Chromium isotopes in marine hydrothermal sediments

Hydrothermal chromium (Cr) cycling contributes to marine Cr inventories and their Cr isotopic composition, yet Cr isotope effects associated with this cycling remain poorly documented. Here we determine the distribution, isotopic composition, and diagenetic mobility of Cr in hydrothermal sediments from the distal flank of the South East Pacific Rise (SEPR, DSDP-site 598). We find that Cr is primarily associated with the metalliferous iron (oxyhydr) oxide and detrital components of the sediment (0.4–3.6 mg kg⁻¹), whereas Cr concentrations are much lower in the dominant carbonate phase (80% Cr from the sediment relative to Fe. We propose this loss is tied to oxidation of authigenic Cr(III) to Cr(VI) followed by diagenetic remobilization and efflux from the sediment pile. The bulk δ⁵³Cr composition of the SEPR sediments is isotopically light (−0.24 to −0.57 ± 0.05‰) and the authigenic δ⁵³Cr is as light as −1.2 ± 0.2‰, and we argue that this light Cr isotopic composition results from the partial reduction of oxic seawater-bearing Cr(VI) by reduced hydrothermal vent fluids enriched in Fe(II)aq. Diagenetic oxidation of the reactive Cr pool by Mn-oxides and loss of Cr(VI) from the sediment may further deplete the sediment in ⁵³Cr during diagenesis. The δ⁵³Cr composition of the detrital Cr fraction of the sediment (average δ⁵³Cr composition = −0.05 ± 0.04‰) falls within the igneous silicate earth (ISE) range, revealing that detrital Cr delivered to this region of the Pacific ocean is unfractionated, and has carried a relatively constant δ⁵³Cr composition over the last 5.7 million years. Together our results show that light δ⁵³Cr compositions in hydrothermal sediments are imparted through a combination of processes previously overlooked in the marine Cr biogeochemical cycle, and that the δ⁵³Cr composition of such sediments may provide a rich source of information on paleo-marine redox conditions

Entropies, volumes, and Einstein metrics

We survey the definitions and some important properties of several asymptotic invariants of smooth manifolds, and discuss some open questions related to them. We prove that the (non-)vanishing of the minimal volume is a differentiable property, which is not invariant under homeomorphisms. We also formulate an obstruction to the existence of Einstein metrics on four-manifolds involving the volume entropy. This generalizes both the Gromov--Hitchin--Thorpe inequality and Sambusetti's obstruction.Comment: This is a substantial revision and expansion of the 2004 preprint, which I prepared in spring of 2010 and which has since been published. The version here is essentially the published one, minus the problems introduced by Springer productio

Intergenerational change and familial aggregation of body mass index

The relationship between parental BMI and that of their adult offspring, when increased adiposity can become a clinical issue, is unknown. We investigated the intergenerational change in body mass index (BMI) distribution, and examined the sex-specific relationship between parental and adult offspring BMI. Intergenerational change in the distribution of adjusted BMI in 1,443 complete families (both parents and at least one offspring) with 2,286 offspring (1,263 daughters and 1,023 sons) from the west of Scotland, UK, was investigated using quantile regression. Familial correlations were estimated from linear mixed effects regression models. The distribution of BMI showed little intergenerational change in the normal range (\25 kg/m2), decreasing overweightness (25– \30 kg/m2) and increasing obesity (C30 kg/m2). Median BMI was static across generations in males and decreased in females by 0.4 (95% CI: 0.0, 0.7) kg/m2; the 95th percentileincreased by 2.2 (1.1, 3.2) kg/m2 in males and 2.7 (1.4, 3.9) kg/m2 in females. Mothers’ BMI was more strongly associated with daughters’ BMI than was fathers’ (correlation coefficient (95% CI): mothers 0.31 (0.27, 0.36), fathers 0.19 (0.14, 0.25); P = 0.001). Mothers’ and fathers’ BMI were equally correlated with sons’ BMI (correlation coefficient: mothers 0.28 (0.22, 0.33), fathers 0.27 (0.22, 0.33). The increase in BMI between generations was concentrated at the upper end of the distribution. This, alongside the strong parent-offspring correlation, suggests that the increase in BMI is disproportionally greater among offspring of heavier parents. Familial influences on BMI among middle-aged women appear significantly stronger from mothers than father

Quantification of the severity of hypoxic-ischemic brain injury in a neonatal preclinical model using measurements of cytochrome-c-oxidase from a miniature broadband-near-infrared spectroscopy system

