381 research outputs found
Transition in incompressible boundary layers with two-dimensional excrescences
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
The velocity field created by a shallow bump in a boundary layer
We report the results of measurements of the disturbance velocity field generated in a boundary layer by a shallow three-dimensional bump oscillating at a very low frequency on the surface of a flat plate. Profiles of the mean velocity, the disturbance velocity at the fundamental frequency and at the first harmonic are presented. These profiles were measured both upstream and downstream of the oscillating bump. Measurements of the disturbance velocity were also made at various spanwise and downstream locations at a fixed distance from the boundary of one displacement thickness. Finally, the spanwise spectrum of the disturbances at three locations downstream of the bump are presented
Growth mechanisms of perturbations in boundary layers over a compliant wall
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
Association Between Parental History of Type 2 Diabetes and Glycemic Control in Urban African Americans
OBJECTIVE—The purpose of this study was to examine the association between parental history of type 2 diabetes and glycemic control among diabetic urban African Americans
Glucosamine-induced endoplasmic reticulum stress affects GLUT4 expression via activating transcription factor 6 in rat and human skeletal muscle cells
AIMS/HYPOTHESIS: Glucosamine, generated during hyperglycaemia, causes insulin resistance in different cells. Here we sought to evaluate the possible role of endoplasmic reticulum (ER) stress in the induction of insulin resistance by glucosamine in skeletal muscle cells. METHODS: Real-time RT-PCR analysis, 2-deoxy-D: -glucose (2-DG) uptake and western blot analysis were carried out in rat and human muscle cell lines. RESULTS: In both rat and human myotubes, glucosamine treatment caused a significant increase in the expression of the ER stress markers immunoglobulin heavy chain-binding protein/glucose-regulated protein 78 kDa (BIP/GRP78 [also known as HSPA5]), X-box binding protein-1 (XBP1) and activating transcription factor 6 (ATF6). In addition, glucosamine impaired insulin-stimulated 2-DG uptake in both rat and human myotubes. Interestingly, pretreatment of both rat and human myotubes with the chemical chaperones 4-phenylbutyric acid (PBA) or tauroursodeoxycholic acid (TUDCA), completely prevented the effect of glucosamine on both ER stress induction and insulin-induced glucose uptake. In both rat and human myotubes, glucosamine treatment reduced mRNA and protein levels of the gene encoding GLUT4 and mRNA levels of the main regulators of the gene encoding GLUT4 (myocyte enhancer factor 2 a [MEF2A] and peroxisome proliferator-activated receptor-gamma coactivator 1alpha [PGC1alpha]). Again, PBA or TUDCA pretreatment prevented glucosamine-induced inhibition of GLUT4 (also known as SLC2A4), MEF2A and PGC1alpha (also known as PPARGC1A). Finally, we showed that overproduction of ATF6 is sufficient to inhibit the expression of genes GLUT4, MEF2A and PGC1alpha and that ATF6 silencing with a specific small interfering RNA is sufficient to completely prevent glucosamine-induced inhibition of GLUT4, MEF2A and PGC1alpha in skeletal muscle cells. CONCLUSIONS/INTERPRETATION: In this work we show that glucosamine-induced ER stress causes insulin resistance in both human and rat myotubes and impairs GLUT4 production and insulin-induced glucose uptake via an ATF6-dependent decrease of the GLUT4 regulators MEF2A and PGC1alpha
Biphosphonate-Mediated Gene Vector Delivery from the Metal Surfaces of Stents
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
Spatial Stability of Incompressible Attachment-Line Flow
