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This paper presents a series of trials of direct detection of the transition process of a squeeze film, from the contacting state into the floating one. The material was initially placed on the surface of a vibrator constituting a squeeze air film. Three electrical trials were performed to certify whether the material could be elevated after the vibrator was excited. When this is done, clearance is expected between the surfaces of the test material and the vibrator. This may be regarded as the equivalent of a change in electrical resistance from almost zero to infinity, with a kind of parallelplate capacitor being formed. First, detection through DC current was carried out. The experimental result, however, reveals that the resistance never does become infinite, although the equivalent contacting area calculated from this value is very small. Second, detection through DC voltage was performed by terminating the clearance with parallel resistance. The experimental results verify the appearance of the floating state. Third, the average clearance could be detected by regarding it as a parallel-plate type capacitor. Here a Langevin type piezoelectric transducer was used as the vibrator. Through these experimental results an important fact was observed: the waveform of the voltage applied to the transducer is closely related to the movement of the clearance in the time domain.

For human identification, the quality and quantity of DNA must be sufficient for amplification and analysis. When DNA extraction from bone tissues and teeth is required, the optimal skeletal elements should be selected as samples for DNA extraction because DNA yield differs among elements. Recently, some studies have reported that a high quantity of high-quality DNA can be extracted from the small cancellous bones of the hands and feet. In this study, we evaluated the effectiveness of small cancellous bones in the human identification of skeletal remains in routine forensic genetic casework. Cancellous bones [phalanges, (meta)carpal bones, and (meta)tarsal bones)] and the cortical bones (femur and petrous bones) and teeth, which have generally been recommended as samples, were collected from the same individuals that needed identifying using DNA analysis in our laboratory. The quantity of DNA from small cancellous bones tended to be higher than that from cortical bones, and the quality from the former was as high as that from the latter. This study showed that in routine forensic casework, the small cancellous bones of the hands and feet should be actively selected as samples for DNA testing., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Codeine is a common analgesic drug that is a pro-drug of morphine. It also has a high risk of abuse as a recreational drug because of its extensive distribution as an OTC drug. Therefore, sensitive and selective screening methods for codeine are crucial in forensic analytical chemistry. To date, a commercial analytical kit has not been developed for dedicated codeine determination, and there is a need for an analytical method to quantify codeine in the field. In the present work, potential modulation was combined with electrochemiluminescence (ECL) for sensitive determination of codeine. The potential modulated technique involved applying a signal to electrodes by superimposing an AC potential on the DC potential. When tris(2,2'-bipyridine)ruthenium(II) ([Ru(bpy) 3 ] 2+ ) was used as an ECL emitter, ECL activity was confirmed for codeine. A detailed investigation of the electrochemical reaction mechanism suggested a characteristic ECL reaction mechanism involving electrochemical oxidation of the opioid framework. Besides the usual ECL reaction derived from the amine framework, selective detection of codeine was possible under the measurement conditions, with clear luminescence observed in an acidic solution. The sensitivity of codeine detection by potential modulated-ECL was one order of magnitude higher than that obtained with the conventional potential sweep method. The proposed method was applied to codeine determination in actual prescription medications and OTC drug samples. Codeine was selectively determined from other compounds in medications and showed good linearity with a low detection limit (150 ng mL -1 ).

In this study, we analyzed DNA samples from 213 Japanese father son pairs with 25 Y-chromosome short tandem repeat (Y-STR) (DYS576, DYS389I, DYS635, DYS389II, DYS627, DYS460, DYS458, DYS19, YGATAH4, DYS448, DYS391, DYS456, DYS390, DYS438, DYS392, DYS518, DYS570, DYS437, DYS385, DYS449, DYS393, DYS439, DYS481, DYF387S1, and DYS533) markers using the Yfiler™ Plus PCR amplification kit. We calculated Y-STR mutation rates for each locus to evaluate the efficacy of the 25 Y-STR markers for paternity testing and forensic identification using samples from male relatives. Six rapidly mutating Y-STR markers (DYS576, DYS627, DYS518, DYS570, DYS449 and DYF387S1), previously reported to have high mutation rates (>1.0 × 10 -2 ), are included in the 25 Y-STR markers, but our findings revealed that the mutation rates for all Y-STR markers except for DYS576 and DYS458 were lower than 1.0 × 10 -2 . Therefore, the use of these 25 Y-STR markers may be useful for forensic identification in the Japanese population., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Competing Interests: The authors disclose no conflicts of interest.

