Examining pelagic carbonate-rich sediments as an archive for authigenic uranium and molybdenum isotopes using reductive cleaning and leaching experiments

Novel metal isotope systematics are increasingly used to understand environmental change in geological history. On a global scale, the isotopic budgets of these metals respond to a range of environmental processes, allowing them to trace complex changes in the global climate system and carbon cycle. In particular, uranium (U) and molybdenum (Mo) isotopes are useful tools for quantifying the global extent of oceanic anoxia and euxinia respectively. The oceanic signature of these metals is recorded in contemporaneous marine sediments. Whilst, traditionally, organic-rich anoxic ‘black shales’ have provided a useful archive of these metals, carbonate sediments are increasingly being used as a passive recorder of ocean chemistry. The majority of published U and Mo isotope studies come from shallow water platform environments. By contrast, pelagic carbonate sediments are an under-explored archive for these metals, yet are widely available for important periods of Earth history. Despite their advantages, carbonates are a complex archive, containing multiple ‘contaminant’ components such as Mn-oxides, organic matter and detrital minerals. Each of these phases can have different metal concentrations and isotopic signatures, giving the potential to distort or bias the true oceanic signature recorded by the carbonate. Reductive cleaning procedures and selective leaching protocols can be used to avoid these contaminant phases, and are tested here on modern and ancient samples to judge their efficacy in isolating a ‘carbonate-bound fraction’. To this end, leaching experiments were performed using different concentration acetic acid, HCl and HNO3, on reductively cleaned and uncleaned sample pairs. The data demonstrate that Mn-oxide coatings and exchangeable phases have a large impact on the Mo isotopic signature (δ98Mo) of carbonates, even when weak leaching techniques are used to preferentially dissolve them. Furthermore, detrital sources of Mo are also easy to liberate with different leaching protocols, and exert a significant control on leachate isotopic composition. The leaching studies identify that the pelagic carbonate end-member has a relatively high δ98Mo, but the precise relationship to seawater compositions remains unclear. For U, significant contributions from non‑carbonate phases can clearly be identified in higher concentration leaching acids using U/Ca ratios. However, U isotopes (δ238U) show no resolvable difference with different leaching procedures and are not affected by reductive cleaning. This result probably reflects (a) the low potential for leaching refractory residual detrital U phases (e.g., zircon) that contain the majority of U in the sample and (b) the low U inventories of Mn oxides versus those of Mo. Instead, leaching likely extracts U that is mineralogically bound in carbonates and authigenic clays, which share a common isotopic signature. These new data suggest that U incorporation into pelagic carbonates may be dominated by adsorption, and be offset from seawater by ~−0.15‰, in a similar manner to that seen for clays

Upper limits on the extent of seafloor anoxia during the PETM from uranium isotopes.

The Paleocene Eocene Thermal Maximum (PETM) represents a major carbon cycle and climate perturbation that was associated with ocean de-oxygenation, in a qualitatively similar manner to the more extensive Mesozoic Oceanic Anoxic Events. Although indicators of ocean de-oxygenation are common for the PETM, and linked to biotic turnover, the global extent and temporal progression of de-oxygenation is poorly constrained. Here we present carbonate associated uranium isotope data for the PETM. A lack of resolvable perturbation to the U-cycle during the event suggests a limited expansion of seafloor anoxia on a global scale. We use this result, in conjunction with a biogeochemical model, to set an upper limit on the extent of global seafloor de-oxygenation. The model suggests that the new U isotope data, whilst also being consistent with plausible carbon emission scenarios and observations of carbon cycle recovery, permit a maximum ~10-fold expansion of anoxia, covering <2% of seafloor area

Latent Disentanglement in Mesh Variational Autoencoders Improves the Diagnosis of Craniofacial Syndromes and Aids Surgical Planning

The use of deep learning to undertake shape analysis of the complexities of the human head holds great promise. However, there have traditionally been a number of barriers to accurate modelling, especially when operating on both a global and local level. In this work, we will discuss the application of the Swap Disentangled Variational Autoencoder (SD-VAE) with relevance to Crouzon, Apert and Muenke syndromes. Although syndrome classification is performed on the entire mesh, it is also possible, for the first time, to analyse the influence of each region of the head on the syndromic phenotype. By manipulating specific parameters of the generative model, and producing procedure-specific new shapes, it is also possible to simulate the outcome of a range of craniofacial surgical procedures. This opens new avenues to advance diagnosis, aids surgical planning and allows for the objective evaluation of surgical outcomes

Improved catalytic activity of ruthenium–arene complexes in the reduction of NAD+

A series of neutral Ru-II half-sandwich complexes of the type [(eta(6)-arene)Ru(N,N')Cl] where the arene is para-cymene (p-cym), hexamethylbenzene (hmb), biphenyl (bip), or benzene (bn) and N,N' is N-(2-aminoethyl) -4-(trifluoromethyl)benzenesulfonamide (TfEn), N-(2-aminoethyl)-4-toluenesulfonamide (TsEn), or N-(2-aminoethyl)-methylenesulfonamide (MsEn) were synthesized and characterized. X-ray crystal structures of [(p-cym)Ru(MsEn)Cl] (1), [(hmb)Ru(TsEn)Cl] (5), [(hmb)Ru(TfEn)Cl] (6), [(bip)Ru(MsEn)Cl] (7), and [(bip)Ru(TsEn)Cl] (8) have been determined. The complexes can regioselectively catalyze the transfer hydrogenation of NAD(+) to give 1,4-NADH in the presence of formate. The turnover frequencies (TOF) when the arene is varied decrease in the order bn > bip > p-cym > hmb for complexes with the same N,N' chelating ligand. The TOF decreased with variation in the N,N' chelating ligand in the order TfEn > TsEn > MsEn for a given arene. [(bn)Ru(TfEn)Cl] (12) was the most active, with a TOP of 10.4 h(-1). The effects of NAD(+) and formate concentration on the reaction rates were determined for [(p-cym)Ru(TsEn)Cl] (2). Isotope studies implicated the formation of [(arene)Ru(N,N')(H)] as the rate-limiting step. The coordination of formate and subsequent CO2 elimination to generate the hydride were modeled computationally by density functional theory (DFT). CO2 elimination occurs via a two-step process with the coordinated formate first twisting to present its hydrogen toward the metal center. The computed barriers for CO2 release for arene = benzene follow the order MsEn > TsEn > TfEn, and for the Ms En system the barrier followed bn < hmb, both consistent with the observed rates. The effect of methanol on transfer hydrogenation rates in aqueous solution was investigated. A study of pH dependence of the reaction in D2O gave the optimum pH* as 7.2 with a TOF of 1.58 h(-1) for 2. The series of compounds reported here show an improvement in the catalytic activity by an order of magnitude compared to the ethylenediamine analogues

Identification of Pik3ca mutation as a genetic driver of prostate cancer that cooperates with Pten loss to accelerate progression and castration-resistant growth

Genetic alterations that potentiate PI3K signalling are frequent in prostate cancer, yet how different genetic drivers of the PI3K cascade contribute to prostate cancer is unclear. Here, we report PIK3CA mutation/amplification correlates with poor prostate cancer patient survival. To interrogate the requirement of different PI3K genetic drivers in prostate cancer, we employed a genetic approach to mutate Pik3ca in mouse prostate epithelium. We show Pik3caH1047R mutation causes p110-dependent invasive prostate carcinoma in-vivo. Furthermore, we report PIK3CA mutation and PTEN loss co-exist in prostate cancer patients, and can cooperate in-vivo to accelerate disease progression via AKT-mTORC1/2 hyperactivation. Contrasting single mutants that slowly acquire castration-resistant prostate cancer (CRPC), concomitant Pik3ca mutation and Pten loss caused de-novo CRPC. Thus, Pik3ca mutation and Pten deletion are not functionally redundant. Our findings indicate that PIK3CA mutation is an attractive prognostic indicator for prostate cancer that may cooperate with PTEN loss to facilitate CRPC in patients

The Bulge Metallicity Distribution from the APOGEE Survey

The Apache Point Observatory Galactic Evolution Experiment (APOGEE) provides spectroscopic information of regions of the inner Milky Way, which are inaccessible to optical surveys. We present the first large study of the metallicity distribution of the innermost Galactic regions based on high-quality measurements for 7545 red giant stars within 4.5 kpc of the Galactic center, with the goal to shed light on the structure and origin of the Galactic bulge. Stellar metallicities are found, through multiple Gaussian decompositions, to be distributed in several components, which is indicative of the presence of various stellar populations such as the bar or the thin and the thick disks. Super-solar ([Fe/H] = +0.32) and solar ([Fe/H] = +0.00) metallicity components, tentatively associated with the thin disk and the Galactic bar, respectively, seem to be major contributors near the midplane. A solar-metallicity component extends outwards in the midplane but is not observed in the innermost regions. The central regions (within 3 kpc of the Galactic center) reveal, on the other hand, the presence of a significant metal-poor population ([Fe/H] = −0.46), tentatively associated with the thick disk, which becomes the dominant component far from the midplane ($| Z| \geqslant +0.75$ kpc). Varying contributions from these different components produce a transition region at +0.5 kpc $\leqslant \,| Z| \,\leqslant \ +1.0\,\mathrm{kpc}$, characterized by a significant vertical metallicity gradient

Effective use of cerium anomalies as a redox proxy in carbonate-dominated marine settings

Rare earth elements and yttrium (REY) have a distinct distribution pattern in seawater, and this pattern may be faithfully preserved in carbonate sediments and rocks. Anomalous concentrations of redox-sensitive cerium (Ce) compared with neighbouring REY originate in oxic water column conditions, and as such, Ce anomalies can provide a potentially useful redox proxy in carbonate-dominated marine settings. The methods used to extract REY from carbonates vary widely, and may suffer from widespread leaching of REY from accessory non-carbonate minerals and organic matter, limiting the application of Ce anomalies for palaeo-redox reconstruction. We have systematically compared different methods on 195 carbonate samples with varying purity (% carbonate) from both modern and ancient environments. We used sequential leaching experiments in nitric acid to identify the most ‘seawater-like’ portion of the carbonate sample where contributions from non-carbonate minerals and organic matter are minimised. We also compared the results of sample dissolution in different types and strengths of acid. Our results confirm that REY concentrations can be inadvertently contaminated by partial leaching of clays and Fe (oxyhydr)oxides during a single-step digestion, and we suggest a pre-leach of 20% of the sample, followed by a partial leach of 40% of the sample to selectively dissolve carbonate. We suggest that REY studies are optimised in carbonates with > 85% CaCO₃, and show that dolomites behave differently during the leaching process and must be treated separately. We present REY patterns for modern carbonate-rich sediments from a range of environments, and show that seawater REY are faithfully preserved in some non-skeletal carbonate, but modified leaching procedures are necessary for impure, unlithified or organic rich carbonate sediments. We combine REY with Fe-speciation data to identify how Fe oxides and clays contribute to the REY signal and explore how the two proxies can be used together to provide a complex and high-resolution redox reconstruction in carbonate-dominated marine environments

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe