Prospecting Period Measurements with LSST - Low Mass X-ray Binaries as a Test Case

The Large Synoptic Survey Telescope (LSST) will provide for unbiased sampling of variability properties of objects with $r$ mag $<$ 24. This should allow for those objects whose variations reveal their orbital periods ($P_{orb}$), such as low mass X-ray binaries (LMXBs) and related objects, to be examined in much greater detail and with uniform systematic sampling. However, the baseline LSST observing strategy has temporal sampling that is not optimised for such work in the Galaxy. Here we assess four candidate observing strategies for measurement of $P_{orb}$ in the range 10 minutes to 50 days. We simulate multi-filter quiescent LMXB lightcurves including ellipsoidal modulation and stochastic flaring, and then sample these using LSST's operations simulator (OpSim) over the (mag, $P_{orb}$) parameter space, and over five sightlines sampling a range of possible reddening values. The percentage of simulated parameter space with correctly returned periods ranges from $\sim$23 %, for the current baseline strategy, to $\sim$70 % for the two simulated specialist strategies. Convolving these results with a $P_{orb}$ distribution, a modelled Galactic spatial distribution and reddening maps, we conservatively estimate that the most recent version of the LSST baseline strategy will allow $P_{orb}$ determination for $\sim$18 % of the Milky Way's LMXB population, whereas strategies that do not reduce observations of the Galactic Plane can improve this dramatically to $\sim$32 %. This increase would allow characterisation of the full binary population by breaking degeneracies between suggested $P_{orb}$ distributions in the literature. Our results can be used in the ongoing assessment of the effectiveness of various potential cadencing strategies.Comment: Replacement after addressing minor corrections from the referee - mainly improvements in clarificatio

Synthesis of a mitochondria-targeted spin trap using a novel Parham-type cyclization

A new cyclic nitrone spin trap, [4-(3′,3′-dibutyl-2′-oxy-3′H-isoindol-5′-yloxy)butyl]triphenylphosphonium bromide (MitoSpin), bearing a lipophilic cation has been prepared by a route that involves a novel Parham-type lithiation–cyclization of an isocyanate to give the isoindolinone core. MitoSpin accumulates in a membrane potential dependent way in energized mitochondria and its oxidation could potentially be used in the study of oxidative stress resulting from reactive oxygen species generated in mitochondria

Recovery of Bennu's Orientation for the OSIRIS-REx Mission: Implications for the Spin State Accuracy and Geolocation Errors

The goal of the OSIRIS-REx mission is to return a sample of asteroid material from Near-Earth Asteroid (101955) Bennu. The role of the navigation and fight dynamics team is critical for the spacecraft to execute a precisely planned sampling maneuver over a specifically-selected landing site. In particular, the orientation of Bennu needs to be recovered with good accuracy during orbital operations to contribute as small an error as possible to the landing error budget. Although Bennu is well characterized from Earth-based radar observations, its orientation dynamics are not sufficiently known to exclude the presence of a small wobble. To better understand this contingency and evaluate how well the orientation can be recovered in the presence of a large 1 degree wobble, we conduct a comprehensive simulation with the NASA GSFC GEODYN orbit determination and geodetic parameter estimation software. We describe the dynamic orientation modeling implemented in GEODYN in support of OSIRIS-REx operations, and show how both altimetry and imagery data can be used as either undifferenced (landmark, direct altimetry) or differenced (image crossover, altimetry crossover) measurements. We find that these two different types of data contribute differently to the recovery of instrument pointing or planetary orientation. When upweighted, the absolute measurements help reduce the geolocation errors, despite poorer astrometric (inertial) performance. We find that with no wobble present, all the geolocation requirements are met. While the presence of a large wobble is detrimental, the recovery is still reliable thanks to the combined use of altimetry and imagery data

Interplay of Mre11 Nuclease with Dna2 plus Sgs1 in Rad51-Dependent Recombinational Repair

