Haemogenic endocardium contributes to transient definitive haematopoiesis.

Haematopoietic cells arise from spatiotemporally restricted domains in the developing embryo. Although studies of non-mammalian animal and in vitro embryonic stem cell models suggest a close relationship among cardiac, endocardial and haematopoietic lineages, it remains unknown whether the mammalian heart tube serves as a haemogenic organ akin to the dorsal aorta. Here we examine the haemogenic activity of the developing endocardium. Mouse heart explants generate myeloid and erythroid colonies in the absence of circulation. Haemogenic activity arises from a subset of endocardial cells in the outflow cushion and atria earlier than in the aorta-gonad-mesonephros region, and is transient and definitive in nature. Interestingly, key cardiac transcription factors, Nkx2-5 and Isl1, are expressed in and required for the haemogenic population of the endocardium. Together, these data suggest that a subset of endocardial/endothelial cells serve as a de novo source for transient definitive haematopoietic progenitors

Decoding the regulatory network of early blood development from single-cell gene expression measurements.

Reconstruction of the molecular pathways controlling organ development has been hampered by a lack of methods to resolve embryonic progenitor cells. Here we describe a strategy to address this problem that combines gene expression profiling of large numbers of single cells with data analysis based on diffusion maps for dimensionality reduction and network synthesis from state transition graphs. Applying the approach to hematopoietic development in the mouse embryo, we map the progression of mesoderm toward blood using single-cell gene expression analysis of 3,934 cells with blood-forming potential captured at four time points between E7.0 and E8.5. Transitions between individual cellular states are then used as input to develop a single-cell network synthesis toolkit to generate a computationally executable transcriptional regulatory network model of blood development. Several model predictions concerning the roles of Sox and Hox factors are validated experimentally. Our results demonstrate that single-cell analysis of a developing organ coupled with computational approaches can reveal the transcriptional programs that underpin organogenesis.We thank J. Downing (St. Jude Children's Research Hospital, Memphis, TN, USA) for the Runx1-ires-GFP mouse. Research in the authors' laboratory is supported by the Medical Research Council, Biotechnology and Biological Sciences Research Council, Leukaemia and Lymphoma Research, the Leukemia and Lymphoma Society, Microsoft Research and core support grants by the Wellcome Trust to the Cambridge Institute for Medical Research and Wellcome Trust - MRC Cambridge Stem Cell Institute. V.M. is supported by a Medical Research Council Studentship and Centenary Award and S.W. by a Microsoft Research PhD Scholarship.This is the accepted manuscript for a paper published in Nature Biotechnology 33, 269–276 (2015) doi:10.1038/nbt.315

Customer Interaction and Innovation in Hybrid Offerings:Investigating Moderation and Mediation Effects for Goods and Services Innovation

Hybrid offerings are bundles of goods and services offerings provided by the same firm. Bundling value offerings affects how firms innovate, interact with customers, and customize their goods and services. However, it remains unclear how customer interaction might drive the innovation performance of various bundled components. Therefore, this study investigates the effects of customer interactions and service customization on both goods and services innovations in a hybrid offering context, using a unique data set of 146 information technology and manufacturing firms. Customer interaction appears beneficial to both goods and services innovation in a hybrid offerings context, but service customization has different direct effects on goods versus services innovation. As a potential mediator, customer knowledge mobilization resources exert different effects on the goods and services elements of hybrid offerings. Furthermore, for high-interaction customers, medium levels of technical modularity lead to most favorable innovation outcomes for services innovation. The results thus suggest that providers of hybrid offerings should foster customer interactions, to drive the innovation performance of the good and service components, while still making sure to implement service customization strategies. These findings have notable implications for service innovation research

The Mass of Kepler-93b and The Composition of Terrestrial Planets

Kepler-93b is a 1.478 +/- 0.019 Earth radius planet with a 4.7 day period around a bright (V=10.2), astroseismically-characterized host star with a mass of 0.911+/-0.033 solar masses and a radius of 0.919+/-0.011 solar radii. Based on 86 radial velocity observations obtained with the HARPS-N spectrograph on the Telescopio Nazionale Galileo and 32 archival Keck/HIRES observations, we present a precise mass estimate of 4.02+/-0.68 Earth masses. The corresponding high density of 6.88+/-1.18 g/cc is consistent with a rocky composition of primarily iron and magnesium silicate. We compare Kepler-93b to other dense planets with well-constrained parameters and find that between 1-6 Earth masses, all dense planets including the Earth and Venus are well-described by the same fixed ratio of iron to magnesium silicate. There are as of yet no examples of such planets with masses > 6 Earth masses: All known planets in this mass regime have lower densities requiring significant fractions of volatiles or H/He gas. We also constrain the mass and period of the outer companion in the Kepler-93 system from the long-term radial velocity trend and archival adaptive optics images. As the sample of dense planets with well-constrained masses and radii continues to grow, we will be able to test whether the fixed compositional model found for the seven dense planets considered in this paper extends to the full population of 1-6 Earth mass planets.Comment: 8 pages, 4 figures. Accepted for publication in Ap

Charming and bewitching : considering the Harry Potter series

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Prediction of second neurological attack in patients with clinically isolated syndrome using support vector machines

The aim of this study is to predict the conversion from clinically isolated syndrome to clinically definite multiple sclerosis using support vector machines. The two groups of converters and non-converters are classified using features that were calculated from baseline data of 73 patients. The data consists of standard magnetic resonance images, binary lesion masks, and clinical and demographic information. 15 features were calculated and all combinations of them were iteratively tested for their predictive capacity using polynomial kernels and radial basis functions with leave-one-out cross-validation. The accuracy of this prediction is up to 86.4% with a sensitivity and specificity in the same range indicating that this is a feasible approach for the prediction of a second clinical attack in patients with clinically isolated syndromes, and that the chosen features are appropriate. The two features gender and location of onset lesions have been used in all feature combinations leading to a high accuracy suggesting that they are highly predictive. However, it is necessary to add supporting features to maximise the accuracy. © 2013 IEEE