Sensitivity of arctic surface temperatures to sea ice thickness changes using the regional climate model mar

Since the beginning of this century, the Arctic Ocean has experienced a rapid decrease in sea ice extent, which strongly contributes to a pronounced regional climate warming known as “Arctic Amplification”, i.e. two times as large as the global average. Sea ice concentration (SIC) and sea ice thickness (SIT) mainly control changes in Arctic Ocean surface temperatures by insulating the warmer ocean water from the colder air above. Changes in atmospheric temperatures could perturb the Arctic climate, by affecting the regional atmospheric circulation. In most regional climate models (RCMs), SIC is prescribed from climate reanalyses whereas SIT is fixed in space and time, despite observations of large seasonal variations. Here, we compare climate simulations from the regional climate model MAR forced by the ERA-Interim and OSTIA reanalyses, using fixed SIT, to MAR simulations where SIT and SIC are prescribed by the GLORYS2V4 data set. The set of simulations covers the Arctic-CORDEX domain spanning the whole Arctic Ocean at a spatial resolution of 50 km for the period 2000-2015. This study aims to (1) improve the representation of surface temperatures, wind speed and direction within the Arctic boundary layer simulated by MAR, and to (2) estimate the sensitivity of Arctic surface temperatures and atmospheric circulation to prescribed SIT in MAR. Although our findings highlight the local sensitivity of surface temperatures to SIT changes, they also reveal that there is no clear benefit of using space and time varying SIT data sets to force MAR at 50 km resolution.Depuis le début de ce siècle, l’Océan Arctique a connu une diminution rapide de son étendue de glace de mer, entrainant un réchauffement climatique régional appelé "Amplification Arctique", i.e. deux fois plus marqué que le réchauffement global. En jouant le rôle d’isolant entre l’océan (plus chaud) et l’atmosphère, l’épaisseur et la concentration de glace de mer contrôlent la température à la surface de l’Océan Arctique. Une modification de la température de surface pourrait entrainer une perturbation du système climatique, par le biais de son influence sur la circulation atmosphérique régionale. Dans la plupart des modèles climatiques régionaux (RCMs), la concentration de glace de mer est prescrite par des réanalyses, tandis que l’épaisseur de glace de mer est fixe dans le temps et l’espace, malgré sa variation saisonnière importante. Dans cette étude, on comparera des simulations du MAR forcé par ERA-intérim et OSTIA, i.e utilisant une épaisseur de glace de mer fixe, avec des simulations ou l’épaisseur et la concentration de glace de mer sont prescrites par GLORYS2v4. L’ensemble des simulations concerne le domaine CORDEX-Arctique et couvre la période 2000-2015. L’objectif de ce travail est (i) d’améliorer la représentation de la température de surface, de la vitesse et direction du vent dans la couche limite atmosphérique du MAR en Arctique et; (ii) d’estimer la sensibilité de la température de surface et de la circulation atmosphérique à différentes épaisseurs de glace de mer prescrites dans le MAR. Bien que nous démontrions la sensibilité locale de la température de surface à un changement d’épaisseur de glace de mer (fixe), nous montrons aussi qu’il n’y a pas de bénéfice clair quant à l’utilisation de l’épaisseur de glace de mer variable dans le temps et l’espace comme forçage à la surface du MAR à 50 km de résolution

Integration of a Frost Mortality Scheme Into the Demographic Vegetation Model FATES

