Nucleosides rescue replication-mediated genome instability of human pluripotent stem cells

Human pluripotent stem cells (PSCs) are subject to the appearance of recurrent genetic variants on prolonged culture. We have now found that, compared with isogenic differentiated cells, PSCs exhibit evidence of considerably more DNA damage during the S phase of the cell cycle, apparently as a consequence of DNA replication stress marked by slower progression of DNA replication, activation of latent origins of replication, and collapse of replication forks. As in many cancers, which, like PSCs, exhibit a shortened G1 phase and DNA replication stress, the resulting DNA damage may underlie the higher incidence of abnormal and abortive mitoses in PSCs, resulting in chromosomal non-dysjunction or cell death. However, we have found that the extent of DNA replication stress, DNA damage, and consequent aberrant mitoses can be substantially reduced by culturing PSCs in the presence of exogenous nucleosides, resulting in improved survival, clonogenicity, and population growth

Changes in the firn structure of the western Greenland Ice Sheet caused by recent warming

Atmospheric warming over the Greenland Ice Sheet during the last 2 decades has increased the amount of surface meltwater production, resulting in the migration of melt and percolation regimes to higher altitudes and an increase in the amount of ice content from refrozen meltwater found in the firn above the superimposed ice zone. Here we present field and airborne radar observations of buried ice layers within the near-surface (0–20 m) firn in western Greenland, obtained from campaigns between 1998 and 2014. We find a sharp increase in firn-ice content in the form of thick widespread layers in the percolation zone, which decreases the capacity of the firn to store meltwater. The estimated total annual ice content retained in the near-surface firn in areas with positive surface mass balance west of the ice divide in Greenland reached a maximum of 74 ± 25 Gt in 2012, compared to the 1958–1999 average of 13 ± 2 Gt, while the percolation zone area more than doubled between 2003 and 2012. Increased melt and column densification resulted in surface lowering averaging −0.80 ± 0.39 m yr−1 between 1800 and 2800 m in the accumulation zone of western Greenland. Since 2007, modeled annual melt and refreezing rates in the percolation zone at elevations below 2100 m surpass the annual snowfall from the previous year, implying that mass gain in the region is retained after melt in the form of refrozen meltwater. If current melt trends over high elevation regions continue, subsequent changes in firn structure will have implications for the hydrology of the ice sheet and related abrupt seasonal densification could become increasingly significant for altimetry-derived ice sheet mass balance estimates

Generation and trapping of a mesoderm biased state of human pluripotency

We postulate that exit from pluripotency involves intermediates that retain pluripotency while simultaneously exhibiting lineage-bias. Using a MIXL1 reporter, we explore mesoderm lineage-bias within the human pluripotent stem cell compartment. We identify a substate, which at the single cell level coexpresses pluripotent and mesodermal gene expression programmes. Functionally these cells initiate stem cell cultures and exhibit mesodermal bias in differentiation assays. By promoting mesodermal identity through manipulation of WNT signalling while preventing exit from pluripotency using lysophosphatidic acid, we ‘trap’ and maintain cells in a lineage-biased stem cell state through multiple passages. These cells correspond to a normal state on the differentiation trajectory, the plasticity of which is evidenced by their reacquisition of an unbiased state upon removal of differentiation cues. The use of ‘cross-antagonistic’ signalling to trap pluripotent stem cell intermediates with different lineage-bias may have general applicability in the efficient production of cells for regenerative medicine

Magnetic field dependence of the exciton energy in a quantum disk

The groundstate energy and binding energy of an exciton, confined in a^M quantum disk, are calculated as a function of an external magnetic field. The confinement potential is a hard wall of finite height. The diamagnetic shift is investigated for magnetic fields up to 40$T$. Our results are applied to $In_{y}Al_{1-y}As/Al_{x}Ga_{1-x}As$ self-assembled quantum dots and very good agreement with experiments is obtained. Furthermore, we investigated the influence of the dot size on the diamagnetic shift by changing the disk radius. The exciton excited states are found as a function of the magnetic field. The relative angular momentum is not a quantum number and changes with the magnetic field strength.Comment: 10 pages, 17 figure

A Large Catalog of Accurate Distances to Molecular Clouds from PS1 Photometry

Distance measurements to molecular clouds are important but are often made separately for each cloud of interest, employing very different data and techniques. We present a large, homogeneous catalog of distances to molecular clouds, most of which are of unprecedented accuracy. We determine distances using optical photometry of stars along lines of sight toward these clouds, obtained from PanSTARRS-1. We simultaneously infer the reddenings and distances to these stars, tracking the full probability distribution function using a technique presented in Green et al. We fit these star-by-star measurements using a simple dust screen model to find the distance to each cloud. We thus estimate the distances to almost all of the clouds in the Magnani et al. catalog, as well as many other well-studied clouds, including Orion, Perseus, Taurus, Cepheus, Polaris, California, and Monoceros R2, avoiding only the inner Galaxy. Typical statistical uncertainties in the distances are 5%, though the systematic uncertainty stemming from the quality of our stellar models is about 10%. The resulting catalog is the largest catalog of accurate, directly measured distances to molecular clouds. Our distance estimates are generally consistent with available distance estimates from the literature, though in some cases the literature estimates are off by a factor of more than two

Low drive field amplitude for improved image resolution in magnetic particle imaging

