Defining the role of common variation in the genomic and biological architecture of adult human height

Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated 1/42,000, 1/43,700 and 1/49,500 SNPs explained 1/421%, 1/424% and 1/429% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/I 2-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants.

New genetic loci link adipose and insulin biology to body fat distribution

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.

Genetic studies of body mass index yield new insights for obesity biology

Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.

Fluence dependence of the surface roughness of InP after N2 + bombardment

InP(1 0 0) surfaces were sputtered under ultrahigh vacuum conditions by 5 keV N2+ ions at an angle of incidence of 41° to the sample normal. The fluence, φ, used in this study, varied from 1 × 10¹⁴ to 5 × 10¹⁸ N2+ cm^-2. The surface topography was investigated using field emission scanning electron microscopy (FE-SEM) and atomic force microscopy (AFM). At the lower fluences (φ ≤ 5 × 10¹⁶ N2+ cm^-2) only conelike features appeared, similar in shape as was found for noble gas ion bombardment of InP. At the higher fluences, ripples also appeared on the surface. The bombardment-induced topography was quantified using the rms roughness. This parameter showed a linear relationship with the logarithm of the fluence. A model is presented to explain this relationship. The ripple wavelength was also determined using a Fourier transform method. These measurements as a function of fluence do not agree with the predictions of the Bradley-Harper theory. © 2004 Elsevier B.V. All rights reserved.

Development of a Diffuse Reflectance Infrared Fourier Transform Spectroscopy (DRIFTS) Cell for the In Situ Analysis of Co-Electrolysis in a Solid Oxide Cell

Co-electrolysis of carbon dioxide and steam has been shown to be an efficient way to produce syngas, however further optimisation requires detailed understanding of the complex reactions, transport processes and degradation mechanisms occurring in the solid oxide cell (SOC) during operation. Whilst electrochemical measurements are currently conducted in situ, many analytical techniques can only be used ex situ and may even be destructive to the cell (e.g. SEM imaging of microstructure). In order to fully understand and characterise co-electrolysis, in situ monitoring of the reactants, products and SOC is necessary. Diffuse Reflectance Infrared Fourier Transform Spectroscopy (DRIFTS) is ideal for in situ monitoring of co-electrolysis as both gaseous and adsorbed CO and CO2 species can be detected, however it has previously not been used for this purpose. The challenges of designing an experimental rig which allows optical access alongside electrochemical measurements at high temperature and operates in a dual atmosphere are discussed. The rig developed has thus far been used for symmetric cell testing at temperatures from 450[degree]C to 600[degree]C. Under a CO atmosphere, significant changes in spectra were observed even over a simple Au|10Sc1CeSZ|Au SOC. The changes relate to a combination of CO oxidation, the water gas shift reaction and carbonate formation and decomposition processes, with the dominant process being both potential and temperature dependent.

CO2 Capture in Wet and Dry Superbase Ionic Liquids

The solubility of carbon dioxide in five tetraalkylphosphonium superbase ionic liquids, namely the trihexyltetradecylphoshonium phenoxide, trihexyltetradecylphoshonium benzotriazolide, trihexyltetradecylphoshonium benzimidazolide, trihexyltetradecylphoshonium 1,2,3-triazolide, and trihexyltetradecylphoshonium 1,2,4-triazolide was studied experimentally under dry and wet conditions at 22 A degrees C and at atmospheric pressure, using a gravimetric saturation technique. The effects of anion structure and of the presence or absence of water in the solution on the carbon dioxide solubility were then deduced from the data. H-1 and C-13-NMR spectroscopy and ab initio calculations were also conducted to probe the interactions in these solutions, as carbon dioxide and water can compete in the ionic liquid structure during the absorption process. Additionally, the viscosity of selected superbase ionic liquids was measured under dry and wet conditions, in the presence or absence of CO2, to evaluate their practical application in carbon dioxide capture processes. Finally, the recyclability of the trihexyltetradecylphoshonium 1,2,4-triazolide under dry and wet conditions was determined to probe the ability of selected solvents to solubilize chemically a high concentration of carbon dioxide and then release it in a low energy demand process.

On the Performances of Ionic Liquid-Based Electrolytes for Li-NMC Batteries

Herein, the N-butyl-N-methylpyrrolidinium bis(fluorosulfonyl)amide and the N-propyl-N-methylpyrrolidinium bis(fluorosulfonyl)amide room temperature ionic liquids, combined with the lithium bis(trifluoromethanesulfonyl)amide salt, are investigated as electrolytes for Li/LiNi1/3Mn1/3Co1/3O2 (Li/NMC) batteries. To conduct this study, volumetric properties, ionic conductivity and viscosity of the pure ionic liquids and selected electrolytes were firstly determined as a function of temperature and composition in solution. These data were then compared with those measured in the case of the standard alkyl carbonate-based electrolyte: e.g. the EC/PC/3DMC + 1 mol·L−1 LiPF6. The compatibility of the selected electrolytes with the lithium electrode was then investigated by following the evolution of Li/electrolyte interfaces through impedance measurements. Interestingly, the impedances of the investigated Li/electrolyte interfaces were found to be more than three times lower than that measured using the standard electrolyte. Finally, electrochemical performances of the ionic liquid-based electrolytes were investigated using galvanostatic charge and discharge and cyclic voltammetry of each Li/NMC cell. Using these electrolytes, each tested Li cell reaches up to 145 mA·h·g−1 at C/10 and 110 mA·h·g−1 at C with a coulombic efficiency close to 100 %.

Thermodynamic Properties of Dichloromethane, Bromochloromethane, and Dibromomethane under Elevated Pressure: Experimental Results and SAFT-VR Mie Predictions

The speeds of sound in dibromomethane, bromochloromethane, and dichloromethane have been measured in the temperature range from 293.15 to 313.15 K and at pressures up to 100 MPa. Densities and isobaric heat capacities at atmospheric pressure have been also determined. Experimental results were used to calculate the densities and isobaric heat capacities as the function of temperature and pressure by means of a numerical integration technique. Moreover, experimental data at atmospheric pressure were then used to determine the SAFT-VR Mie molecular parameters for these liquids. The accuracy of the model has been then evaluated using a comparison of derived experimental high-pressure data with those predicted using SAFT. It was found that the model provide the possibility to predict also the isobaric heat capacity of all selected haloalkanes within an error up to 6%.

Enhancing Liquid-Phase Olefin-Paraffin Separations Using Novel Silver-Based Ionic Liquids

This paper describes the extraction of C5-C8 linear α-olefins from olefin/paraffin mixtures of the same carbon number using silver(I)/N,N-dimethylbenzamide bis(trifluoromethylsulfonyl)imide ([Ag(DMBA)₂][Tf₂N]) or silver(I)/propylamine bis(trifluoromethylsulfonyl)imide ([Ag(PrNH₂)₂][Tf₂N]) as the extracting agent. The separation performance of the system increased with increasing chain length. [Ag(DMBA)₂][Tf₂N] appeared to outperform [Ag(PrNH₂)₂][Tf₂N] in terms of both selectivity and distribution coefficient. The [Ag(DMBA)₂][Tf₂N] system was successfully modeled using the universal quasi-chemical activity coefficient (UNIQUAC) model. These results support the potential future development of amine/amide-based ligands for producing soluble silver complexes useful for the separation of olefins from paraffins.

Chaotropicity: a key factor in product tolerance of biofuel-producing microorganisms

Fermentation products can chaotropically disorder macromolecular systems and induce oxidative stress, thus inhibiting biofuel production. Recently, the chaotropic activities of ethanol, butanol and vanillin have been quantified (5.93, 37.4, 174kJkg(-1)m(-1) respectively). Use of low temperatures and/or stabilizing (kosmotropic) substances, and other approaches, can reduce, neutralize or circumvent product-chaotropicity. However, there may be limits to the alcohol concentrations that cells can tolerate; e.g. for ethanol tolerance in the most robust Saccharomyces cerevisiae strains, these are close to both the solubility limit (<25%, w/v ethanol) and the water-activity limit of the most xerotolerant strains (0.880). Nevertheless, knowledge-based strategies to mitigate or neutralize chaotropicity could lead to major improvements in rates of product formation and yields, and also therefore in the economics of biofuel production.

