Low-Mass X-Ray Binaries, Millisecond Radio Pulsars, and the Cosmic Star Formation Rate

We report on the implications of the peak in the cosmic star-formation rate (SFR) at redshift z ~ 1.5 for the resulting population of low-mass X-ray binaries(LMXB) and for that of their descendants, the millisecond radio pulsars (MRP). Since the evolutionary timescales of LMXBs, their progenitors, and their descendants are thought be significant fractions of the time-interval between the SFR peak and the present epoch, there is a lag in the turn-on of the LMXB population, with the peak activity occurring at z ~ 0.5 - 1.0. The peak in the MRP population is delayed further, occurring at z < 0.5. We show that the discrepancy between the birthrate of LMXBs and MRPs, found under the assumption of a stead-state SFR, can be resolved for the population as a whole when the effects of a time-variable SFR are included. A discrepancy may persist for LMXBs with short orbital periods, although a detailed population synthesis will be required to confirm this. Further, since the integrated X-ray luminosity distribution of normal galaxies is dominated by X-ray binaries, it should show strong luminosity evolution with redshift. In addition to an enhancement near the peak (z ~ 1.5) of the SFR due to the prompt turn-on of the relatively short-lived massive X-ray binaries and young supernova remnants, we predict a second enhancement by a factor ~10 at a redshift between ~ 0.5 and ~ 1 due to the delayed turn-on of the LMXB population. Deep X-ray observations of galaxies out to z ~ 1 by AXAF will be able to observe this enhancement, and, by determining its shape as a function of redshift, will provide an important new method for constraining evolutionary models of X-ray binaries.Comment: 13 pages, including 1 figure. Accepted for publication in ApJ Letter

Chandra and XMM Observations of the ADC Source 0921-630

We analyze observations of the low mass X-ray binary 2S0921-63 obtained with the gratings and CCDs on Chandra and XMM. This object is a high inclination system showing evidence for an accretion disk corona (ADC). Such a corona has the potential to constrain the properties of the heated accretion disk in this system, and other LMXBs by extension. We find evidence for line emission which is generally consistent with that found by previous experiments, although we are able to detect more lines. For the first time in this source, we find that the iron K line has multiple components. We set limits on the line widths and velocity offsets, and we fit the spectra to photoionization models and discuss the implications for accretion disk corona models. For the first time in any ADC source we use these fits, together with density constraints based on the O VII line ratio, in order to constrain the flux in the medium-ionization region of the ADC. Under various assumptions about the source luminosity this constrains the location of the emitting region. These estimates, together with estimates for the emission measure, favor a scenario in which the intrinsic luminosity of the source is comparable to what we observe.Comment: 40 pages, 11 figures submitted to Ap.

In vivo parasitological measures of artemisinin susceptibility

Parasite clearance data from 18,699 patients with falciparum malaria treated with an artemisinin derivative in areas of low (n=14,539), moderate (n=2077), and high (n=2083) levels of malaria transmission across the world were analyzed to determine the factors that affect clearance rates and identify a simple in vivo screening measure for artemisinin resistance. The main factor affecting parasite clearance time was parasite density on admission. Clearance rates were faster in high-transmission settings and with more effective partner drugs in artemisinin-based combination treatments (ACTs). The result of the malaria blood smear on day 3 (72 h) was a good predictor of subsequent treatment failure and provides a simple screening measure for artemisinin resistance. Artemisinin resistance is highly unlikely if the proportion of patients with parasite densities of <100,000 parasites/microL given the currently recommended 3-day ACT who have a positive smear result on day 3 is <3%; that is, for n patients the observed number with a positive smear result on day 3 does not exceed (n + 60)/24

Brain Specificity of Diffuse Optical Imaging: Improvements from Superficial Signal Regression and Tomography

Functional near infrared spectroscopy (fNIRS) is a portable monitor of cerebral hemodynamics with wide clinical potential. However, in fNIRS, the vascular signal from the brain is often obscured by vascular signals present in the scalp and skull. In this paper, we evaluate two methods for improving in vivo data from adult human subjects through the use of high-density diffuse optical tomography (DOT). First, we test whether we can extend superficial regression methods (which utilize the multiple source–detector pair separations) from sparse optode arrays to application with DOT imaging arrays. In order to accomplish this goal, we modify the method to remove physiological artifacts from deeper sampling channels using an average of shallow measurements. Second, DOT provides three-dimensional image reconstructions and should explicitly separate different tissue layers. We test whether DOT's depth-sectioning can completely remove superficial physiological artifacts. Herein, we assess improvements in signal quality and reproducibility due to these methods using a well-characterized visual paradigm and our high-density DOT system. Both approaches remove noise from the data, resulting in cleaner imaging and more consistent hemodynamic responses. Additionally, the two methods act synergistically, with greater improvements when the approaches are used together

