The effect of functionalizing lipid nanocapsules with NFL-TBS.40-63 peptide on their uptake by glioblastoma cells.

We previously described a neurofilament derived cell-penetrating peptide, NFL-TBS.40-63, that specifically enters in glioblastoma cells where it disturbs the microtubule network both in vitro and in vivo. The aim of this study is to test whether this peptide can increase the targeted uptake by glioblastoma cells of lipid nanocapsules filled with Paclitaxel, and thus can increase their anti-proliferation in vitro and in vivo. Here, using the drop tensiometry we show that approximately 60 NFL-TBS.40-63 peptides can bind to one 50 nm lipid nanocapsule. When nanocapsules are filled with a far-red fluorochrome (DiD) and Paclitaxel, the presence of the NFL-TBS.40-63 peptide increases their uptake by glioblastoma cells in culture as evaluated by FACS analysis, and thus reduces their proliferation. Finally, when such nanocapsules were injected in mice bearing a glioma tumour, they are preferentially targeted to the tumour and reduce its progression. These results show that nanocapsules functionalized with the NFL-TBS.40-63 peptide represent a powerful drug-carrier system for glioma targeted treatment

Space Launch System Booster Separation Supersonic Powered Testing with Surface and Off-Body Measurements

A wind tunnel test was run in the NASA Langley Unitary Plan Wind Tunnel simulating the separation of the two solid rocket boosters (SRB) from the core stage of the NASA Space Launch System (SLS). The test was run on a 0.9% scale model of the SLS Block 1B Cargo (27005) configuration and the SLS Block 1B Crew (28005) configuration at a Mach of 4.0. High pressure air was used to simulate plumes from the booster separation motors located at the nose and aft skirt of the two boosters. Force and moment data were taken on both SRBs and on the core stage. Schlieren still photos and video were recorded throughout testing. A set of points were acquired using Cross-correlation Doppler Global Velocimetry (CCDGV) readings to get 3 component velocity measurements between the core and the left-hand SRB. The CCDGV laser was utilized to record flow visualization in the same location, between the core and the left-hand SRB. Pressure Sensitive Paint data were taken on a separate set of runs. Computational Fluid Dynamics (CFD) runs were computed on a subset of the wind tunnel data points for comparison. A combination of the force/moment, CCDGV and Pressure Sensitive Paint (PSP) data (as well as schlieren images) at the CFD-specified test conditions will be used te the CFD simulations that will be used to build an SLS booster separation database flight conditions

Axonal regeneration is compromised in NFH-LacZ transgenic mice but not in NFH-GFP mice

To investigate neurofilament (NF) dynamics during the cytoskeleton reorganization in regenerating axons, and their electrophysiological and histological consequences, we used two transgenic lines of mice: neurofilament high (NFH)-LacZ and NFH-green fluorescent protein (GFP). In NFH-LacZ mice, NFs are retained in cell bodies and deficient in axons (Eyer and Peterson, 1994), while in NFH-GFP mice the fluorescent fusion protein is normally transported along axons (Letournel et al., 2006). Following a crush of the sciatic nerve, conduction recovery in NFH-GFP mice is similar to wild-type (wt) mice, but it is reduced in NFH-LacZ mice. Moreover, changes of axonal calibres following regeneration are similar between NFH-GFP and wt mice, but they are systematically reduced in NFH-LacZ mice. Finally, the axonal transport of NFH-GFP fusion protein and NFs is re-initiated after the crush as evidenced by the fluorescent and immunolabelling of axons distal from the crushed point, but NFs and the fusion protein are not transported along axons during regeneration in NFH-LacZ mice. Together, these results argue that the absence of axonal NFs in NFH-LacZ mice compromises the axonal regeneration, and that the NFH-GFP reporter fusion protein represents an efficient model to evaluate the NF dynamics during axonal regeneration

Space Launch System Ascent Static Aerodynamic Database Development

This paper describes the wind tunnel testing work and data analysis required to characterize the static aerodynamic environment of NASA's Space Launch System (SLS) ascent portion of flight. Scaled models of the SLS have been tested in transonic and supersonic wind tunnels to gather the high fidelity data that is used to build aerodynamic databases. A detailed description of the wind tunnel test that was conducted to produce the latest version of the database is presented, and a representative set of aerodynamic data is shown. The wind tunnel data quality remains very high, however some concerns with wall interference effects through transonic Mach numbers are also discussed. Post-processing and analysis of the wind tunnel dataset are crucial for the development of a formal ascent aerodynamics database

Host Responses to Intestinal Microbial Antigens in Gluten-Sensitive Mice

BACKGROUND AND AIMS: Excessive uptake of commensal bacterial antigens through a permeable intestinal barrier may influence host responses to specific antigen in a genetically predisposed host. The aim of this study was to investigate whether intestinal barrier dysfunction induced by indomethacin treatment affects the host response to intestinal microbiota in gluten-sensitized HLA-DQ8/HCD4 mice. METHODOLOGY/PRINCIPAL FINDINGS: HLA-DQ8/HCD4 mice were sensitized with gluten, and gavaged with indomethacin plus gluten. Intestinal permeability was assessed by Ussing chamber; epithelial cell (EC) ultra-structure by electron microscopy; RNA expression of genes coding for junctional proteins by Q-real-time PCR; immune response by in-vitro antigen-specific T-cell proliferation and cytokine analysis by cytometric bead array; intestinal microbiota by fluorescence in situ hybridization and analysis of systemic antibodies against intestinal microbiota by surface staining of live bacteria with serum followed by FACS analysis. Indomethacin led to a more pronounced increase in intestinal permeability in gluten-sensitized mice. These changes were accompanied by severe EC damage, decreased E-cadherin RNA level, elevated IFN-gamma in splenocyte culture supernatant, and production of significant IgM antibody against intestinal microbiota. CONCLUSION: Indomethacin potentiates barrier dysfunction and EC injury induced by gluten, affects systemic IFN-gamma production and the host response to intestinal microbiota antigens in HLA-DQ8/HCD4 mice. The results suggest that environmental factors that alter the intestinal barrier may predispose individuals to an increased susceptibility to gluten through a bystander immune activation to intestinal microbiota