Spontaneous Chelation-Driven Reduction of the Neptunyl Cation in Aqueous Solution.

Octadentate hydroxypyridinone (HOPO) and catecholamide (CAM) siderophore analogues are known to be efficacious chelators of the actinide cations, and these ligands are also capable of facilitating both activation and reduction of actinyl species. Utilizing X-ray absorption near edge structure (XANES) and extended X-ray absorption fine structure (EXAFS) spectroscopies, as well as cyclic voltammetry measurements, herein, we elucidate chelation-based mechanisms for driving reactivity and initiating redox processes in a family of neptunyl-HOPO and CAM complexes. Based on the selected chelator, the ability to control the oxidation state of neptunium and the speed of reduction and concurrent oxo group activation was demonstrated. Most notably, reduction kinetics for the NpV O2 +/ /NpIV redox couple upon chelation by the ligands 3,4,3-LI(1,2-HOPO) and 3,4,3-LI(CAM)2 (1,2-HOPO)2 was observed to be faster than ever reported, and in fact quicker than we could measure using either X-ray absorption spectroscopy or electrochemical techniques

Dynamical Imaging with Interferometry

By linking widely separated radio dishes, the technique of very long baseline interferometry (VLBI) can greatly enhance angular resolution in radio astronomy. However, at any given moment, a VLBI array only sparsely samples the information necessary to form an image. Conventional imaging techniques partially overcome this limitation by making the assumption that the observed cosmic source structure does not evolve over the duration of an observation, which enables VLBI networks to accumulate information as the Earth rotates and changes the projected array geometry. Although this assumption is appropriate for nearly all VLBI, it is almost certainly violated for submillimeter observations of the Galactic Center supermassive black hole, Sagittarius A* (Sgr A*), which has a gravitational timescale of only ~20 seconds and exhibits intra-hour variability. To address this challenge, we develop several techniques to reconstruct dynamical images ("movies") from interferometric data. Our techniques are applicable to both single-epoch and multi-epoch variability studies, and they are suitable for exploring many different physical processes including flaring regions, stable images with small time-dependent perturbations, steady accretion dynamics, or kinematics of relativistic jets. Moreover, dynamical imaging can be used to estimate time-averaged images from time-variable data, eliminating many spurious image artifacts that arise when using standard imaging methods. We demonstrate the effectiveness of our techniques using synthetic observations of simulated black hole systems and 7mm Very Long Baseline Array observations of M87, and we show that dynamical imaging is feasible for Event Horizon Telescope observations of Sgr A*.Comment: 16 Pages, 12 Figures, Accepted for publication in Ap

Deep-Sea Oxygen Depletion and Ocean Carbon Sequestration During the Last Ice Age

Enhanced ocean carbon storage during the Pleistocene ice ages lowered atmospheric CO2 concentrations by 80 to 100 ppm relative to interglacial levels. Leading hypotheses to explain this phenomenon invoke a greater efficiency of the ocean's biological pump, in which case carbon storage in the deep sea would have been accompanied by a corresponding reduction in dissolved oxygen. We exploit the sensitivity of organic matter preservation in marine sediments to bottom water oxygen concentration to constrain the level of dissolved oxygen in the deep central equatorial Pacific Ocean during the last glacial period (18,000–28,000 years BP) to have been within the range of 20–50 μmol/kg, much less than the modern value of ~168 μmol/kg. We further demonstrate that reduced oxygen levels characterized the water column below a depth of ~1,000 m. Converting the ice age oxygen level to an equivalent concentration of respiratory CO2, and extrapolating globally, we estimate that deep‐sea CO2 storage during the last ice age exceeded modern values by as much as 850 Pg C, sufficient to balance the loss of carbon from the atmosphere (~200 Pg C) and from the terrestrial biosphere (~300–600 Pg C). In addition, recognizing the enhanced preservation of organic matter in ice age sediments of the deep Pacific Ocean helps reconcile previously unexplained inconsistencies among different geochemical and micropaleontological proxy records used to assess past changes in biological productivity of the ocean.Several grants from the U.S. National Science Foundation supported the production of the data reported here during the course of previous studies. However, the synthesis of results presented here was carried out without directed grant support except that S. L. J. acknowledges financial support by the Swiss National Science Foundation (grants PP00P2‐144811 and PP00P2‐172915)

Widespread nitrogen fixation in sediments from diverse deep-sea sites of elevated carbon loading

