A Dark Spot on a Massive White Dwarf

We present the serendipitous discovery of eclipse-like events around the massive white dwarf SDSS J152934.98+292801.9 (hereafter J1529+2928). We selected J1529+2928 for time-series photometry based on its spectroscopic temperature and surface gravity, which place it near the ZZ Ceti instability strip. Instead of pulsations, we detect photometric dips from this white dwarf every 38 minutes. Follow-up optical spectroscopy observations with Gemini reveal no significant radial velocity variations, ruling out stellar and brown dwarf companions. A disintegrating planet around this white dwarf cannot explain the observed light curves in different filters. Given the short period, the source of the photometric dips must be a dark spot that comes into view every 38 min due to the rotation of the white dwarf. Our optical spectroscopy does not show any evidence of Zeeman splitting of the Balmer lines, limiting the magnetic field strength to B<70 kG. Since up to 15% of white dwarfs display kG magnetic fields, such eclipse-like events should be common around white dwarfs. We discuss the potential implications of this discovery on transient surveys targeting white dwarfs, like the K2 mission and the Large Synoptic Survey Telescope.Comment: ApJ Letters, in pres

Parent Satisfaction with Outpatient Pediatric Endoscopy Procedures at University of New Mexico Children\u27s Hospital

As a part of endoscopy quality improvement (EQI) project, we decided to measure parent satisfaction about pediatric endoscopy service at University of New Mexico Children\u27s Hospital

A Flexible Method of Estimating Luminosity Functions

We describe a Bayesian approach to estimating luminosity functions. We derive the likelihood function and posterior probability distribution for the luminosity function, given the observed data, and we compare the Bayesian approach with maximum-likelihood by simulating sources from a Schechter function. For our simulations confidence intervals derived from bootstrapping the maximum-likelihood estimate can be too narrow, while confidence intervals derived from the Bayesian approach are valid. We develop our statistical approach for a flexible model where the luminosity function is modeled as a mixture of Gaussian functions. Statistical inference is performed using Markov chain Monte Carlo (MCMC) methods, and we describe a Metropolis-Hastings algorithm to perform the MCMC. The MCMC simulates random draws from the probability distribution of the luminosity function parameters, given the data, and we use a simulated data set to show how these random draws may be used to estimate the probability distribution for the luminosity function. In addition, we show how the MCMC output may be used to estimate the probability distribution of any quantities derived from the luminosity function, such as the peak in the space density of quasars. The Bayesian method we develop has the advantage that it is able to place accurate constraints on the luminosity function even beyond the survey detection limits, and that it provides a natural way of estimating the probability distribution of any quantities derived from the luminosity function, including those that rely on information beyond the survey detection limits.Comment: 26 pages, 13 figures, emulateapj format, accepted by ApJ. An IDL computer routine is available from B. Kelly for implementing our technique of estimating luminosity function

Interruption of intrachromosomal looping by CCCTC binding factor decoy proteins abrogates genomic imprinting of human insulin-like growth factor II

CCCTC binding factor (CTCF) mutants that cannot bind components of the polycomb repressive complex-2 (PRC2) do not form the chromatin loops that regulate monoallelic gene expression

Strong suppression of heat conduction in a laboratory replica of galaxy-cluster turbulent plasmas

In conventional gases and plasmas, it is known that heat fluxes are proportional to temperature gradients, with collisions between particles mediating energy flow from hotter to colder regions and the coefficient of thermal conduction given by Spitzer's theory. However, this theory breaks down in magnetized, turbulent, weakly collisional plasmas, although modifications are difficult to predict from first principles due to the complex, multiscale nature of the problem. Understanding heat transport is important in astrophysical plasmas such as those in galaxy clusters, where observed temperature profiles are explicable only in the presence of a strong suppression of heat conduction compared to Spitzer's theory. To address this problem, we have created a replica of such a system in a laser laboratory experiment. Our data show a reduction of heat transport by two orders of magnitude or more, leading to large temperature variations on small spatial scales (as is seen in cluster plasmas)

Microenvironmental Ammonia Enhances T Cell Exhaustion in Colorectal Cancer

Effective therapies are lacking for patients with advanced colorectal cancer (CRC). The CRC tumor microenvironment has elevated metabolic waste products due to altered metabolism and proximity to the microbiota. The role of metabolite waste in tumor development, progression, and treatment resistance is unclear. We generated an autochthonous metastatic mouse model of CRC and used unbiased multi-omic analyses to reveal a robust accumulation of tumoral ammonia. The high ammonia levels induce T cell metabolic reprogramming, increase exhaustion, and decrease proliferation. CRC patients have increased serum ammonia, and the ammonia-related gene signature correlates with altered T cell response, adverse patient outcomes, and lack of response to immune checkpoint blockade. We demonstrate that enhancing ammonia clearance reactivates T cells, decreases tumor growth, and extends survival. Moreover, decreasing tumor-associated ammonia enhances anti-PD-L1 efficacy. These findings indicate that enhancing ammonia detoxification can reactivate T cells, highlighting a new approach to enhance the efficacy of immunotherapies

