressed or known to act in the central nervous system (CNS), emphasizing, as in rare monogenic forms of obesity, the role of the CNS in predisposition to obesity.

Evaluation of seven European aerosol optical depth retrieval algorithms for climate analysis

Satellite data are increasingly used to provide observation-based estimates of the effects of aerosols on climate. The Aerosol-cci project, part of the European Space Agency's Climate Change Initiative (CCI), was designed to provide essential climate variables for aerosols from satellite data. Eight algorithms, developed for the retrieval of aerosol properties using data from AATSR (4), MERIS (3) and POLDER, were evaluated to determine their suitability for climate studies. The primary result from each of these algorithms is the aerosol optical depth (AOD) at several wavelengths, together with the Ångström exponent (AE) which describes the spectral variation of the AOD for a given wavelength pair. Other aerosol parameters which are possibly retrieved from satellite observations are not considered in this paper. The AOD and AE (AE only for Level 2) were evaluated against independent collocated observations from the ground-based AERONET sun photometer network and against “reference” satellite data provided by MODIS and MISR. Tools used for the evaluation were developed for daily products as produced by the retrieval with a spatial resolution of 10 × 10 km2 (Level 2) and daily or monthly aggregates (Level 3). These tools include statistics for L2 and L3 products compared with AERONET, as well as scoring based on spatial and temporal correlations. In this paper we describe their use in a round robin (RR) evaluation of four months of data, one month for each season in 2008. The amount of data was restricted to only four months because of the large effort made to improve the algorithms, and to evaluate the improvement and current status, before larger data sets will be processed. Evaluation criteria are discussed. Results presented show the current status of the European aerosol algorithms in comparison to both AERONET and MODIS and MISR data. The comparison leads to a preliminary conclusion that the scores are similar, including those for the references, but the coverage of AATSR needs to be enhanced and further improvements are possible for most algorithms. None of the algorithms, including the references, outperforms all others everywhere. AATSR data can be used for the retrieval of AOD and AE over land and ocean. PARASOL and one of the MERIS algorithms have been evaluated over ocean only and both algorithms provide good results.

Improved method for ex ovo-cultivation of developing chicken embryos for human stem cell xenografts

The characterization of human stem cells for the usability in regenerative medicine is particularly based on investigations regarding their differentiation potential in vivo. In this regard, the chicken embryo model represents an ideal model organism. However, the access to the chicken embryo is only achievable by windowing the eggshell resulting in limited visibility and accessibility in subsequent experiments. On the contrary, ex ovo-culture systems avoid such negative side effects. Here, we present an improved ex ovo-cultivation method enabling the embryos to survive 13 days in vitro. Optimized cultivation of chicken embryos resulted in a normal development regarding their size and weight. Our ex ovo-approach closely resembles the development of chicken embryos in ovo, as demonstrated by properly developed nervous system, bones, and cartilage at expected time points. Finally, we investigated the usability of our method for trans-species transplantation of adult stem cells by injecting human neural crest-derived stem cells into late Hamburger and Hamilton stages (HH26-HH28/E5-E6) of ex ovo-incubated embryos. We demonstrated the integration of human cells allowing experimentally easy investigation of the differentiation potential in the proper developmental context. Taken together, this ex ovo-method supports the prolonged cultivation of properly developing chicken embryos enabling integration studies of xenografted mammalian stem cells at late developmental stages.

1,8-Cineol inhibits nuclear translocation of NF-κB p65 and NF-κB-dependent transcriptional activity

