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.     

Evaluation of environmentally friendly lubricants for cold forging

The authors proposed double-layer-type environmentally friendly lubricants, which were composed of an undercoat, superior in adhering to a material, and an overcoat, superior in reducing the friction between the material and the die. The performance of these lubricants for cold forging was evaluated by the ring compression test, the combined forward rod-backward can extrusion-type friction test and the combined forward conical can-backward straight can extrusion-type friction test. The double-layer-type lubricants showed comparable friction characteristics and anti-pick-up properties to a conversion coating lubricant, when the film thickness and surface treatment before coating were improved. In a practical application by cold multistage forging, the double-layer-type lubricants showed a similar performance to a conversion coating lubricant.     

Possibility of Japanese Cedar Pollen Causing False Positives in the Deep Mycosis Test

Because Japanese cedar pollen (JCP) contains beta-1,3-d-glucan (BG), there is concern that its lingering presence in the atmosphere, especially during its scattering period, may cause false positives in the factor-G-based Limulus amebocyte lysate (LAL) assay used to test for deep mycosis (i.e., G-test). Hence, we examined whether the LAL assay would react positively with substances contained in JCP by using the G-test to measure JCP particles and extracts. BG was purified from the JCP extract on a BG-specific affinity column, and the percentage extractability was measured using three different BG-specific quantitative methods. The G-test detected 0.4 pg BG in a single JCP particle and 10 fg from a single particle in the extract. The percentage extractability of JCP-derived BG was not significantly different among the three quantitative methods. As the JCP particles should technically have been removed during serum separation, they should be less likely to be a direct false-positive factor. However, given that the LAL-assay-positive substances in the JCP extract were not distinguishable by the three BG-specific quantitative methods, we conclude that they may cause the background to rise. Therefore, in Japan false positives arising from JCP contamination should be considered when testing patients for deep mycosis.     

Effect of optimal spinning reserve requirement on system pollution emission considering reserve supplying demand response in the electricity market

Pollution emission reduction is becoming an inevitable global goal. Incorporating pollution reduction goals into power system operation affects several different aspects, such as unit scheduling and system reliability. At the same time, changes in the energy scheduling change the required optimal reserve amount. Optimal spinning reserve scheduling also affects the energy market scheduling. Optimal reserve allocation changes the energy scheduling, which affect the amount of pollution emission. Therefore, incorporating pollution emission reduction and optimal spinning reserve scheduling cannot be studied separately. Analysis of the system effects of pollution reduction should be performed considering the ancillary service market, specificity the optimal spinning reserve scheduling. This problem is addressed in this paper by incorporating optimal spinning reserve scheduling in a combined environment economic dispatch (CEED) in one objective function. The framework of this paper enables the study of the effect of optimal reserve scheduling and emission reduction as well as an analysis of the system effects of pollution reduction. With the increased AMI and smart grid realization, the reserve supplying demand response (RSDR) is becoming an important player in the reserve market, and thus, these resources are also taken into account. In this paper, the objective function is social cost minimization, including the costs associated with energy provision, reserve procurement, expected interruptions and environmental pollution. A MIP-based optimization method is developed, which reduces the computational burden considerably while maintaining the ability to reach to the optimal solution. The IEEE RTS 1996 is used as a test case for numerical simulations, and the results are presented. The numerical results show that optimal reserve scheduling and RSDR utilization resources have a considerable impact on environmental–economic cost characteristics.     

Eddy current analysis of thin metal container in induction heating by line integral equations

In recent years, induction‐heating cookers have spread rapidly. It is desirable to commercialize flexible and disposable food containers that are suitable for induction heating. In order to develop a good‐quality food container for moderate heating, the eddy currents induced in a thin metal plate must be accurately analyzed. The integral equation method is widely used for solving induction‐heating problems. If the plate thickness approaches zero, the surface integral equations on the upper and lower plate surfaces tend to become the same and the equations become ill‐conditioned. In this paper, we first derive line integral equations from the boundary integral equations under the assumption that the electromagnetic fields in the metal are attenuated more rapidly than those along the metal surface. Next, to test the validity of the line integral equations, we solve for the eddy current induced in a thin metal container in induction heating and obtain the power density imparted to the container and the impedance characteristics of the heating coil. We then compare the computed results with those obtained by the FEM. © 2009 Wiley Periodicals, Inc. Electr Eng Jpn, 168(2): 20–27, 2009; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/eej.20813     

TEM/STEM Observation of ZrC Coating Layer for Advanced High-Temperature Gas-Cooled Reactor Fuel, Part II

The Japan Atomic Energy Agency (JAEA) has started to study and develop zirconium carbide (ZrC)-coated fuel particles for advanced high-temperature gas-cooled reactors. The ZrC coating layer has been fabricated at JAEA by chemical vapor deposition using a pyrolytic reaction of zirconium bromide. The microstructures of the ZrC layers, whose nominal deposition temperatures could be measured and controlled during the deposition process, were characterized by means of TEM and STEM. In the present study, three batches were prepared and compared with each other as well as the previous batches. The crystallographic orientation of ZrC with regard to the growth direction in the ZrC layers deposited at a constant temperature of 1630 K was different from that deposited at varying temperatures in the 1493–1823 K range. A thin layer of turbostratic carbon was observed at the boundary between pyrolytic carbon and ZrC in particles deposited at the highest temperature among those used in this study (the nominal temperature was 1769 K); no such structure was found in a batch deposited at a lower temperature (the nominal temperature was 1632 K). Therefore, precise control of temperature is shown to be critical to the formation of good ZrC coatings.     