Understanding Changes in Modeled Land Surface Characteristics Prior to Lightning-Initiated Holdover Fire Breakout

Lightning initiated wildfires are only 16% of the total number of wildfires within the United States, but account for 56% of the acreage burned. One of the challenges with lightning-initiated wildfires is their ability to "holdover" which means smolder for up to 2+ weeks before breaking out into a full fledged fire. This work helps characterize the percentage of holdover events due to lightning, and helps quantify changes in the land surface characteristics to help understand trends in soil moisture and vegetation stress that potentially contribute to the fire breaking out into a full wildfire

Using natural experimental studies to guide public health action: turning the evidence-based medicine paradigm on its head.

Despite smaller effect sizes, interventions delivered at population level to prevent non-communicable diseases generally have greater reach, impact and equity than those delivered to high-risk groups. Nevertheless, how to shift population behaviour patterns in this way remains one of the greatest uncertainties for research and policy. Evidence about behaviour change interventions that are easier to evaluate tends to overshadow that for population-wide and system-wide approaches that generate and sustain healthier behaviours. Population health interventions are often implemented as natural experiments, which makes their evaluation more complex and unpredictable than a typical randomised controlled trial (RCT). We discuss the growing importance of evaluating natural experiments and their distinctive contribution to the evidence for public health policy. We contrast the established evidence-based practice pathway, in which RCTs generate 'definitive' evidence for particular interventions, with a practice-based evidence pathway in which evaluation can help adjust the compass bearing of existing policy. We propose that intervention studies should focus on reducing critical uncertainties, that non-randomised study designs should be embraced rather than tolerated and that a more nuanced approach to appraising the utility of diverse types of evidence is required. The complex evidence needed to guide public health action is not necessarily the same as that which is needed to provide an unbiased effect size estimate. The practice-based evidence pathway is neither inferior nor merely the best available when all else fails. It is often the only way to generate meaningful evidence to address critical questions about investing in population health interventions.DO, JP and NW are supported by the Medical Research Council (Unit Programme numbers MC_UU_12015/6 and MC_UU_12015/1). The paper was initially developed in the course of a visiting appointment as Thought Leader in Residence at the School of Public Health at the University of Sydney, for which the intellectual environment and financial support provided by the Prevention Research Collaboration is gratefully acknowledged. It was further developed under the auspices of the Centre for Diet and Activity Research (CEDAR), a UKCRC Public Health Research Centre of Excellence at the University of Cambridge, for which funding from the British Heart Foundation, Economic and Social Research Council, Medical Research Council, National Institute for Health Research and the Wellcome Trust, under the auspices of the United Kingdom Clinical Research Collaboration, is gratefully acknowledge

Discovery of Extremely Embedded X-ray Sources in the R Coronae Australis Star Forming Core

With the XMM-Newton and Chandra observatories, we detected two extremely embedded X-ray sources in the R Corona Australis (R CrA) star forming core, near IRS 7. These sources, designated as XB and XA, have X-ray absorption columns of ~3e23 cm-2 equivalent to AV ~180 mag. They are associated with the VLA centimeter radio sources 10E and 10W, respectively. XA is the counterpart of the near-infrared source IRS 7, whereas XB has no K-band counterpart above 19.4 mag. This indicates that XB is younger than typical Class I protostars, probably a Class 0 protostar or in an intermediate phase between Class 0 and Class I. The X-ray luminosity of XB varied between 29<log LX <31.2 ergs s-1 on timescales of 3-30 months. XB also showed a monotonic increase in X-ray brightness by a factor of two in 30 ksec during an XMM-Newton observation. The XMM-Newton spectra indicate emission from a hot plasma with kT ~3-4 keV and also show fluorescent emission from cold iron. Though the X-ray spectrum from XB is similar to flare spectra from Class I protostars in luminosity and temperature, the light curve does not resemble the lightcurves of magnetically generated X-ray flares because the variability timescale of XB is too long and because variations in X-ray count rate were not accompanied by variations in spectral hardness. The short-term variation of XB may be caused by the partial blocking of the X-ray plasma, while the month-long flux enhancement may be driven by mass accretion.Comment: 26 pages, 8 figures, To be published in ApJ in April 200

