Dense Cores in Dark Clouds. XIV. N2H+(1-0) maps of dense cloud cores

We present results of an extensive mapping survey of N2H+(1-0) in about 60 low mass cloud cores already mapped in the NH3(1,1) inversion transition line. The survey has been carried out at the FCRAO antenna with an angular resolution about 1.5 times finer than the previous ammonia observations. Cores with stars typically have map sizes about a factor of two smaller for N2H+ than for NH3, indicating the presence of denser and more centrally concentrated gas compared to starless cores. Significant correlations are found between NH3 and N2H+ column densities and excitation temperatures in starless cores, but not in cores with stars, suggesting a different chemical evolution of the two species. Velocity gradients range between 0.5 and 6 km/s/pc, similar to what has been found with NH3 data. ``Local'' velocity gradients show significant variation in both magnitude and direction, suggesting the presence of complexmotions not interpretable as simple solid body rotation. Integrated intensity profiles of starless cores present a ``central flattening'' and are consistent with a spherically symmetric density law n ~ r^{-1.2} for r < ~0.03 pc and n ~ r^{-2} at larger r. Cores with stars are better modelled with single density power laws with n ~ r^{-2}. Line widths change across the core but we did not find a general trend. The deviation in line width correlates with the mean line width, suggesting that the line of sight contains ~ 10 coherence lengths. The corresponding value of the coherence length, ~ 0.01 pc, is similar to the expected cutoff wavelength for MHD waves. This similarity may account for the increased ``coherence'' of line widths on small scales. Despite of the finer angular resolution, the majority of N2H+ and NH3 maps show a similar ``simple'' structure, with single peaks and no elongation.Comment: 62 pages, 11 figures, ApJ, in pres

An Optical Study of BG Geminorum: An Ellipsoidal Binary with an Unseen Primar Star

We describe optical photometric and spectroscopic observations of the bright variable BG Geminorum. Optical photometry shows a pronounced ellipsoidal variation of the K0 I secondary, with amplitudes of ~0.5 mag at VRI and a period of 91.645 days. A deep primary eclipse is visible for wavelengths < 4400A; a shallower secondary eclipse is present at longer wavelengths. Eclipse timings and the radial velocity curve of the K0 secondary star indicate an interacting binary where a lobe-filling secondary, M_2 ~ 0.5 Msun, transfers material into a extended disk around a massive primary, M_1 ~ 4.5 Msun. The primary star is either an early B-type star or a black hole. If it did contain a black hole, BG Gem would be the longest period black hole binary known by a factor of 10, as well as the only eclipsing black hole binary system.Comment: 27 pages, includes 8 figures and 5 tables, accepted to A

The Eclipsing Binary BG Geminorum: Improved Constraints on the Orbit and the Structure of the Accretion Disk

We describe new optical photometric and spectroscopic observations of the semi-detached eclipsing binary BG Geminorum. A large change in the amount of Mg I absorption at secondary maximum indicates the presence of cool material in the outer edge of the disk surrounding the unseen primary star. Detection of weak He I emission implies a hot radiation source at the inner edge of the disk. If the velocity variations in the Hbeta emission line track the orbital motion of the primary star, the primary star has an orbital semiamplitude of K1 = K(Hbeta) = 16.0 +- 4.6 km/sec. This result yields a mass ratio, q = 0.22 +- 0.07, consistent with the q = 0.1 derived from the large ellipsoidal variation. Despite this progress, the nature of the primary star - B-type star or black hole - remains uncertain.Comment: 9 pages of text, 3 tables, and 4 figures; to appear in AJ, August 200

