481 research outputs found

    Transition in incompressible boundary layers with two-dimensional excrescences

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    An experimental investigation of the transition process in boundary layers subjected to forward- or aft-facing two-dimensional step excrescences is described. The objective of the work was to characterize the variation of transition Reynolds numbers with measurable roughness and boundary layer parameters, with the specific goal of specifying new tolerance criteria for laminar flow airfoils, alongside a fundamental investigation of linear boundary layer stability mechanisms. Results from an ongoing program of increasing complexity on effects of pressure gradient on excrescence-induced transition are presented. Preliminary N-factor calculations are used to determine the effects of boundary layer stability and attempt to isolate the effect of the disturbance due to the excrescence

    Fatty Acid Incubation of Myotubes From Humans With Type 2 Diabetes Leads to Enhanced Release of β-Oxidation Products Because of Impaired Fatty Acid Oxidation: Effects of Tetradecylthioacetic Acid and Eicosapentaenoic Acid

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    OBJECTIVE—Increased availability of fatty acids is important for accumulation of intracellular lipids and development of insulin resistance in human myotubes. It is unknown whether different types of fatty acids like eicosapentaenoic acid (EPA) or tetradecylthioacetic acid (TTA) influence these processes

    Growth mechanisms of perturbations in boundary layers over a compliant wall

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    The temporal modal and nonmodal growth of three-dimensional perturbations in the boundary-layer flow over an infinite compliant flat wall is considered. Using a wall-normal velocity/wall-normal vorticity formalism, the dynamic boundary condition at the compliant wall admits a linear dependence on the eigenvalue parameter, as compared to a quadratic one in the canonical formulation of the problem. This greatly simplifies the accurate calculation of the continuous spectrum by means of a spectral method, thereby yielding a very effective filtering of the pseudospectra as well as a clear identification of instability regions. The regime of global instability is found to be matching the regime of the favorable phase of the forcing by the flow on the compliant wall so as to enhance the amplitude of the wall. An energy-budget analysis for the least-decaying hydroelastic (static-divergence, traveling-wave-flutter and near-stationary transitional) and Tollmien--Schlichting modes in the parameter space reveals the primary routes of energy flow. Moreover, the flow exhibits a slower transient growth for the maximum growth rate of a superposition of streamwise-independent modes due to a complex dependence of the wall-boundary condition with the Reynolds number. The initial and optimal perturbations are compared with the boundary-layer flow over a solid wall; differences and similarities are discussed. Unlike the solid-wall case, viscosity plays a pivotal role in the transient growth. A slowdown of the maximum growth rate with the Reynolds number is uncovered and found to originate in the transition of the fluid-solid interaction from a two-way to a one-way coupling. Finally, a term-by-term energy budget analysis is performed to identify the key contributors to the transient growth mechanism

    Acoustic excitation of Tollmien–Schlichting waves due to localised surface roughness

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    Experiments on the receptivity of two-dimensional boundary layers to acoustic disturbances from two-dimensional roughness strips were performed in a low-turbulence wind tunnel on a flat plate model. The free stream was subjected to a plane acoustic wave so that a Stokes layer (SL) was created on the plate, thus generating a Tollmien-Schlichting (T-S) wave through the receptivity process. An improved technique to measure the T-S component is described based on a retracting two-dimensional roughness, which allowed for phase-locked measurements at the acoustic wave frequency to be made. This improved technique enables both protuberances and cavities to be explored in the range < |h| (equivalent to 0.025 < |h|/ γ B ∗) in relative roughness height to the local unperturbed Blasius boundary layer displacement thickness). These depths are designed to cover both the predicted linear and nonlinear response of the T-S excitation. Experimentally, cavities had not previously been explored. Results show that a linear regime is identifiable for both positive and negative roughness heights up to ≈ 150 μm (|h| γ B ∗ ≈ 0.126). The departure from the linear behaviour is, however, dependent on the geometry of the surface imperfection. For cavities of significant depth, the nonlinear behaviour is found to be milder than in the case of protuberances - this is attributed to the flow physics in the near field of the surface features. Nonetheless, results for positive heights agree well with previous theoretical work which predicted a linear disturbance response for small-height perturbations

    Increased FAT/CD36 Cycling and Lipid Accumulation in Myotubes Derived from Obese Type 2 Diabetic Patients

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    BACKGROUND: Permanent fatty acid translocase (FAT/)CD36 relocation has previously been shown to be related to abnormal lipid accumulation in the skeletal muscle of type 2 diabetic patients, however mechanisms responsible for the regulation of FAT/CD36 expression and localization are not well characterized in human skeletal muscle. METHODOLOGY/PRINCIPAL FINDINGS: Primary muscle cells derived from obese type 2 diabetic patients (OBT2D) and from healthy subjects (Control) were used to examine the regulation of FAT/CD36. We showed that compared to Control myotubes, FAT/CD36 was continuously cycling between intracellular compartments and the cell surface in OBT2D myotubes, independently of lipid raft association, leading to increased cell surface FAT/CD36 localization and lipid accumulation. Moreover, we showed that FAT/CD36 cycling and lipid accumulation were specific to myotubes and were not observed in reserve cells. However, in Control myotubes, the induction of FAT/CD36 membrane translocation by the activation of (AMP)-activated protein kinase (AMPK) pathway did not increase lipid accumulation. This result can be explained by the fact that pharmacological activation of AMPK leads to increased mitochondrial beta-oxidation in Control cells. CONCLUSION/SIGNIFICANCE: Lipid accumulation in myotubes derived from obese type 2 diabetic patients arises from abnormal FAT/CD36 cycling while lipid accumulation in Control cells results from an equilibrium between lipid uptake and oxidation. As such, inhibiting FAT/CD36 cycling in the skeletal muscle of obese type 2 diabetic patients should be sufficient to diminish lipid accumulation

