280 research outputs found
Correlated evolution of structure and mechanical loss of a sputtered silica film
Energy dissipation in amorphous coatings severely affects high-precision
optical and quantum transducers. In order to isolate the source of coating
loss, we performed an extensive study of Raman scattering and mechanical loss
of a thermally-treated sputtered silica coating. Our results show that loss is
correlated with the population of three-membered rings of Si-O tetrahedral
units, and support the evidence that thermal treatment reduces the density of
metastable states separated by a characteristic energy of about 0.5 eV, in
favour of an increase of the states separated by smaller activation energies.
Finally, we conclude that three-fold rings are involved in the relaxation
mechanisms only if they belong to more complex chain-like structures of 10 to
100 tetrahedra.Comment: 5 pages, 3 figure
High-reflection coatings for gravitational-wave detectors: State of the art and future developments
We report on the optical, mechanical and structural characterization of the sputtered coating materials of Advanced LIGO, Advanced Virgo and KAGRA gravitational-waves detectors. We present the latest results of our research program aiming at decreasing coating thermal noise through doping, optimization of deposition parameters and post-deposition annealing. Finally, we propose sputtered Si3N4as a candidate material for the mirrors of future detectors
Elastin-derived peptides potentiate atherosclerosis through the immune Neu1-PI3Kγ pathway
Aims Elastin is degraded during vascular ageing and its products, elastin-derived peptides (EP), are present in the human blood circulation. EP binds to the elastin receptor complex (ERC) at the cell surface, composed of elastin-binding protein (EBP), a cathepsin A and a neuraminidase 1. Some in vitro functions have clearly been attributed to this binding, but the in vivo implications for arterial diseases have never been clearly investigated. Methods and results Here, we demonstrate that chronic doses of EP injected into mouse models of atherosclerosis increase atherosclerotic plaque size formation. Similar effects were observed following an injection of a VGVAPG peptide, suggesting that the ERC mediates these effects. The absence of phosphoinositide 3-kinase γ (PI3Kγ) in bone marrow-derived cells prevented EP-induced atherosclerosis development, demonstrating that PI3Kγ drive EP-induced arterial lesions. Accordingly, in vitro studies showed that PI3Kγ was required for EP-induced monocyte migration and ROS production and that this effect was dependent upon neuraminidase activity. Finally, we showed that degradation of elastic lamellae in LDLR−/− mice fed an atherogenic diet correlated with atherosclerotic plaque formation. At the same time, the absence of the cathepsin A-neuraminidase 1 complex in cells of the haematopoietic lineage abolished atheroma plaque size progression and decreased leucocytes infiltration, clearly demonstrating the role of this complex in atherogenesis and suggesting the involvement of endogenous EP. Conclusion Altogether, this work identifies EP as an enhancer of atherogenesis and defines the Neuraminidase 1/PI3Kγ signalling pathway as a key mediator of this function in vitro and in viv
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Insulin and leptin oscillations license food-entrained browning and metabolic flexibility
Timed feeding drives adipose browning, although the integrative mechanisms for the same remain unclear. Here, we show that twice-a-night (TAN) feeding generates biphasic oscillations of circulating insulin and leptin, representing their entrainment by timed feeding. Insulin and leptin surges lead to marked cellular, functional, and metabolic remodeling of subcutaneous white adipose tissue (sWAT), resulting in increased energy expenditure. Single-cell RNA-sequencing (scRNA-seq) analyses and flow cytometry demonstrate a role for insulin and leptin surges in innate lymphoid type 2 (ILC2) cell recruitment and sWAT browning, since sWAT depot denervation or loss of leptin or insulin receptor signaling or ILC2 recruitment each dampens TAN feeding-induced sWAT remodeling and energy expenditure. Consistently, recreating insulin and leptin oscillations via once-a-day timed co-injections is sufficient to favorably remodel innervated sWAT. Innervation is necessary for sWAT remodeling, since denervation of sWAT, but not brown adipose tissue (BAT), blocks TAN-induced sWAT remodeling and resolution of inflammation. In sum, reorganization of nutrient-sensitive pathways remodels sWAT and drives the metabolic benefits of timed feeding
Extending the Minimum Information About BIobank Data Sharing Terminology to Describe Samples, Sample Donors, and Events