Frost is damaging to plants when air temperature drops below their tolerance threshold. The set of mechanisms used by cold-tolerant plants to withstand freezing is called “hardening” and typically take place in autumn to protect against winter damage. The recent incorporation of a hardening scheme in the demographic vegetation model FATES opens up the possibility to investigate frost mortality to vegetation. Previously, the hardening scheme was used to improve hydraulic processes in cold-tolerant plants. In this study, we expand upon the existing hardening scheme by implementing hardiness-dependent frost mortality into CLM5.0-FATES to study the impacts of frost on vegetation in temperate and boreal sites from 1950 to 2015. Our results show that the original freezing mortality approach of FATES, where each plant type had a fixed freezing tolerance threshold—an approach common to many other dynamic vegetation models, was restricted to predicting plant type distribution. The main results emerging from the new scheme are a high autumn and spring frost mortality, especially at colder sites, and increasing mid-winter frost mortality due to global warming, especially at warmer sites. We demonstrate that the new frost scheme is a major step forward in dynamically representing vegetation in ESMs by for the first time including a level of frost tolerance that is responding to the environment and includes some level of cost (implicitly) and benefit. By linking hardening and frost mortality in a land surface model, we open new ways to explore the impact of frost events in the context of global warming.publishedVersio

oxLDL Downregulates the Dendritic Cell Homing Factors CCR7 and CCL21

Introduction. Dendritic cells (DCs) and oxLDL play an important role in the atherosclerotic process with DCs accumulating in the plaques during plaque progression. Our aim was to investigate the role of oxLDL in the modulation of the DC homing-receptor CCR7 and endothelial-ligand CCL21. Methods and Results. The expression of the DC homing-receptor CCR7 and its endothelial-ligand CCL21 was examined on atherosclerotic carotic plaques of 47 patients via qRT-PCR and immunofluorescence. In vitro, we studied the expression of CCR7 on DCs and CCL21 on human microvascular endothelial cells (HMECs) in response to oxLDL. CCL21- and CCR7-mRNA levels were significantly downregulated in atherosclerotic plaques versus non-atherosclerotic controls [90% for CCL21 and 81% for CCR7 (P < 0.01)]. In vitro, oxLDL reduced CCR7 mRNA levels on DCs by 30% and protein levels by 46%. Furthermore, mRNA expression of CCL21 was significantly reduced by 50% (P < 0.05) and protein expression by 24% in HMECs by oxLDL (P < 0.05). Conclusions. The accumulation of DCs in atherosclerotic plaques appears to be related to a downregulation of chemokines and their ligands, which are known to regulate DC migration. oxLDL induces an in vitro downregulation of CCR7 and CCL21, which may play a role in the reduction of DC migration from the plaques

Synthesis of Functionalized 1,4-Azaborinines by the Cyclization of Di-tert-butyliminoborane and Alkynes

Di-tert-butyliminoborane is found to be a very useful synthon for the synthesis of a variety of functionalized 1,4-azaborinines by the Rh-mediated cyclization of iminoboranes with alkynes. The reactions proceed via [2 + 2] cycloaddition of iminoboranes and alkynes in the presence of [RhCl(PiPr3)2]2, which gives a rhodium η4-1,2-azaborete complex that yields 1,4-azaborinines upon reaction with acetylene. This reaction is compatible with substrates containing more than one alkynyl unit, cleanly affording compounds containing multiple 1,4-azaborinines. The substitution of terminal alkynes for acetylene also led to 1,4-azaborinines, enabling ring substitution at a predetermined location. We report the first general synthesis of this new methodology, which provides highly regioselective access to valuable 1,4-azaborinines in moderate yields. A mechanistic rationale for this reaction is supported by DFT calculations, which show the observed regioselectivity to arise from steric effects in the B-C bond coupling en route to the rhodium η4-1,2-azaborete complex and the selective oxidative cleavage of the B-N bond of the 1,2-azaborete ligand in its subsequent reaction with acetylene.</p

Development of a PNGase Rc column for online deglycosylation of complex glycoproteins during HDX-MS