Natural plant-derived products are commonly applied to treat a broad range of human diseases, including cancer as well as chronic and acute airway inflammation. In this regard, the monoterpene oxide 1,8-cineol, the active ingredient of the clinically approved drug Soledum®, is well-established for the therapy of airway diseases, such as chronic sinusitis and bronchitis, chronic obstructive pulmonary disease and bronchial asthma. Although clinical trials underline the beneficial effects of 1,8-cineol in treating inflammatory diseases, the molecular mode of action still remains unclear. Here, we demonstrate for the first time a 1,8-cineol-depending reduction of NF-κB-activity in human cell lines U373 and HeLa upon stimulation using lipopolysaccharides (LPS). Immunocytochemistry further revealed a reduced nuclear translocation of NF-κB p65, while qPCR and western blot analyses showed strongly attenuated expression of NF-κB target genes. Treatment with 1,8-cineol further led to increased protein levels of IκBα in an IKK-independent matter, while FRET-analyses showed restoring of LPS-associated loss of interaction between NF-κB p65 and IκBα. We likewise observed reduced amounts of phosphorylated c-Jun N-terminal kinase 1/2 protein in U373 cells after exposure to 1,8-cineol. In addition, 1,8-cineol led to decreased amount of nuclear NF-κB p65 and reduction of its target gene IκBα at protein level in human peripheral blood mononuclear cells. Our findings suggest a novel mode of action of 1,8-cineol through inhibition of nuclear NF-κB p65 translocation via IκBα resulting in decreased levels of proinflammatory NF-κB target genes and may therefore broaden the field of clinical application of this natural drug for treating inflammatory diseases.

An overview on the urban boundary-layer atmosphere network in Helsinki

The Helsinki Urban Boundary-Layer Atmosphere Network (UrBAN: http://urban.fmi.fi) is a dedicated research-grade observational network where the physical processes in the atmosphere above the city are studied. Helsinki UrBAN is the most poleward intensive urban research observation network in the world and thus will allow studying some unique features such as strong seasonality. The network's key purpose is for the understanding of the physical processes in the urban boundary layer and associated fluxes of heat, momentum, moisture, and other gases. A further purpose is to secure a research-grade database, which can be used internationally to validate and develop numerical models of air quality and weather prediction. Scintillometers, a scanning Doppler lidar, ceilometers, a sodar, eddy-covariance stations, and radiometers are used. This equipment is supplemented by auxiliary measurements, which were primarily set up for general weather and/or air-quality mandatory purposes, such as vertical soundings and the operational Doppler radar network. Examples are presented as a testimony to the potential of the network for urban studies, such as (i) evidence of a stable boundary layer possibly coupled to an urban surface, (ii) the comparison of scintillometer data with sonic anemometry above an urban surface, (iii) the application of scanning lidar over a city, and (iv) combination of sodar and lidar to give a fuller range of sampling heights for boundary layer profiling.

Growth factor receptor-bound protein 2 contributes to (hem)immunoreceptor tyrosine-based activation motif-mediated signaling in platelets

Rationale: Platelets are anuclear cell fragments derived from bone marrow megakaryocytes (MKs) that safeguard vascular integrity but may also cause pathological vessel occlusion. One major pathway of platelet activation is triggered by 2 receptors that signal through an (hem)immunoreceptor tyrosine-based activation motif (ITAM), the activating collagen receptor glycoprotein (GP) VI and the C-type lectin-like receptor 2 (CLEC-2). Growth factor receptor–bound protein 2 (Grb2) is a ubiquitously expressed adapter molecule involved in signaling processes of numerous receptors in different cell types, but its function in platelets and MKs is unknown. Objective: We tested the hypothesis that Grb2 is a crucial adapter protein in (hem)immunoreceptor tyrosine-based activation motif signaling in platelets. Methods and Results: Here, we show that genetic ablation of Grb2 in MKs and platelets did not interfere with MK differentiation or platelet production. However, Grb2-deficiency severely impaired glycoprotein VI–mediated platelet activation because of defective stabilization of the linker of activated T-cell (LAT) signalosome and activation of downstream signaling proteins that resulted in reduced adhesion, aggregation, and coagulant activity on collagen in vitro. Similarly, CLEC-2–mediated signaling was impaired in Grb2-deficient platelets, whereas the cells responded normally to stimulation of G protein–coupled receptors. In vivo, this selective (hem)immunoreceptor tyrosine-based activation motif signaling defect resulted in prolonged bleeding times but affected arterial thrombus formation only after concomitant treatment with acetylsalicylic acid, indicating that defective glycoprotein VI signaling in the absence of Grb2 can be compensated through thromboxane A2–induced G protein–coupled receptor signaling pathways. Conclusions: These results reveal an important contribution of Grb2 in (hem)immunoreceptor tyrosine-based activation motif signaling in platelets in hemostasis and thrombosis by stabilizing the LAT signalosome.