The Mre11/Rad50/Xrs2 complex initiates IR repair by binding to the end of a double-strand break, resulting in 5′ to 3′ exonuclease degradation creating a single-stranded 3′ overhang competent for strand invasion into the unbroken chromosome. The nuclease(s) involved are not well understood. Mre11 encodes a nuclease, but it has 3′ to 5′, rather than 5′ to 3′ activity. Furthermore, mutations that inactivate only the nuclease activity of Mre11 but not its other repair functions, mre11-D56N and mre11-H125N, are resistant to IR. This suggests that another nuclease can catalyze 5′ to 3′ degradation. One candidate nuclease that has not been tested to date because it is encoded by an essential gene is the Dna2 helicase/nuclease. We recently reported the ability to suppress the lethality of a dna2Δ with a pif1Δ. The dna2Δ pif1Δ mutant is IR-resistant. We have determined that dna2Δ pif1Δ mre11-D56N and dna2Δ pif1Δ mre11-H125N strains are equally as sensitive to IR as mre11Δ strains, suggesting that in the absence of Dna2, Mre11 nuclease carries out repair. The dna2Δ pif1Δ mre11-D56N triple mutant is complemented by plasmids expressing Mre11, Dna2 or dna2K1080E, a mutant with defective helicase and functional nuclease, demonstrating that the nuclease of Dna2 compensates for the absence of Mre11 nuclease in IR repair, presumably in 5′ to 3′ degradation at DSB ends. We further show that sgs1Δ mre11-H125N, but not sgs1Δ, is very sensitive to IR, implicating the Sgs1 helicase in the Dna2-mediated pathway

Miscarriage and stillbirth following maternal Zika virus infection in nonhuman primates.

Zika virus (ZIKV) infection is associated with congenital defects and pregnancy loss. Here, we found that 26% of nonhuman primates infected with Asian/American ZIKV in early gestation experienced fetal demise later in pregnancy despite showing few clinical signs of infection. Pregnancy loss due to asymptomatic ZIKV infection may therefore be a common but under-recognized adverse outcome related to maternal ZIKV infection

Templates for Convex Cone Problems with Applications to Sparse Signal Recovery

This paper develops a general framework for solving a variety of convex cone problems that frequently arise in signal processing, machine learning, statistics, and other fields. The approach works as follows: first, determine a conic formulation of the problem; second, determine its dual; third, apply smoothing; and fourth, solve using an optimal first-order method. A merit of this approach is its flexibility: for example, all compressed sensing problems can be solved via this approach. These include models with objective functionals such as the total-variation norm, ||Wx||_1 where W is arbitrary, or a combination thereof. In addition, the paper also introduces a number of technical contributions such as a novel continuation scheme, a novel approach for controlling the step size, and some new results showing that the smooth and unsmoothed problems are sometimes formally equivalent. Combined with our framework, these lead to novel, stable and computationally efficient algorithms. For instance, our general implementation is competitive with state-of-the-art methods for solving intensively studied problems such as the LASSO. Further, numerical experiments show that one can solve the Dantzig selector problem, for which no efficient large-scale solvers exist, in a few hundred iterations. Finally, the paper is accompanied with a software release. This software is not a single, monolithic solver; rather, it is a suite of programs and routines designed to serve as building blocks for constructing complete algorithms.Comment: The TFOCS software is available at http://tfocs.stanford.edu This version has updated reference

Phylogenetic Codivergence Supports Coevolution of Mimetic Heliconius Butterflies

The unpalatable and warning-patterned butterflies _Heliconius erato_ and _Heliconius melpomene_ provide the best studied example of mutualistic M&#xfc;llerian mimicry, thought &#x2013; but rarely demonstrated &#x2013; to promote coevolution. Some of the strongest available evidence for coevolution comes from phylogenetic codivergence, the parallel divergence of ecologically associated lineages. Early evolutionary reconstructions suggested codivergence between mimetic populations of _H. erato_ and _H. melpomene_, and this was initially hailed as the most striking known case of coevolution. However, subsequent molecular phylogenetic analyses found discrepancies in phylogenetic branching patterns and timing (topological and temporal incongruence) that argued against codivergence. We present the first explicit cophylogenetic test of codivergence between mimetic populations of _H. erato_ and _H. melpomene_, and re-examine the timing of these radiations. We find statistically significant topological congruence between multilocus coalescent population phylogenies of _H. erato_ and _H. melpomene_, supporting repeated codivergence of mimetic populations. Divergence time estimates, based on a Bayesian coalescent model, suggest that the evolutionary radiations of _H. erato_ and _H. melpomene_ occurred over the same time period, and are compatible with a series of temporally congruent codivergence events. This evidence supports a history of reciprocal coevolution between M&#xfc;llerian co-mimics characterised by phylogenetic codivergence and parallel phenotypic change

