NUTRITIONAL AND PHYSIOLOGICAL SIGNIFICANCE OF LIPIDS

This paper reviews how intricately dietary fat regulates cholesterol metabolism. The effects of fats on plasma cholesterol are far more complex than predicted. Not only the fatty acid composition but also the triacylglycerol configuration of dietary fat influence its function. Extensive comprehension is thus required for this problem.     

Generalisations of the Haagerup approximation property to arbitrary von Neumann algebras

The notion of the Haagerup approximation property, originally introduced for von Neumann algebras equipped with a faithful normal tracial state, is generalised to arbitrary von Neumann algebras. We discuss two equivalent characterisations, one in term of the standard form and the other in term of the approximating maps with respect to a fixed faithful normal semifinite weight. Several stability properties, in particular regarding the crossed product construction are established and certain examples are introduced.     

Protonation of Pyridyl‐Substituted TTF Derivatives: Substituent Effects in Solution and in the Proton–Electron Correlated Charge‐Transfer Complexes

Protonated pyridyl‐substituted tetrathiafulvalene electron‐donor molecules (PyH⁺‐TTF) showed significant changes in the electron‐donating ability and HOMO–LUMO energy gap compared to the neutral analogues and gave a unique N⁺?H???N hydrogen‐bonded (H‐bonded) dimer unit in the proton–electron correlated charge‐transfer (CT) complex crystals. We have evaluated these features from the viewpoint of the molecular structure of the PyH⁺‐TTF derivatives, that is, the substitution position of the Py group and/or the presence or absence of the ethylenedithio (EDT) group. Among 2‐PyH⁺‐TTF ( 1 o H⁺ ), 3‐PyH⁺‐TTF ( 1 m H⁺ ), 4‐PyH⁺‐TTF ( 1 p H⁺ ), and 4‐PyH⁺‐EDT‐TTF ( 2 p H⁺ ) systems, the para‐pyridyl‐substituted donors 1 p H⁺ and 2 p H⁺ exhibit more marked changes upon protonation in solution; a larger redshift in the intramolecular CT absorption band and a larger decrease in the electron‐donating ability. Furthermore, the EDT system 2 p H⁺ has the smallest intramolecular Coulombic repulsion energy. These differences are reasonably interpreted by considering the energy levels and distributions of the HOMO and LUMO obtained by quantum chemical calculations. Such substituent effects related to protonation were also examined by comparing the structure and properties of a new H‐bonded CT complex crystal based on 2 p H⁺ with those of its 1 p H⁺ analogue recently prepared by us: Both of them form a similar type of H‐bonded dimer unit, however, its charge distribution as well as the overall molecular arrangement, electronic structure, and conductivity were significantly modulated by the introduction of the EDT group. These results provide a new insight into the structural and electronic features of the PyH⁺‐TTF‐based proton–electron correlated molecular conductors.     

Formation and characterization of microemulsions containing polymeric silicone

We have prepared microemulsions consisting of water/[40 wt % polyoxyethylene (20 mol) glycerin isostearate (abbreviated as POE-GIS) + 60 wt % random copolymer of polyoxyethylene (POE, 38 mol)/polyoxypropylene (POP, 10 mol) pentaerythritol tetramethyl ether {abbreviated as PEPTME (38/10)}]/[polyoxyethylene (POE, 19 mol)/polyoxypropylene (POP, 19 mol) polydimethylsiloxane copolymer (abbreviated as POE/POP-PDMS)] and water/[40 wt % POE-GIS + 60 wt % PEPTME (38/10)]/[95 wt % POE/POP-PDMS + 5 wt % oleic acid (abbreviated as OA)] systems and characterized them with optical observation, rheometry, and freeze-fracture transmission electron microscopy (FF-TEM) images. Bicontinuous and droplet-type O/W (oil-in-water) microemulsions are formed depending on the volume fraction of water. The bicontinuous structure observed in the oil-rich region, upon successive dilution with water, is transformed into a droplet-type microemulsion without phase separation.The prepared droplet-type microemulsion containing polymeric silicone and random copolymer PEPTME (38/10) as a cosurfactant in the water-rich region has potential applications in cosmetics.     

