A New Lead Identification Strategy: Screening an sp3-rich and Lead-like Compound Library Composed of 7-Azanorbornane Derivatives

Although the advantages of sp³-rich, sterically complicated molecules in drug development have been pointed out, modern screening libraries are filled with planar, sp²-rich components. Compounds that are sp³-rich are difficult to synthesize, and thus we aimed to invent an efficient method to construct sp³-rich libraries. By modifying sp³-rich 7-azanorbornane scaffolds through click chemistry, we efficiently prepared a small set of compounds. These compounds were not only sp³-rich, but also had sufficient “lead-like” properties in view of molecular weights and hydrophobicity. Screening assays of this library provided weak κ opioid receptor agonists and growth hormone secretagogue receptor agonists with high hit rates. These results indicate that the 7-azanorbornane scaffold may be a “privileged structure” for lead identification in drug discovery.     

Preparation of avidin-containing polyelectrolyte microcapsules and their uptake and release properties

Avidin-containing polyelectrolyte microcapsules were prepared by a layer-by-layer deposition technique and uptake and release of biotin-labelled fluorescein (b-FITC) was studied. The polyelectrolyte microcapsules were prepared by coating the surface of calcium carbonate (CaCO₃) microparticles containing avidin-poly(styrene sulfonate) (PSS) conjugate, followed by dissolution of CaCO₃ core in an ethylenediaminetetraacetic acid solution. Release of avidin from the microcapsules was markedly suppressed due to formation of a high molecular weight of avidin-PSS conjugate in the microcapsules. The uptake of b-FITC into the microcapsules was highly enhanced through a strong binding of b-FITC to avidin, as compared to the uptake into avidin-free microcapsules. Release of b-FITC from the microcapsules was accelerated upon addition of biotin, 2-iminobiotin, or lipoic acid in the solution due to the competitive binding of the additives to the binding site of avidin.     

Dietary Guar Gum Reduces Lymph Flow and Diminishes Lipid Transport in Thoracic Duct-Cannulated Rats

Guar gum has a well-recognized hypolipidemic effect. This effect is thought to be due to the physicochemical properties of guar gum, which may cause changes in adsorption of lipids or the viscosity of the intestinal contents. Guar gum is a non-specific absorption inhibitor of any type of lipid-soluble compound. Permanent lymph duct cannulation was performed on rats to investigate the effects of dietary guar gum on lymph flow and lipid transport. Rats fed a 5% guar gum diet were compared with those fed a 5% cellulose diet, and lymph was collected after feeding. The water-holding capacity (WHC), settling volume in water (SV), and viscosity of guar gum were compared with those of cellulose. Rats fed with the guar gum diet had significantly lower lymph flow and lymphatic lipid transport than did rats fed with the cellulose diet. The WHC, SV, and viscosity of guar gum were significantly higher than those of cellulose. We propose that dietary guar gum reduces lymph flow and thereby diminishes lipid transport by means of its physicochemical properties related to water behavior in the intestine.     

Analysis of proton exchange membrane fuel cell catalyst layers for reduction of platinum loading at Nissan

The biggest issue that must be addressed in promoting widespread use of fuel cell vehicles (FCVs) is to reduce the cost of the fuel cell system. Especially, it is of vital importance to reduce platinum (Pt) loading of catalyst layers (CLs) in the membrane electrode assembly (MEA) of a proton exchange membrane fuel cell (PEMFC). In order to lower the Pt loading of the MEA, mass transport of reactants related to the performance in high current density should be enhanced significantly as well as kinetics of the catalyst, which can result in the better Pt utilization and effectiveness. In this study, we summarized our analytical approach and methods for reduction of Pt loading in CLs. Microstructure, mass transport properties of the reactants, and their relation in CLs were elucidated by applying experimental analyses and computational methods. A simple CL model for I–V performance prediction was then established, where experimentally elucidated parameters of the microstructure and the properties in CLs were taken into account. Finally, we revealed the impact of lowering the Pt loading on the transport properties, polarization, and the I–V performance.     

In situ time-resolved X-ray diffraction of tobermorite formation in autoclaved aerated concrete: Influence of silica source reactivity and Al addition

The hydrothermal formation of tobermorite during the processing of autoclaved aerated concrete was investigated by in situ X-ray diffraction (XRD) analysis. High-energy X-rays from a synchrotron radiation source in combination with a newly developed autoclave cell and a photon-counting pixel array detector were used.To investigate the effects of the silica source, reactive quartz from chert and less-reactive quartz from quartz sand were used as starting materials. The effect of Al addition on tobermorite formation was also studied. In all cases, C-S-H, hydroxylellestadite and katoite were clearly observed as intermediates.Acceleration of tobermorite formation by Al addition was clearly observed. However, Al addition did not affect the dissolution rate of quartz. Two pathways, via C-S-H and katoite, were also observed in the Al-containing system. These results suggest that the structure of initially formed C-S-H is important for the subsequent tobermorite formation reactions.     

Analysis of water in oil-impregnated kraft paper and its effect onconductivity

Oil impregnated paper or polymer film is the main insulating system for many kinds of power apparatus. The oil impregnated materials, especially oil impregnated kraft paper, include a significant amount of water, and this water disturbs the insulating performance of the devices. The amount of water in the materials usually is represented by the difference in weight between the normal material and the same material after drying. However it is difficult to measure the absolute value of the water content and to determine the state in which the water exists in the materials. In this study, we examined the IR spectra of water in oil impregnated kraft paper, because the IR spectrum of the water indicates not only the amount of water but also its state. It was found that most of the water behaves as liquid water, and some as hydrogen bonded water, interacting with the paper fiber. The dc conductivity of the kraft paper depends only on the amount and state of the water associated with it whether or not the paper is impregnated with the oil     

State of water in hydrocarbon liquids and its effect onconductivity [transformer oil]

The humidity or the dissolved water in insulating oils influences conduction and breakdown phenomena. The corrections between the amount of dissolved water and the electrical properties have been investigated. However, the effect of water has been based only on the total amount of water because in the past there was no way to observe the state of water in oil in an electrical field. With the availability of Fourier transform infrared (FTIR) spectroscopy to characterize water clusters, the effect of water in transformer oil can be reassessed based not only on the amount of water, but also on the state of water. In this paper, IR spectra of water in several liquid hydrocarbons and conduction current were measured at the same time. The selection of the liquid hydrocarbons was made on the basis of the degree of polarizability of the liquids. Because the water molecules combine with the polar structures by hydrogen bonding, the state of water depends on the polarizability of the oil. As a result, there is a difference in conduction phenomena depending on whether water is free or combined with the polar structure of the liquid     

Reduction of higher harmonic sequences in terminal voltage of an AC exciting synchronous generator using magnetically anisotropic slot wedges

This paper describes relationships between characteristics of a magnetically anisotropic slot wedge and voltage higher harmonics in an ac exciting synchronous generator terminal due to permeance ripple caused by an open-slot-type rotor. From the relationships obtained, practical guidelines were formulated for machine designs applying the magnetically anisotropic slot wedge. The results are as follows.

• 1 (1) Equivalent permeability of the magnetically anisotropic slot wedge became isotropic wedge permeability for air-gap flux ripple.
• 2 (2) Two ways were identified to reduce voltage-higher harmonics by using the slot wedges.
• 3 (3) The level of leakage flux passing through the anisotropic slot wedge was determined only by its permeability in the width direction.
• 4 (4) Effectiveness of the magnetic anisotropic slot wedges inserted into the stator slots was verified from experimental results using a model machine of the open- slot-type rotor.

     

Decomposition kinetics and recycle of binary hydrogen‐tetrahydrofuran clathrate hydrate

Decomposition kinetics and recycle of hydrogen–tetrahydrofuran (H₂–THF) clathrate hydrates were investigated with a pressure decay method at temperatures from 265.1 to 273.2 K, at initial pressures from 3.1 to 8.0 MPa, and at stoichiometric THF hydrate concentrations for particle sizes between 250 and 1000 μm. The decomposition was modeled as a two‐step process consisting of H₂ diffusion in the hydrate phase and desorption from the hydrate cage. The adsorption process occurred at roughly two to three times faster than the desorption process, whereas the diffusion process during formation was slightly higher (ca. 20%) than that during decomposition. Successive formation and decomposition cycles showed that occupancy seemed to decrease only slightly with cycling and that there were no large changes in hydrate structure due to cycling. Results provide evidence that the formation and decomposition of H₂ clathrate hydrates occur reversibly and that H₂ clathrate hydrates can be recycled with pressure. © 2010 American Institute of Chemical Engineers AIChE J, 2011     

Electrospun curcumin/polycaprolactone/copolymer F-108 fibers as a new therapy for wound healing

The application of fibers associated with drugs is a promising alternative to meet the clinical needs of tissue repair. Curcumin exhibits great cicatricial potential because it has numerous pharmacological properties. This research aimed to produce fibers of polycaprolactone and copolymer F-108 associated with curcumin and to evaluate in vivo their action on the process of wound healing. The fibers were produced by electrospinning technique and characterized by scanning electron microscopy (SEM), X-ray diffractometry (XRD), and fluorescence microscopy. They were applied in cutaneous wounds of rats for the analysis of photoacoustic permeation and histological study. The characterization showed that the electrospinning allowed the preparation of homogeneous material with curcumin. The fibers benefited healing of the wounds and allowed the permeation of curcumin at all stages. The use of PCL/F-108 fibers allowed the elaboration of a new curcumin delivery system, improving its bioavailability and action in the healing of excisional wound. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020 , 137, 48415.