Tides modulate crevasse opening prior to a major calving event at Bowdoin Glacier, Northwest Greenland

This research is part of the Sun2ice project (ETH Grant ETH-12 16-2), supported by the Dr. Alfred and Flora Spälti and the ETH Zurich Foundation. Field work was funded by the Swiss National Science Foundation, grant 200021-153179/1, and the Japanese Ministry of Education, Culture, Sports, Science and Technology through the Arctic Challenge for Sustainability (ArCS) project. Implementation of the remeshing routine has been performed under the Project HPC-EUROPA3 (INFRAIA-2016-1-730897), with the support of the EC Research Innovation Action under the H2020 Programme.Retreat of calving glaciers worldwide has contributed substantially to sea-level rise in recent decades. Mass loss by calving contributes significantly to the uncertainty of sea-level rise projections. At Bowdoin Glacier, Northwest Greenland, most calving occurs by a few large events resulting from kilometre-scale fractures forming parallel to the calving front. High-resolution terrestrial radar interferometry data of such an event reveal that crevasse opening is fastest at low tide and accelerates during the final 36 h before calving. Using the ice flow model Elmer/Ice, we identify the crevasse water level as a key driver of modelled opening rates. Sea water-level variations in the range of local tidal amplitude (1 m) can reproduce observed opening rate fluctuations, provided crevasse water level is at least 4 m above the low-tide sea level. The accelerated opening rates within the final 36 h before calving can be modelled by additional meltwater input into the crevasse, enhanced ice cliff undercutting by submarine melt, ice damage increase due to tidal cyclic fatigue, crevasse deepening or a combination of these processes. Our results highlight the influence of surface meltwater and tides on crevasse opening leading to major calving events at grounded tidewater glaciers such as Bowdoin.Publisher PDFPeer reviewe

Thinning leads to calving-style changes at Bowdoin Glacier, Greenland

This research has been supported by the Alfred and Flora Spälti Fund and the ETH Zurich Foundation (Sun2ice; grant no. ETH-12 16-2); the Swiss National Science Foundation (grant nos. 200021-153179/1 and PP00P2_183719); the SPI Exploratory Grants 2018 awarded to Fabian Walter and Guillaume Jouvet; the Japanese Ministry of Education, Culture, Sports, Science and Technology through the GRENE Arctic Climate Research Project and the Arctic Challenge for Sustainability (ArCS) project; and by NERC (CALISMO: Calving Laws for Ice Sheet Models; grant no. NE/P011365/1).Ice mass loss from the Greenland ice sheet is the largest single contributor to sea level rise in the 21st century. The mass loss rate has accelerated in recent decades mainly due to thinning and retreat of its outlet glaciers. The diverse calving mechanisms responsible for tidewater glacier retreat are not fully understood yet. Since a tidewater glacier's sensitivity to external forcings depends on its calving style, detailed insight into calving processes is necessary to improve projections of ice sheet mass loss by calving. As tidewater glaciers are mostly thinning, their calving styles are expected to change. Here, we study calving behaviour changes under a thinning regime at Bowdoin Glacier, north-western Greenland, by combining field and remote-sensing data from 2015 to 2019. Previous studies showed that major calving events in 2015 and 2017 were driven by hydro-fracturing and melt-undercutting. New observations from uncrewed aerial vehicle (UAV) imagery and a GPS network installed at the calving front in 2019 suggest ungrounding and buoyant calving have recently occurred as they show (1) increasing tidal modulation of vertical motion compared to previous years, (2) absence of a surface crevasse prior to calving, and (3) uplift and horizontal surface compression prior to calving. Furthermore, an inventory of calving events from 2015 to 2019 based on satellite imagery provides additional support for a change towards buoyant calving since it shows an increasing occurrence of calving events outside of the melt season. The observed change in calving style could lead to a possible retreat of the terminus, which has been stable since 2013. We therefore highlight the need for high-resolution monitoring to detect changing calving styles and numerical models that cover the full spectrum of calving mechanisms to improve projections of ice sheet mass loss by calving.Publisher PDFPeer reviewe

Biochemical effect evaluation of perfluorooctane sulfonic acid-contaminated wood mice (Apodemus sylvaticus).

