Effect of the ACAT inhibitor, HL-004, on cholesterol metabolism in macrophages

The effects of a novel acyl-CoA: cholesterol acyltransferase (ACAT) inhibitor, HL-004, on cholesterol metabolism were examined in mice peritoneal macrophages. Cholesteryl ester-rich foam cells were induced by incubating macrophages with acetylated LDL. HL-004 prevented the accumulation of cholesteryl ester in the presence of the cholesterol acceptor, HDL. In the absence of HDL, HL-004 generated large amounts of free cholesterol in the cell. Moreover, HL-004 stimulated the efflux of cholesterol from preestablished foam cells in the presence of HDL. These results suggest that the inhibition of foam cell formation and the stimulation of foam cell regression by HL-004 are attributed to intracellular ACAT inhibition, and that HL-004 would be expected to exhibit an antiatherosclerotic effect through direct action on arterial wall.     

Motivational bases of the public goods problem.

Compared 2 motivational bases for not contributing to a public good, desire to "free ride" (or greed) and fear of being a "sucker," among 110 Japanese undergraduates. It was hypothesized that these 2 types of motivation would be activated under different situations. When a public good was provided conjunctively, fear would have a strong effect but greed would not; when a public good was disjunctively provided, greed would have a strong effect but fear would not. In addition, it was predicted that the greater mutual trust existing among friends would make them contribute more than strangers would in the conjunctive condition but would make no difference in the disjunctive condition. Three types of production rules, in which a public good was conjunctively, disjunctively, or additively produced on the basis of members' contributions, were experimentally created. Half of the groups in each condition consisted of total strangers, and the other half consisted of friends. The hypotheses were supported when the size of the public good (bonus points) was relatively large. Also, Ss responded similarly in the conjunctive condition and in the additive condition. (25 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Analysis of Speaker Adaptation Algorithms for HMM-Based Speech Synthesis and a Constrained SMAPLR Adaptation Algorithm

In this paper, we analyze the effects of several factors and configuration choices encountered during training and model construction when we want to obtain better and more stable adaptation in HMM-based speech synthesis. We then propose a new adaptation algorithm called constrained structural maximum a posteriori linear regression (CSMAPLR) whose derivation is based on the knowledge obtained in this analysis and on the results of comparing several conventional adaptation algorithms. Here, we investigate six major aspects of the speaker adaptation: initial models; the amount of the training data for the initial models; the transform functions, estimation criteria, and sensitivity of several linear regression adaptation algorithms; and combination algorithms. Analyzing the effect of the initial model, we compare speaker-dependent models, gender-independent models, and the simultaneous use of the gender-dependent models to single use of the gender-dependent models. Analyzing the effect of the transform functions, we compare the transform function for only mean vectors with that for mean vectors and covariance matrices. Analyzing the effect of the estimation criteria, we compare the ML criterion with a robust estimation criterion called structural MAP. We evaluate the sensitivity of several thresholds for the piecewise linear regression algorithms and take up methods combining MAP adaptation with the linear regression algorithms. We incorporate these adaptation algorithms into our speech synthesis system and present several subjective and objective evaluation results showing the utility and effectiveness of these algorithms in speaker adaptation for HMM-based speech synthesis.     

Order-disorder transition and its effect on microwave quality factor Q in Ba(Zn1/3Nb2/3)O3 system

Influences of composition deviation from stoichiometry and heat treatment on crystal phases and Q factor in Ba(Zn_1/3Nb_2/3)O₃(BZN) were studied. The structural order and the crystal phases strongly depended on the slight composition deviation from stoichiometric BZN. The maximum Q factor was obtained at the vicinity of the stoichiometric BZN. In the other regions, non-stoichiometric disordered BZN or ordered BZN with secondary phase were formed, and their Q factors were found to be low. For the stoichiometric BZN, the order-disorder phase transition occurred between 1300 and 1400^°C. The crystal-structural ordering of the stoichiometric BZN was improved by post-annealing at below its transition temperature, conserving the density and the grain size. However, no significant Q factor improvement was found. The Q factor of the stoichiometric BZN strongly depends on the density and grain size not on the crystal-structural order. These results suggest that the ceramic microstructure such as the pore and grain boundary, the secondary phase and lattice defect caused by non-stoichiometry affect the variation of the Q factor in BZN system than the crystal-structural ordering.     

