The function of tcf3 in medaka embryos: efficient knockdown with pePNAs

Background: The application of antisense molecules, such as morpholino oligonucleotides, is an efficient method of gene inactivation in vivo. We recently introduced phosphonic ester modified peptide nucleic acids (PNA) for in vivo loss-of-function experiments in medaka embryos. Here we tested novel modifications of the PNA backbone to knockdown the medaka tcf3 gene. Results: A single tcf3 gene exists in the medaka genome and its inactivation strongly affected eye development of the embryos, leading to size reduction and anophthalmia in severe cases. The function of Tcf3 strongly depends on co-repressor interactions. We found interactions with Groucho/Tle proteins to be most important for eye development. Using a dominant negative approach for combined inactivation of all groucho/tle genes also resulted in eye phenotypes, as did interference with three individual tle genes. Conclusions: Our results show that side chain modified PNAs come close to the knockdown efficiency of morpholino oligonucleotides in vivo. A single medaka tcf3 gene combines the function of the two zebrafish paralogs hdl and tcf3b. In combination with Groucho/Tle corepressor proteins Tcf3 acts in anterior development and is critical for eye formation

Rapid identification of PAX2/5/8 direct downstream targets in the otic vesicle by combinatorial use of bioinformatics tools

A novel bioinformatics pipeline is used to discover PAX2/5/8 direct downstream targets involved in inner ear development

High redshift X-ray cooling-core cluster associated with the luminous radio loud quasar 3C186

We present the first results from a new, deep (200ks) Chandra observation of the X-ray luminous galaxy cluster surrounding the powerful (L ~10^47 erg/s), high-redshift (z=1.067), compact-steep-spectrum radio-loud quasar 3C186. The diffuse X-ray emission from the cluster has a roughly ellipsoidal shape and extends out to radii of at least ~60 arcsec (~500 kpc). The centroid of the diffuse X-ray emission is offset by 0.68(+/-0.11) arcsec (5.5+/-0.9 kpc) from the position of the quasar. We measure a cluster mass within the radius at which the mean enclosed density is 2500 times the critical density, r_2500=283(+18/-13)kpc, of 1.02 (+0.21/-0.14)x10^14 M_sun. The gas mass fraction within this radius is f_gas=0.129(+0.015/-0.016). This value is consistent with measurements at lower redshifts and implies minimal evolution in the f_gas(z) relation for hot, massive clusters at 0<z<1.1. The measured metal abundance of 0.42(+0.08/-0.07) Solar is consistent with the abundance observed in other massive, high redshift clusters. The spatially-resolved temperature profile for the cluster shows a drop in temperature, from kT~8 keV to kT~3 keV, in its central regions that is characteristic of cooling core clusters. This is the first spectroscopic identification of a cooling core cluster at z>1. We measure cooling times for the X-ray emitting gas at radii of 50 kpc and 25 kpc of 1.7(+/-0.2)x10^9 years and 7.5(+/-2.6)x 10^8 years, as well as a nominal cooling rate (in the absence of heating) of 400(+/-190)M_sun/year within the central 100 kpc. In principle, the cooling gas can supply enough fuel to support the growth of the supermassive black hole and to power the luminous quasar. The radiative power of the quasar exceeds by a factor of 10 the kinematic power of the central radio source, suggesting that radiative heating may be important at intermittent intervals in cluster cores.Comment: 15 pages, 9 figures, ApJ in pres

Structure–Thermodynamic-Property Relationships in Cyanovinyl-Based Microporous Polymer Networks for the Future Design of Advanced Carbon Capture Materials

Nitrogen-rich solid absorbents, which have been immensely tested for carbon dioxide capture, seem until this date to be without decisive molecular engineering or design rules. Here, a family of cyanovinylene-based microporous polymers synthesized under metal-catalyzed conditions is reported as a promising candidate for advanced carbon capture materials. These networks reveal that isosteric heats of CO2 adsorption are directly proportional to the amount of their functional group. Motivated by this finding, polymers produced under base-catalyzed conditions with tailored quantities of cyanovinyl content confirm the systematical tuning of their sorption enthalpies to reach 40 kJ mol−1. This value is among the highest reported to date in carbonaceous networks undergoing physisorption. A six-point-plot reveals that the structure–thermodynamic-property relationship is linearly proportional and can thus be perfectly fitted to tailor-made values prior to experimental measurements. Dynamic simulations show a bowl-shaped region within which CO2 is able to sit and interact with its conjugated surrounding, while theoretical calculations confirm the increase of binding sites with the increase of PhCC(CN)Ph functionality in a network. This concept presents a distinct method for the future design of carbon dioxide capturing materials

Effects of CO2 perturbation on phosphorus pool sizes and uptake in a mesocosm experiment during a low productive summer season in the northern Baltic Sea

