The case for a neoproterozoic oxygenation event: Geochemical evidence and biological consequences

The Neoproterozoic era marked a turning point in the development of the modern earth system. The irreversible environmental changes of that time were rooted in tectonic upheavals that drove chain reactions between the oceans, atmosphere, climate, and life. Key biological innovations took place amid carbon cycle instability that pushed climate to unprecedented extremes and resulted in the ventilation of the deep ocean. Despite a dearth of supporting evidence, it is commonly presumed that a rise in oxygen triggered the evolution of animals. Although geochemical evidence for oxygenation is now convincing, our understanding of the Neoproterozoic earth system and of early animal evolution has changed apace, revealing an altogether more complicated picture in which the spread of anoxia played an important role. The challenge to future researchers lies in unraveling the complex entanglement of earth system changes during this pivotal episode in Earth’s history

A Search for Binary Active Galactic Nuclei: Double-Peaked [OIII] AGN in the Sloan Digital Sky Survey

We present AGN from the Sloan Digital Sky Survey (SDSS) having double-peaked profiles of [OIII] 5007,4959 and other narrow emission-lines, motivated by the prospect of finding candidate binary AGN. These objects were identified by means of a visual examination of 21,592 quasars at z < 0.7 in SDSS Data Release 7 (DR7). Of the spectra with adequate signal-to-noise, 148 spectra exhibit a double-peaked [OIII] profile. Of these, 86 are Type 1 AGN and 62 are Type 2 AGN. Only two give the appearance of possibly being optically resolved double AGN in the SDSS images, but many show close companions or signs of recent interaction. Radio-detected quasars are three times more likely to exhibit a double-peaked [OIII] profile than quasars with no detected radio flux, suggesting a role for jet interactions in producing the double-peaked profiles. Of the 66 broad line (Type 1) AGN that are undetected in the FIRST survey, 0.9% show double peaked [OIII] profiles. We discuss statistical tests of the nature of the double-peaked objects. Further study is needed to determine which of them are binary AGN rather than disturbed narrow line regions, and how many additional binaries may remain undetected because of insufficient line-of-sight velocity splitting. Previous studies indicate that 0.1% of SDSS quasars are spatially resolved binaries, with typical spacings of ~10 to 100 kpc. If a substantial fraction of the double-peaked objects are indeed binaries, then our results imply that binaries occur more frequently at smaller separations (< 10 kpc). This suggests that simultaneous fueling of both black holes is more common as the binary orbit decays through these spacings.Comment: 33 pages, 5 figures, LaTeX. Major revisions. Accepted for publication in ApJ

Predicting post one-year durability of glucose-lowering monotherapies in patients with newly-diagnosed type 2 diabetes mellitus – A MASTERMIND precision medicine approach (UKPDS 87)

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record Aims: Predicting likely durability of glucose-lowering therapies for people with type 2 diabetes (T2D) could help inform individualised therapeutic choices. Methods: We used data from UKPDS patients with newly-diagnosed T2D randomised to first-line glucose-lowering monotherapy with chlorpropamide–glibenclamide–basal insulin or metformin. In 2339 participants who achieved one-year HbA1c values <7.5% (<59 mmol/mol)–we assessed relationships between one-year characteristics and time to monotherapy-failure (HbA1c ≥ 7.5% or requiring second-line therapy). Model validation was performed using bootstrap sampling. Results: Follow-up was median (IQR) 11.0 (8.0–14.0) years. Monotherapy-failure occurred in 72%–82%–75% and 79% for those randomised to chlorpropamide–glibenclamide–basal insulin or metformin respectively–after median 4.5 (3.0–6.6)–3.7 (2.6–5.6)–4.2 (2.7–6.5) and 3.8 (2.6– 5.2) years. Time-to-monotherapy-failure was predicted primarily by HbA1c and BMI values–with other risk factors varying by type of monotherapy–with predictions to within ±2.5 years for 55%–60%–56% and 57% of the chlorpropamide–glibenclamide–basal insulin and metformin monotherapy cohorts respectively. Conclusions: Post one-year glycaemic durability can be predicted robustly in individuals with newly-diagnosed T2D who achieve HbA1c values < 7.5% one year after commencing traditional monotherapies. Such information could be used to help guide glycaemic management for individual patients.Medical Research Council (MRC

