Cobalt-Porphyrin Catalyzed Electrochemical Reduction of Carbon Dioxide in Water II: Mechanism from First Principles

We apply first principles computational techniques to analyze the two-electron, multi-step, electrochemical reduction of CO2 to CO in water using cobalt porphyrin as a catalyst. Density Functional Theory calculations with hybrid functionals and dielectric continuum solvation are used to determine the steps at which electrons are added. This information is corroborated with ab initio molecular dynamics simulations in an explicit aqueous environment which reveal the critical role of water in stabilizing a key intermediate formed by CO2 bound to cobalt. Using potential of mean force calculations, the intermediate is found to spontaneously accept a proton to form a carboxylate acid group at pH<9.0, and the subsequent cleavage of a C-OH bond to form CO is exothermic and associated with a small free energy barrier. These predictions suggest that the proposed reaction mechanism is viable if electron transfer to the catalyst is sufficiently fast. The variation in cobalt ion charge and spin states during bond breaking, DFT+U treatment of cobalt 3d orbitals, and the need for computing electrochemical potentials are emphasized.Comment: 33 pages, 7 figure

Intervention effects on dietary intake among children by maternal education level: results of the Copenhagen School Child Intervention Study (CoSCIS)

Dietary intake among Danish children, in general, does not comply with the official recommendations. The objectives of the present study were to evaluate the 3-year effect of a multi-component school-based intervention on nutrient intake in children, and to examine whether an intervention effect depended on maternal education level. A total of 307 children (intervention group: n 184; comparison group: n 123) were included in the present study. All had information on dietary intake pre- and post-intervention (mean age 6·8 and 9·5 years for intervention and comparison groups, respectively) assessed by a 7-d food record. Analyses were conducted based on the daily intake of macronutrients (energy percentage (E%)), fatty acids (E%), added sugar (E%) and dietary fibre (g/d and g/MJ). Analyses were stratified by maternal education level into three categories. Changes in nutrient intake were observed in the intervention group, mainly among children of mothers with a short education ( < 10 years). Here, intake of dietary fibre increased (β = 2·1 g/d, 95 % CI 0·5, 3·6, P= 0·01). Intake of protein tended to increase (β = 0·6 E%, 95 % CI − 0·01, 1·2, P= 0·05), while intake of fat (β = − 1·7 E%, 95 % CI − 3·8, 0·3, P= 0·09) and SFA (β = − 0·9, 95 % CI − 2·0, 0·2, P= 0·10) tended to decrease. Also, a significant intervention effect was observed on the intake of SFA among children of mothers with a long education (β = − 0·8, 95 % CI − 1·5, − 0·03, P= 0·04). This multi-component school-based intervention resulted in changes in the dietary intake, particularly among children of mothers with a short education. As the dietary intake of this subgroup generally differs most from the recommendations, the results of the present study are particularly encouraging

Impaired Reproductive Development in Sons of Women Occupationally Exposed to Pesticides during Pregnancy

OBJECTIVES: The aim of this prospective study was to investigate whether occupational pesticide exposure during pregnancy causes adverse effects on the reproductive development in the male infants. DESIGN AND MEASUREMENTS: Pregnant women employed in greenhouses in Denmark were consecutively recruited, and 113 mother–son pairs were included. The mothers were categorized as occupationally exposed (91 sons) or unexposed (22 sons) to pesticides during pregnancy. Testicular position and volume, penile length, and position of urethral opening were determined at 3 months of age using standardized techniques. Concentrations of reproductive hormones in serum from the boys were analyzed. RESULTS: The prevalence of cryptorchidism at 3 months of age was 6.2 % [95 % confidence interval (CI), 3.0–12.4]. This prevalence was considerably higher than among Danish boys born in the Copenhagen area (1.9%; 95 % CI, 1.2–3.0) examined by the same procedure. Boys of pesticideexposed mothers showed decreased penile length, testicular volume, serum concentrations of testosterone, and inhibin B. Serum concentrations of sex hormone-binding globulin, follicle-stimulating hormone, and the luteinizing hormone:testosterone ratio were increased compared with boys of nonexposed mothers. For individual parameters, only the decreased penile length was statisticall

Loss-of-function genomic variants highlight potential therapeutic targets for cardiovascular disease

Pharmaceutical drugs targeting dyslipidemia and cardiovascular disease (CVD) may increase the risk of fatty liver disease and other metabolic disorders. To identify potential novel CVD drug targets without these adverse effects, we perform genome-wide analyses of participants in the HUNT Study in Norway (n = 69,479) to search for protein-altering variants with beneficial impact on quantitative blood traits related to cardiovascular disease, but without detrimental impact on liver function. We identify 76 (11 previously unreported) presumed causal protein-altering variants associated with one or more CVD- or liver-related blood traits. Nine of the variants are predicted to result in loss-of-function of the protein. This includes ZNF529:p.K405X, which is associated with decreased low-density-lipoprotein (LDL) cholesterol (P = 1.3 × 10-8) without being associated with liver enzymes or non-fasting blood glucose. Silencing of ZNF529 in human hepatoma cells results in upregulation of LDL receptor and increased LDL uptake in the cells. This suggests that inhibition of ZNF529 or its gene product should be prioritized as a novel candidate drug target for treating dyslipidemia and associated CVD

