Disrupted Maturation of the Microbiota and Metabolome among Extremely Preterm Infants with Postnatal Growth Failure

Growth failure during infancy is a major global problem that has adverse effects on long-term health and neurodevelopment. Preterm infants are disproportionately affected by growth failure and its effects. Herein we found that extremely preterm infants with postnatal growth failure have disrupted maturation of the intestinal microbiota, characterized by persistently low diversity, dominance of pathogenic bacteria within the Enterobacteriaceae family, and a paucity of strictly anaerobic taxa including Veillonella relative to infants with appropriate postnatal growth. Metabolomic profiling of infants with growth failure demonstrated elevated serum acylcarnitines, fatty acids, and other byproducts of lipolysis and fatty acid oxidation. Machine learning algorithms for normal maturation of the microbiota and metabolome among infants with appropriate growth revealed a pattern of delayed maturation of the microbiota and metabolome among infants with growth failure. Collectively, we identified novel microbial and metabolic features of growth failure in preterm infants and potentially modifiable targets for intervention

Synthesis of Organosilicon Ligands for Europium (III) and Gadolinium (III) as Potential Imaging Agents

The relaxivity of MRI contrast agents can be increased by increasing the size of the contrast agent and by increasing concentration of the bound gadolinium. Large multi-site ligands able to coordinate several metal centres show increased relaxivity as a result. In this paper, an “aza-type Michael” reaction is used to prepare cyclen derivatives that can be attached to organosilicon frameworks via hydrosilylation reactions. A range of organosilicon frameworks were tested including silsesquioxane cages and dimethylsilylbenzene derivatives. Michael donors with strong electron withdrawing groups could be used to alkylate cyclen on three amine centres in a single step. Hydrosilylation successfully attached these to mono-, di-, and tri-dimethylsilyl-substituted benzene derivatives. The europium and gadolinium complexes were formed and studied using luminescence spectroscopy and relaxometry. This showed the complexes to contain two bound water moles per lanthanide centre and T1 relaxation time measurements demonstrated an increase in relaxivity had been achieved, in particular for the trisubstituted scaffold 1,3,5-tris((pentane-sDO3A)dimethylsilyl)benzene-Gd3. This showed a marked increase in the relaxivity (13.1 r1p/mM−1s−1)

Using H-alpha Morphology and Surface Brightness Fluctuations to Age-Date Star Clusters in M83

We use new WFC3 observations of the nearby grand design spiral galaxy M83 to develop two independent methods for estimating the ages of young star clusters. The first method uses the physical extent and morphology of Halpha emission to estimate the ages of clusters younger than tau ~10 Myr. It is based on the simple premise that the gas in very young (tau < few Myr) clusters is largely coincident with the cluster stars, is in a small, ring-like structure surrounding the stars in slightly older clusters (e.g., tau ~5 Myr), and is in a larger ring-like bubble for still older clusters (i.e., ~5-10 Myr). The second method is based on an observed relation between pixel-to-pixel flux variations within clusters and their ages. This method relies on the fact that the brightest individual stars in a cluster are most prominent at ages around 10 Myr, and fall below the detection limit (i.e., M_V < -3.5) for ages older than about 100 Myr. These two methods are the basis for a new morphological classification system which can be used to estimate the ages of star clusters based on their appearance. We compare previous age estimates of clusters in M83 determined from fitting UBVI Halpha measurements using predictions from stellar evolutionary models with our new morphological categories and find good agreement at the ~95% level. The scatter within categories is ~0.1 dex in log tau for young clusters (10 Myr) clusters. A by-product of this study is the identification of 22 "single-star" HII regions in M83, with central stars having ages ~4 Myr.Comment: 33 pages, 10 figures, 3 tables; published in March Ap

