88 research outputs found
Macroeconomic consequences of global endogenous migration: a general equilibrium analysis
In this paper, we analyze the consequences of endogenous migration flows over the coming decades in a dynamic general equilibrium model of the world economy. Such an approach has two major benefits. First, it offers a global perspective on the economic consequences of international migration flows by taking into account effects on both the destination and the origin regions. Second, by allowing migration flows to be related to economic fundamentals, they are determined endogenously in the model. We proceed by estimating the determinants of migration in an econometric model and then endogenizing migration flows by introducing the estimated relationships between demographic and income developments in our world model. We show that (i) migration could have a substantial impact on GDP growth in sending and destination regions; (ii) endogenizing migration induces important changes in the volume and the distribution of migration flows between regions compared to the United-Nations projections; (iii) the size of these flows, although substantial, will not be sufficient to counteract the impact of population ageing in the receiving regions.CGEM, Migration, International capital flows.
Photocytotoxicity of mTHPC (Temoporfin) Loaded Polymeric Micelles Mediated by Lipase Catalyzed Degradation
Purpose. To study the in vitro photocytotoxicity and cellular uptake of biodegradable polymeric micelles loaded with the photosensitizer mTHPC, including the effect of lipase-catalyzed micelle degradation. Methods. Micelles of mPEG750-b-oligo(ɛ-caprolactone)5 (mPEG750-b-OCL5) with a hydroxyl (OH), benzoyl (Bz) or naphthoyl (Np) end group were formed and loaded with mTHPC by the film hydration method. The cellular uptake of the loaded micelles, and their photocytotoxicity on human neck squamous carcinoma cells in the absence and presence of lipase were compared with free and liposomal mTHPC (Fospeg ®). Results. Micelles composed of mPEG750-b-OCL5 with benzoyl and naphtoyl end groups had the highest loading capacity up to 30 % (w/w), likely due to π–π interactions between the aromatic end group and the photosensitizer. MTHPC-loaded benzoylated micelles (0.5 mg/mL polymer) did not display photocytotoxicity or any mTHPC-uptake by the cells, in contrast to free and liposomal mTHPC. After dilution of the micelles below the critical aggregation concentration (CAC), or after micelle degradation by lipase, photocytotoxicity and cellular uptake of mTHPC were restored. Conclusion. The high loading capacity of the micelles, the high stability of mTHPC-loaded micelles above the CAC, and the lipase-induced release of the photosensitizer makes these micelles very promising carriers for photodynamic therapy in vivo. KEY WORDS: drug release; enzymatic degradation; meta-tetra(hydroxyphenyl)chlorin (mTHPC); photodynamic therapy (PDT); polymeric micelles
Self-Assembled Polymeric Micellar Nanoparticles as Nanocarriers for Poorly Soluble Anticancer Drug Ethaselen
A series of monomethoxy poly(ethylene glycol)-poly(lactide) (mPEG-PLA) diblock copolymers were synthesized, and mPEG-PLA micelle was fabricated and used as a nanocarrier for solubilization and delivery of a promising anticancer drug ethaselen. Ethaselen was efficiently encapsulated into the micelles by the dialysis method, and the solubility of ethaselen in water was remarkably increased up to 82 μg/mL before freeze-drying. The mean diameter of ethaselen-loaded micelles ranged from 51 to 98 nm with a narrow size distribution and depended on the length of PLA block. In vitro hemolysis study indicated that mPEG-PLA copolymers and ethaselen-loaded polymeric micelles had no hemolytic effect on the erythrocyte. The enhanced antitumor efficacy and reduced toxic effect of ethaselen-loaded polymeric micelle when compared with ethaselen-HP-β-CD inclusion were observed at the same dose in H22human liver cancer cell bearing mouse models. These suggested that mPEG-PLA polymeric micelle nanoparticles had great potential as nanocarriers for effective solubilization of poorly soluble ethaselen and further reducing side effects and toxicities of the drug
Genetic Control of Organ Shape and Tissue Polarity
A combination of experimental analysis and mathematical modelling shows how the genetic control of tissue polarity plays a fundamental role in the development and evolution of form
Large-Scale Clonal Analysis Reveals Unexpected Complexity in Surface Ectoderm Morphogenesis
Background: Understanding the series of morphogenetic processes that underlie the making of embryo structures is a highly topical issue in developmental biology, essential for interpreting the massive molecular data currently available. In mouse embryo, long-term in vivo analysis of cell behaviours and movements is difficult because of the development in utero and the impossibility of long-term culture. Methodology/Principal Findings: We improved and combined two genetic methods of clonal analysis that together make practicable large-scale production of labelled clones. Using these methods we performed a clonal analysis of surface ectoderm (SE), a poorly understood structure, for a period that includes gastrulation and the establishment of the body plan. We show that SE formation starts with the definition at early gastrulation of a pool of founder cells that is already dorso-ventrally organized. This pool is then regionalized antero-posteriorly into three pools giving rise to head, trunk and tail. Each pool uses its own combination of cell rearrangements and mode of proliferation for elongation, despite a common clonal strategy that consists in disposing along the antero-posterior axis precursors of dorso-ventrally-oriented stripes of cells. Conclusions/Significance: We propose that these series of morphogenetic processes are organized temporally and spatially in a posterior zone of the embryo crucial for elongation. The variety of cell behaviours used by SE precursor cells indicates that these precursors are not equivalent, regardless of a common clonal origin and a common clonal strategy. Anothe
Numerical simulation of turbulence interaction noise applied to a serrated airfoil
