Genome-wide association studies (GWAS) with intermediate phenotypes, like changes in metabolite and protein levels, provide functional evidence to map disease associations and translate them into clinical applications. However, although hundreds of genetic variants have been associated with complex disorders, the underlying molecular pathways often remain elusive. Associations with intermediate traits are key in establishing functional links between GWAS-identified risk-variants and disease end points. Here we describe a GWAS using a highly multiplexed aptamer-based affinity proteomics platform. We quantify 539 associations between protein levels and gene variants (pQTLs) in a German cohort and replicate over half of them in an Arab and Asian cohort. Fifty-five of the replicated pQTLs are located in trans. Our associations overlap with 57 genetic risk loci for 42 unique disease end points. We integrate this information into a genome-proteome network and provide an interactive web-tool for interrogations. Our results provide a basis for novel approaches to pharmaceutical and diagnostic applications.
SUMMARYParticle size distributions measured by the UK C-130 aircraft in ice stratiform cloud around the British Isles are analysed. Probability distribution functions over large scales show that the zeroth, second and fourth moments (equivalent to concentration, ice water content and radar reflectivity) as well as mean particle size have monomodal distributions. Rescaling of the size distributions requiring knowledge of two moments reveals a 'universal' distribution that has been fitted with analytically integrable functions. The existence of the 'universal' distribution implies that two-moment microphysics schemes are adequate to represent particle size distributions (PSDs). In large-scale models it may be difficult to predict two moments, and so power laws between moments have been found as functions of in-cloud temperature. This means that a model capable of predicting ice water content and temperature can predict ice PSDs to use for calculations requiring knowledge of the size distribution (e.g. precipitation rate, radar reflectivity) or to make direct use of the power laws relating moments of the size distribution.
Abstract. The deposition mode ice nucleation efficiency of various dust aerosols was investigated at cirrus cloud temperatures between 196 and 223 K using the aerosol and cloud chamber facility AIDA (Aerosol Interaction and Dynamics in the Atmosphere). Arizona test dust (ATD) as a reference material and two dust samples from the Takla Makan desert in Asia (AD1) and the Sahara (SD2) were used for the experiments at simulated cloud conditions. The dust particle sizes were almost lognormally distributed with mode diameters between 0.3 and 0.5 µm and geometric standard deviations between 1.6 and 1.9. Deposition ice nucleation was most efficient on ATD particles with ice-active particle fractions of about 0.6 and 0.8 at an ice saturation ratio S i <1.15 and temperatures of 223 and 209 K, respectively. No significant change of the ice nucleation efficiency was found in up to three subsequent cycles of ice activation and evaporation with the same ATD aerosol. This indicates that the phenomenon of preactivation does not apply to ATD particles. The desert dust samples SD2 and AD1 showed a significantly lower fraction of active deposition nuclei, about 0.25 at 223 K and S i <1.35. For all samples the ice activated aerosol fraction could be approximated by an exponential equation as function of S i . This indicates that deposition ice nucleation on mineral particles may not be treated in the same stochastic sense as homogeneous freezing. The suggested formulation of ice activation spectra may be used to calculate the formation rate of ice crystals in models, if the number concentration of dust particles is known. More experimental work is needed to quantify the variability of the Correspondence to: O. Möhler (ottmar.moehler@imk.fzk. de) ice activation spectra as function of the temperature and dust particle properties.
The Cirrus Parcel Model Comparison Project, a project of the GCSS [Global Energy and Water Cycle Experiment (GEWEX) Cloud System Studies] Working Group on Cirrus Cloud Systems, involves the systematic comparison of current models of ice crystal nucleation and growth for specified, typical, cirrus cloud environments. In Phase 1 of the project reported here, simulated cirrus cloud microphysical properties from seven models are compared for ''warm'' (Ϫ40ЊC) and ''cold'' (Ϫ60ЊC) cirrus, each subject to updrafts of 0.04, 0.2, and 1 m s Ϫ1. The models employ explicit microphysical schemes wherein the size distribution of each class of particles (aerosols and ice crystals) is resolved into bins or the evolution of each individual particle is traced. Simulations are made including both homogeneous and heterogeneous ice nucleation mechanisms (all-mode simulations). A single initial aerosol population of sulfuric acid particles is prescribed for all simulations. Heterogeneous nucleation is disabled for a second parallel set of simulations in order to isolate the treatment of the homogeneous freezing (of haze droplets) nucleation process. Analysis of these latter simulations is the primary focus of this paper. Qualitative agreement is found for the homogeneous-nucleation-only simulations; for example, the number density of nucleated ice crystals increases with the strength of the prescribed updraft. However, significant quantitative differences are found. Detailed analysis reveals that the homogeneous nucleation rate, haze particle solution concentration, and water vapor uptake rate by ice crystal growth (particularly as controlled by the deposition coefficient) are critical components that lead to differences in the predicted microphysics. Systematic differences exist between results based on a modified classical theory approach and models using an effective freezing temperature approach to the treatment of nucleation. Each method is constrained by critical freezing data from laboratory studies, but each includes assumptions that can only be justified by further laboratory research. Consequently, it is not yet clear if the two approaches can be made consistent. Large haze particles may deviate considerably from equilibrium size in moderate to strong updrafts (0.2-1 m s Ϫ1) at Ϫ60ЊC. The equilibrium assumption is commonly invoked in cirrus parcel models. The resulting difference in particlesize-dependent solution concentration of haze particles may significantly affect the ice particle formation rate during the initial nucleation interval. The uptake rate for water vapor excess by ice crystals is another key component regulating the total number of nucleated ice crystals. This rate, the product of particle number concentration and ice crystal diffusional growth rate, which is particularly sensitive to the deposition coefficient when ice particles are small, modulates the peak particle formation rate achieved in an air parcel and the duration of the active nucleation time period. The consequent differences in cloud microphys...
Abstract. The deposition mode ice nucleation efficiency of various dust aerosols was investigated at cirrus cloud temperatures between 196 K and 223 K using the aerosol chamber facility AIDA (Aerosol Interaction and Dynamics in the Atmosphere). Arizona test dust (ATD) as a reference material and two dust samples from the Takla Makan desert in Asia (AD1) and Sahara (SD2) were used for the experiments at simulated cloud conditions. The dust particle sizes were almost lognormally distributed with mode diameters between 0.3 µm and 0.5 µm and geometric standard deviations between 1.6 and 1.9. Deposition ice nucleation was most efficient on ATD particles with ice-active particle fractions of about 0.6 and 0.8 at an ice saturation ratio Si<1.15 and temperatures of 223 K and 209 K, respectively. No significant change of the ice nucleation efficiency was found in up to three subsequent cycles of ice activation and evaporation with the same ATD aerosol. The desert dust samples SD2 and AD1 showed a significantly lower fraction of active deposition nuclei, about 0.25 at 223 K and Si<1.35. For all samples the ice activated aerosol fraction could be approximated by an exponential equation as function of Si. This formulation of ice activation spectra may be used to calculate the formation rate of ice crystals in models, if the number concentration of dust particles is known. More experimental work is needed to quantify the variability of the ice activation spectra as function of the temperature and dust particle properties.
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