Measuring the Invisible Higgs Width at the 7 and 8 TeV LHC

The LHC is well on track toward the discovery or exclusion of a light Standard Model (SM)-like Higgs boson. Such a Higgs has a very small SM width and can easily have large branching fractions to physics beyond the SM, making Higgs decays an excellent opportunity to observe new physics. Decays into collider-invisible particles are particularly interesting as they are theoretically well motivated and relatively clean experimentally. In this work we estimate the potential of the 7 and 8 TeV LHC to observe an invisible Higgs branching fraction. We analyze three channels that can be used to directly study the invisible Higgs branching ratio at the 7 TeV LHC: an invisible Higgs produced in association with (i) a hard jet; (ii) a leptonic Z; and (iii) forward tagging jets. We find that the last channel, where the Higgs is produced via weak boson fusion, is the most sensitive, allowing branching fractions as small as 40% to be probed at 20 inverse fb for masses in the range between 120 and 170 GeV, including in particular the interesting region around 125 GeV. We provide an estimate of the 8 TeV LHC sensitivity to an invisibly-decaying Higgs produced via weak boson fusion and find that the reach is comparable to but not better than the reach at the 7 TeV LHC. We further estimate the discovery potential at the 8 TeV LHC for cases where the Higgs has substantial branching fractions to both visible and invisible final states.Comment: 23 pages, 7 figures. v2: version published in JHEP. 8 TeV analysis adde

The Dark Side of the Electroweak Phase Transition

Recent data from cosmic ray experiments may be explained by a new GeV scale of physics. In addition the fine-tuning of supersymmetric models may be alleviated by new O(GeV) states into which the Higgs boson could decay. The presence of these new, light states can affect early universe cosmology. We explore the consequences of a light (~ GeV) scalar on the electroweak phase transition. We find that trilinear interactions between the light state and the Higgs can allow a first order electroweak phase transition and a Higgs mass consistent with experimental bounds, which may allow electroweak baryogenesis to explain the cosmological baryon asymmetry. We show, within the context of a specific supersymmetric model, how the physics responsible for the first order phase transition may also be responsible for the recent cosmic ray excesses of PAMELA, FERMI etc. We consider the production of gravity waves from this transition and the possible detectability at LISA and BBO

Hubble Space Telescope WFC3 Early Release Science: Emission-Line Galaxies from Infrared Grism Observations

We present grism spectra of emission-line galaxies (ELGs) from 0.6-1.6 microns from the Wide Field Camera 3 on the Hubble Space Telescope. These new infrared grism data augment previous optical Advanced Camera for Surveys G800L 0.6-0.95 micron grism data in GOODS-South from the PEARS program, extending the wavelength covereage well past the G800L red cutoff. The ERS grism field was observed at a depth of 2 orbits per grism, yielding spectra of hundreds of faint objects, a subset of which are presented here. ELGs are studied via the Ha, [OIII], and [OII] emission lines detected in the redshift ranges 0.2<z<1.4, 1.2<z<2.2 and 2.0<z<3.3 respectively in the G102 (0.8-1.1 microns; R~210) and G141 (1.1-1.6 microns; R~130) grisms. The higher spectral resolution afforded by the WFC3 grisms also reveals emission lines not detectable with the G800L grism (e.g., [SII] and [SIII] lines). From these relatively shallow observations, line luminosities, star-formation rates, and grism spectroscopic redshifts are determined for a total of 48 ELGs to m(AB)~25 mag. Seventeen GOODS-South galaxies that previously only had photometric redshifts now have new grism-spectroscopic redshifts, in some cases with large corrections to the photometric redshifts (Delta(z)~0.3-0.5). Additionally, one galaxy had no previously-measured redshift but now has a secure grism-spectroscopic redshift, for a total of 18 new GOODS-South spectroscopic redshifts. The faintest source in our sample has a magnitude m(AB)=26.9 mag. The ERS grism data also reflect the expected trend of lower specific star formation rates for the highest mass galaxies in the sample as a function of redshift, consistent with downsizing and discovered previously from large surveys. These results demonstrate the remarkable efficiency and capability of the WFC3 NIR grisms for measuring galaxy properties to faint magnitudes and redshifts to z>2.Comment: Accepted for publication in AJ. Updated to include referee comments. Updated sample using improved reduction contains 23 new galaxies (Table 1; Figures 2 & 3