Linear stability analysis of incompressible attachment-line flow is presented within the spatial framework. The system of perturbation equations is solved using spectral collocation. This system has been solved in the past using the temporal approach and the current results are shown to be in excellent agreement with neutral temporal calculations. Results amenable to direct comparison with experiments are then presented for the case of zero suction. The global solution method utilized for solving the eigenproblem yields, aside from the well-understood primary mode, the full spectrum of least-damped waves. Of those, a new mode, well separated from the continuous spectrum is singled out and discussed. Further, relaxation of the condition of decaying perturbations in the far-field results in the appearance of sinusoidal modes akin to those found in the classical Orr-Sommerfeld problem. Finally, the continuous spectrum is demonstrated to be amenable to asymptotic analysis. Expressions are derived for the location, in parameter space, of the continuous spectrum, as well as for the limiting cases of practical interest. In the large Reynolds number limit the continuous spectrum is demonstrated to be identical to that of the Orr-Sommerfeld equation
Peroxisome Proliferator–Activated Receptor-γ Coactivator-1α Overexpression Increases Lipid Oxidation in Myocytes From Extremely Obese Individuals
Patient Access to U.S. Physicians Who Conduct Internet or E-mail Consults
BACKGROUND: E-mail communication has the potential to improve communication between patients and doctors. OBJECTIVE: The objective of the study is to describe the access of patients to physicians who conduct e-mail consults. METHODS: We analyzed data from the National Ambulatory Medical Care Survey (NAMCS), a nationally representative cross-sectional survey of office-based physician visits, in 2001, 2002, and 2003. The main outcome measure was the percentage of visits to a provider who reported doing internet or e-mail consults. RESULTS: There was fewer than 1 in 10 outpatient visits in 2001 (9.2%) to physicians who reported doing internet or e-mail consults, and this did not increase in 2002 (5.8%) or 2003 (5.5%). Access to these physicians was greater among patients who were male, nonminority, lived in the Western United States, seen for pre-/postoperative care, seen by a primary care provider, and not seen by a nurse during their visit. Access to physicians who conducted internet or e-mail consults was independent of other patient (e.g., chronic conditions), provider (e.g., office setting), and visit (e.g., medications prescribed) characteristics. CONCLUSIONS: Access to physicians who do internet or e-mail consults is generally low and did not increase between 2001 and 2003, despite growth in internet access and in other internet-related activities
Electrical Pulse Stimulation of Cultured Human Skeletal Muscle Cells as an In Vitro Model of Exercise
Background and Aims
Physical exercise leads to substantial adaptive responses in skeletal muscles and plays a central role in a healthy life style. Since exercise induces major systemic responses, underlying cellular mechanisms are difficult to study in vivo. It was therefore desirable to develop an in vitro model that would resemble training in cultured human myotubes.
Methods
Electrical pulse stimulation (EPS) was applied to adherent human myotubes. Cellular contents of ATP, phosphocreatine (PCr) and lactate were determined. Glucose and oleic acid metabolism were studied using radio-labeled substrates, and gene expression was analyzed using real-time RT-PCR. Mitochondrial content and function were measured by live imaging and determination of citrate synthase activity, respectively. Protein expression was assessed by electrophoresis and immunoblotting.
Results
High-frequency, acute EPS increased deoxyglucose uptake and lactate production, while cell contents of both ATP and PCr decreased. Chronic, low-frequency EPS increased oxidative capacity of cultured myotubes by increasing glucose metabolism (uptake and oxidation) and complete fatty acid oxidation. mRNA expression level of pyruvate dehydrogenase complex 4 (PDK4) was significantly increased in EPS-treated cells, while mRNA expressions of interleukin 6 (IL-6), cytochrome C and carnitin palmitoyl transferase b (CPT1b) also tended to increase. Intensity of MitoTracker®Red FM was doubled after 48 h of chronic, low-frequency EPS. Protein expression of a slow fiber type marker (MHCI) was increased in EPS-treated cells.
Conclusions
Our results imply that in vitro EPS (acute, high-frequent as well as chronic, low-frequent) of human myotubes may be used to study effects of exercise.This work was funded by the University of Oslo, Oslo University College, the Norwegian Diabetes Foundation, the Freia Chocolade Fabriks Medical Foundation and the Anders Jahre’s Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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