Comparative hypocholesterolemic effects of six dietary oils in cholesterol-fed rats after long-term feeding

Rats (8 wk of age) fed a conventional diet were shifted to diets containing 10% Oenothera biennis Linn oil (OBLO, linoleic acid + gamma-linolenic acid) from a wild plant, evening primrose oil (EPO, linoleic acid + gamma-linolenic acid) from a cultivated plant, bio-gamma-linolenic acid oil from mold (BIO, palmitic acid + oleic acid + linoleic acid + gamma-linolenic acid), safflower oil (linoleic acid), palm oil (PLO, palmitic acid + oleic acid + linoleic acid), or soybean oil (linoleic acid + alpha-linolenic acid) with 0.5% cholesterol for 13 wk. Though there were no significant differences in the food intake among the groups, the body weight gain of the OBLO group was significantly lower than that of the other groups except for the BIO and PLO groups, and that of the EPO and SBO groups were the highest among the groups. The liver weight of the OBLO group was significantly lower than that of other groups, and that of the PLO group was the highest among the groups. The serum total cholesterol and very low density lipoprotein (VLDL) + intermediate density lipoprotein (IDL) + low density lipoprotein (LDL) cholesterol concentrations of the OBLO and EPO groups were consistently lower than those in the other groups. However, those of the BIO group were higher than those in the OBLO and EPO groups. The liver cholesterol concentration of the PLO group was the highest among all groups except for the EPO group. The fecal neutral sterol and bile acid extraction of the BIO group tended to increase compared to the other groups. The results of this study demonstrate that OBLO and EPO inhibit the increasing of serum total cholesterol and VLDL + IDL + LDL-cholesterol concentrations in the presence of excess cholesterol in the diet compared with the other dietary oils.     

Bile Acid–Drug Interaction via Organic Anion-Transporting Polypeptide 4C1 Is a Potential Mechanism of Altered Pharmacokinetics of Renally Excreted Drugs

Patients with liver diseases not only experience the adverse effects of liver-metabolized drugs, but also the unexpected adverse effects of renally excreted drugs. Bile acids alter the expression of renal drug transporters, however, the direct effects of bile acids on drug transport remain unknown. Renal drug transporter organic anion-transporting polypeptide 4C1 (OATP4C1) was reported to be inhibited by chenodeoxycholic acid. Therefore, we predicted that the inhibition of OATP4C1-mediated transport by bile acids might be a potential mechanism for the altered pharmacokinetics of renally excreted drugs. We screened 45 types of bile acids and calculated the IC₅₀, K_i values, and bile acid–drug interaction (BDI) indices of bile acids whose inhibitory effect on OATP4C1 was >50%. From the screening results, lithocholic acid (LCA), glycine-conjugated lithocholic acid (GLCA), and taurine-conjugated lithocholic acid (TLCA) were newly identified as inhibitors of OATP4C1. Since the BDI index of LCA was 0.278, LCA is likely to inhibit OATP4C1-mediated transport in clinical settings. Our findings suggest that dose adjustment of renally excreted drugs may be required in patients with renal failure as well as in patients with hepatic failure. We believe that our findings provide essential information for drug development and safe drug treatment in clinics.     

Degradation behavior of moduli in extruded pure magnesium during low- to giga-scale cyclic tension fatigue

The mechanical properties of extruded pure magnesium during cyclic tension fatigue in the low- to giga-scale regime at room temperature have been investigated using ultrasonic reflection methods with longitudinal and shear waves. The acoustic velocities and calculated Young’s and shear moduli decreased by a large percentage with an increase in the number of cycles in all cycle modes due to growth of grain boundary voids. The eventual degradation of the properties was largest during giga-cycle fatigue, in which the moduli decreased by ～9%. The elastic behavior depended on the drive stress and the number of cycles rather than on fatigue time. Longitudinal and shear wave propagation characteristics and investigations of a grain boundary before and after fatigue using electron backscatter diffraction based on field-emission scanning electron microscopy and focused ion beam transmission electron microscopy revealed that the largest boundary void gap width was less than several nanometers (almost closed). The Poisson’s ratio and bulk modulus were affected notably by the void gap, in which the threshold corresponds to the longitudinal wave amplitude. Other damage phase data were determined using scanning electron microscopy, Vickers hardness, and surface roughness tests under progressive fatigue; these results also indicated slight grain boundary degradation.     

The role of livestock diversification in ensuring household food security under a changing climate in Borana,Ethiopia

While food insecurity is a growing concern across the developing nations, accentuated by climate variability and change, it could be even worse for pastoralists given their unpredictable exposure to climate risks. The Borana herders experience food insecurity as a result of recurring droughts causing huge losses of cattle, and are thus increasingly shifting from cattle pastoralism to multi-species herding. The present study examines the role of livestock diversification in combating household food insecurity using herders’ perceptions, a modified household food insecurity access scale (mHFIAS) and dietary diversity score. Herders perceived child growth, adult height and body condition to be decreasing as a result of declining milk production and changing dietary trends. Results also revealed a high level of seasonal food insecurity and low dietary diversity with the majority (81 %) consuming one to three food groups. Livestock diversification was a major factor affecting household food security. Households practising diversification had significantly fewer months of food deficit (2.3 vs. 3.8), lower mHFIAS (5.5 vs. 8.7) and a higher average off-take in the form of livestock sales (7.4 vs. 4.0) than non-diversified ones. Diversification improved dietary intake of specific food groups and the average number of meals consumed per day. While fruits, eggs and fish are not part of the Borana diet, a large number of respondents consumed no vegetables (93 %) or meat (96 %), potentiating the risk of micronutrient deficiencies. This study highlights the particular significance of livestock diversification, among other socio-demographic factors, in attaining food security under a changing climate in the study area.