Transgenic (Tg) FVB/N mice were produced that overexpress human lipoprotein lipase (LPL) in skeletal muscle using the muscle creatine kinase promoter and enhancers. It was hypothesized that, by overexpressing LPL in muscle, high fat feeding-induced obesity would be prevented by diverting lipoprotein-derived triglyceride fatty acids away from storage in adipose tissue to oxidation in muscle. Mice were examined both at 6 wk of age before high fat (HF) feeding and at 19 wk of age after 13 wk of HF (46.1% fat) or high carbohydrate (HC) feeding (11.5% fat). At 6 wk in heterozygous Tg mice, LPL was increased 11-fold in white muscle and 2.5-fold in red muscle, but not in cardiac muscle or spleen, brain, lung, kidney, or adipose tissue. Plasma triglycerides (mg/dl) were lower in Tg mice (87 +/- 7 vs. 117 +/- 7, P < 0.0001), and glucose increased (201 +/- 9 vs. 167 +/- 8 mg/dl, P = 0.029). There were no differences in body weight between Tg and nontransgenic (nTg) mice; however, carcass lipid content (% body wt) was significantly decreased in male Tg mice at 6 wk (7.5 +/- 1.0 vs. 9.0 +/- 1.0%, P = 0.035). Body composition was not different in female Tg mice at 6 wk. Overall, when Tg mice were fed either a HC or HF diet for 13 wk, plasma triglycerides (P < 0.001) and free fatty acids (P < 0.001) were decreased, whereas plasma glucose (P = 0.01) and insulin (P = 0.05) were increased compared with nTg mice. HF feeding increased carcass lipid content twofold in both male (10.3 +/- 1.1 vs. 21.4 +/- 2.6%, HC vs. HF, P < 0.001) and female nTg mice (6.7 +/- 0.9 vs. 12.9 +/- 1.8%, P = 0.01). However, the targeted overexpression of LPL in skeletal muscle prevented HF diet-induced lipid accumulation in both Tg male (10.2 +/- 0.7 vs. 13.5 +/- 2.2%, HC vs. HF, P = NS) and female Tg mice (6.8 +/- 0.6 vs. 10.1 +/- 1.4%, P = NS). The potential to increase LPL activity in muscle by gene or drug delivery may prove to be an effective tool in preventing and/or treating obesity in humans.
The framework of anisotropic elasticity has been used to develop relationships between various anisotropic stiffness parameters found in the literature. It is shown that they are functions of the two Young's moduli and two Poisson's ratios that describe a cross-anisotropic soil, but not of the independent shear modulus. Multiple drained triaxial stress path excursions have been performed on 100 mm dia. samples of natural Gault Clay from Madingley in a stress path cell. Anisotropic parameters at small strains along different stress paths are reported and compared. It is shown that there are some advantages in performing tests at constant vertical and constant horizontal effective stress. Horizontally mounted bender elements on the same trixial samples have enabled the two anisotropic elastic shear moduli to be measured. Combining results from both sets of tests has enabled all five independent cross-anisotropic elastic parameters to be estimated. The Gault Clay at Madingley is highly anisotropic, although the degree of anisotropy depends on the way it is defined.
The inclusion of anisotropic stiffness parameters in sophisticated constitutive models necessitates their determination in the field and laboratory. Hitherto, anisotropy of small-strain stiffness of clays has occasionally been examined in the laboratory by measurements on specimens sampled at different orientations. The authors have developed a device to propagate and receive horizontal shear waves with both vertical and horizontal polarization through 100 mm triaxial samples. The device incorporates bender elements embedded in the pads of a horizontal belt. In tests on both reconstituted and natural samples of Gault Clay, each of the transmission velocities Vs(xh), Vs(hx) and Fs(hh) has been measured during stress path tests. The ratio G0(hh)/G0(vh) has been shown to be highly dependent on stress state. Laboratory data on natural samples show results broadly consistent with in situ results. Pour pouvoir inclure des paramètres de rigidité anisotrope dans des modèles constitutifs perfectionnés, il faut les déterminer sur le terrain et en laboratoire. Jusqu'à présent, on a parfois examiné l'anisotropie de la rigidité d'argiles aux petites contraintes en mesurant des échantillons prélevés à diverses orientations. Les auteurs ont mis au point un dispositif qui permet la propagation et la réception d'ondes de cisaillement horizontals avec polarisation verticale et horizontal dans des échantillons de compression triaxiale de 100mm. Le dispositif comprend des elements de flexion noyés dans les plaquettes d'une bande horizontal. Dans des essais de parcours de contrainte sur des échantillons reconstitués et naturels d'argile de Gault, on a mesuré les vitesses de transmission Vs(vh), Vs(hv) et Vs(hh). On a montré que le rapport G0(hh)/G0(vh) depend en grande partie de l'etat de contrainte. Les résultats obtenus en laboratoire sur des échantillons naturels concordent assez bien avec les résultats obtenus sur le terrain.
Novel horizontally mounted bender element devices capable of high-quality transmission and reception of horizontally propagated shear waves polarized in orthogonal planes across the mid-height of a triaxial clay specimen are described. Mounting of these mini benders, in a T-shaped configuration, is in the pads of a radial strain belt on 100 mm diameter triaxial samples, or alternatively as bender probes (similar in concept to mid-height pore pressure probes) suitable for use on triaxial samples down to 38 mm diameter. This latter type may also be used in bench-top tests or on site. The effective fabrication procedures that have been developed are described. The instrumentation systems used to drive and receive signals are outlined, and estimates of the magnitude of the shear strains developed by the bender elements and the accuracy with which shear wave velocities can be determined are discussed. These new bender elements enable both anisotropic shear moduli to be measured over the same path length on a single triaxial specimen that can be taken to a wide variety of anisotropic stress states. Comparison with measurements using conventional platen-mounted bender elements suggests these may underestimate the shear modulus by up to 20%.
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