A new view of electrochemistry at highly oriented pyrolytic graphite

Major new insights on electrochemical processes at graphite electrodes are reported, following extensive investigations of two of the most studied redox couples, Fe(CN)64–/3– and Ru(NH3)63+/2+. Experiments have been carried out on five different grades of highly oriented pyrolytic graphite (HOPG) that vary in step-edge height and surface coverage. Significantly, the same electrochemical characteristic is observed on all surfaces, independent of surface quality: initial cyclic voltammetry (CV) is close to reversible on freshly cleaved surfaces (>400 measurements for Fe(CN)64–/3– and >100 for Ru(NH3)63+/2+), in marked contrast to previous studies that have found very slow electron transfer (ET) kinetics, with an interpretation that ET only occurs at step edges. Significantly, high spatial resolution electrochemical imaging with scanning electrochemical cell microscopy, on the highest quality mechanically cleaved HOPG, demonstrates definitively that the pristine basal surface supports fast ET, and that ET is not confined to step edges. However, the history of the HOPG surface strongly influences the electrochemical behavior. Thus, Fe(CN)64–/3– shows markedly diminished ET kinetics with either extended exposure of the HOPG surface to the ambient environment or repeated CV measurements. In situ atomic force microscopy (AFM) reveals that the deterioration in apparent ET kinetics is coupled with the deposition of material on the HOPG electrode, while conducting-AFM highlights that, after cleaving, the local surface conductivity of HOPG deteriorates significantly with time. These observations and new insights are not only important for graphite, but have significant implications for electrochemistry at related carbon materials such as graphene and carbon nanotubes

MicroRNAs in pulmonary arterial remodeling

Pulmonary arterial remodeling is a presently irreversible pathologic hallmark of pulmonary arterial hypertension (PAH). This complex disease involves pathogenic dysregulation of all cell types within the small pulmonary arteries contributing to vascular remodeling leading to intimal lesions, resulting in elevated pulmonary vascular resistance and right heart dysfunction. Mutations within the bone morphogenetic protein receptor 2 gene, leading to dysregulated proliferation of pulmonary artery smooth muscle cells, have been identified as being responsible for heritable PAH. Indeed, the disease is characterized by excessive cellular proliferation and resistance to apoptosis of smooth muscle and endothelial cells. Significant gene dysregulation at the transcriptional and signaling level has been identified. MicroRNAs are small non-coding RNA molecules that negatively regulate gene expression and have the ability to target numerous genes, therefore potentially controlling a host of gene regulatory and signaling pathways. The major role of miRNAs in pulmonary arterial remodeling is still relatively unknown although research data is emerging apace. Modulation of miRNAs represents a possible therapeutic target for altering the remodeling phenotype in the pulmonary vasculature. This review will focus on the role of miRNAs in regulating smooth muscle and endothelial cell phenotypes and their influence on pulmonary remodeling in the setting of PAH

Genome-Wide Association Analysis of Ischemic Stroke in Young Adults

Ischemic stroke (IS) is among the leading causes of death in Western countries. There is a significant genetic component to IS susceptibility, especially among young adults. To date, research to identify genetic loci predisposing to stroke has met only with limited success. We performed a genome-wide association (GWA) analysis of early-onset IS to identify potential stroke susceptibility loci. The GWA analysis was conducted by genotyping 1 million SNPs in a biracial population of 889 IS cases and 927 controls, ages 15–49 years. Genotypes were imputed using the HapMap3 reference panel to provide 1.4 million SNPs for analysis. Logistic regression models adjusting for age, recruitment stages, and population structure were used to determine the association of IS with individual SNPs. Although no single SNP reached genome-wide significance (P < 5 × 10−8), we identified two SNPs in chromosome 2q23.3, rs2304556 (in FMNL2; P = 1.2 × 10−7) and rs1986743 (in ARL6IP6; P = 2.7 × 10−7), strongly associated with early-onset stroke. These data suggest that a novel locus on human chromosome 2q23.3 may be associated with IS susceptibility among young adults