The Radius of Baryonic Collapse in Disc Galaxy Formation

In the standard picture of disc galaxy formation, baryons and dark matter receive the same tidal torques, and therefore approximately the same initial specific angular momentum. However, observations indicate that disc galaxies typically have only about half as much specific angular momentum as their dark matter haloes. We argue this does not necessarily imply that baryons lose this much specific angular momentum as they form galaxies. It may instead indicate that galaxies are most directly related to the inner regions of their host haloes, as may be expected in a scenario where baryons in the inner parts of haloes collapse first. A limiting case is examined under the idealised assumption of perfect angular momentum conservation. Namely, we determine the density contrast Delta, with respect to the critical density of the Universe, by which dark matter haloes need to be defined in order to have the same average specific angular momentum as the galaxies they host. Under the assumption that galaxies are related to haloes via their characteristic rotation velocities, the necessary Delta is ~600. This Delta corresponds to an average halo radius and mass which are ~60% and ~75%, respectively, of the virial values (i.e., for Delta = 200). We refer to this radius as the radius of baryonic collapse R_BC, since if specific angular momentum is conserved perfectly, baryons would come from within it. It is not likely a simple step function due to the complex gastrophysics involved, therefore we regard it as an effective radius. In summary, the difference between the predicted initial and the observed final specific angular momentum of galaxies, which is conventionally attributed solely to angular momentum loss, can more naturally be explained by a preference for collapse of baryons within R_BC, with possibly some later angular momentum transfer.Comment: MNRAS accepted, 7 page

Late veneer and late accretion to the terrestrial planets

It is generally accepted that silicate-metal (`rocky') planet formation relies on coagulation from a mixture of sub-Mars sized planetary embryos and (smaller) planetesimals that dynamically emerge from the evolving circum-solar disc in the first few million years of our Solar System. Once the planets have, for the most part, assembled after a giant impact phase, they continue to be bombarded by a multitude of planetesimals left over from accretion. Here we place limits on the mass and evolution of these planetesimals based on constraints from the highly siderophile element (HSE) budget of the Moon. Outcomes from a combination of N-body and Monte Carlo simulations of planet formation lead us to four key conclusions about the nature of this early epoch. First, matching the terrestrial to lunar HSE ratio requires either that the late veneer on Earth consisted of a single lunar-size impactor striking the Earth before 4.45 Ga, or that it originated from the impact that created the Moon. An added complication is that analysis of lunar samples indicates the Moon does not preserve convincing evidence for a late veneer like Earth. Second, the expected chondritic veneer component on Mars is 0.06 weight percent. Third, the flux of terrestrial impactors must have been low ( <=10^(-6) M_earth/Myr) to avoid wholesale melting of Earth's crust after 4.4~Ga, and to simultaneously match the number of observed lunar basins. This conclusion leads to an Hadean eon which is more clement than assumed previously. Last, after the terrestrial planets had fully formed, the mass in remnant planetesimals was ~10^(-3) M_earth, lower by at least an order of magnitude than most previous models suggest. Our dynamically and geochemically self-consistent scenario requires that future N-body simulations of rocky planet formation either directly incorporate collisional grinding or rely on pebble accretion.Comment: Accepted for publication in Earth and Planetary Science Letter

Targeting enhancer switching overcomes non-genetic drug resistance in acute myeloid leukaemia.

Non-genetic drug resistance is increasingly recognised in various cancers. Molecular insights into this process are lacking and it is unknown whether stable non-genetic resistance can be overcome. Using single cell RNA-sequencing of paired drug naïve and resistant AML patient samples and cellular barcoding in a unique mouse model of non-genetic resistance, here we demonstrate that transcriptional plasticity drives stable epigenetic resistance. With a CRISPR-Cas9 screen we identify regulators of enhancer function as important modulators of the resistant cell state. We show that inhibition of Lsd1 (Kdm1a) is able to overcome stable epigenetic resistance by facilitating the binding of the pioneer factor, Pu.1 and cofactor, Irf8, to nucleate new enhancers that regulate the expression of key survival genes. This enhancer switching results in the re-distribution of transcriptional co-activators, including Brd4, and provides the opportunity to disable their activity and overcome epigenetic resistance. Together these findings highlight key principles to help counteract non-genetic drug resistance