Telomeric NAP1L4 and OSBPL5 of the KCNQ1 cluster, and the DECORIN gene are not imprinted in human trophoblast stem cells

Background: Genomic imprinting of the largest known cluster, the Kcnq1/KCNQ1 domain on mChr7/hChr11, displays significant differences between mouse and man. Of the fourteen transcripts in this cluster, imprinting of six is ubiquitous in mice and humans, however, imprinted expression of the other eight transcripts is only found in the mouse placenta. The human orthologues of the latter eight transcripts are biallelically expressed, at least from the first trimester onwards. However, as early development is less divergent between species, placental specific imprinting may be present in very early gestation in both mice and humans. Methodology/Principal Findings: Human embryonic stem (hES) cells can be differentiated to embryoid bodies and then to trophoblast stem (EB-TS) cells. Using EB-TS cells as a model of post-implantation invading cytotrophoblast, we analysed allelic expression of two telomeric transcripts whose imprinting is placental specific in the mouse, as well as the ncRNA KCNQ1OT1, whose imprinted expression is ubiquitous in early human and mouse development. KCNQ1OT1 expression was monoallelic in all samples but OSBPL5 and NAP1L4 expression was biallelic in EB-TS cells, as well as undifferentiated hES cells and first trimester human fetal placenta. DCN on hChr12, another gene imprinted in the mouse placenta only, was also biallelically expressed in EB-TS cells. The germline maternal methylation imprint at the KvDMR was maintained in both undifferentiated hES cells and EB-TS cells. Conclusions/Significance: The question of placental specific imprinting in the human has not been answered fully. Using a model of human trophoblast very early in gestation we show a lack of imprinting of two telomeric genes in the KCNQ1 region and of DCN, whose imprinted expression is placental specific in mice, providing further evidence to suggest that humans do not exhibit placental specific imprinting. The maintenance of both differential methylation of the KvDMR and monoallelic expression of KCNQ1OT1 indicates that the region is appropriately regulated epigenetically in vitro. Human gestational load is less than in the mouse, resulting in reduced need for maternal resource competition, and therefore maybe also a lack of placental specific imprinting. If genomic imprinting exists to control fetal acquisition of maternal resources driven by the placenta, placenta-specific imprinting may be less important in the human than the mouse

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Improving Scalability and Maintenance of Software for High-Performance Scientific Computing by Combining MDE and Frameworks

International audienceIn recent years, numerical simulation has attracted increasing interest within industry and among academics. Paradoxically, the development and maintenance of high performance scientific computing software has become more complex due to the diversification of hardware architectures and their related programming languages and libraries. In this paper, we share our experience in using model-driven development for numerical simulation software. Our approach called MDE4HPC proposes to tackle development complexity by using a domain specific modeling language to describe abstract views of the software. We present and analyse the results obtained with its implementation when deriving this abstract model to target Arcane, a development framework for 2D and 3D numerical simulation software

Existence and Stability of Symmetric Periodic Simultaneous Binary Collision Orbits in the Planar Pairwise Symmetric Four-Body Problem

We extend our previous analytic existence of a symmetric periodic simultaneous binary collision orbit in a regularized fully symmetric equal mass four-body problem to the analytic existence of a symmetric periodic simultaneous binary collision orbit in a regularized planar pairwise symmetric equal mass four-body problem. We then use a continuation method to numerically find symmetric periodic simultaneous binary collision orbits in a regularized planar pairwise symmetric 1, m, 1, m four-body problem for $m$ between 0 and 1. Numerical estimates of the the characteristic multipliers show that these periodic orbits are linearly stability when $0.54\leq m\leq 1$, and are linearly unstable when $0<m\leq0.53$.Comment: 6 figure

Spectrum of the Vortex Bound States of the Dirac and Schrodinger Hamiltonian in the presence of Superconducting Gaps

We investigate the vortex bound states both Schrodinger and Dirac Hamiltonian with the s-wave superconducting pairing gap by solving the mean-field Bogoliubov-de-Gennes equations. The exact vortex bound states spectrum is numerically determined by the integration method, and also accompanied by the quasi-classical analysis. It is found that the bound state energies is proportional to the vortex angular momentum when the chemical potential is large enough. By applying the external magnetic field, the vortex bound state energies of the Dirac Hamiltonian are almost unchanged; whereas the energy shift of the Schrodinger Hamiltonian is proportional to the magnetic field. These qualitative differences may serve as an indirect evidence of the existence of Majorana fermions in which the zero mode exists in the case of the Dirac Hamiltonian only.Comment: 8 pages, 9 figure

E-Therapies in England for stress, anxiety or depression: How are apps developed? A survey of NHS e-therapy developers

© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. To document the quality of web and smartphone apps used and recommended for stress, anxiety or depression by examining the manner in which they were developed. Design The study was conducted using a survey sent to developers of National Health Service (NHS) e-therapies. Data sources Data were collected via a survey sent out to NHS e-therapy developers during October 2015 and review of development company websites during October 2015. Data collection/extraction methods Data were compiled from responses to the survey and development company websites of the NHS e-therapies developers. Results A total of 36 (76.6%) out of the 48 app developers responded. One app was excluded due to its contact details and developer website being unidentifiable. Data from the missing 10 was determined from the app developer's website. The results were that 12 out of 13 web apps and 20 out of 34 smartphone apps had clinical involvement in their development. Nine out of 13 web apps and nine out of 34 smartphone apps indicated academic involvement in their development. Twelve out of 13 web apps and nine out of 34 smartphone apps indicated published research evidence relating to their app. Ten out of 13 web apps and 10 out of 34 smartphone apps indicated having other evidence relating to their app. Nine out of 13 web apps and 19 out of 34 smartphone apps indicated having a psychological approach or theory behind their app. Conclusions As an increasing number of developers are looking to produce e-therapies for the NHS it is essential they apply clinical and academic best practices to ensure the creation of safe and effective apps

Precis of epistemic angst:Book Symposium: Duncan Pritchard, Epistemic Angst (Princeton University Press, 2015, xiii + 236 pages)

ABSTRACT This book symposium features three critical pieces dealing with Duncan Pritchard's book, 'Epistemic Angst'; the symposium also contains Pritchard's replies to his critics

Effects of a large-scale, natural sediment deposition event on plant cover in a Massachusetts salt marsh

In mid-winter 2018, an unprecedented sediment deposition event occurred throughout portions of the Great Marsh in Massachusetts. Evaluation of this event in distinct marsh areas spanning three towns (Essex, Ipswich, and Newbury) revealed deposition covering 29.2 hectares with an average thickness of 30.1±2.1 mm measured shortly after deposition. While sediment deposition helps marshes survive sea level rise by building elevation, effects of such a large-scale deposition on New England marshes are unknown. This natural event provided an opportunity to study effects of large-scale sediment addition on plant cover and soil chemistry, with implications for marsh resilience. Sediment thickness did not differ significantly between winter and summer, indicating sediment is not eroding or compacting. The deposited sediment at each site had similar characteristics to that of the adjacent mudflat (e.g., texture, bivalve shells), suggesting that deposited materials resulted from ice rafting from adjacent flats, a natural phenomenon noted by other authors. Vegetative cover was significantly lower in plots with rafted sediment (75.6±2.3%) than sediment-free controls (93.1±1.6%) after one growing season. When sorted by sediment thickness categories, the low thickness level (1-19 mm) had significantly greater percent cover than medium (20-39 mm) and high (40-90 mm) categories. Given that sediment accretion in the Great Marsh was found to average 2.7 mm per year, the sediment thickness documented herein represents ~11 years of sediment accretion with only a 25% reduction in plant cover, suggesting this natural sediment event will likely increase long-term marsh resilience to sea level rise.Published versio

Do the Unidentified EGRET Sources Trace Annihilating Dark Matter in the Local Group?

In a cold dark matter (CDM) framework of structure formation, the dark matter haloes around galaxies assemble through successive mergers with smaller haloes. This merging process is not completely efficient, and hundreds of surviving halo cores, or {\it subhaloes}, are expected to remain in orbit within the halo of a galaxy like the Milky Way. While the dozen visible satellites of the Milky Way may trace some of these subhaloes, the majority are currently undetected. A large number of high-velocity clouds (HVCs) of neutral hydrogen {\it are} observed around the Milky Way, and it is plausible that some of the HVCs may trace subhaloes undetected in the optical. Confirming the existence of concentrations of dark matter associated with even a few of the HVCs would represent a dramatic step forward in our attempts to understand the nature of dark matter. Supersymmetric (SUSY) extensions of the Standard Model of particle physics currently suggest neutralinos as a natural well-motivated candidate for the non-baryonic dark matter of the universe. If this is indeed the case, then it may be possible to detect dark matter indirectly as it annihilates into neutrinos, photons or positrons. In particular, the centres of subhaloes might show up as point sources in gamma-ray observations. In this work we consider the possibility that some of the unidentified EGRET $\gamma$-ray sources trace annihilating neutralino dark matter in the dark substructure of the Local Group. We compare the observed positions and fluxes of both the unidentified EGRET sources and the HVCs with the positions and fluxes predicted by a model of halo substructure, to determine to what extent any of these three populations could be associated.Comment: 12 Pages, 4 figures, to appear in a special issue of ApSS. Presented at "The Multiwavelength Approach to Unidentified Gamma-Ray Sources" (Hong Kong, June 1 - 4, 2004; Conference organizers: K.S. Cheng and G.E. Romero