Nitrogen fixation, the biological conversion of N_2 to NH_3, is critical to alleviating nitrogen limitation in many marine ecosystems. To date, few measurements exist of N_2 fixation in deep‐sea sediments. Here, we conducted > 400 bottle incubations with sediments from methane seeps, whale falls and background sites off the western coast of the United States from 600 to 2893 m water depth to investigate the potential rates, spatial distribution and biological mediators of benthic N_2 fixation. We found that N2 fixation was widespread, yet heterogeneously distributed with sediment depth at all sites. In some locations, rates exceeded previous measurements by > 10×, and provided up to 30% of the community anabolic growth requirement for nitrogen. Diazotrophic activity appeared to be inhibited by pore water ammonium: N_2 fixation was only observed if incubation ammonium concentrations were ≤ 25 μM, and experimental additions of ammonium reduced diazotrophy. In seep sediments, N_2 fixation was dependent on CH_4 and coincident with sulphate reduction, consistent with previous work showing diazotrophy by microorganisms mediating sulphate‐coupled methane oxidation. However, the pattern of diazotrophy was different in whale‐fall and associated reference sediments, where it was largely unaffected by CH_4, suggesting catabolically different diazotrophs at these sites

Association of BCG, DTP, and measles containing vaccines with childhood mortality:systematic review

Objectives To evaluate the effects on non-specific and all cause mortality, in children under 5, of Bacillus Calmette-Guérin (BCG), diphtheria-tetanus-pertussis (DTP), and standard titre measles containing vaccines (MCV); to examine internal validity of the studies; and to examine any modifying effects of sex, age, vaccine sequence, and co-administration of vitamin A. Design Systematic review, including assessment of risk of bias, and meta-analyses of similar studies. Study eligibility criteria Clinical trials, cohort studies, and case-control studies of the effects on mortality of BCG, whole cell DTP, and standard titre MCV in children under 5. Data sources Searches of Medline, Embase, Global Index Medicus, and the WHO International Clinical Trials Registry Platform, supplemented by contact with experts in the field. To avoid overlap in children studied across the included articles, findings from non-overlapping birth cohorts were identified. Results Results from 34 birth cohorts were identified. Most evidence was from observational studies, with some from short term clinical trials. Most studies reported on all cause (rather than non-specific) mortality. Receipt of BCG vaccine was associated with a reduction in all cause mortality: the average relative risks were 0.70 (95% confidence interval 0.49 to 1.01) from five clinical trials and 0.47 (0.32 to 0.69) from nine observational studies at high risk of bias. Receipt of DTP (almost always with oral polio vaccine) was associated with a possible increase in all cause mortality on average (relative risk 1.38, 0.92 to 2.08) from 10 studies at high risk of bias; this effect seemed stronger in girls than in boys. Receipt of standard titre MCV was associated with a reduction in all cause mortality (relative risks 0.74 (0.51 to 1.07) from four clinical trials and 0.51 (0.42 to 0.63) from 18 observational studies at high risk of bias); this effect seemed stronger in girls than in boys. Seven observational studies, assessed as being at high risk of bias, have compared sequences of vaccines; results of a subset of these suggest that administering DTP with or after MCV may be associated with higher mortality than administering it before MCV. Conclusions Evidence suggests that receipt of BCG and MCV reduce overall mortality by more than would be expected through their effects on the diseases they prevent, and receipt of DTP may be associated with an increase in all cause mortality. Although efforts should be made to ensure that all children are immunised on schedule with BCG, DTP, and MCV, randomised trials are needed to compare the effects of different sequences

Human Tra2 proteins jointly control a CHEK1 splicing switch among alternative and constitutive target exons

Alternative splicing—the production of multiple messenger RNA isoforms from a single gene—is regulated in part by RNA binding proteins. While the RBPs transformer2 alpha (Tra2α) and Tra2β have both been implicated in the regulation of alternative splicing, their relative contributions to this process are not well understood. Here we find simultaneous—but not individual—depletion of Tra2α and Tra2β induces substantial shifts in splicing of endogenous Tra2β target exons, and that both constitutive and alternative target exons are under dual Tra2α–Tra2β control. Target exons are enriched in genes associated with chromosome biology including CHEK1, which encodes a key DNA damage response protein. Dual Tra2 protein depletion reduces expression of full-length CHK1 protein, results in the accumulation of the DNA damage marker γH2AX and decreased cell viability. We conclude Tra2 proteins jointly control constitutive and alternative splicing patterns via paralog compensation to control pathways essential to the maintenance of cell viability

Knowledge practices in design: The role of visual representations as 'epistemic objects'

We use a detailed study of the knowledge work around visual representations to draw attention to the multidimensional nature of `objects'. Objects are variously described in the literatures as relatively stable or in flux; as abstract or concrete; and as used within or across practices. We clarify these dimensions, drawing on and extending the literature on boundary objects, and connecting it with work on epistemic and technical objects. In particular, we highlight the epistemic role of objects, using our observations of knowledge work on an architectural design project to show how, in this setting, visual representations are characterized by a `lack' or incompleteness that precipitates unfolding. The conceptual design of a building involves a wide range of technical, social and aesthetic forms of knowledge that need to be developed and aligned. We explore how visual representations are used, and how these are meaningful to different stakeholders, eliciting their distinct contributions. As the project evolves and the drawings change, new issues and needs for knowledge work arise. These objects have an `unfolding ontology' and are constantly in flux, rather than fully formed. We discuss the implications for wider understandings of objects in organizations and for how knowledge work is achieved in practice

Multidecadal observations of the Antarctic ice sheet from restored analog radar records.

Airborne radar sounding can measure conditions within and beneath polar ice sheets. In Antarctica, most digital radar-sounding data have been collected in the last 2 decades, limiting our ability to understand processes that govern longer-term ice-sheet behavior. Here, we demonstrate how analog radar data collected over 40 y ago in Antarctica can be combined with modern records to quantify multidecadal changes. Specifically, we digitize over 400,000 line kilometers of exploratory Antarctic radar data originally recorded on 35-mm optical film between 1971 and 1979. We leverage the increased geometric and radiometric resolution of our digitization process to show how these data can be used to identify and investigate hydrologic, geologic, and topographic features beneath and within the ice sheet. To highlight their scientific potential, we compare the digitized data with contemporary radar measurements to reveal that the remnant eastern ice shelf of Thwaites Glacier in West Antarctica had thinned between 10 and 33% between 1978 and 2009. We also release the collection of scanned radargrams in their entirety in a persistent public archive along with updated geolocation data for a subset of the data that reduces the mean positioning error from 5 to 2.5 km. Together, these data represent a unique and renewed extensive, multidecadal historical baseline, critical for observing and modeling ice-sheet change on societally relevant timescales

Prescription opioid use disorder and heroin use among 12-34 year-olds in the United States from 2002 to 2014

Trend analyses of prescription opioids in the U.S. indicate use, especially use of prescription opioids stronger than morphine, has more than doubled among adults since the early 1990's (Frenk, Porter, & Paulozzi, 2015). Prescription opioids, like Oxycontin®, are effective pharmacological treatments for acute and chronic pain (Fitzcharles and Shir, 2009 ; Gallagher and Rosenthal, 2008). When used as indicated, these medications can be an important component of pain management. However, their high abuse potential presents concerns regarding their nonmedical use, which can be defined as ‘use of a prescription opioid that was not prescribed, or taken for the experience or feeling it caused’ (SAMHSA, 2014). In the United States, nonmedical use of prescription opioids (NMPO) is increasingly recognized as a serious public health problem among adults (Blanco et al., 2007; Han et al., 2015 ; Huang et al., 2006). Nonmedical prescription drug use, specifically nonmedical use of prescription opioids, is also a growing problem in other countries such as Canada (Fischer et al., 2014 ; Fischer et al., 2013) and Australia (Degenhardt et al., 2006 ; Rintoul et al., 2011)

Rapid emergence of multidrug resistant, H58-lineage Salmonella typhi in Blantyre, Malawi.

INTRODUCTION: Between 1998 and 2010, S. Typhi was an uncommon cause of bloodstream infection (BSI) in Blantyre, Malawi and it was usually susceptible to first-line antimicrobial therapy. In 2011 an increase in a multidrug resistant (MDR) strain was detected through routine bacteriological surveillance conducted at Queen Elizabeth Central Hospital (QECH). METHODS: Longitudinal trends in culture-confirmed Typhoid admissions at QECH were described between 1998-2014. A retrospective review of patient cases notes was conducted, focusing on clinical presentation, prevalence of HIV and case-fatality. Isolates of S. Typhi were sequenced and the phylogeny of Typhoid in Blantyre was reconstructed and placed in a global context. RESULTS: Between 1998-2010, there were a mean of 14 microbiological diagnoses of Typhoid/year at QECH, of which 6.8% were MDR. This increased to 67 in 2011 and 782 in 2014 at which time 97% were MDR. The disease predominantly affected children and young adults (median age 11 [IQR 6-21] in 2014). The prevalence of HIV in adult patients was 16.7% [8/48], similar to that of the general population (17.8%). Overall, the case fatality rate was 2.5% (3/94). Complications included anaemia, myocarditis, pneumonia and intestinal perforation. 112 isolates were sequenced and the phylogeny demonstrated the introduction and clonal expansion of the H58 lineage of S. Typhi. CONCLUSIONS: Since 2011, there has been a rapid increase in the incidence of multidrug resistant, H58-lineage Typhoid in Blantyre. This is one of a number of reports of the re-emergence of Typhoid in Southern and Eastern Africa. There is an urgent need to understand the reservoirs and transmission of disease and how to arrest this regional increase