Wood mice (Apodemus sylvaticus) were captured at Blokkersdijk, a nature reserve in the immediate vicinity of a fluorochemical plant in Antwerp, Belgium, and at Galgenweel, 3 kilometers farther away. The liver perfluorooctane sulfonic acid (PFOS) concentrations in the Blokkersdijk mice were extremely high (0.47-178.55 micro g/g wet weight). Perfluorononanoic, perfluorodecanoic, perfluoroundecanoic, and perfluorododecanoic acids were found sporadically in the liver tissue of the Blokkersdijk mice. The liver PFOS concentrations at Galgenweel were significantly lower than those at Blokkersdijk (0.14-1.11 micro g/g wet weight). Further results suggest sex independence of the liver PFOS levels, increased levels of PFOS bioaccumulation in older mice, and maternal PFOS transfer to the young. Several liver end points were significantly elevated in the Blokkersdijk mice: liver weight, relative liver weight, peroxisomal beta-oxidation activity, microsomal lipid peroxidation level, and mitochondrial fraction protein content. For the mitochondrial fraction catalase activity, no significant difference between locations was found. The liver weight, relative liver weight, and liver microsomal lipid peroxidation level increased significantly with the liver PFOS concentration. No indications for PFOS-mediated effects on the serum triglyceride, cholesterol, or potassium levels were obtained. The liver PFOS concentration was negatively related to the serum alanine aminotransferase activity

Renormalized perturbation theory for Fermi systems: Fermi surface deformation and superconductivity in the two-dimensional Hubbard model

Divergencies appearing in perturbation expansions of interacting many-body systems can often be removed by expanding around a suitably chosen renormalized (instead of the non-interacting) Hamiltonian. We describe such a renormalized perturbation expansion for interacting Fermi systems, which treats Fermi surface shifts and superconductivity with an arbitrary gap function via additive counterterms. The expansion is formulated explicitly for the Hubbard model to second order in the interaction. Numerical soutions of the self-consistency condition determining the Fermi surface and the gap function are calculated for the two-dimensional case. For the repulsive Hubbard model close to half-filling we find a superconducting state with d-wave symmetry, as expected. For Fermi levels close to the van Hove singularity a Pomeranchuk instability leads to Fermi surfaces with broken square lattice symmetry, whose topology can be closed or open. For the attractive Hubbard model the second order calculation yeilds s-wave superconductivity with a weakly momentum dependent gap, whose size is reduced compared to the mean-field result.Comment: 18 pages incl. 6 figure

Similar recombination-activating gene (RAG) mutations result in similar immunobiological effects but in different clinical phenotypes

Background: V(D)J recombination takes place during lymphocyte development to generate a large repertoire of T- and B-cell receptors. Mutations in recombination-activating gene 1 (RAG1) and RAG2 result in loss or reduction of V(D) J recombination. It is known that different mutations in RAG genes vary in residual recombinase activity and give rise to a broad spectrum of clinical phenotypes. Objective: We sought to study the immunologic mechanisms causing the clinical spectrum of RAG deficiency. Methods: We included 22 patients with similar RAG1 mutations (c.519delT or c.368_369delAA) resulting in N-terminal truncated RAG1 protein with residual recombination activity but presenting with different clinical phenotypes. We studied precursor B-cell development, immunoglobulin and T-cell receptor repertoire formation, receptor editing, and B- and T-cell numbers. Results: Clinically, patients were divided into 3 main categories: T2B2 severe combined immunodeficiency, Omenn syndrome, and combined immunodeficiency. All patients showed a block in the precursor B-cell development, low B- and T-cell numbers, normal immunoglobulin gene use, limited B- and T-cell repertoires, and slightly impaired receptor editing. Conclusion: This study demonstrates that similar RAG mutations can result in similar immunobiological effects but different clinical phenotypes, indicating that the level of residual recombinase activity is not the only determinant for clinical outcome. We postulate a model in which the type and moment of antigenic pressure affect the clinical phenotypes of these patients