Histamine modulates high-voltage-activated calcium channels in neurons dissociated from the rat tuberomammillary nucleus

Insects are known to be useful in estimating the postmortem interval (PMI). Here several cases are reported which show that a wide range of applications in medicolegal questions and hygiene together or apart from estimating the PMI can be answered by use of forensic entomology techniques, including close observation of larval development. Case 1 describes how blowfly larvae fell from a putrefied corpse, hid, and finally emerged from pupae three months after disinfection and renovation. In case 2, the entomological state of the decomposed corpse of a heroin user is described. Case 3 deals with a single adult Protophormia terranovae found in the skull of a partially mummified woman. Case 4 reports the finding of Serratia marcescens bacteria in red Muscina stabulans pupae which were found on a 5-day-old corpse. In case 5, blowfly eggs on the corpse of another heroin user are interpreted as an indication of the decedent being laid outside at night after his death in a flat. Case 6 deals with the finding of Parasarcophaga argyrostoma, which in Cologne might be an indicator species which tells if a corpse was lying outside at least for some time.     

Fast agglomerative hierarchical clustering algorithm using Locality-Sensitive Hashing

The single linkage method is a fundamental agglomerative hierarchical clustering algorithm. This algorithm regards each point as a single cluster initially. In the agglomeration step, it connects a pair of clusters such that the distance between the nearest members is the shortest. This step is repeated until only one cluster remains. The single linkage method can efficiently detect clusters in arbitrary shapes. However, a drawback of this method is a large time complexity of O(n ²), where n represents the number of data points. This time complexity makes this method infeasible for large data. This paper proposes a fast approximation algorithm for the single linkage method. Our algorithm reduces the time complexity to O(nB) by rapidly finding the near clusters to be connected by Locality-Sensitive Hashing, a fast algorithm for the approximate nearest neighbor search. Here, B represents the maximum number of points going into a single hash entry and it practically diminishes to a small constant as compared to n for sufficiently large hash tables. Experimentally, we show that (1) the proposed algorithm obtains clustering results similar to those obtained by the single linkage method and (2) it runs faster for large data than the single linkage method. Hisashi Koga received the M.S. and Ph.D. degree in information science in 1995 and 2002, respectively, from the University of Tokyo. From 1995 to 2003, he worked as a researcher at Fujitsu Laboratories Ltd. Since 2003, he has been a faculty member at the University of Electro-Communications, Tokyo (Japan). Currently, he is an associate professor at the Graduate School of Information Systems, University of Electro-Communications. His research interest includes various kinds of algorithms such as clustering algorithms, on-line algorithms, and algorithms in network communications. Tetsuo Ishibashi received the M.E. degree in information systems design from the Graduate School of Information Systems at the University of Electro-Communications in 2004. Presently, he is a system engineer at Fujitsu Broad Solution & Consulting Inc. Toshinori Watanabe received the B.E. degree in aeronautical engineering in 1971 and the D.E. degree in 1985, both from the University of Tokyo. In 1971, he worked at Hitachi as a researcher in the field of information systems design. His experience includes demand forecasting, inventory and production management, VLSI design automation, knowledge-based nonlinear optimizer, and a case-based evolutionary learning system nicknamed TAMPOPO. He also engaged in FGCS (Fifth Generation Computer System) project of Japan and developed a new hierarchical message-passing parallel cooperative VLSI layout problem solver that ran on PIM (Parallel Inference Machine) in 1991. Since 1992, he has been a professor at the Graduate School of Information Systems, University of Electro-Communications, Tokyo, Japan. His areas of interest include media analysis, learning intelligence, and the semantics of information systems. He is a member of the IEEE.     

Synthesis of sulfonated organic–inorganic hybrids through the radical copolymerization of vinyl sulfonate esters and vinyl trialkoxysilanes

Novel organic–inorganic hybrids with sulfonic acid groups were prepared using random copolymers composed of vinyl sulfonate esters and vinyl trialkoxysilanes. Five vinyl sulfonate esters with different substituent groups were employed as protecting monomers for the production of the poly(vinyl sulfonic acid) component, and three vinyl trialkoxysilanes were used as cross-linkable monomers. Free radical and reversible addition-fragmentation chain transfer (RAFT) copolymerizations were performed for the production of random copolymers with two different functional groups. The selective deprotection of the sulfonate esters of the copolymers proceeded smoothly and resulted in the formation of copolymers with lithium vinyl sulfonate units and cross-linkable trialkoxysilane units. The co-condensation of the trialkoxysilane moieties in the deprotected copolymers with cross-linkers yielded transparent hybrid films that contained lithium sulfonate groups without aromatic rings or ester linkages.