Reconstructing Tonian seawater 87Sr/86Sr using calcite microspar

The Tonian Period followed a long interval of relative stasis and led into the climatic extremes and biological radiations of multicellular life during the Cryogenian and Ediacaran Periods, respectively. However, despite its pivotal situation, it remains relatively understudied, in large part due to the lack of robust age constraints. A combination of fossil evidence, radiometric ages, and isotopic constraints reveal that carbonate strata on the North China craton were deposited between ca. 980 and ca. 920 Ma, thereby filling a gap in marine archives. Here we present 87Sr/86Sr data from selected calcite microspar cements, which filled early diagenetic “molar tooth” cracks, along with data from demonstrably well-preserved bulk carbonate samples. These new data show that seawater 87Sr/87Sr rose in stages from ~0.7052 at ca. 980 Ma to ~0.7063 by ca. 920 Ma, after which a return to low values coincided with the eruption of the Dashigou large igneous province across the North China craton. We also present a new Neoproterozoic seawater 87Sr/86Sr curve, which reveals that the general trend toward higher 87Sr/87Sr during the Tonian Period was checked repeatedly by the input of less-radiogenic strontium from a series of eruptive events, both coincident with and prior to the main breakup of Rodinia. The weathering of Tonian volcanic provinces has been linked to higher carbon burial, glaciation, and oxygenation due to the high phosphorus content of flood basalts. Here we show that the weathering of major volcanic provinces affected material fluxes and ocean chemistry much earlier than previously envisaged

The radio luminosity, black hole mass and Eddington ratio for quasars from the Sloan Digital Sky Survey

We investigate the \mbh- \sigma_* relation for radio-loud quasars with redshift $z<0.83$ in Data Release 3 of the Sloan Digital Sky Survey (SDSS). The sample consists of 3772 quasars with better model of H$\beta$ and \oiii lines and available radio luminosity, including 306 radio-loud quasars, 3466 radio-quiet quasars with measured radio luminosity or upper-limit of radio luminosity (181 radio-quiet quasars with measured radio luminosity). The virial supermassive black hole mass (\mbh) is calculated from the broad \hb line, the host stellar velocity dispersion ($\sigma_*$) is traced by the core \oiii gaseous velocity dispersion, and the radio luminosity and the radio loudness are derived from the FIRST catalog. Our results are follows: (1) For radio-quiet quasars, we confirm that there is no obvious deviation from the \mbh- \sigma_* relation defined in inactive galaxies when \mbh uncertainties and luminosity bias are concerned. (2) We find that radio-loud quasars deviate much from the \mbh- \sigma_* relation respect to that for radio-quiet quasars. This deviation is only partly due to the possible cosmology evolution of the \mbh- \sigma_* relation and the luminosity bias. (3) The radio luminosity is proportional to \mbh^{1.28^{+0.23}_{-0.16}}(\lb/\ledd)^{1.29^{+0.31}_{-0.24}} for radio-quiet quasars and \mbh^{3.10^{+0.60}_{-0.70}}(\lb/\ledd)^{4.18^{+1.40}_{-1.10}} for radio-loud quasars. The weaker correlation of the radio luminosity dependence upon the mass and the Eddington ratio for radio-loud quasars shows that other physical effects would account for their radio luminosities, such as the black hole spin.Comment: 15 pages, 8 figures, 2 tables, accepted for publication in ChJA

Hybrid Mechanical Systems

We discuss hybrid systems in which a mechanical oscillator is coupled to another (microscopic) quantum system, such as trapped atoms or ions, solid-state spin qubits, or superconducting devices. We summarize and compare different coupling schemes and describe first experimental implementations. Hybrid mechanical systems enable new approaches to quantum control of mechanical objects, precision sensing, and quantum information processing.Comment: To cite this review, please refer to the published book chapter (see Journal-ref and DOI). This v2 corresponds to the published versio

A global transition to ferruginous conditions in the early Neoproterozoic oceans

Eukaryotic life expanded during the Proterozoic eon1, 2.5 to 0.542 billion years ago, against a background of fluctuating ocean chemistry2, 3, 4. After about 1.8 billion years ago, the global ocean is thought to have been characterized by oxygenated surface waters, with anoxic and sulphidic waters in middle depths along productive continental margins and anoxic and iron-containing (ferruginous) deeper waters5, 6, 7. The spatial extent of sulphidic waters probably varied through time5, 6, but this surface-to-deep redox structure is suggested to have persisted until the first Neoproterozoic glaciation about 717 million years ago8, 9, 10, 11. Here we report an analysis of ocean redox conditions throughout the Proterozoic using new and existing iron speciation and sulphur isotope data from multiple cores and outcrops. We find a global transition from sulphidic to ferruginous mid-depth waters in the earliest Neoproterozoic, coincident with the amalgamation of the supercontinent Rodinia at low latitudes. We suggest that ferruginous conditions were initiated by an increase in the oceanic influx of highly reactive iron relative to sulphate, driven by a change in weathering regime and the uptake of sulphate by extensive continental evaporites on Rodinia. We propose that this transition essentially detoxified ocean margin settings, allowing for expanded opportunities for eukaryote diversification following a prolonged evolutionary stasis before one billion years ago

Different Effects of Farrerol on an OVA-Induced Allergic Asthma and LPS-induced Acute Lung Injury