Introduction: The Minimum Information About BIobank data Sharing (MIABIS) was initiated in 2012. MIABIS aims to create a common biobank terminology to facilitate data sharing in biobanks and sample collections. The MIABIS Core terminology consists of three components describing biobanks, sample collections, and studies, in which information on samples and sample donors is provided at aggregated form. However, there is also a need to describe samples and sample donors at an individual level to allow more elaborate queries on available biobank samples and data. Therefore the MIABIS terminology has now been extended with components describing samples and sample donors at an individual level. Materials and Methods: The components were defined according to specific scope and use cases by a large group of experts, and through several cycles of reviews, according to the new MIABIS governance model of BBMRI-ERIC (Biobanking and Biomolecular Resources Research Infrastructure-European Research Infrastructure Consortium). The guiding principles applied in developing these components included the following terms: model should consider only samples of human origin, model should be applicable to all types of samples and all sample donors, and model should describe the current status of samples stored in a given biobank. Results: A minimal set of standard attributes for defining samples and sample donors is presented here. We added an "event" component to describe attributes that are not directly describing samples or sample donors but are tightly related to them. To better utilize the generic data model, we suggest a procedure by which interoperability can be promoted, using specific MIABIS profiles. Discussion: The MIABIS sample and donor component extensions and the new generic data model complement the existing MIABIS Core 2.0 components, and substantially increase the potential usability of this terminology for better describing biobank samples and sample donors. They also support the use of individual level data about samples and sample donors to obtain accurate and detailed biobank availability queries
Phenological changes of oceanic phytoplankton in the 1980s and 2000s as revealed by remotely sensed ocean-color observations
We investigated the phenology of oceanic phytoplankton at large scales over two 5-year time periods: 1979–1983 and 1998–2002. Two ocean-color satellite data archives (Coastal Zone Color Scanner (CZCS) and Sea-viewing Wide Field-of-view Sensor (SeaWiFS)) were used to investigate changes in seasonal patterns of concentration-normalized chlorophyll. The geographic coverage was constrained by the CZCS data distribution. It was best for the Northern Hemisphere and also encompassed large areas of the Indian, South Pacific, and Equatorial Atlantic regions. For each 2° pixel, monthly climatologies were developed for satellite-derived chlorophyll, and the resulting seasonal cycles were statistically grouped using cluster analysis. Five distinct groups of mean seasonal cycles were identified for each half-decade period. Four types were common to both time periods and correspond to previously identified phytoplankton regimes: Bloom, Tropical, Subtropical North, and Subtropical South. Two other mean seasonal cycles, one in each of the two compared 5-year periods, were related to transitional or intermediate states (Transitional Tropical and Transitional Bloom). Five mean seasonal cycles (Bloom, Tropical, Subtropical North, and Subtropical South, Transitional Bloom) were further confirmed when the whole SeaWiFS data set (1998–2010) was analyzed. For ~35% of the pixels analyzed, characteristic seasonal cycles of the 1979–1983 years differed little from those of the 1998–2002 period. For ~65% of the pixels, however, phytoplankton seasonality patterns changed markedly, especially in the Northern Hemisphere. Subtropical regions of the North Pacific and Atlantic experienced a widespread expansion of the Transitional Bloom regime, which appeared further enhanced in the climatology based on the full SeaWiFS record (1998–2010), and, as showed by a more detailed analysis, is associated to La Niña years. This spatial pattern of Transitional Bloom regime reflects a general smoothing of seasonality at macroscale, coming into an apparent greater temporal synchrony of the Northern Hemisphere. The Transitional Bloom regime is also the result of a higher variability, both in space and time. The observed change in phytoplankton dynamics may be related not only to biological interactions but also to large-scale changes in the coupled atmosphere–ocean system. Some connections are indeed found with climate indices. Changes were observed among years belonging to opposite phases of ENSO, though discernible from the change among the two periods and within the SeaWiFS era (1998–2010). These linkages are considered preliminary at present and are worthy of further investigation