Turbulent wakes generated by turbofan blades and interacting with the outlet guide vanes are known to bemainly contributing to broadband noise emission of aero-engines at approach conditions. Analytical approaches,such as the well-known Amiet's model can be adopted to estimate the noise generated by turbulent flowsimpacting thin airfoils, but they are limited by the flat-plate assumptions. The development of numericalmethods allowing more complex geometries and realistic flows is required. The method, described in the presentpaper, is based on a CAA code solving the nonlinear Euler equations. The upstream turbulence is synthesizedfrom a stochastic model and injected into the computational domain through an adapted boundary condition. It isfirst validated in 2D and 3D against academic flat plate configurations by comparison with Amiet solutions(exact in such cases). Then, 3D computations are applied to simulate the effect of a passive treatment (leadingedge serrations) aiming at reducing turbulence interaction noise of an isolated airfoil studied in the framework ofEuropean project FLOCON. First calculations on baseline conditions are shown to be able to reproduce themeasured spectra and far-field directivities, and the acoustic performances of the serrations (3-4 dB PWLreduction) are fairly well assessed too
CAA methodology to simulate turbulence-airfoil noise
Turbulent wakes generated by turbofan blades and interacting with the outlet guide vanes are known to be mainly contributing to broadband noise emission of aero-engines at approach conditions. Analytical approaches, such as the well-known Amiet model can be adopted to estimate the noise generated by turbulent flows impinging thin airfoils, but they are limited by the flat-plate assumptions. The development of numerical methods allowing to consider more complex geometries and realistic flows is required. The method described in the present paper, is based on a CAA code solving the nonlinear Euler equations. The upstream turbulence is synthesized from a stochastic model and injected into the computational domain through an adapted boundary condition. It is first validated in 2D and 3D against academic flat plate configurations by comparison with Amiet solutions (exact in such cases). Then, 3D computations are applied to simulate the effect of a passive treatment (leading edge serrations) aiming at reducing turbulence interaction noise of an isolated airfoil studied in the framework of European project FLOCON. First calculations on baseline conditions are shown to be able to reproduce the measured spectra and far-field directivities, and the acoustic performances of the serrations (3-4 dB PWL reduction) are fairly well assessed to
Regulation of the expression on mouse T lymphocytes of the epitope identified by monoclonal antibody 3A35
Monoclonal antibody 3A35 (MA 3A35) has previously been shown to be an activation marker of macrophages and T lymphocytes. It immunoprecipitated from macrophages a 200-kDa molecule belonging to the T200 family and from T cells a 85-kDa antigen. In the present work, the factors controlling the expression of the epitope identified by MA 3A35 on polyclonal activated T cells and T-cell clones, as well as the ability of 3A35 alone or together with complement to interfere with T-cell functions, were investigated. Corticoresistant thymocytes unreactive with MA 3A35 became fully reactive after 2 days of in vitro stimulation by PMA and IL-2 and the level of reactivity per cell declined to a low level thereafter. In helper and cytolytic T-cell clones, the expression of the epitope defined by MA 3A35 was also maximal soon after antigenic stimulation then declined. In helper-T-cell clones, the epitope remained detectable during the entire culture period, whereas in cytolytic clones its expression was markedly reduced at the end of the culture. The lineage of cytotoxic T lymphocytes (CTL) as studied in a bulk culture of spleen cells primed in vivo against a syngeneic tumor exhibited similar regulation by antigenic stimulation. The CTL precursors were resistant to lysis by MA 3A35 plus complement; after 3 days of culture with the stimulatory antigen, they became highly sensitive but their sensitivity then diminished and mature CTL were completely resistant. MA 3A35 plus complement also killed the activated T cells which responded to macrophage-presented antigens and were thought to be mainly Lyt-1+. Therefore, the epitope identified by MA 3A35 was expressed predominantly at an early stage of T-cell activation. At a late stage, it persisted almost exclusively on helper and Lyt-1+ cells. In addition, MA 3A35 plus complement lysed NK cells, AK cells, and their precursors present in normal spleen. In the absence of complement, MA 3A35 had no detectable effect on T-cell functions
Experimental and numerical investigation of turbulence-airfoil noise reduction using wavy edges
A passive leading-edge treatment based on sinusoidal serrations aimed at reducing turbofan interaction noise has been recently studied in the framework of a European project (FLOCON). The turbulence-airfoil interaction mechanism is achieved using a turbulence grid located upstream of an isolated NACA airfoil tested in the Institute of Sound and Vibration Research anechoic open jet wind tunnel. The experimental setup with several airfoils designed and manufactured by ONERA is first presented with main acoustic results, highlighting the sound power level reductions obtained for all studied flow speeds (about 3–4 dB reduction) without altering the aerodynamic performances (as shown by available measurements and Reynolds-averaged Navier–Stokes calculations). The experimental investigations are supplemented by numerical predictions in order to assess the acoustic performances of the serrations. The method described in the second part of the paper is based on a computational aeroacoustics code solving the nonlinear Euler equations applied to the disturbances and is coupled to a Ffowcs-Williams and Hawkings formulation. Convection effects are achieved from a Reynolds-averaged Navier–Stokes solution or approximated by a fully uniform flow. The upstream turbulence is synthesized by means of a stochastic model and injected into the computational domain through an adapted boundary condition. It is first validated in two and three dimensions against academic flat-plate configurations by comparison with Amiet solutions (exact in such cases). Finally, three-dimensional computations are applied to FLOCON configurations. The present methodology is shown to reproduce the measured spectra and far-field directivities with a reasonably good precision. Radiated sound level attenuation due to the serrations versus frequency is fairly well assessed too
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