Fluid evolution in CM carbonaceous chondrites tracked through the oxygen isotopic compositions of carbonates

The oxygen isotopic compositions of calcite grains in four CM carbonaceous chondrites have been determined by NanoSIMS, and results reveal that aqueous solutions evolved in a similar manner between parent body regions with different intensities of aqueous alteration. Two types of calcite were identified in Murchison, Mighei, Cold Bokkeveld and LaPaz Icefield 031166 by differences in their petrographic properties and oxygen isotope values. Type 1 calcite occurs as small equant grains that formed by filling of pore spaces in meteorite matrices during the earliest stages of alteration. On average, the type 1 grains have a δ18O of ∼32–36‰ (VSMOW), and Δ17O of between ∼2‰ and −1‰. Most grains of type 2 calcite precipitated after type 1. They contain micropores and inclusions, and have replaced ferromagnesian silicate minerals. Type 2 calcite has an average δ18O of ∼21–24‰ (VSMOW) and a Δ17O of between ∼−1‰ and −3‰. Such consistent isotopic differences between the two calcite types show that they formed in discrete episodes and from solutions whose δ18O and δ17O values had changed by reaction with parent body silicates, as predicted by the closed-system model for aqueous alteration. Temperatures are likely to have increased over the timespan of calcite precipitation, possibly owing to exothermic serpentinisation. The most highly altered CM chondrites commonly contain dolomite in addition to calcite. Dolomite grains in two previously studied CM chondrites have a narrow range in δ18O (∼25–29‰ VSMOW), with Δ17O ∼−1‰ to −3‰. These grains are likely to have precipitated between types 1 and 2 calcite, and in response to a transient heating event and/or a brief increase in fluid magnesium/calcium ratios. In spite of this evidence for localised excursions in temperature and/or solution chemistry, the carbonate oxygen isotope record shows that fluid evolution was comparable between many parent body regions. The CM carbonaceous chondrites studied here therefore sample either several parent bodies with a very similar initial composition and evolution or, more probably, a single C-type asteroid

Interacting one dimensional electron gas with open boundaries

We discuss the properties of interacting electrons on a finite chain with open boundary conditions. We extend the Haldane Luttinger liquid description to these systems and study how the presence of the boundaries modifies various correlation functions. In view of possible experimental applications to quantum wires, we analyse how tunneling measurements can reveal the underlying Luttinger liquid properties. The two terminal conductance is calculated. We also point out possible applications to quasi one dimensional materials and study the effects of magnetic impurities.Comment: 38 pages, ReVTeX, 7 figures (available upon request

Resonance in One--Dimensional Fermi--Edge Singularity

The problem of the Fermi--edge singularity in a one--dimensional Tomonaga--Luttinger liquid is reconsidered. The backward scattering of the conduction band electrons on the impurity--like hole in the valence band is analyzed by mapping the problem onto a Coulomb gas theory. For the case when the electron--electron interaction is repulsive the obtained exponent of the one--dimensional Fermi--edge singularity appears to be different from the exponent found in the previous studies. It is shown that the infrared physics of the Fermi--edge singularity in the presence of backward scattering and electron--electron repulsion resembles the physics of the Kondo problem.Comment: 38 pages and 1 figure, to be published in PR

Exact Fermi-edge singularity exponent in a Luttinger liquid

We report the exact calculation of the Fermi-edge singularity exponent for correlated electrons in one dimension (Luttinger liquid). Focusing on the special interaction parameter g=1/2, the asymptotic long-time behavior can be obtained using the Wiener-Hopf method. The result confirms the previous assumption of an open boundary fixed point. In addition, a dynamic k-channel Kondo impurity is studied via Abelian bosonization for k=2 and k=4. It is shown that the corresponding orthogonality exponents are related to the orthogonality exponent in a Luttinger liquid.Comment: 8 Pages RevTeX, no figure