Swiss public health measures associated with reduced SARS-CoV-2 transmission using genome data
Genome sequences from evolving infectious pathogens allow quantification of case introductions and local transmission dynamics. We sequenced 11,357 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes from Switzerland in 2020 - the sixth largest effort globally. Using a representative subset of these data, we estimated viral introductions to Switzerland and their persistence over the course of 2020. We contrasted these estimates with simple null models representing the absence of certain public health measures. We show that Switzerland's border closures de-coupled case introductions from incidence in neighboring countries. Under a simple model, we estimate an 86-98% reduction in introductions during Switzerland's strictest border closures. Furthermore, the Swiss 2020 partial lockdown roughly halved the time for sampled introductions to die out. Last, we quantified local transmission dynamics once introductions into Switzerland occurred, using a phylodynamic model. We found that transmission slowed 35-63% upon outbreak detection in summer 2020, but not in fall. This finding may indicate successful contact tracing over summer before overburdening in fall. The study highlights the added value of genome sequencing data for understanding transmission dynamics
Dynamic biogeochemical provinces in the global ocean
In recent decades, it has been found useful to partition the pelagic environment using the concept of biogeochemical provinces, or BGCPs, within each of which it is assumed that environmental conditions are distinguishable and unique at global scale. The boundaries between provinces respond to features of physical oceanography and, ideally, should follow seasonal and interannual changes in ocean dynamics. But this ideal has not been fulfilled except for small regions of the oceans. Moreover, BGCPs have been used only as static entities having boundaries that were originally established to compute global primary production. In the present study, a new statistical methodology based on non-parametric procedures is implemented to capture the environmental characteristics within 56 BGCPs. Four main environmental parameters (bathymetry, chlorophyll a concentration, surface temperature, and salinity) are used to infer the spatial distribution of each BGCP over 1997–2007. The resulting dynamic partition allows us to integrate changes in the distribution of BGCPs at seasonal and interannual timescales, and so introduces the possibility of detecting spatial shifts in environmental conditions
DNA methylation in glioblastoma: impact on gene expression and clinical outcome
International audienceBACKGROUND: Changes in promoter DNA methylation pattern of genes involved in key biological pathways have been reported in glioblastoma. Genome-wide assessments of DNA methylation levels are now required to decipher the epigenetic events involved in the aggressive phenotype of glioblastoma, and to guide new treatment strategies. RESULTS: We performed a whole-genome integrative analysis of methylation and gene expression profiles in 40 newly diagnosed glioblastoma patients. We also screened for associations between the level of methylation of CpG sites and overall survival in a cohort of 50 patients uniformly treated by surgery, radiotherapy and chemotherapy with concomitant and adjuvant temozolomide (STUPP protocol). The methylation analysis identified 616 CpG sites differentially methylated between glioblastoma and control brain, a quarter of which was differentially expressed in a concordant way. Thirteen of the genes with concordant CpG sites displayed an inverse correlation between promoter methylation and expression level in glioblastomas: B3GNT5, FABP7, ZNF217, BST2, OAS1, SLC13A5, GSTM5, ME1, UBXD3, TSPYL5, FAAH, C7orf13, and C3orf14. Survival analysis identified six CpG sites associated with overall survival. SOX10 promoter methylation status (two CpG sites) stratified patients similarly to MGMT status, but with a higher Area Under the Curve (0.78 vs. 0.71, p-value < 5e-04). The methylation status of the FNDC3B, TBX3, DGKI, and FSD1 promoters identified patients with MGMT-methylated tumors that did not respond to STUPP treatment (p-value < 1e-04). CONCLUSIONS: This study provides the first genome-wide integrative analysis of DNA methylation and gene expression profiles obtained from the same GBM cohort. We also present a methylome-based survival analysis for one of the largest uniformly treated GBM cohort ever studied, for more than 27,000 CpG sites. We have identified genes whose expression may be tightly regulated by epigenetic mechanisms and markers that may guide treatment decisions
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