Catalytic reactor for operando spatially resolved structure–activity profiling using high-energy X-ray diffraction

In heterogeneous catalysis, operando measurements probe catalysts in their active state and are essential for revealing complex catalyst structure–activity relationships. The development of appropriate operando sample environments for spatially resolved studies has come strongly into focus in recent years, particularly when coupled to the powerful and multimodal characterization tools available at synchrotron light sources. However, most catalysis studies at synchrotron facilities only measure structural information about the catalyst in a spatially resolved manner, whereas gas analysis is restricted to the reactor outlet. Here, a fully automated and integrated catalytic profile reactor setup is shown for the combined measurement of temperature, gas composition and high-energy X-ray diffraction (XRD) profiles, using the oxidative de­hydrogenation of C$_{2}$H$_{6}$ to C$_{2}$H$_{4}$ over MoO$_{3}$/γ-Al$_{2}$O$_{3}$ as a test system. The profile reactor methodology was previously developed for X-ray absorption spectroscopy and is here extended for operando XRD. The profile reactor is a versatile and accessible research tool for combined spatially resolved structure–activity profiling, enabling the use of multiple synchrotron-based characterization methods to promote a knowledge-based optimization of a wide range of catalytic systems in a time- and resource-efficient wa

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

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

Mapping the Shores of the Brown Dwarf Desert III: Young Moving Groups

We present the results of an aperture masking interferometry survey for substellar companions around 67 members of the young (~8-200Myr) nearby (~5-86pc) AB Doradus, Beta Pictoris, Hercules-Lyra, TW Hya, and Tucana-Horologium stellar associations. Observations were made at near infrared wavelengths between 1.2-3.8 microns using the adaptive optics facilities of the Keck II, VLT UT4, and Palomar Hale Telescopes. Typical contrast ratios of ~100-200 were achieved at angular separations between ~40-320mas, with our survey being 100% complete for companions with masses below 0.25\msolar across this range. We report the discovery of a $0.52 \pm 0.09$\msolar companion to HIP14807, as well as the detections and orbits of previously known stellar companions to HD16760, HD113449, and HD160934. We show that the companion to HD16760 is in a face-on orbit, resulting in an upward revision of its mass from $M_2 \sin i \sim 14$\mjupiter to $M_2 = 0.28 \pm 0.04$\msolar. No substellar companions were detected around any of our sample members, despite our ability to detect companions with masses below 80\mjupiter for 50 of our targets: of these, our sensitivity extended down to 40\mjupiter around 30 targets, with a subset of 22 subject to the still more stringent limit of 20\mjupiter. A statistical analysis of our non-detection of substellar companions allows us to place constraints on their frequency around ~0.2-1.5\msolar stars. In particular, considering companion mass distributions that have been proposed in the literature, we obtain an upper limit estimate of ~9-11% for the frequency of 20-80\mjupiter companions between 3-30AU at 95% confidence, assuming that their semimajor axes are distributed according to $d\mathcal{N}/da \propto a^{-1}$ in this range.Comment: Accepted by Ap

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

Identification of known and novel recurrent viral sequences in data from multiple patients and multiple cancers

Virus discovery from high throughput sequencing data often follows a bottom-up approach where taxonomic annotation takes place prior to association to disease. Albeit effective in some cases, the approach fails to detect novel pathogens and remote variants not present in reference databases. We have developed a species independent pipeline that utilises sequence clustering for the identification of nucleotide sequences that co-occur across multiple sequencing data instances. We applied the workflow to 686 sequencing libraries from 252 cancer samples of different cancer and tissue types, 32 non-template controls, and 24 test samples. Recurrent sequences were statistically associated to biological, methodological or technical features with the aim to identify novel pathogens or plausible contaminants that may associate to a particular kit or method. We provide examples of identified inhabitants of the healthy tissue flora as well as experimental contaminants. Unmapped sequences that co-occur with high statistical significance potentially represent the unknown sequence space where novel pathogens can be identified

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

1Identification of genes differentially expressed in the embryonic pig cerebral cortex before and after appearance of gyration

<p>Abstract</p> <p>Background</p> <p>Mammalian evolution is characterized by a progressive expansion of the surface area of the cerebral cortex, an increase that is accompanied by gyration of the cortical surface. The mechanisms controlling this gyration process are not well characterized but mutational analyses indicate that genes involved in neuronal migration play an important function. Due to the lack of gyration of the rodent brain it is important to establish alternative models to examine brain development during the gyration process. The pig brain is gyrated and accordingly is a candidate alternative model.</p> <p>Findings</p> <p>In this study we have identified genes differentially expressed in the pig cerebral cortex before and after appearance of gyration. Pig cortical tissue from two time points in development representing a non-folded, lissencephalic, brain (embryonic day 60) and primary-folded, gyrencephalic, brain (embryonic day 80) were examined by whole genome expression microarray studies. 91 differentially expressed transcripts (fold change >3) were identified. 84 transcripts were annotated and encoding proteins involved in for example neuronal migration, calcium binding, and cytoskeletal structuring. Quantitative real-time PCR was used to confirm the regulation of a subset of the identified genes.</p> <p>Conclusion</p> <p>This study provides identification of genes which are differentially expressed in the pig cerebral cortex before and after appearance of brain gyration. The identified genes include novel candidate genes which could have functional importance for brain development.</p