The Arabidopsis leucine-rich repeat receptor kinase BIR3 negatively regulates BAK1 receptor complex formation and stabilizes BAK1

BAK1 is a co-receptor and positive regulator of multiple ligand-binding leucine-rich-repeat receptor kinases (LRR-RKs) and is involved in brassinosteroid (BR)-dependent growth and development, innate immunity and cell death control. The BAK1-interacting LRR-RKs BIR2 and BIR3 were previously identified by proteomics analyses of in vivo BAK1 complexes. Here we show that BAK1-related pathways such as innate immunity and cell death control are affected by BIR3 in Arabidopsis thaliana. BIR3 also has a strong negative impact on BR signaling. BIR3 directly interacts with the BR receptor BRI1 and other ligand-binding receptors and negatively regulates BR signaling by competitive inhibition of BRI1. BIR3 is released from BAK1 and BRI1 after ligand exposure and directly affects the formation of BAK1 complexes with BRI1 or FLAGELLIN SENSING2. Double mutants of bak1 and bir3 show spontaneous cell death and constitutive activation of defense responses. BAK1 and its closest homolog BKK1 interact with and are stabilized by BIR3, suggesting that bak1 bir3 double mutants mimic the spontaneous cell death phenotype observed in bak1 bkk1 mutants via destabilization of BIR3 target proteins. Our results provide evidence for a negative regulatory mechanism for BAK1 receptor complexes in which BIR3 interacts with BAK1 and inhibits ligand-binding receptors to prevent BAK1 receptor complex formation

Priorities for health economic methodological research: Results of an expert consultation

Background: The importance of economic evaluation in decision making is growing with increasing budgetary pressures on health systems. Diverse economic evidence is available for a range of interventions across national contexts within Europe, but little attention has been given to identifying evidence gaps that, if filled, could contribute to more efficient allocation of resources. One objective of the Research Agenda for Health Economic Evaluation project is to determine the most important methodological evidence gaps for the ten highest burden conditions in the European Union (EU), and to suggest ways of filling these gaps. Methods: The highest burden conditions in the EU by Disability Adjusted Life Years were determined using the Global Burden of Disease study. Clinical interventions were identified for each condition based on published guidelines, and economic evaluations indexed in MEDLINE were mapped to each intervention. A panel of public health and health economics experts discussed the evidence during a workshop and identified evidence gaps. Results: The literature analysis contributed to identifying cross-cutting methodological and technical issues, which were considered by the expert panel to derive methodological research priorities. Conclusions: The panel suggests a research agenda for health economics which incorporates the use of real-world evidence in the assessment of new and existing interventions; increased understanding of cost-effectiveness according to patient characteristics beyond the “-omics” approach to inform both investment and disinvestment decisions; methods for assessment of complex interventions; improved cross-talk between economic evaluations from health and other sectors; early health technology assessment; and standardized, transferable approaches to economic modeling

Associations of Arterial Stiffness With Cognitive Performance, and the Role of Microvascular Dysfunction:The Maastricht Study

The mechanisms underlying cognitive impairment are incompletely understood but may include arterial stiffness and microvascular dysfunction. In the population-based Maastricht Study, we investigated the association between arterial stiffness and cognitive performance, and whether any such association was mediated by microvascular dysfunction. We included cross-sectional data of 2544 participants (age, 59.7 years; 51.0% men; 26.0% type 2 diabetes mellitus). We used carotid-femoral pulse wave velocity and carotid distensibility coefficient as measures of aortic and carotid stiffness, respectively. We calculated a composite score of microvascular dysfunction based on magnetic resonance imaging features of cerebral small vessel disease, flicker light-induced retinal arteriolar and venular dilation response, albuminuria, and plasma biomarkers of microvascular dysfunction (sICAM-1 [soluble intercellular adhesion molecule-1], sVCAM-1 [soluble vascular adhesion molecule-1], sE-selectin [soluble E-selectin], and vWF [von Willebrand factor]). Cognitive domains assessed were memory, processing speed, and executive function. A cognitive function score was calculated as the average of these domains. Higher aortic stiffness (per m/s) was associated with lower cognitive function (β, -0.018 SD [95% CI, -0.036 to -0.000]) independent of age, sex, education, and cardiovascular risk factors, but higher carotid stiffness was not. Higher aortic stiffness (per m/s) was associated with a higher microvascular dysfunction score (β, 0.034 SD [95% CI, 0.014 to 0.053]), and a higher microvascular dysfunction score (per SD) was associated with lower cognitive function (β, -0.089 SD [95% CI, -0.124 to -0.053]). Microvascular dysfunction significantly explained 16.2% of the total effect of aortic stiffness on cognitive function. The present study showed that aortic stiffness, but not carotid stiffness, is independently associated with worse cognitive performance, and that this association is in part explained by microvascular dysfunction