BACKGROUND: Farrerol, isolated from rhododendron, has been shown to have the anti-bacterial activity, but no details on the anti-inflammatory activity. We further evaluated the effects of this compound in two experimental models of lung diseases. METHODOLOGY/PRINCIPAL FINDINGS: For the asthma model, female BALB/c mice were challenged with ovalbumin (OVA), and then treated daily with farrerol (20 and 40 mg/kg, i.p.) as a therapeutic treatment from day 22 to day 26 post immunization. To induce acute lung injury, female BALB/c mice were injected intranasally with LPS and treated with farrerol (20 and 40 mg/kg, i.p.) 1 h prior to LPS stimulation. Inflammation in the two different models was determined using ELISA, histology, real-time PCR and western blot. Farrerol significantly regulated the phenotype challenged by OVA, like cell number, Th1 and Th2 cytokines levels in the BALF, the OVA-specific IgE level in the serum, goblet cell hyperplasia in the airway, airway hyperresponsiveness to inhaled methacholine and mRNA expression of chemokines and their receptors. Furthermore, farrerol markedly attenuated the activation of phosphorylation of Akt and nuclear factor-κB (NF-κB) subunit p65 both in vivo and in vitro. However, farrerol has no effect on the acute lung injury model. CONCLUSION/SIGNIFICANCE: Our finding demonstrates that the distinct anti-inflammatory effect of farrerol in the treatment of asthma acts by inhibiting the PI3K and NF-κB pathway

Systematic review and meta-analysis of the diagnostic accuracy of ultrasonography for deep vein thrombosis

Background Ultrasound (US) has largely replaced contrast venography as the definitive diagnostic test for deep vein thrombosis (DVT). We aimed to derive a definitive estimate of the diagnostic accuracy of US for clinically suspected DVT and identify study-level factors that might predict accuracy. Methods We undertook a systematic review, meta-analysis and meta-regression of diagnostic cohort studies that compared US to contrast venography in patients with suspected DVT. We searched Medline, EMBASE, CINAHL, Web of Science, Cochrane Database of Systematic Reviews, Cochrane Controlled Trials Register, Database of Reviews of Effectiveness, the ACP Journal Club, and citation lists (1966 to April 2004). Random effects meta-analysis was used to derive pooled estimates of sensitivity and specificity. Random effects meta-regression was used to identify study-level covariates that predicted diagnostic performance. Results We identified 100 cohorts comparing US to venography in patients with suspected DVT. Overall sensitivity for proximal DVT (95% confidence interval) was 94.2% (93.2 to 95.0), for distal DVT was 63.5% (59.8 to 67.0), and specificity was 93.8% (93.1 to 94.4). Duplex US had pooled sensitivity of 96.5% (95.1 to 97.6) for proximal DVT, 71.2% (64.6 to 77.2) for distal DVT and specificity of 94.0% (92.8 to 95.1). Triplex US had pooled sensitivity of 96.4% (94.4 to 97.1%) for proximal DVT, 75.2% (67.7 to 81.6) for distal DVT and specificity of 94.3% (92.5 to 95.8). Compression US alone had pooled sensitivity of 93.8 % (92.0 to 95.3%) for proximal DVT, 56.8% (49.0 to 66.4) for distal DVT and specificity of 97.8% (97.0 to 98.4). Sensitivity was higher in more recently published studies and in cohorts with higher prevalence of DVT and more proximal DVT, and was lower in cohorts that reported interpretation by a radiologist. Specificity was higher in cohorts that excluded patients with previous DVT. No studies were identified that compared repeat US to venography in all patients. Repeat US appears to have a positive yield of 1.3%, with 89% of these being confirmed by venography. Conclusion Combined colour-doppler US techniques have optimal sensitivity, while compression US has optimal specificity for DVT. However, all estimates are subject to substantial unexplained heterogeneity. The role of repeat scanning is very uncertain and based upon limited data

Defective Cell Cycle Checkpoint Functions in Melanoma Are Associated with Altered Patterns of Gene Expression

Defects in DNA damage responses may underlie genetic instability and malignant progression in melanoma. Cultures of normal human melanocytes (NHMs) and melanoma lines were analyzed to determine whether global patterns of gene expression could predict the efficacy of DNA damage cell cycle checkpoints that arrest growth and suppress genetic instability. NHMs displayed effective G1 and G2 checkpoint responses to ionizing radiation-induced DNA damage. A majority of melanoma cell lines (11/16) displayed significant quantitative defects in one or both checkpoints. Melanomas with B-RAF mutations as a class displayed a significant defect in DNA damage G2 checkpoint function. In contrast the epithelial-like subtype of melanomas with wild-type N-RAS and B-RAF alleles displayed an effective G2 checkpoint but a significant defect in G1 checkpoint function. RNA expression profiling revealed that melanoma lines with defects in the DNA damage G1 checkpoint displayed reduced expression of p53 transcriptional targets, such as CDKN1A and DDB2, and enhanced expression of proliferation-associated genes, such as CDC7 and GEMININ. A Bayesian analysis tool was more accurate than significance analysis of microarrays for predicting checkpoint function using a leave-one-out method. The results suggest that defects in DNA damage checkpoints may be recognized in melanomas through analysis of gene expression