We describe the development of a miniaturized broadband near-infrared spectroscopy system (bNIRS), which measures changes in cerebral tissue oxyhemoglobin (  [  HbO₂ ]  ) and deoxyhemoglobin ([HHb]) plus tissue metabolism via changes in the oxidation state of cytochrome-c-oxidase ([oxCCO]). The system is based on a small light source and a customized mini-spectrometer. We assessed the instrument in a preclinical study in 27 newborn piglets undergoing transient cerebral hypoxia-ischemia (HI). We aimed to quantify the recovery of the HI insult and estimate the severity of the injury. The recovery in brain oxygenation (Δ  [  HbDiff  ]    =  Δ  [  HbO₂  ]    −  Δ  [  HHb  ]  ), blood volume (Δ  [  HbT  ]    =  Δ  [  HbO₂  ]    +  Δ  [  HHb  ]  ), and metabolism (Δ  [  oxCCO  ]  ) for up to 30 min after the end of HI were quantified in percentages using the recovery fraction (RF) algorithm, which quantifies the recovery of a signal with respect to baseline. The receiver operating characteristic analysis was performed on bNIRS-RF measurements compared to proton (H1) magnetic resonance spectroscopic (MRS)-derived thalamic lactate/N-acetylaspartate (Lac/NAA) measured at 24-h post HI insult; Lac/NAA peak area ratio is an accurate surrogate marker of neurodevelopmental outcome in babies with neonatal HI encephalopathy. The Δ  [  oxCCO  ]  -RF cut-off threshold of 79% within 30 min of HI predicted injury severity based on Lac/NAA with high sensitivity (100%) and specificity (93%). A significant difference in thalamic Lac/NAA was noticed (p  <  0.0001) between the two groups based on this cut-off threshold of 79% Δ  [  oxCCO  ]  -RF. The severe injury group (n  =  13) had ∼30  %   smaller recovery in Δ  [  HbDiff  ]  -RF (p  =  0.0001) and no significant difference was observed in Δ  [  HbT  ]  -RF between groups. At 48 h post HI, significantly higher P31-MRS-measured inorganic phosphate/exchangeable phosphate pool (epp) (p  =  0.01) and reduced phosphocreatine/epp (p  =  0.003) were observed in the severe injury group indicating persistent cerebral energy depletion. Based on these results, the bNIRS measurement of the oxCCO recovery fraction offers a noninvasive real-time biomarker of brain injury severity within 30 min following HI insult

A Class of Non-Parametric Statistical Manifolds modelled on Sobolev Space

We construct a family of non-parametric (infinite-dimensional) manifolds of finite measures on Rd. The manifolds are modelled on a variety of weighted Sobolev spaces, including Hilbert-Sobolev spaces and mixed-norm spaces. Each supports the Fisher-Rao metric as a weak Riemannian metric. Densities are expressed in terms of a deformed exponential function having linear growth. Unusually for the Sobolev context, and as a consequence of its linear growth, this "lifts" to a nonlinear superposition (Nemytskii) operator that acts continuously on a particular class of mixed-norm model spaces, and on the fixed norm space W²'¹ i.e. it maps each of these spaces continuously into itself. It also maps continuously between other fixed-norm spaces with a loss of Lebesgue exponent that increases with the number of derivatives. Some of the results make essential use of a log-Sobolev embedding theorem. Each manifold contains a smoothly embedded submanifold of probability measures. Applications to the stochastic partial differential equations of nonlinear filtering (and hence to the Fokker-Planck equation) are outlined

Performance Analysis of Effective Methods for Solving Band Matrix SLAEs after Parabolic Nonlinear PDEs

This paper presents an experimental performance study of implementations of three different types of algorithms for solving band matrix systems of linear algebraic equations (SLAEs) after parabolic nonlinear partial differential equations -- direct, symbolic, and iterative, the former two of which were introduced in Veneva and Ayriyan (arXiv:1710.00428v2). An iterative algorithm is presented -- the strongly implicit procedure (SIP), also known as the Stone method. This method uses the incomplete LU (ILU(0)) decomposition. An application of the Hotelling-Bodewig iterative algorithm is suggested as a replacement of the standard forward-backward substitutions. The upsides and the downsides of the SIP method are discussed. The complexity of all the investigated methods is presented. Performance analysis of the implementations is done using the high-performance computing (HPC) clusters "HybriLIT" and "Avitohol". To that purpose, the experimental setup and the results from the conducted computations on the individual computer systems are presented and discussed.Comment: 10 pages, 2 figure

Systems Biology Model of Cerebral Oxygen Delivery and Metabolism During Therapeutic Hypothermia: Application to the Piglet Model

Hypoxic ischaemic encephalopathy (HIE) is a significant cause of death and disability. Therapeutic hypothermia (TH) is the only available standard of treatment, but 45-55% of cases still result in death or neurodevelopmental disability following TH. This work has focussed on developing a new brain tissue physiology and biochemistry systems biology model that includes temperature effects, as well as a Bayesian framework for analysis of model parameter estimation. Through this, we can simulate the effects of temperature on brain tissue oxygen delivery and metabolism, as well as analyse clinical and experimental data to identify mechanisms to explain differing behaviour and outcome. Presented here is an application of the model to data from two piglets treated with TH following hypoxic-ischaemic injury showing different responses and outcome following treatment. We identify the main mechanism for this difference as the Q10 temperature coefficient for metabolic reactions, with the severely injured piglet having a median posterior value of 0.133 as opposed to the mild injury value of 5.48. This work demonstrates the use of systems biology models to investigate underlying mechanisms behind the varying response to hypothermic treatment