Purpose: Magnetic particle imaging (MPI) is a new imaging technology that directly detects superparamagnetic iron oxide nanoparticles. The technique has potential medical applications in angiography, cell tracking, and cancer detection. In this paper, the authors explore how nanoparticle relaxation affects image resolution. Historically, researchers have analyzed nanoparticle behavior by studying the time constant of the nanoparticle physical rotation. In contrast, in this paper, the authors focus instead on how the time constant of nanoparticle rotation affects the final image resolution, and this reveals nonobvious conclusions for tailoring MPI imaging parameters for optimal spatial resolution. Methods: The authors first extend x-space systems theory to include nanoparticle relaxation. The authors then measure the spatial resolution and relative signal levels in an MPI relaxometer and a 3D MPI imager at multiple drive field amplitudes and frequencies. Finally, these image measurements are used to estimate relaxation times and nanoparticle phase lags. Results: The authors demonstrate that spatial resolution, as measured by full-width at half-maximum, improves at lower drive field amplitudes. The authors further determine that relaxation in MPI can be approximated as a frequency-independent phase lag. These results enable the authors to accurately predict MPI resolution and sensitivity across a wide range of drive field amplitudes and frequencies. Conclusions: To balance resolution, signal-to-noise ratio, specific absorption rate, and magnetostimulation requirements, the drive field can be a low amplitude and high frequency. Continued research into how the MPI drive field affects relaxation and its adverse effects will be crucial for developing new nanoparticles tailored to the unique physics of MPI. Moreover, this theory informs researchers how to design scanning sequences to minimize relaxation-induced blurring for better spatial resolution or to exploit relaxation-induced blurring for MPI with molecular contrast. © 2016 American Association of Physicists in Medicine

Detection of a supervoid aligned with the cold spot of the cosmic microwave background

We use the WISE-2MASS infrared galaxy catalogue matched with Pan-STARRS1 (PS1) galaxies to search for a supervoid in the direction of the cosmic microwave background (CMB) cold spot (CS). Our imaging catalogue has median redshift z ≃ 0.14, and we obtain photometric redshifts from PS1 optical colours to create a tomographic map of the galaxy distribution. The radial profile centred on the CS shows a large low-density region, extending over tens of degrees. Motivated by previous CMB results, we test for underdensities within two angular radii, 5°, and 15°. The counts in photometric redshift bins show significantly low densities at high detection significance, ≳5σ and ≳6σ, respectively, for the two fiducial radii. The line-of-sight position of the deepest region of the void is z ≃ 0.15–0.25. Our data, combined with an earlier measurement by Granett, Szapudi & Neyrinck, are consistent with a large Rvoid = (220 ± 50) h−1 Mpc supervoid with δm ≃ −0.14 ± 0.04 centred at z = 0.22 ± 0.03. Such a supervoid, constituting at least a ≃3.3σ fluctuation in a Gaussian distribution of the Λ cold dark matter model, is a plausible cause for the CS

Pan-STARRS Pixel Analysis: Source Detection and Characterization

Over 3 billion astronomical sources have been detected in the more than 22 million orthogonal transfer CCD images obtained as part of the Pan-STARRS1 3π survey. Over 85 billion instances of those sources have been automatically detected and characterized by the Pan-STARRS Image Processing Pipeline photometry software, psphot. This fast, automatic, and reliable software was developed for the Pan-STARRS project but is easily adaptable to images from other telescopes. We describe the analysis of the astronomical sources by psphot in general as well as for the specific case of the third processing version used for the first two public releases of the Pan-STARRS 3π Survey data

A Map of Dust Reddening to 4.5 kpc from Pan-STARRS1

We present a map of the dust reddening to 4.5 kpc derived from Pan-STARRS1 stellar photometry. The map covers almost the entire sky north of declination –30° at a resolution of 7'-14', and is based on the estimated distances and reddenings to more than 500 million stars. The technique is designed to map dust in the Galactic plane, where many other techniques are stymied by the presence of multiple dust clouds at different distances along each line of sight. This reddening-based dust map agrees closely with the Schlegel et al. (SFD) far-infrared emission-based dust map away from the Galactic plane, and the most prominent differences between the two maps stem from known limitations of SFD in the plane. We also compare the map with Planck, finding likewise good agreement in general at high latitudes. The use of optical data from Pan-STARRS1 yields reddening uncertainty as low as 25 mmag E(B – V)

Ecological management of cereal stemborers in African smallholder agriculture through behavioural manipulation

1. Africa faces serious challenges in feeding its rapidly growing human population owing to the poor productivity of maize and sorghum, the most important staple crops formillions of smallholder farmers in the continent,with yields being among the lowest in the world. 2. A complex of lepidopterous stemborers attack cereals in Africa. However, their effective control is difficult, largely as a result of the cryptic and nocturnal habits of moths, and protection provided by host stem for immature pest stages.Moreover, current control measures are uneconomical and impractical for resource-poor farmers. 3. An ecological approach, based on companion planting, known as ‘push–pull’, provides effective management of these pests, and involves combined use of inter- and trap cropping systems where stemborers are attracted and trapped on trap plants with added economic value (‘pull’), and are driven away from the cereal crop by antagonistic intercrops (‘push’). 4. Novel defence strategies inducible by stemborer oviposition have recently been discovered, leading to the attraction of egg and larval parasitoids, in locally adapted maize lines but not in elite hybrids. We also established that landscape complexity did not improve the ecosystem service of biological control, but rather provided a disservice by acting as a ‘source’ of stemborer pests colonising the crop. 5. Here we review and provide new data on the direct and indirect effects of the push–pull approach on stemborers and their natural enemies, including the mechanisms involved, and highlight opportunities for exploiting intrinsic plant defences and natural ecosystem services in pest management in smallholder farming systems in Africa