Acoustic and Volumetric Properties of Diluted Solutions of Water in Ionic Liquids

Herein, we report the densities and speeds of sound in binary mixtures of three hydrophobic and one hydrophilic ionic liquids: 1-butyl-3-methylimidazolium bis[(trifluoromethyl)sulfonyl]imide, [C4mim][NTf2], 1-butyl-1-methylpyrrolidinium bis[(trifluoromethyl)sulfonyl]imide, [C4mpyr][NTf2], 1-propyl-3-methylimidazolium bis[(trifluoromethyl)sulfonyl]imide, [C3mim][NTf2] and 1-ethyl-3-methylimidazolium thiocyanate, [C2mim][SCN], with water at 298.15 K and 0.1 MPa. The concentration range of water, which encompassed relatively small values well below the saturation point, is often regarded as an impurity for hydrophobic ionic liquids. On the basis of experimental results the molar volume, adiabatic molar compressibility, partial molar volume and apparent molar volume, as well as, partial molar and apparent molar isentropic compressibility properties were then calculated. Interesting results are obtained using the solutions based on the hydrophilic [C2mim][SCN], since these mixtures are characterized by relatively low density and high values of speed of sound. Furthermore, the partial molar volumes and partial molar adiabatic compressibilities of water in solution with [C2mim][SCN] are the lowest among the investigated in mixtures with ionic liquids. However, in the case of the hydrophobic ionic liquid solutions, only small differences are observed for molar adiabatic compressibilities with the change of the cation structure, i.e. for water + [C4mim][NTf2] or + [C4mpyr][NTf2]. A more pronounced difference has been observed for the partial molar compressibility of water in solutions with these two ionic liquids.

Thermal Properties of Alkyl-triethylammonium bis{(trifluoromethyl)sulfonyl}imide Ionic Liquids

In this work, we address the thermal properties of selected members of a
homologous series of alkyltriethylammonium bisf(trifluoromethyl)sulfonylgimide ionic
liquids. Their phase and glass transition behavior, as well as their standard isobaric heat
capacities at 298.15 K, were studied using differential scanning calorimetry (DSC),
whereas their decomposition temperature was determined by thermal gravimetry analysis.
DSC was further used to measure standard molar heat capacities of the studied ionic liquids
and standard molar heat capacity as a function of temperature for hexyltriethylammonium,
octyltriethylammonium, and dodecyltriethylammonium bisf(trifluoromethyl)sulfonylgimide
ionic liquids. Based on the data obtained, we discuss the influence of the alkyl chain
length of the cation on the studied ionic liquids on the measured properties. Using viscosity
data obtained in a previous work, the liquid fragility of the ionic liquids is then discussed.
Viscosity data were correlated by the VTF equation using a robust regression along a
gnostic influence function. In this way, more reliable VTF model parameters were obtained than in our previous work and a good estimate of the liquid fragility of the ionic liquids was made.

Social Services of General Interest: The EU Competence Regime and a Constitution of Social Governance

In discussing the potential role of the EU, the Member States, their composite parts and civil society organisations in establishing social services of general interest at sub-national, national, transnational and EU wide levels, this chapter explores the EU competence regime for social services of general interest. Its analysis contradicts a tendency in academic writing to demand protection of national prerogatives for shaping welfare states against EU intervention at all costs, because this would be counterproductive for the progress of the EU project. It submits that an EU constitution of social governance should create mixed responsibilities so that the EU, states and civil society actors support each other in creating preconditions for social integration in the EU. It uses the field of social services of general interests as an example of applying this general theoretical concept.

Solid–liquid equilibria in systems [Cxmim][Tf2N] with diethylamine

In the present work, the solid–liquid–liquid equilibrium in the binary system of diethylamine (1) and ionic liquid (2) 1-methyl-3-ethylimidazolium bis(trifluoromethylsulfonyl)imide and solid–liquid equilibrium in system 1-methyl-3-butylimidazolium bis(trifluoromethylsulfonyl)imide was studied. Phase equilibrium was determined experimentally by means of a polythermic method. These data were then used to determine the activity coefficients for both ionic liquids. For the pure diethylamine the enthalpy of fusion was determined by differential scanning calorimetry, because to the best of our knowledge, this data is not yet reported in the open literature, a contrario of pure ionic liquids tested during this work.