New PLGA-P188-PLGA matrix enhances TGF-β3 release from pharmacologically active microcarriers and promotes chondrogenesis of mesenchymal stem cells

The use of injectable scaffolding materials for in vivo tissue regeneration has raised great interest in various clinical applications because it allows cell implantation through minimally invasive surgical procedures. In case of cartilage repair, a tissue engineered construct should provide a support for the cell and allow sustained in situ delivery of bioactive factors capable of inducing cell differentiation into chondrocytes. Pharmacologically active microcarriers (PAMs), made of biodegradable poly(d,l-lactide-co-glycolide acid) (PLGA), are a unique system, which combines these properties in an adaptable and simple microdevice. However, a limitation of such scaffold is low and incomplete protein release that occurs using the hydrophobic PLGA based microspheres. To circumvent this problem, we developed a novel formulation of polymeric PAMs containing a P188 poloxamer, which protects the protein from denaturation and may positively affect chondrogenesis. This poloxamer was added as a free additive for protein complexation and as a component of the scaffold covalently linked to PLGA. This procedure allows getting a more hydrophilic scaffold but also retaining the protective polymer inside the microcarriers during their degradation. The novel PLGA-P188-PLGA PAMs presenting a fibronectin-covered surface allowed enhanced MSC survival and proliferation. When engineered with TGFβ3, they allowed the sustained release of 70% of the incorporated TGF-β3 over time. Importantly, they exerted superior chondrogenic differentiation potential compared to previous FN-PAM-PLGA-TGF-β3, as shown by an increased expression of specific cartilage markers such as cartilage type II, aggrecan and COMP. Therefore, this microdevice represents an efficient easy-to-handle and injectable tool for cartilage repair

Operator Learning with Neural Fields: Tackling PDEs on General Geometries

Machine learning approaches for solving partial differential equations require learning mappings between function spaces. While convolutional or graph neural networks are constrained to discretized functions, neural operators present a promising milestone toward mapping functions directly. Despite impressive results they still face challenges with respect to the domain geometry and typically rely on some form of discretization. In order to alleviate such limitations, we present CORAL, a new method that leverages coordinate-based networks for solving PDEs on general geometries. CORAL is designed to remove constraints on the input mesh, making it applicable to any spatial sampling and geometry. Its ability extends to diverse problem domains, including PDE solving, spatio-temporal forecasting, and inverse problems like geometric design. CORAL demonstrates robust performance across multiple resolutions and performs well in both convex and non-convex domains, surpassing or performing on par with state-of-the-art models

Covalent grafting onto self-adhesive surfaces based on aryldiazonium salt seed layers

International audienceThe chemistry of aryldiazonium salts has been thoroughly used in recent years to graft in a very simple and robust way ultrathin polyphenylene-like films on a broad range of surfaces. We show here that the same chemistry can be used to obtain self-adhesive surfaces. This target was reached in a simple way by coating various surfaces with chemisorbed organic films containing active aryldiazonium salts. These self-adhesive surfaces are then put into contact with various species (molecules, polymers, nanoparticles, nanotubes, graphene flakes, etc.) that react either spontaneously or under activation with the immobilized aryldiazonium salts. Our self-adhesive surfaces were synthesized following a simple aqueous two-step protocol based on p-phenylenediamine diazotisation. The first diazotisation step results in the robust grafting of thin polyaminophenylene (PAP) layers onto the surface. The second diazotisation step changed the grafted PAP film into a poly-aryldiazonium polymer (PDP) film. The covalent grafting between those self-adhesive surfaces and the target species was achieved by direct contact or by immersion of the self-adhesive surfaces in solution. We present in this preliminary work the grafting of multi-wall carbon nanotubes (MWCNTs), flakes of highly oriented pyrolytic graphite (HOPG), various organic compounds and copper nanoparticles. We also tested these immobilized aryldiazonium salts as electropolymerization initiators for the grafting-to process

Probing the LMC age gap at intermediate cluster masses

The LMC has a rich star cluster system spanning a wide range of ages and masses. One striking feature of the LMC cluster system is the existence of an age gap between 3-10 Gyrs. But this feature is not as clearly seen among field stars. Three LMC fields containing relatively poor and sparse clusters whose integrated colours are consistent with those of intermediate age simple stellar populations have been imaged in BVI with the Optical Imager (SOI) at the Southern Telescope for Astrophysical Research (SOAR). A total of 6 clusters, 5 of them with estimated initial masses M < 10^4M_sun, were studied in these fields. Photometry was performed and Colour-Magnitude Diagrams (CMD) were built using standard point spread function fitting methods. The faintest stars measured reach V ~ 23. The CMD was cleaned from field contamination by making use of the three-dimensional colour and magnitude space available in order to select stars in excess relative to the field. A statistical CMD comparison method was developed for this purpose. The subtraction method has proven to be successful, yielding cleaned CMDs consistent with a simple stellar population. The intermediate age candidates were found to be the oldest in our sample, with ages between 1-2 Gyrs. The remaining clusters found in the SOAR/SOI have ages ranging from 100 to 200 Myrs. Our analysis has conclusively shown that none of the relatively low-mass clusters studied by us belongs to the LMC age-gap.Comment: 9 pages, 8 figures. Accepted to MNRA

A daily, 1 km resolution data set of downscaled Greenland ice sheet surface mass balance (1958–2015)