Prediction of Alzheimer's diagnosis using semi-supervised distance metric learning with label propagation

Alzheimer's disease (AD) is the most common form of dementia and leads to irreversible neurogenerative damage of the brain. However, the current diagnostic tools have poor sensitivity, especially for the early stages of AD and do not allow for diagnosis until AD has lead to irreversible brain damage. Therefore, it is crucial that AD is detected as early as possible. Although it is very hard, laborious and time-consuming to gather many AD and non-AD labeled samples, gathering unlabeled samples is easier than labeled samples. Since standard learning algorithms learn a diagnosis model from labeled samples only, they require many labeled samples and do not work well when the number of training samples is small. Therefore, it is very desirable to develop a predictive learning method to achieve high performance using both labeled samples and unlabeled samples. To address these problems, we propose semi-supervised distance metric learning using Random Forests with label propagation (SRF-LP) which incorporates labeled data for obtaining good metrics and propagates labels based on them. Experimental results showed that SRF-LP outperformed standard supervised learning algorithms, i.e., RF, SVM, Adaboost and CART and reached 93.1% accuracy at a maximum. Especially, SRF-LP largely outperformed when the number of training samples is very small. Our results also suggested that SRF-LP exhibits a synergistic effect of semi-supervised distance metric learning and label propagation.     

Structure-based virtual screening with supervised consensus scoring: evaluation of pose prediction and enrichment factors

Since the evaluation of ligand conformations is a crucial aspect of structure-based virtual screening, scoring functions play significant roles in it. However, it is known that a scoring function does not always work well for all target proteins. When one cannot know which scoring function works best against a target protein a priori, there is no standard scoring method to know it even if 3D structure of a target protein-ligand complex is available. Therefore, development of the method to achieve high enrichments from given scoring functions and 3D structure of protein-ligand complex is a crucial and challenging task. To address this problem, we applied SCS (supervised consensus scoring), which employs a rough linear correlation between the binding free energy and the root-mean-square deviation (rmsd) of a native ligand conformations and incorporates protein-ligand binding process with docked ligand conformations using supervised learning, to virtual screening. We evaluated both the docking poses and enrichments of SCS and five scoring functions (F-Score, G-Score, D-Score, ChemScore, and PMF) for three different target proteins: thymidine kinase (TK), thrombin (thrombin), and peroxisome proliferator-activated receptor gamma (PPARgamma). Our enrichment studies show that SCS is competitive or superior to a best single scoring function at the top ranks of screened database. We found that the enrichments of SCS could be limited by a best scoring function, because SCS is obtained on the basis of the five individual scoring functions. Therefore, it is concluded that SCS works very successfully from our results. Moreover, from docking pose analysis, we revealed the connection between enrichment and average centroid distance of top-scored docking poses. Since SCS requires only one 3D structure of protein-ligand complex, SCS will be useful for identifying new ligands.     

Total syntheses of (+)-polygalolide a and (+)-polygalolide b: elucidation of the absolute stereochemistry and biogenetic implications

The total syntheses of (+)-polygalolide?A and (+)-polygalolide?B have been completed by using a carbonyl ylide cycloaddition strategy. Three of the four stereocenters, including two consecutive tetrasubstituted carbon atoms at C2 and C8, were incorporated through internal asymmetric induction from the stereocenter at C7 by a [Rh(2) (OAc)(4)]-catalyzed carbonyl ylide formation/intramolecular 1,3-dipolar cycloaddition sequence. The arylmethylidene moiety of these natural products was successfully installed by a Mukaiyama aldol-type reaction of a silyl enol ether with a dimethyl acetal, followed by elimination under basic conditions. We have also developed an alternative approach to the carbonyl ylide precursor based on a hetero-Michael reaction. This approach requires 18 steps, and the natural products were obtained in 9.8 and 9.3?% overall yields. Comparison of specific rotations of the synthetic materials and natural products suggests that polygalolides are biosynthesized in nearly racemic forms through a [5+2] cycloaddition between a fructose-derived oxypyrylium zwitterion with an isoprene derivative.     

Large dielectric susceptibility associated with proton transfer in a supramolecular structure of chloranilic acid and 5,5'-dimethyl-2,2'-bipyridine

A 1:1 adduct of chloranilic acid with 5,5'-dimethyl-2,2'-bipyridine, in which two kinds of molecules are connected by infinite hydrogen bond chains, exhibits a distinct dielectric phase transition when cooled. Below T(c)(=318 K) the hydrogen atoms participating in hydrogen bonding undergo long-range ordering and form an antiferroelectric-like state, taking a single minimum potential in the high-temperature phase (T>T(c)) due to the bifurcate hydrogen bond system. The proton-transfer phenomenon was clearly observed by electron density distribution analysis using a maximum entropy method of synchrotron x-ray diffraction data.