Thermochemistry of Alane Complexes for Hydrogen Storage: A Theoretical and Experimental Comparison

Knowledge of the relative stabilities of alane (AlH3) complexes with electron donors is essential for identifying hydrogen storage materials for vehicular applications that can be regenerated by off-board methods; however, almost no thermodynamic data are available to make this assessment. To fill this gap, we employed the G4(MP2) method to determine heats of formation, entropies, and Gibbs free energies of formation for thirty-eight alane complexes with NH3-nRn (R = Me, Et; n = 0-3), pyridine, pyrazine, triethylenediamine (TEDA), quinuclidine, OH2-nRn (R = Me, Et; n = 0-2), dioxane, and tetrahydrofuran (THF). Monomer, bis, and selected dimer complex geometries were considered. Using these data, we computed the thermodynamics of the key formation and dehydrogenation reactions that would occur during hydrogen delivery and alane regeneration, from which trends in complex stability were identified. These predictions were tested by synthesizing six amine-alane complexes involving trimethylamine, triethylamine, dimethylethylamine, TEDA, quinuclidine, and hexamine, and obtaining upper limits of delta G for their formation from metallic aluminum. Combining these computational and experimental results, we establish a criterion for complex stability relevant to hydrogen storage that can be used to assess potential ligands prior to attempting synthesis of the alane complex. Based on this, we conclude that only a subset of the tertiary amine complexes considered and none of the ether complexes can be successfully formed by direct reaction with aluminum and regenerated in an alane-based hydrogen storage system.Comment: Accepted by the Journal of Physical Chemistry

Effect of glass on the frictional behavior of basalts at seismic slip rates

We performed 31 friction experiments on glassy basalts (GB) and glass-free basalts (GFB) at slip rates up to 6.5 m s−1 and normal stress up to 40 MPa (seismic conditions). Frictional weakening was associated to bulk frictional melting and lubrication. The weakening distance (Dw) was about 3 times shorter in GB than in GFB, but the steady state friction was systematically higher in GB than in GFB. The shorter Dw in GB may be explained by the thermal softening occurring at the glass transition temperature (Tg ~500°C), which is lower than the bulk melting temperature (Tm ~1250°C) of GFB. Postexperiment microanalyses suggest that the larger crystal fraction measured in GB melts results in the higher steady state friction value compared to the GFB melts. The effect of interstitial glass is to facilitate frictional instability and rupture propagation in GB with respect to GFB

A vaccine displaying a trimeric influenza-A HA stem protein on capsid-like particles elicits potent and long-lasting protection in mice

Due to constant antigenic drift and shift, current influenza-A vaccines need to be redesigned and administered annually. A universal flu vaccine (UFV) that provides long-lasting protection against both seasonal and emerging pandemic influenza strains is thus urgently needed. The hemagglutinin (HA) stem antigen is a promising target for such a vaccine as it contains neutralizing epitopes, known to induce cross-protective IgG responses against a wide variety of influenza subtypes. In this study, we describe the development of a UFV candidate consisting of a HAstem trimer displayed on the surface of rigid capsid-like particles (CLP). Compared to soluble unconjugated HAstem trimer, the CLP-HAstem particles induced a more potent, long-lasting immune response and were able to protect mice against both homologous and heterologous H1N1 influenza challenge, even after a single dose

Impaired Reproductive Development in Sons of Women Occupationally Exposed to Pesticides during Pregnancy

Objectives The aim of this prospective study was to investigate whether occupational pesticide exposure during pregnancy causes adverse effects on the reproductive development in the male infants. Design and measurements Pregnant women employed in greenhouses in Denmark were consecutively recruited, and 113 mother–son pairs were included. The mothers were categorized as occupationally exposed (91 sons) or unexposed (22 sons) to pesticides during pregnancy. Testicular position and volume, penile length, and position of urethral opening were determined at 3 months of age using standardized techniques. Concentrations of reproductive hormones in serum from the boys were analyzed. Results The prevalence of cryptorchidism at 3 months of age was 6.2% [95% confidence interval (CI), 3.0–12.4]. This prevalence was considerably higher than among Danish boys born in the Copenhagen area (1.9%; 95% CI, 1.2–3.0) examined by the same procedure. Boys of pesticide-exposed mothers showed decreased penile length, testicular volume, serum concentrations of testosterone, and inhibin B. Serum concentrations of sex hormone-binding globulin, follicle-stimulating hormone, and the luteinizing hormone:testosterone ratio were increased compared with boys of nonexposed mothers. For individual parameters, only the decreased penile length was statistically significant (p = 0.04). However, all observed effects were in the anticipated direction, and a joint multivariate test showed that this finding had a p-value of 0.012. Conclusions Our findings suggest an adverse effect of maternal occupational pesticide exposure on reproductive development in the sons despite current greenhouse safeguards and special measures to protect pregnant women