Protein glycosylation is one of the most common PTMs and many cell surface receptors, extracellular proteins, and biopharmaceuticals are glycosylated. However, HDX-MS analysis of such important glycoproteins has so far been limited by difficulties in determining the HDX of the protein segments that contain glycans. We have developed a column containing immobilized PNGase Rc (from Rudaea cellulosilytica) that can readily be implemented into a conventional HDX-MS setup to allow improved analysis of glycoproteins. We show that HDX-MS with the PNGase Rc column enables efficient online removal of N-linked glycans and the determination of the HDX of glycosylated regions in several complex glycoproteins. Additionally, we use the PNGase Rc column to perform a comprehensive HDX-MS mapping of the binding epitope of a mAb to c-Met, a complex glycoprotein drug target. Importantly, the column retains high activity in the presence of common quench-buffer additives like TCEP and urea and performed consistent across 114 days of extensive use. Overall, our work shows that HDX-MS with the integrated PNGase Rc column can enable fast and efficient online deglycosylation at harsh quench conditions to provide comprehensive analysis of complex glycoproteins

Experimental evidence for temporal uncoupling of brain Aβ deposition and neurodegenerative sequelae

Brain A beta deposition is a key early event in the pathogenesis of Alzheimer ' s disease (AD), but the long presymptomatic phase and poor correlation between A beta deposition and clinical symptoms remain puzzling. To elucidate the dependency of downstream pathologies on A beta, we analyzed the trajectories of cerebral A beta accumulation, A beta seeding activity, and neurofilament light chain (NfL) in the CSF (a biomarker of neurodegeneration) in A beta-precursor protein transgenic mice. We find that A beta deposition increases linearly until it reaches an apparent plateau at a late age, while A beta seeding activity increases more rapidly and reaches a plateau earlier, coinciding with the onset of a robust increase of CSF NfL. Short-term inhibition of A beta generation in amyloid-laden mice reduced A beta deposition and associated glial changes, but failed to reduce A beta seeding activity, and CSF NfL continued to increase although at a slower pace. When short-term or long-term inhibition of A beta generation was started at pre-amyloid stages, CSF NfL did not increase despite some A beta deposition, microglial activation, and robust brain A beta seeding activity. A dissociation of A beta load and CSF NfL trajectories was also found in familial AD, consistent with the view that A beta aggregation is not kinetically coupled to neurotoxicity. Rather, neurodegeneration starts when A beta seeding activity is saturated and before A beta deposition reaches critical (half-maximal) levels, a phenomenon reminiscent of the two pathogenic phases in prion disease. The poor correlation between brain A beta deposition and clinical symptoms in Alzheimer ' s disease remains puzzling. Here, the authors show a temporal dissociation of A beta deposition and neurodegeneration

Prediction of underlying atrial fibrillation in patients with a cryptogenic stroke: results from the NOR-FIB Study

Background - Atrial fibrillation (AF) detection and treatment are key elements to reduce recurrence risk in cryptogenic stroke (CS) with underlying arrhythmia. The purpose of the present study was to assess the predictors of AF in CS and the utility of existing AF-predicting scores in The Nordic Atrial Fibrillation and Stroke (NOR-FIB) Study. Method - The NOR-FIB study was an international prospective observational multicenter study designed to detect and quantify AF in CS and cryptogenic transient ischaemic attack (TIA) patients monitored by the insertable cardiac monitor (ICM), and to identify AF-predicting biomarkers. The utility of the following AF-predicting scores was tested: AS5F, Brown ESUS-AF, CHA2DS2-VASc, CHASE-LESS, HATCH, HAVOC, STAF and SURF. Results - In univariate analyses increasing age, hypertension, left ventricle hypertrophy, dyslipidaemia, antiarrhythmic drugs usage, valvular heart disease, and neuroimaging findings of stroke due to intracranial vessel occlusions and previous ischemic lesions were associated with a higher likelihood of detected AF. In multivariate analysis, age was the only independent predictor of AF. All the AF-predicting scores showed significantly higher score levels for AF than non-AF patients. The STAF and the SURF scores provided the highest sensitivity and negative predictive values, while the AS5F and SURF reached an area under the receiver operating curve (AUC) > 0.7. Conclusion - Clinical risk scores may guide a personalized evaluation approach in CS patients. Increasing awareness of the usage of available AF-predicting scores may optimize the arrhythmia detection pathway in stroke units