Switching of magnetic domains reveals evidence for spatially inhomogeneous superconductivity

The interplay of magnetic and charge fluctuations can lead to quantum phases with exceptional electronic properties. A case in point is magnetically-driven superconductivity, where magnetic correlations fundamentally affect the underlying symmetry and generate new physical properties. The superconducting wave-function in most known magnetic superconductors does not break translational symmetry. However, it has been predicted that modulated triplet p-wave superconductivity occurs in singlet d-wave superconductors with spin-density wave (SDW) order. Here we report evidence for the presence of a spatially inhomogeneous p-wave Cooper pair-density wave (PDW) in CeCoIn5. We show that the SDW domains can be switched completely by a tiny change of the magnetic field direction, which is naturally explained by the presence of triplet superconductivity. Further, the Q-phase emerges in a common magneto-superconducting quantum critical point. The Q-phase of CeCoIn5 thus represents an example where spatially modulated superconductivity is associated with SDW order

Celecoxib exerts protective effects in the vascular endothelium via COX-2-independent activation of AMPK-CREB-Nrf2 signalling

Although concern remains about the athero-thrombotic risk posed by cyclo-oxygenase (COX)-2-selective inhibitors, recent data implicates rofecoxib, while celecoxib appears equivalent to NSAIDs naproxen and ibuprofen. We investigated the hypothesis that celecoxib activates AMP kinase (AMPK) signalling to enhance vascular endothelial protection. In human arterial and venous endothelial cells (EC), and in contrast to ibuprofen and naproxen, celecoxib induced the protective protein heme oxygenase-1 (HO-1). Celecoxib derivative 2,5-dimethyl-celecoxib (DMC) which lacks COX-2 inhibition also upregulated HO-1, implicating a COX-2-independent mechanism. Celecoxib activated AMPKα(Thr172) and CREB-1(Ser133) phosphorylation leading to Nrf2 nuclear translocation. Importantly, these responses were not reproduced by ibuprofen or naproxen, while AMPKα silencing abrogated celecoxib-mediated CREB and Nrf2 activation. Moreover, celecoxib induced H-ferritin via the same pathway, and increased HO-1 and H-ferritin in the aortic endothelium of mice fed celecoxib (1000 ppm) or control chow. Functionally, celecoxib inhibited TNF-α-induced NF-κB p65(Ser536) phosphorylation by activating AMPK. This attenuated VCAM-1 upregulation via induction of HO-1, a response reproduced by DMC but not ibuprofen or naproxen. Similarly, celecoxib prevented IL-1β-mediated induction of IL-6. Celecoxib enhances vascular protection via AMPK-CREB-Nrf2 signalling, a mechanism which may mitigate cardiovascular risk in patients prescribed celecoxib. Understanding NSAID heterogeneity and COX-2-independent signalling will ultimately lead to safer anti-inflammatory drugs

Matrix metalloproteinase-9 activity and a downregulated Hedgehog pathway impair blood-brain barrier function in an <i>in vitro</i> model of CNS tuberculosis

Central nervous system tuberculosis (CNS TB) has a high mortality and morbidity associated with severe inflammation. The blood-brain barrier (BBB) protects the brain from inflammation but the mechanisms causing BBB damage in CNS TB are uncharacterized. We demonstrate that Mycobacterium tuberculosis (Mtb) causes breakdown of type IV collagen and decreases tight junction protein (TJP) expression in a co-culture model of the BBB. This increases permeability, surface expression of endothelial adhesion molecules and leukocyte transmigration. TJP breakdown was driven by Mtb-dependent secretion of matrix metalloproteinase (MMP)-9. TJP expression is regulated by Sonic hedgehog (Shh) through transcription factor Gli-1. In our model, the hedgehog pathway was downregulated by Mtb-stimulation, but Shh levels in astrocytes were unchanged. However, Scube2, a glycoprotein regulating astrocyte Shh release was decreased, inhibiting Shh delivery to brain endothelial cells. Activation of the hedgehog pathway by addition of a Smoothened agonist or by addition of exogenous Shh, or neutralizing MMP-9 activity, decreased permeability and increased TJP expression in the Mtb-stimulated BBB co-cultures. In summary, the BBB is disrupted by downregulation of the Shh pathway and breakdown of TJPs, secondary to increased MMP-9 activity which suggests that these pathways are potential novel targets for host directed therapy in CNS TB