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.     

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.     

High‐strength regenerated cellulose fibers spun from 1‐butyl‐3‐methylimidazolium chloride solutions

High‐performance regenerated cellulose fibers were prepared from cellulose/1‐butyl‐3‐methylimidazolium chloride (BMIMCl) solutions via dry‐jet wet spinning. The spinnability of the solution was initially evaluated using the maximum winding speed of the solution spinning line under various ambient temperatures and relative humidities in the air gap. The subsequent spinning trials were conducted under various air gap conditions in a water coagulation bath. It was found that low temperature and low relative humidity in the air gap were important to obtain fibers with high tensile strength at a high draw ratio. From a 10 wt % cellulose/BMIMCl solution, regenerated fibers with tensile strength up to 886 MPa were prepared below 22 °C and relative humidity of 50%. High strengthening was also strongly linked with the fixation effect on fibers during washing and drying processes. Furthermore, an effective attempt to prepare higher performance fibers was conducted from a higher polymer concentration solution using a high molecular weight dissolving pulp. Eventually, fibers with a tensile strength of ～1 GPa and Young's modulus over 35 GPa were prepared. These tensile properties were ranked at the highest level for regenerated cellulose fibers prepared by an ionic liquid–based process. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 45551.     

Mutational analysis of structure--activity relationships in human tumor necrosis factor-alpha

To determine the region of human tumor necrosis factor-alpha(TNF-), essential for cytotoxic activity against mouse L-M cells,single amino-acid-substituted TNF- mutant proteins (muteins)were produced in Escherichia coli by protein engineering techniques.An expression plasmid for TNF- was mutagenized by passage throughan E.coli mutD5 mutator strain and by oligonucleotide-directedmutagenesis. Approximately 100 single amino-acid-substitutedTNF- muteins were produced and assayed for cytotoxic activity.The cytotoxic activities of purified TNF- muteins, e.g. TNF-31T,-32Y, -82D, -85H, -115L, -141Y, -144K and -146E, were < 1%of that of parent TNF-. These results indicate that the integrityof at least four distinct regions of the TNF- molecule is requiredfor full biological activity. These regions are designated asfollows: region I, from position 30 to 32; region II, from position82 to 89; region III, from position 115 to 117; region FV, fromposition 141 to 146. In addition, TNF-141Y could not completelycompete with parent TNF- for binding to the receptor. This demonstratesthat region IV, and at least aspartk acid at position 141, mustbe involved in the TNF receptor binding site.