This study presents a data set of daily, 1 km resolution Greenland ice sheet (GrIS) surface mass balance (SMB) covering the period 1958–2015. Applying corrections for elevation, bare ice albedo and accumulation bias, the high-resolution product is statistically downscaled from the native daily output of the polar regional climate model RACMO2.3 at 11 km. The data set includes all individual SMB components projected to a down-sampled version of the Greenland Ice Mapping Project (GIMP) digital elevation model and ice mask. The 1 km mask better resolves narrow ablation zones, valley glaciers, fjords and disconnected ice caps. Relative to the 11 km product, the more detailed representation of isolated glaciated areas leads to increased precipitation over the southeastern GrIS. In addition, the downscaled product shows a significant increase in runoff owing to better resolved low-lying marginal glaciated regions. The combined corrections for elevation and bare ice albedo markedly improve model agreement with a newly compiled data set of ablation measurements

Electron Cloud and Beam Scrubbing in the LHC

An adequate dose of photoelectrons, accelerated by low-intensity proton bunches and hitting the LHC beam screen wall, will substantially reduce secondary emission and avoid the fast build-up of an electron cloud for the nominal LHC beam. The conditioning period of the liner surface can be considerably shortened thanks to secondary electrons, provided heat load and beam stability can be kept under control; for example this may be possible using a special proton beam, including satellite bunches with an intensity of 15-20% of the nominal bunch intensity and a spacing of one or two RF wavelengths. Based on recent measurements of secondary electron emission, on multipacting tests and simulation results, we discuss possible "beam scrubbing" scenarios in the LHC and present an updat

Increased variability in Greenland Ice Sheet runoff from satellite observations

Runoff from the Greenland Ice Sheet has increased over recent decades affecting global sea level, regional ocean circulation, and coastal marine ecosystems, and it now accounts for most of the contemporary mass imbalance. Estimates of runoff are typically derived from regional climate models because satellite records have been limited to assessments of melting extent. Here, we use CryoSat-2 satellite altimetry to produce direct measurements of Greenland's runoff variability, based on seasonal changes in the ice sheet's surface elevation. Between 2011 and 2020, Greenland's ablation zone thinned on average by 1.4 ± 0.4 m each summer and thickened by 0.9 ± 0.4 m each winter. By adjusting for the steady-state divergence of ice, we estimate that runoff was 357 ± 58 Gt/yr on average - in close agreement with regional climate model simulations (root mean square difference of 47 to 60 Gt/yr). As well as being 21 % higher between 2011 and 2020 than over the preceding three decades, runoff is now also 60 % more variable from year-to-year as a consequence of large-scale fluctuations in atmospheric circulation. Because this variability is not captured in global climate model simulations, our satellite record of runoff should help to refine them and improve confidence in their projections

Internal states of model isotropic granular packings. III. Elastic properties

In this third and final paper of a series, elastic properties of numerically simulated isotropic packings of spherical beads assembled by different procedures and subjected to a varying confining pressure P are investigated. In addition P, which determines the stiffness of contacts by Hertz's law, elastic moduli are chiefly sensitive to the coordination number, the possible values of which are not necessarily correlated with the density. Comparisons of numerical and experimental results for glass beads in the 10kPa-10MPa range reveal similar differences between dry samples compacted by vibrations and lubricated packings. The greater stiffness of the latter, in spite of their lower density, can hence be attributed to a larger coordination number. Voigt and Reuss bounds bracket bulk modulus B accurately, but simple estimation schemes fail for shear modulus G, especially in poorly coordinated configurations under low P. Tenuous, fragile networks respond differently to changes in load direction, as compared to load intensity. The shear modulus, in poorly coordinated packings, tends to vary proportionally to the degree of force indeterminacy per unit volume. The elastic range extends to small strain intervals, in agreement with experimental observations. The origins of nonelastic response are discussed. We conclude that elastic moduli provide access to mechanically important information about coordination numbers, which escape direct measurement techniques, and indicate further perspectives.Comment: Published in Physical Review E 25 page

Stellar jitter from variable gravitational redshift: implications for RV confirmation of habitable exoplanets

A variation of gravitational redshift, arising from stellar radius fluctuations, will introduce astrophysical noise into radial velocity measurements by shifting the centroid of the observed spectral lines. Shifting the centroid does not necessarily introduce line asymmetries. This is fundamentally different from other types of stellar jitter so far identified, which do result from line asymmetries. Furthermore, only a very small change in stellar radius, ~0.01%, is necessary to generate a gravitational redshift variation large enough to mask or mimic an Earth-twin. We explore possible mechanisms for stellar radius fluctuations in low-mass stars. Convective inhibition due to varying magnetic field strengths and the Wilson depression of starspots are both found to induce substantial gravitational redshift variations. Finally, we investigate a possible method for monitoring/correcting this newly identified potential source of jitter and comment on its impact for future exoplanet searches.Comment: 6 pages, 1 figure, 1 tabl

Earlier onset of tumoral anglogenesis in matrix metalloproteinase-19-deficient mice

Among matrix metalloproteinases (MMP), MMP-19 displays unique structural features and tissue distribution. In contrast to most MMPs, MMP-19 is expressed in normal human epidermis and down-regulated during malignant transformation and dedifferentiation. The contribution of MMP-19 during tumor angiogenesis is presently unknown. In an attempt to give new insights into MMP-19 in vivo functions, angiogenic response of mutant mice lacking MMP-19 was analyzed after transplantation of murine malignant PDVA keratinocytes and after injection of Matrigel supplemented with basic fibroblast growth factor. In situ hybridization and immunohistochemical analysis revealed that MMP-19 is produced by host mesenchymal cells but not by endothelial capillary cells or CD11b-positive inflammatory cells. Based on a new computer-assisted method of quantification, we provide evidence that host MMP-19 deficiency was associated with an increased early angiogenic response. In addition, increased tumor invasion was observed in MMP-19-/- mice. We conclude that, in contrast to most MMPs that promote tumor progression, MMP-19 is a negative regulator of early steps of tumor angiogenesis and invasion. These data highlight the requirement to understand the individual functions of each MMP to improve anticancer strategies