The role of beach morphology on coastal cliff erosion under extreme waves

Erosion of hard-rock coastal cliffs is understood to be caused by a combination of both marine and sub-aerial processes. Beach morphology, tidal elevation and significant wave heights, especially under extreme storm conditions, can lead to variability in wave energy flux to the cliff-toe. Wave and water level measurements in the nearshore under energetic conditions are difficult to obtain and in-situ observations are rare. Here we use monthly cliff-face volume changes detected using terrestrial laser scanning alongside beach morphological changes and modelled nearshore hydrodynamics to examine how exposed cliffs respond to changes in extreme wave conditions and beach morphology. The measurements cover the North Atlantic storms of 2013-2014 and consider two exposed stretches of coastline (Porthleven and Godrevy, UK) with contrasting beach morphology fronting the cliffs; a flat dissipative sandy beach at Godrevy and a steep reflective gravel beach at Porthleven. Beach slope and the elevation of the beach-cliff junction were found to influence the frequency of cliff inundation and the power of wave-cliff impacts. Numerical modelling (XBeach-G) showed that under highly energetic wave conditions, i.e. those that occurred in the North Atlantic during winter 2013–2014, with Hs = 5.5 m (dissipative site) and 8 m (reflective site), the combination of greater wave height and steeper beach at the reflective site led to amplified wave run-up, subjecting these cliffs to waves over 4 times as powerful as those impacting the cliffs at the dissipative site (39 kWm-1 compared with 9 kWm-1). This study highlighted the sensitivity of cliff erosion to extreme wave conditions, where the majority (over 90% of the annual value) of cliff-face erosion ensued during the winter. The significance of these short-term erosion rates in the context of long-term retreat illustrates the importance of incorporating short-term beach and wave dynamics into geomorphological studies of coastal cliff change

SEASTAR: a mission to study ocean submesoscale dynamics and small-scale atmosphere-ocean processes in coastal, shelf and polar seas

High-resolution satellite images of ocean color and sea surface temperature reveal an abundance of ocean fronts, vortices and filaments at scales below 10 km but measurements of ocean surface dynamics at these scales are rare. There is increasing recognition of the role played by small scale ocean processes in ocean-atmosphere coupling, upper-ocean mixing and ocean vertical transports, with advanced numerical models and in situ observations highlighting fundamental changes in dynamics when scales reach 1 km. Numerous scientific publications highlight the global impact of small oceanic scales on marine ecosystems, operational forecasts and long-term climate projections through strong ageostrophic circulations, large vertical ocean velocities and mixed layer re-stratification. Small-scale processes particularly dominate in coastal, shelf and polar seas where they mediate important exchanges between land, ocean, atmosphere and the cryosphere, e.g., freshwater, pollutants. As numerical models continue to evolve toward finer spatial resolution and increasingly complex coupled atmosphere-wave-ice-ocean systems, modern observing capability lags behind, unable to deliver the high-resolution synoptic measurements of total currents, wind vectors and waves needed to advance understanding, develop better parameterizations and improve model validations, forecasts and projections. SEASTAR is a satellite mission concept that proposes to directly address this critical observational gap with synoptic two-dimensional imaging of total ocean surface current vectors and wind vectors at 1 km resolution and coincident directional wave spectra. Based on major recent advances in squinted along-track Synthetic Aperture Radar interferometry, SEASTAR is an innovative, mature concept with unique demonstrated capabilities, seeking to proceed toward spaceborne implementation within Europe and beyond

Oral Abstracts 7: RA ClinicalO37. Long-Term Outcomes of Early RA Patients Initiated with Adalimumab Plus Methotrexate Compared with Methotrexate Alone Following a Targeted Treatment Approach