Blood pressure variability and microvascular dysfunction:the Maastricht Study

Background: Microvascular dysfunction (MVD) contributes to stroke, dementia, depression, retinopathy and chronic kidney disease. However, the determinants of MVD are incompletely understood. Greater blood pressure variability (BPV) may be one such determinant. Methods and results: We used cross-sectional data of The Maastricht Study (n = 2773, age 59.9 years; 51.9% men) to investigate whether greater very short- to mid-term BPV is associated with various MVD measures. We standardized and averaged within-visit, 24-h and 7-day BPV into a systolic and a diastolic BPV composite score. MVD measures included a composite score of MRI cerebral small vessel disease (CSVD) features (total brain parenchymal volume, white matter hyperintensity volume, lacunar infarcts and cerebral microbleeds), a composite score of flicker light-induced retinal arteriolar and venular dilation response, albuminuria, heat-induced skin hyperemia and a composite score of plasma biomarkers of MVD (sICAM-1, sVCAM-1, sE-selectin and von Willebrand Factor). We used linear regression adjusted for age, sex, glucose metabolism status, mean 24-h systolic or DBP, cardiovascular risk factors and antihypertensive medication. We found that higher systolic and diastolic BPV composite scores (per SD) were associated with higher albuminuria [higher ratio, 1.04 (95% CI 1.00–1.08) and 1.07 (1.03–1.11), respectively], but not with other measures of MVD tested. Conclusion: Greater systolic and diastolic BPV was associated with higher albuminuria, but not with CSVD features, flicker light-induced retinal arteriolar and venular dilation response, heat-induced skin hyperemia and plasma biomarkers of MVD. This suggests that the microvasculature of the kidneys is most vulnerable to the detrimental effects of greater BPV

Towards Heat-stable Oxytocin Formulations: Analysis of Degradation Kinetics and Identification of Degradation Products

Purpose. To investigate degradation kinetics of oxytocin as a function of temperature and pH, and identify the degradation products. Materials and Methods. Accelerated degradation of oxytocin formulated at pH 2.0, 4.5, 7.0 and 9.0 was performed at 40, 55, 70 and 80°C. Degradation rate constants were determined from RP-HPLC data. Formulations were characterized by HP-SEC, UV absorption and fluorescence spectroscopy. Degradation products were identified by ESI-MS/MS. Results. The loss of intact oxytocin in RP-HPLC was pH- and temperature-dependent and followed (pseudo) first order kinetics. Degradation was fastest at pH 9.0, followed by pH 7.0, pH 2.0 and pH 4.5. The Arrhenius equation proved suitable to describe the kinetics, with the highest activation energy (116.3 kJ/mol) being found for pH 4.5 formulations. At pH 2.0 deamidation of Gln 4, Asn 5, and Gly 9-NH2, as well as combinations thereof were found. At pH 4.5, 7.0 and 9.0, the formation of tri- and tetrasulfidecontaining oxytocin as well as different types of disulfide and dityrosine-linked dimers were found to occur. Beta-elimination and larger aggregates were also observed. At pH 9.0, mono-deamidation of Gln 4, Asn 5, and Gly 9-NH2 additionally occurred. Conclusions. Multiple degradation products of oxytocin have been identified unequivocally, including various deamidated species, intramolecular oligosulfides and covalent aggregates. The strongly pH dependent degradation can be described by the Arrhenius equation. KEY WORDS: aggregation; Arrhenius kinetics; degradation; mass spectrometry; oxytocin