    Hot-Wire Measurements of the Influence of Surface Steps on Transition in Favorable Pressure Gradient Boundary Layers

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    An examination of the effects of surface step excrescences on boundary layer transition was performed, using a unique experimental facility. The objective of the work was to characterize the variation of transition Reynolds numbers with measurable step size and boundary layer parameters, with the specific goal of specifying new tolerance criteria for laminar flow airfoils, alongside a fundamental investigation of boundary layer transition mechanisms. This paper focuses on interpretation of hot-wire measurements, including supporting stability calculations, undertaken as part of the study. The results for both forward and aft-facing steps indicated a substantial stabilizing effect of favorable pressure gradient on excrescence-induced boundary layer transition. These findings suggest that manufacturing tolerances for laminar flow aircraft could be loosened in areas where even mild favorable pressure gradients exist

    Impaired Cell Surface Expression of HLA-B Antigens on Mesenchymal Stem Cells and Muscle Cell Progenitors

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    HLA class-I expression is weak in embryonic stem cells but increases rapidly during lineage progression. It is unknown whether all three classical HLA class-I antigens follow the same developmental program. In the present study, we investigated allele-specific expression of HLA-A, -B, and -C at the mRNA and protein levels on human mesenchymal stem cells from bone marrow and adipose tissue as well as striated muscle satellite cells and lymphocytes. Using multicolour flow cytometry, we found high cell surface expression of HLA-A on all stem cells and PBMC examined. Surprisingly, HLA-B was either undetectable or very weakly expressed on all stem cells protecting them from complement-dependent cytotoxicity (CDC) using relevant human anti-B and anti-Cw sera. IFNγ stimulation for 48–72 h was required to induce full HLA–B protein expression. Quantitative real-time RT-PCR showed that IFNγ induced a 9–42 fold increase of all six HLA-A,-B,-C gene transcripts. Interestingly, prior to stimulation, gene transcripts for all but two alleles were present in similar amounts suggesting that post-transcriptional mechanisms regulate the constitutive expression of HLA-A,-B, and -C. Locus-restricted expression of HLA-A, -B and -C challenges our current understanding of the function of these molecules as regulators of CD8+ T-cell and NK-cell function and should lead to further inquiries into their expression on other cell types

    Biphosphonate-Mediated Gene Vector Delivery from the Metal Surfaces of Stents

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    The clinical use of metallic expandable intravascular stents has resulted in imporved therapeutic outcomes for coronary artery disease. However, arterial reobstruction after stenting, in-stent restenosis, remains an important problem. Gene therapy to treat in-stent restenosis by using gene vector delivery from the metallic stent surfaces has never been demonstrated. The present studies investigated the hypothesis that metal-biphosphonate binding can enable site-specific gene vector delivery from metal surfaces. Polyallylamine biphosphonate (PAA-BP) was synthesized by using Michael addition methodology. Exposure to aqueous solutions of PAA-BP resulted in the formation of a monomolecular biphosphonate later on metal alloy surfaces (steel, nitinol, and cobalt-chromium), as demonstrated by x-ray photoelectron spectroscopy. Surface-bound PAA-BP enabled adenoviral (Ad) tethering due to covalent thiol-binding of either anti-Ad antibody or a recombinant Ad-receptor protein, D1. In arterial smooth muscle cell cultures, alloy samples configured with surface-tethered Ad were demonstrated to achieve site-specific transduction with a reporter gene, (GFP). Rat carotid stent angioplasties using metal stents exposed to aqueous PAA-BP and derivatized with anti-knob antibody or D1 resulted in extensive localized Ad-GFP expression in the arterial wall. In a separate study with a model therapeutic vector, Ad-inducible nitric oxide synthase (iNOS) attached to the biphosphonate-treated metal stent surface via D1, significant inhibition of restenosis was demonstrated (neointimal/media ration 1.68 ± 0.27 and 3.4 ± 0.35; Ad-iNOS vs. control, P \u3c 0.01). Is is concluded that effective gene vector delivery from metallic stent surfaces can be achieved using this approach

    Elaboration of tetra-orthogonally-substituted aromatic scaffolds towards novel EGFR-kinase inhibitors

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    Nitration of three regioisomers of bromo-fluorobenzaldehyde proceeds regioselectively, notably with H2SO4/HNO3 at 0 °C. The thereby synthesized tetrasubstituted aromatics, endowed with orthogonal substituents, can be elaborated via Pd-catalysed coupling, reduction and reductive amination reactions. As a test-case, these compounds were converted into EGFR inhibitors related to Gefitinib, whose activity was rationalised by docking studies
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