The type Ia supernova 1998bu in M96 and the Hubble constant

We present optical and near-infrared photometry and spectroscopy of the Type Ia SN 1998bu in the Leo I Group galaxy M96 (NGC 3368). The data set consists of 356 photometric measurements and 29 spectra of SN 1998bu between UT 1998 May 11 and July 15. The well-sampled light curve indicates the supernova reached maximum light in B on UT 1998 May 19.3 (JD 2450952.8^0.8) with B\12.22^0.03 and V \11.88^0.02. Application of a revised version of the Multicolor Light Curve Shape (MLCS) method yields an extinction toward the supernova of AV\0.94^0.15 mag, and indicates the supernova was of average luminosity compared to other normal Type Ia supernovae. Using the HST Cepheid distance modulus to M96 and the MLCS Ðtted parameters for the supernova, we derive an extinction-corrected absolute magnitude for SN 1998bu at maximum, MV\[19.42^0.22. Our independent results for this supernova are consistent with those of Suntzeff et al. Combining SN 1998bu with three other well-observed local calibrators and 42 supernovae in the Hubble Ñow yields a Hubble constant, H0\64 km s~1 Mpc~1, where the error estimate incorporates possible sources of systematic uncertainty including the calibration of the Cepheid period-luminosity relation, the metallicity dependence of the Cepheid distance scale, and the distance to the LMC.E. K. G. gratefully acknowledges support by Dennis Zaritsky through NASA LTSA grant NAG-5-3501 and by NASA through grant HF01108.01-98A from the Space Telescope Science Institute, which is operated by the Association of Universities for Research in Astronomy, Inc., under NASA contract NAS5- 26555. This work was also supported by NSF grants AST9528899 (R. P. K.), AST-9417213 (A. V. F.), and AST-9417359 (P. J. B.), as well as through an NSF Graduate Research Fellowship (S. J.)

Assembling a global database of malaria parasite prevalence for the Malaria Atlas Project

BACKGROUND: Open access to databases of information generated by the research community can synergize individual efforts and are epitomized by the genome mapping projects. Open source models for outputs of scientific research funded by tax-payers and charities are becoming the norm. This has yet to be extended to malaria epidemiology and control. METHODS: The exhaustive searches and assembly process for a global database of malaria parasite prevalence as part of the Malaria Atlas Project (MAP) are described. The different data sources visited and how productive these were in terms of availability of parasite rate (PR) data are presented, followed by a description of the methods used to assemble a relational database and an associated geographic information system. The challenges facing spatial data assembly from varied sources are described in an effort to help inform similar future applications. RESULTS: At the time of writing, the MAP database held 3,351 spatially independent PR estimates from community surveys conducted since 1985. These include 3,036 Plasmodium falciparum and 1,347 Plasmodium vivax estimates in 74 countries derived from 671 primary sources. More than half of these data represent malaria prevalence after the year 2000. CONCLUSION: This database will help refine maps of the global spatial limits of malaria and be the foundation for the development of global malaria endemicity models as part of MAP. A widespread application of these maps is envisaged. The data compiled and the products generated by MAP are planned to be released in June 2009 to facilitate a more informed approach to global malaria control

US Cosmic Visions: New Ideas in Dark Matter 2017: Community Report

This white paper summarizes the workshop "U.S. Cosmic Visions: New Ideas in Dark Matter" held at University of Maryland on March 23-25, 2017.Comment: 102 pages + reference

Decidual-Secreted Factors Alter Invasive Trophoblast Membrane and Secreted Proteins Implying a Role for Decidual Cell Regulation of Placentation

Inadequate or inappropriate implantation and placentation during the establishment of human pregnancy is thought to lead to first trimester miscarriage, placental insufficiency and other obstetric complications. To create the placental blood supply, specialized cells, the ‘extravillous trophoblast’ (EVT) invade through the differentiated uterine endometrium (the decidua) to engraft and remodel uterine spiral arteries. We hypothesized that decidual factors would regulate EVT function by altering the production of EVT membrane and secreted factors. We used a proteomics approach to identify EVT membrane and secreted proteins regulated by decidual cell factors. Human endometrial stromal cells were decidualized in vitro by treatment with estradiol (10−8 M), medroxyprogesterone acetate (10−7 M) and cAMP (0.5 mM) for 14 days. Conditioned media (CM) was collected on day 2 (non-decidualized CM) and 14 (decidualized CM) of treatment. Isolated primary EVT cultured on Matrigel™ were treated with media control, non-decidualized or decidualized CM for 16 h. EVT CM was fractionated for proteins <30 kDa using size-exclusion affinity nanoparticles (SEAN) before trypsin digestion and HPLC-MS/MS. 43 proteins produced by EVT were identified; 14 not previously known to be expressed in the placenta and 12 which had previously been associated with diseases of pregnancy including preeclampsia. Profilin 1, lysosome associated membrane glycoprotein 1 (LAMP1), dipeptidyl peptidase 1 (DPP1/cathepsin C) and annexin A2 expression by interstitial EVT in vivo was validated by immunhistochemistry. Decidual CM regulation in vitro was validated by western blotting: decidualized CM upregulated profilin 1 in EVT CM and non-decidualized CM upregulated annexin A2 in EVT CM and pro-DPP1 in EVT cell lysate. Here, non-decidualized factors induced protease expression by EVT suggesting that non-decidualized factors may induce a pro-inflammatory cascade. Preeclampsia is a pro-inflammatory condition. Overall, we have demonstrated the potential of a proteomics approach to identify novel proteins expressed by EVT and to uncover the mechanisms leading to disease states