Carbon dynamics of the Weddell Gyre, Southern Ocean

The accumulation of carbon within the Weddell Gyre and its exchanges across the gyre boundaries are investigated with three recent full-depth oceanographic sections enclosing this climatically important region. The combination of carbonmeasurements with ocean circulation transport estimates from a box inverse analysis reveals that deepwater transports associated with Warm Deep Water (WDW) and Weddell Sea Deep Water dominate the gyre’s carbon budget, while a dual-cell vertical overturning circulation leads to both upwelling and the delivery of large quantities of carbon to the deep ocean. Historical sea surface pCO2 observations, interpolated using a neural network technique, confirm the net summertime sink of 0.044 to 0.058 ± 0.010 Pg C / yr derived from the inversion. However, a wintertime outgassing signal similar in size results in a statistically insignificant annual air-to-sea CO2 flux of 0.002± 0.007 Pg C / yr (mean 1998–2011) to 0.012 ± 0.024 Pg C/ yr (mean 2008–2010) to be diagnosed for the Weddell Gyre. A surface layer carbon balance, independently derived fromin situ biogeochemical measurements, reveals that freshwater inputs and biological drawdown decrease surface ocean inorganic carbon levels more than they are increased by WDW entrainment, resulting in an estimated annual carbon sink of 0.033 ± 0.021 Pg C / yr. Although relatively less efficient for carbon uptake than the global oceans, the summertime Weddell Gyre suppresses the winter outgassing signal, while its biological pump and deepwater formation act as key conduits for transporting natural and anthropogenic carbon to the deep ocean where they can reside for long time scales

Cardiodynamic state is associated with systemic inflammation and fatal acute‐on‐chronic liver failure

Background & Aims: Acute-on-chronic liver failure (ACLF) is characterized by high short-term mortality and systemic inflammation (SI). Recently, different cardiodynamic states were shown to independently predict outcomes in cirrhosis. The relationship between cardiodynamic states, SI, and portal hypertension and their impact on ACLF development remains unclear. The aim of this study was therefore to evaluate the interplay of cardiodynamic state and SI on fatal ACLF development in cirrhosis. Results: At inclusion, hemodynamic measures including cardiac index (CI) and hepatic venous pressure gradient of 208 patients were measured. Patients were followed prospectively for fatal ACLF development (primary endpoint). SI was assessed by proinflammatory markers such as interleukins (ILs) 6 and 8 and soluble IL-33 receptor (sIL-33R). Patients were divided according to CI (4.2 L/min/m2) in hypo- (n = 84), normo- (n = 69) and hyperdynamic group (n = 55). After a median follow-up of 3 years, the highest risk of fatal ACLF was seen in hyperdynamic (35%) and hypodynamic patients (25%) compared with normodynamic (14%) (P =.011). Hyperdynamic patients showed the highest rate of SI. The detectable level of IL-6 was an independent predictor of fatal ACLF development. Conclusions: Cirrhotic patients with hyperdynamic and hypodynamic circulation have a higher risk of fatal ACLF. Therefore, the cardiodynamic state is strongly associated with SI, which is an independent predictor of development of fatal ACLF

Single-cell paired-end genome sequencing reveals structural variation per cell cycle

The nature and pace of genome mutation is largely unknown. Because standard methods sequence DNA from populations of cells, the genetic composition of individual cells is lost, de novo mutations in cells are concealed within the bulk signal and per cell cycle mutation rates and mechanisms remain elusive. Although single-cell genome analyses could resolve these problems, such analyses are error-prone because of whole-genome amplification (WGA) artefacts and are limited in the types of DNA mutation that can be discerned. We developed methods for paired-end sequence analysis of single-cell WGA products that enable (i) detecting multiple classes of DNA mutation, (ii) distinguishing DNA copy number changes from allelic WGA-amplification artefacts by the discovery of matching aberrantly mapping read pairs among the surfeit of paired-end WGA and mapping artefacts and (iii) delineating the break points and architecture of structural variants. By applying the methods, we capture DNA copy number changes acquired over one cell cycle in breast cancer cells and in blastomeres derived from a human zygote after in vitro fertilization. Furthermore, we were able to discover and fine-map a heritable inter-chromosomal rearrangement t(1;16)(p36;p12) by sequencing a single blastomere. The methods will expedite applications in basic genome research and provide a stepping stone to novel approaches for clinical genetic diagnosis