Background: This analysis assessed, on a group level, whether there is a long-term advantage for early RA patients treated with adalimumab (ADA) + MTX vs those initially treated with placebo (PBO) + MTX who either responded to therapy or added ADA following inadequate response (IR). Methods: OPTIMA was a 78- week, randomized, controlled trial of ADA + MTX vs PBO + MTX in MTX-naïve early (<1 year) RA patients. Therapy was adjusted at week 26: ADA + MTX-responders (R) who achieved DAS28 (CRP) <3.2 at weeks 22 and 26 (Period 1, P1) were re-randomized to withdraw or continue ADA and PBO + MTX-R continued randomized therapy for 52 weeks (P2); IR-patients received open-label (OL) ADA + MTX during P2. This post hoc analysis evaluated the proportion of patients at week 78 with DAS28 (CRP) <3.2, HAQ-DI <0.5, and/or ΔmTSS ≤0.5 by initial treatment. To account for patients who withdrew ADA during P2, an equivalent proportion of R was imputed from ADA + MTX-R patients. Results: At week 26, significantly more patients had low disease activity, normal function, and/or no radiographic progression with ADA + MTX vs PBO + MTX (Table 1). Differences in clinical and functional outcomes disappeared following additional treatment, when PBO + MTX-IR (n = 348/460) switched to OL ADA + MTX. Addition of OL ADA slowed radiographic progression, but more patients who received ADA + MTX from baseline had no radiographic progression at week 78 than patients who received initial PBO + MTX. Conclusions: Early RA patients treated with PBO + MTX achieved comparable long-term clinical and functional outcomes on a group level as those who began ADA + MTX, but only when therapy was optimized by the addition of ADA in PBO + MTX-IR. Still, ADA + MTX therapy conferred a radiographic benefit although the difference did not appear to translate to an additional functional benefit. Disclosures: P.E., AbbVie, Merck, Pfizer, UCB, Roche, BMS—Provided Expert Advice, Undertaken Trials, AbbVie—AbbVie sponsored the study, contributed to its design, and participated in the collection, analysis, and interpretation of the data, and in the writing, reviewing, and approval of the final version. R.F., AbbVie, Pfizer, Merck, Roche, UCB, Celgene, Amgen, AstraZeneca, BMS, Janssen, Lilly, Novartis—Research Grants, Consultation Fees. S.F., AbbVie—Employee, Stocks. A.K., AbbVie, Amgen, AstraZeneca, BMS, Celgene, Centocor-Janssen, Pfizer, Roche, UCB—Research Grants, Consultation Fees. H.K., AbbVie—Employee, Stocks. S.R., AbbVie—Employee, Stocks. J.S., AbbVie, Amgen, AstraZeneca, BMS, Celgene, Centocor-Janssen, GlaxoSmithKline, Lilly, Pfizer (Wyeth), MSD (Schering-Plough), Novo-Nordisk, Roche, Sandoz, UCB—Research Grants, Consultation Fees. R.V., AbbVie, BMS, GlaxoSmithKline, Human Genome Sciences, Merck, Pfizer, Roche, UCB Pharma—Consultation Fees, Research Support. Table 1.Week 78 clinical, functional, and radiographic outcomes in patients who received continued ADA + MTX vs those who continued PBO + MTX or added open-label ADA following an inadequate response ADA + MTX, n/N (%)a PBO + MTX, n/N (%)b Outcome Week 26 Week 52 Week 78 Week 26 Week 52 Week 78 DAS28 (CRP) <3.2 246/466 (53) 304/465 (65) 303/465 (65) 139/460 (30)*** 284/460 (62) 300/460 (65) HAQ-DI <0.5 211/466 (45) 220/466 (47) 224/466 (48) 150/460 (33)*** 203/460 (44) 208/460 (45) ΔmTSS ≤0.5 402/462 (87) 379/445 (86) 382/443 (86) 330/459 (72)*** 318/440 (72)*** 318/440 (72)*** DAS28 (CRP) <3.2 + ΔmTSS ≤0.5 216/462 (47) 260/443 (59) 266/443 (60) 112/459 (24)*** 196/440 (45) 211/440 (48)*** DAS28 (CRP) <3.2 + HAQ-DI <0.5 + ΔmTSS ≤0.5 146/462 (32) 168/443 (38) 174/443 (39) 82/459 (18)*** 120/440 (27)*** 135/440 (31)** aIncludes patients from the ADA Continuation (n = 105) and OL ADA Carry On (n = 259) arms, as well as the proportional equivalent number of responders from the ADA Withdrawal arm (n = 102). bIncludes patients from the MTX Continuation (n = 112) and Rescue ADA (n = 348) arms. Last observation carried forward: DAS28 (CRP) and HAQ-DI; Multiple imputations: ΔmTSS. ***P < 0.001 and **iP < 0.01, respectively, for differences between initial treatments from chi-squar

Genetic Drivers of Heterogeneity in Type 2 Diabetes Pathophysiology

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P \u3c 5 × 10-8) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores5 in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care

Genetic drivers of heterogeneity in type 2 diabetes pathophysiology

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P &lt; 5 × 10-8) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores5 in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care.</p

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes