Flat plate and turbine vane film-cooling performance with laid-back fan-shaped holes

Shaped holes are considered as an effective solution to enhance gas turbine film-cooling performance, as they allow to increase the coolant mass-flux, while limiting the detrimental lift-off phenomena. A great amount of work has been carried out in past years on basic flat plate configurations while a reduced number of experimental works deals with a quantitative assessment of the influence of curvature and vane pressure gradient. In the present work PSP (Pressure Sensitive Paint) technique is used to detail the adiabatic effectiveness generated by axial shaped holes with high value of Area Ratio close to 7, in three different configurations with the same 1:1 scale: first of all, a flat plate configuration is examined; after that, the film-cooled pressure and suction sides of a turbine vane model are investigated. Tests were performed varying the blowing ratio and imposing a density ratio of 2.5 . The experimental results are finally compared to the predictions of two different correlations, developed for flat plate configurations

Perineuronal nets control visual input via thalamic recruitment of cortical PV interneurons

In the neocortex, critical periods (CPs) of plasticity are closed following the accumulation of perineuronal nets (PNNs) around parvalbumin (PV)-positive inhibitory interneurons. However, how PNNs tune cortical function and plasticity is unknown. We found that PNNs modulated the gain of visual responses and \u3b3-oscillations in the adult mouse visual cortex in vivo, consistent with increased interneuron function. Removal of PNNs in adult V1 did not affect GABAergic neurotransmission from PV cells, nor neuronal excitability in layer 4. Importantly, PNN degradation coupled to sensory input potentiated glutamatergic thalamic synapses selectively onto PV cells. In the absence of PNNs, increased thalamic PV-cell recruitment modulated feed-forward inhibition differently on PV cells and pyramidal neurons. These effects depended on visual input, as they were strongly attenuated by monocular deprivation in PNN-depleted adult mice. Thus, PNNs control visual processing and plasticity by selectively setting the strength of thalamic recruitment of PV cells

Untangling the extracellular matrix of idiopathic epiretinal membrane: a path winding among structure, interactomics and translational medicine

Idiopathic epiretinal membranes (iERMs) are fibrocellular sheets of tissue that develop at the vit-reoretinal interface. iERMs consist of cells and extracellular matrix (ECM) formed by a complex array of structural proteins and a large number of proteins that regulate cell-matrix interaction, matrix deposition and remodelling. Many components of the ECM tend to produce a layered pat-tern that can influence the tractional properties of the membranes. We applied a bioinformatics approach on a list of proteins previously identified with an MS-based proteomic analysis on sam-ples of iERM to report the interactome of some key proteins. The performed pathway analysis highlights interactions occurring among ECM molecules, their cell receptors, and intra or extra-cellular proteins that may play a role in matrix biology, in this special context. In particular, integ-rin β1, cathepsin B, epidermal growth factor receptor, protein-glutamine gam-ma-glutamyltransferase 2, and prolow-density lipoprotein receptor-related protein 1 are key hubs in the outlined protein-protein cross-talks. A section on the biomarkers that can be found in the vitreous humor of patients affected by iERM and that can modulate matrix deposition is also pre-sented. Finally, translational medicine in iERM treatment has been summed up taking stock of the techniques that have been proposed for pharmacologic vitreolysi

Co-Expression of Podoplanin and CD44 in Proliferative Vitreoretinopathy Epiretinal Membranes

Epiretinal membranes (ERMs) are sheets of tissue that pathologically develop in the vitreoretinal interface leading to progressive vision loss. They are formed by different cell types and by an exuberant deposition of extracellular matrix proteins. Recently, we reviewed ERMs’ extracellular matrix components to better understand molecular dysfunctions that trigger and fuel the onset and development of this disease. The bioinformatics approach we applied delineated a comprehensive overview on this fibrocellular tissue and on critical proteins that could really impact ERM physiopathology. Our interactomic analysis proposed the hyaluronic-acid-receptor cluster of differentiation 44 (CD44) as a central regulator of ERM aberrant dynamics and progression. Interestingly, the interaction between CD44 and podoplanin (PDPN) was shown to promote directional migration in epithelial cells. PDPN is a glycoprotein overexpressed in various cancers and a growing body of evidence indicates its relevant function in several fibrotic and inflammatory pathologies. The binding of PDPN to partner proteins and/or its ligand results in the modulation of signaling pathways regulating proliferation, contractility, migration, epithelial–mesenchymal transition, and extracellular matrix remodeling, all processes that are vital in ERM formation. In this context, the understanding of the PDPN role can help to modulate signaling during fibrosis, hence opening a new line of therap

TGF-β concentrations and activity are down-regulated in the aqueous humor of patients with neovascular age-related macular degeneration

Controversy still exists regarding the role of the TGF-β in neovascular age-related macular degeneration (nAMD), a major cause of severe visual loss in the elderly in developed countries. Here, we measured the concentrations of active TGF-β1, TGF-β2, and TGF-β3 by ELISA in the aqueous humor of 20 patients affected by nAMD, who received 3 consecutive monthly intravitreal injections of anti-VEGF-A antibody. Samples were collected at baseline (before the first injection), month 1 (before the second injection), and month 2 (before the third injection). The same samples were used in a luciferase-based reporter assay to test the TGF-β pathway activation. Active TGF-β1 concentrations in the aqueous humor were below the minimum detectable dose. Active TGF-β2 concentrations were significantly lower at baseline and at month 1, compared to controls. No significant differences in active TGF-β3 concentration were found among the sample groups. Moreover, TGF-β pathway activation was significantly lower at baseline compared to controls. Our data corroborate an anti-angiogenic role for TGF-β2 in nAMD. This should be considered from the perspective of a therapy using TGF-β inhibitors

Prostaglandin F2-alpha receptor (FPr) expression on porcine corpus luteum microvascular endothelial cells (pCL-MVECs)

<p>Abstract</p> <p>Background</p> <p>The corpus luteum (CL) is a transient endocrine gland and prostaglandin F2-alpha is considered to be the principal luteolysin in pigs. In this species, the in vivo administration of prostaglandin F2-alpha induces apoptosis in large vessels as early as 6 hours after administration. The presence of the prostaglandin F2-alpha receptor (FPr) on the microvascular endothelial cells (pCL-MVECs) of the porcine corpus luteum has not yet been defined. The aim of the study was to assess FPr expression in pCL-MVECs in the early and mid-luteal phases (EL-p, ML-p), and during pregnancy (P-p). Moreover, the effectiveness of prostaglandin F2-alpha treatment in inducing pCL-MVEC apoptosis was tested.</p> <p>Methods</p> <p>Porcine CLs were collected in the EL and ML phases and during P-p. All CLs from each animal were minced together and the homogenates underwent enzymatic digestion. The pCL-MVECs were then positively selected by an immunomagnetic separation protocol using Dynabeads coated with anti-CD31 monoclonal antibody and seeded in flasks in the presence of EGM 2-MV (Microvascular Endothelial Cell Medium-2). After 4 days of culture, the cells underwent additional immunomagnetic selection and were seeded in flasks until the confluent stage.</p> <p>PCR Real time, western blot and immunodetection assays were utilized to assess the presence of FPr on pCL-MVEC primary cultures. Furthermore, the influence of culture time (freshly isolated, cultured overnight and at confluence) and hormonal treatment (P4 and E2) on FPr expression in pCL-MVECs was also investigated. Apoptosis was detected by TUNEL assay of pCL-MVECs exposed to prostaglandin F2-alpha.</p> <p>Results</p> <p>We obtained primary cultures of pCL-MVECs from all animals. FPr mRNA and protein levels showed the highest value (ANOVA) in CL-MVECs derived from the early-luteal phase. Moreover, freshly isolated MVECs showed a higher FPr mRNA value than those cultured overnight and confluent cells (ANOVA). prostaglandin F2-alpha treatment failed to induce an apoptotic response in all the pCL-MVEC cultures.</p> <p>Conclusion</p> <p>Our data showing the presence of FPr on MVECs and the inability of prostaglandin F2-alpha to evoke an in vitro apoptotic response suggest that other molecules or mechanisms must be considered in order to explain the in vivo direct pro-apoptotic effect of prostaglandin F2-alpha at the endothelial level.</p