Studies investigating the effect of increasing CO2 levels on the phosphorus cycle in natural waters are lacking although phosphorus often controls phytoplankton development in many aquatic systems. The aim of our study was to analyse effects of elevated CO2 levels on phosphorus pool sizes and uptake. The phosphorus dynamic was followed in a CO2-manipulation mesocosm experiment in the Storfjarden (western Gulf of Finland, Baltic Sea) in summer 2012 and was also studied in the surrounding fjord water. In all mesocosms as well as in surface waters of Storfjarden, dissolved organic phosphorus (DOP) concentrations of 0.26aEuro-+/- aEuro-0.03 and 0.23aEuro-+/- aEuro-0.04aEuro-A mu molaEuro-L-1, respectively, formed the main fraction of the total P-pool (TP), whereas phosphate (PO4) constituted the lowest fraction with mean concentration of 0.15aEuro-A +/- aEuro-0.02 in the mesocosms and 0.17aEuro-A +/- aEuro-0.07aEuro-A mu molaEuro-L-1 in the fjord. Transformation of PO4 into DOP appeared to be the main pathway of PO4 turnover. About 82aEuro-% of PO4 was converted into DOP whereby only 18aEuro-% of PO4 was transformed into particulate phosphorus (PP). PO4 uptake rates measured in the mesocosms ranged between 0.6 and 3.9aEuro-nmolaEuro-L(-1)aEuro-h(-1). About 86aEuro-% of them was realized by the size fraction aEuro-1000aEuro-A mu atm during periods when phytoplankton biomass increased. In addition, we found significant relationships (e.g., between PP and Chl a) in the untreated mesocosms which were not observed under high fCO(2) conditions. Consequently, it can be hypothesized that the relationship between PP formation and phytoplankton growth changed with CO2 elevation. It can be deduced from the results, that visible effects of CO2 on P pools are coupled to phytoplankton growth when the transformation of PO4 into POP was stimulated. The transformation of PO4 into DOP on the other hand does not seem to be affected. Additionally, there were some indications that cellular mechanisms of P regulation might be modified under CO2 elevation changing the relationship between cellular constituents.Peer reviewe

D-brane potentials in the warped resolved conifold and natural inflation

In this paper we obtain a model of Natural Inflation from string theory with a Planckian decay constant. We investigate D-brane dynamics in the background of the warped resolved conifold (WRC) throat approximation of Type IIB string compactifications on Calabi-Yau manifolds. When we glue the throat to a compact bulk Calabi-Yau, we generate a D-brane potential which is a solution to the Laplace equation on the resolved conifold. We can exactly solve this equation, including dependence on the angular coordinates. The solutions are valid down to the tip of the resolved conifold, which is not the case for the more commonly used deformed conifold. This allows us to exploit the effect of the warping, which is strongest at the tip. We inflate near the tip using an angular coordinate of a D5-brane in the WRC which has a discrete shift symmetry, and feels a cosine potential, giving us a model of Natural Inflation, from which it is possible to get a Planckian decay constant whilst maintaining control over the backreaction. This is because the decay constant for a wrapped brane contains powers of the warp factor, and so can be made large, while the wrapping parameter can be kept small enough so that backreaction is under control.Comment: 41 pages, 3 appendices, 1 figure, PDFLaTex; various clarifications added along with a new appendix on b-axions and wrapped D5 branes;version matches the one published in JHE

2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for Vascular Surgery (ESVS) : Document covering atherosclerotic disease of extracranial carotid and vertebral, mesenteric, renal, upper and lower extremity arteries

Endorsed by: the European Stroke Organization (ESO), The Task Force for the Diagnosis and Treatment of Peripheral Arterial Diseases of the European Society of Cardiology (ESC) and of the European Society for Vascular Surgery (ESVS)Peer reviewe

Chandra Survey of Radio-quiet, High-redshift Quasars

We observed 17 optically-selected, radio-quiet high-redshift quasars with the Chandra Observatory ACIS, and detected 16 of them. The quasars have redshift between 3.70 and 6.28 and include the highest redshift quasars known. When compared to low-redshift quasars observed with ROSAT, these high redshift quasars are significantly more X-ray quiet. We also find that the X-ray spectral index of the high redshift objects is flatter than the average at lower redshift. These trends confirm the predictions of models where the accretion flow is described by a cold, optically-thick accretion disk surrounded by a hot, optically thin corona, provided the viscosity parameter alpha >= 0.02. The high redshift quasars have supermassive black holes with masses ~10^{10} M_{sun}, and are accreting material at ~0.1 the Eddington limit. We detect 10 X-ray photons from the z=6.28 quasar SDS 1030+0524, which may have a Gunn-Peterson trough and be near the redshift of reionization of the intergalactic medium. The X-ray data place an upper limit on the optical depth of the intergalactic medium tau(IGM) < 10^6, compared to the lower limit from the spectrum of Lyalpha and Lybeta, which implies tau(IGM) > 20.Comment: Accepted for publication in the Astrophysical Journa

Fitting the integrated Spectral Energy Distributions of Galaxies

Fitting the spectral energy distributions (SEDs) of galaxies is an almost universally used technique that has matured significantly in the last decade. Model predictions and fitting procedures have improved significantly over this time, attempting to keep up with the vastly increased volume and quality of available data. We review here the field of SED fitting, describing the modelling of ultraviolet to infrared galaxy SEDs, the creation of multiwavelength data sets, and the methods used to fit model SEDs to observed galaxy data sets. We touch upon the achievements and challenges in the major ingredients of SED fitting, with a special emphasis on describing the interplay between the quality of the available data, the quality of the available models, and the best fitting technique to use in order to obtain a realistic measurement as well as realistic uncertainties. We conclude that SED fitting can be used effectively to derive a range of physical properties of galaxies, such as redshift, stellar masses, star formation rates, dust masses, and metallicities, with care taken not to over-interpret the available data. Yet there still exist many issues such as estimating the age of the oldest stars in a galaxy, finer details ofdust properties and dust-star geometry, and the influences of poorly understood, luminous stellar types and phases. The challenge for the coming years will be to improve both the models and the observational data sets to resolve these uncertainties. The present review will be made available on an interactive, moderated web page (sedfitting.org), where the community can access and change the text. The intention is to expand the text and keep it up to date over the coming years.Comment: 54 pages, 26 figures, Accepted for publication in Astrophysics & Space Scienc