The large-scale Quasar-Lyman \alpha\ Forest Cross-Correlation from BOSS

We measure the large-scale cross-correlation of quasars with the Lyman \alpha\ forest absorption in redshift space, using ~ 60000 quasar spectra from Data Release 9 (DR9) of the Baryon Oscillation Spectroscopic Survey (BOSS). The cross-correlation is detected over a wide range of scales, up to comoving separations r of 80 Mpc/h. For r > 15 Mpc/h, we show that the cross-correlation is well fitted by the linear theory prediction for the mean overdensity around a quasar host halo in the standard \Lambda CDM model, with the redshift distortions indicative of gravitational evolution detected at high confidence. Using previous determinations of the Lyman \alpha\ forest bias factor obtained from the Lyman \alpha\ autocorrelation, we infer the quasar bias factor to be b_q = 3.64^+0.13_-0.15 at a mean redshift z=2.38, in agreement with previous measurements from the quasar auto-correlation. We also obtain a new estimate of the Lyman \alpha\ forest redshift distortion factor, \beta_F = 1.1 +/- 0.15, slightly larger than but consistent with the previous measurement from the Lyman \alpha\ forest autocorrelation. The simple linear model we use fails at separations r < 15 Mpc/h, and we show that this may reasonably be due to the enhanced ionization due to radiation from the quasars. We also provide the expected correction that the mass overdensity around the quasar implies for measurements of the ionizing radiation background from the line-of-sight proximity effect.Comment: 24 pages, 6 figures, published in JCA

Estimation of the Rate of SNP Genotyping Errors From DNA Extracted From Different Tissues

High density single nucleotide polymorphism (SNP) genotyping panels provide an alternative to microsatellite markers for genome scans. However, genotype errors have a major impact on power to detect linkage or association and are difficult to detect for SNPs. We estimated error rates with the Affymetrix GeneChip® SNP platform in samples from a family with a mixed set of monozygotic (MZ) and dizygotic (DZ) triplets using lymphocyte, buccal DNA and samples from whole genome amplification using the multiple displacement amplification (MDA) technique. The average call rate from 58,960 SNPs for five genomic samples was 99.48%. Comparison of results for the MZ twins showed only three discordant genotypes (concordance rate 99.995%). The mean concordance rate for comparisons of samples from lymphocyte and buccal DNA was 99.97%. Mendelian inconsistencies were identified in 46 SNPs with errors in one or more family members, a rate of 0.022%. Observed genotype concordance rates between parents, between parents and children, and among siblings were consistent with previously reported allele frequencies and Hardy-Weinberg equilibrium. Using the MDA technique, results for two samples had equivalent high accuracy to results with genomic samples. However, the SNP call rate for the remaining seven samples varied from 72.5% to 99.5%, with an average of 86.11%. Quality of the DNA sample following the MDA reaction appears to be the critical factor in SNP call rate for MDA samples. Our results demonstrate highly accurate and reproducible genotyping for the Affymetrix GeneChip® Human Mapping Set in lymphocyte and buccal DNA samples.</p

MicroRNA-143 activation regulates smooth muscle and endothelial cell crosstalk in pulmonary arterial hypertension

Rationale: The pathogenesis of PAH remains unclear. The four microRNAs representing the miR-143 and miR-145 stem loops are genomically clustered. Objective: To elucidate the transcriptional regulation of the miR-143/145 cluster, and the role of miR-143 in PAH. Methods and Results: We identified the promoter region that regulates miR-143/145 miRNA expression in pulmonary artery smooth muscle cells (PASMCs). We mapped PAH-related signalling pathways, including estrogens receptor (ER), liver X factor/retinoic X receptor (LXR/RXR), TGF-β (Smads), and hypoxia (HRE) that regulated levels of all pri-miR stem loop transcription and resulting miRNA expression. We observed that miR-143-3p is selectively upregulated compared to miR-143-5p during PASMC migration. Modulation of miR-143 in PASMCs significantly altered cell migration and apoptosis. In addition, we found high abundance of miR-143-3p in PASMCs-derived exosomes. Using assays with pulmonary arterial endothelial cells (PAECs) we demonstrated a paracrine pro-migratory and pro-angiogenic effect of miR-143-3p enriched exosomes from PASMC. Quantitative PCR and in situ hybridisation showed elevated expression of miR-143 in calf models of PAH as well as in samples from PAH patients. Moreover, in contrast to our previous findings that had not supported a therapeutic role in vivo, we now demonstrate a protective role for miR-143 in experimental PH in vivo in miR-143-/- and antimiR143-3p-treated mice exposed to chronic hypoxia in both preventative and reversal settings. Conclusions: MiR-143-3p modulated both cellular and exosome-mediated responses in pulmonary vascular cells, while inhibition of miR-143-3p blocked experimental PH. Taken together these findings confirm an important role for the miR-143/145 cluster in PAH pathobiology