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Dolutegravir twice-daily dosing in children with HIV-associated tuberculosis: a pharmacokinetic and safety study within the open-label, multicentre, randomised, non-inferiority ODYSSEY trial

Background: Children with HIV-associated tuberculosis (TB) have few antiretroviral therapy (ART) options. We aimed to evaluate the safety and pharmacokinetics of dolutegravir twice-daily dosing in children receiving rifampicin for HIV-associated TB. Methods: We nested a two-period, fixed-order pharmacokinetic substudy within the open-label, multicentre, randomised, controlled, non-inferiority ODYSSEY trial at research centres in South Africa, Uganda, and Zimbabwe. Children (aged 4 weeks to <18 years) with HIV-associated TB who were receiving rifampicin and twice-daily dolutegravir were eligible for inclusion. We did a 12-h pharmacokinetic profile on rifampicin and twice-daily dolutegravir and a 24-h profile on once-daily dolutegravir. Geometric mean ratios for trough plasma concentration (Ctrough), area under the plasma concentration time curve from 0 h to 24 h after dosing (AUC0–24 h), and maximum plasma concentration (Cmax) were used to compare dolutegravir concentrations between substudy days. We assessed rifampicin Cmax on the first substudy day. All children within ODYSSEY with HIV-associated TB who received rifampicin and twice-daily dolutegravir were included in the safety analysis. We described adverse events reported from starting twice-daily dolutegravir to 30 days after returning to once-daily dolutegravir. This trial is registered with ClinicalTrials.gov (NCT02259127), EudraCT (2014–002632-14), and the ISRCTN registry (ISRCTN91737921). Findings: Between Sept 20, 2016, and June 28, 2021, 37 children with HIV-associated TB (median age 11·9 years [range 0·4–17·6], 19 [51%] were female and 18 [49%] were male, 36 [97%] in Africa and one [3%] in Thailand) received rifampicin with twice-daily dolutegravir and were included in the safety analysis. 20 (54%) of 37 children enrolled in the pharmacokinetic substudy, 14 of whom contributed at least one evaluable pharmacokinetic curve for dolutegravir, including 12 who had within-participant comparisons. Geometric mean ratios for rifampicin and twice-daily dolutegravir versus once-daily dolutegravir were 1·51 (90% CI 1·08–2·11) for Ctrough, 1·23 (0·99–1·53) for AUC0–24 h, and 0·94 (0·76–1·16) for Cmax. Individual dolutegravir Ctrough concentrations were higher than the 90% effective concentration (ie, 0·32 mg/L) in all children receiving rifampicin and twice-daily dolutegravir. Of 18 children with evaluable rifampicin concentrations, 15 (83%) had a Cmax of less than the optimal target concentration of 8 mg/L. Rifampicin geometric mean Cmax was 5·1 mg/L (coefficient of variation 71%). During a median follow-up of 31 weeks (IQR 30–40), 15 grade 3 or higher adverse events occurred among 11 (30%) of 37 children, ten serious adverse events occurred among eight (22%) children, including two deaths (one tuberculosis-related death, one death due to traumatic injury); no adverse events, including deaths, were considered related to dolutegravir. Interpretation: Twice-daily dolutegravir was shown to be safe and sufficient to overcome the rifampicin enzyme-inducing effect in children, and could provide a practical ART option for children with HIV-associated TB