Cirrhotic cardiomyopathy (CCM) is a chronic cardiac dysfunction in patients with cirrhosis and is characterized by altered diastolic relaxation, blunted contractile response to stress, and electrophysiological abnormalities;however, causes of CCM are unknown. Moreover, reduced cardiac afterload due to cirrhosis-related vasodilatation often masks cardiac insufficiency, whereas rapid hemodynamic overload reveals the presence of cirrhotic cardiomyopathy. Herein, we present the case of previously unrecognized cirrhotic cardiomyopathy that became overt with the development of severe acute cardiac failure. The rapidly worsening hepatic hydrothorax increased cardiac preload and intrathoracic pressure, which impaired cardiac filling. Furthermore, cardiac contractile function might have been worsened by hypoxia due to passive atelectasis and concomitant anemia.

Psychotropic drugs can pose the risk of acquired long QT syndrome (LQTS). Unexpected autopsy-negative sudden death in patients taking psychotropic drugs may be associated with prolonged QT intervals and life-threatening arrhythmias. We analyzed genes that encode for cardiac ion channels and potentially associated with LQTS, examining specifically the potassium channel genes KCNQ1 and KCNH2 in 10 cases of sudden death involving patients administered psychotropic medication in which autopsy findings identified no clear cause of death. We amplified and sequenced all exons of KCNQ1 and KCNH2, identifying G643S, missense polymorphism in KCNQ1, in 6 of the 10 cases. A study analysis indicated that only 11% of 381 healthy Japanese individuals carry this polymorphism. Reports of previous functional analyses indicate that the G643S polymorphism in the KCNQ1 potassium channel protein causes mild I(Ks) channel dysfunction. Our present study suggests that administering psychotropic drug therapy to individuals carrying the G643S polymorphism may heighten the risk of prolonged QT intervals and life-threatening arrhythmias. Thus, screening for the G643S polymorphism before prescribing psychotropic drugs may help reduce the risk of unexpected sudden death.

We designed three mini multiplex PCR systems using single-base extension reactions to identify Japanese Y chromosome haplogroups. We selected a group of 22 Y chromosome single nucleotide polymorphisms (SNPs) from the haplogroups most commonly reported in East Asia. To make the systems more useful in analyzing degraded DNA samples, we designed primers to render amplicons of ≤ 150 bp. Applying these systems, we classified the Japanese population into major haplogroups and confirmed the applicability of these systems in forensic DNA analysis., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Several p38 MAPK inhibitors have been shown to effectively block the production of cytokines such as IL-1β, TNFα, and IL-6. Inhibitors of p38 MAP kinase therefore have significant therapeutic potential for the treatment of autoimmune disease. Compound 2a was identified as a potent TNFα production inhibitor in vitro but suffered from poor oral bioavailability. Structural modification of 2a led to the discovery of tetrahydropyrazolopyrimidine derivatives, exemplified by compound 3, with an improved pharmacokinetic profile. We found that blocking metabolism at the methyl group of the amine and constructing the tetrahydropyrimidine core were important to obtaining compounds with good biological profiles and oral bioavailability. Pursuing the structure-activity relationships of this series led to the discovery of AS1940477 (3f), with excellent cellular activity and a favorable pharmacokinetic profile. This compound represents a highly potent inhibitor of p38 MAP kinase with regard to in vivo activity in an adjuvant-induced arthritis model.

Various analogues of the marine alkaloids, discorhabdins, have been synthesized. The strategy contains spirocyclization with phenyliodine(III) bis(trifluoroacetate) (PIFA), oxidative fragmentation of the β-amino alcohols with the hypervalent iodine reagent C(6)F(5)I(OCOCF(3))(2), the detosylation and dehydrogenation reaction of the pyrroloiminoquinone unit in the presence of a catalytic amount of NaN(3) and the bridged ether synthesis with HBr-AcOH as the key reactions. All the synthesized compounds were evaluated by in vitro MTT assay for cytotoxic activity against the human colon cancer cell line HCT-116. Furthermore, the discorhabdin A oxa analogues were also evaluated against four kinds of tumor model cells, a human colon cancer cell line (WiDr), a human prostate cancer cell line (DU-145) and murine leukemia cell lines (P388 and L1210). For the identification of the target, discorhabdin A and the discorhabdin A oxa analogue were evaluated by an HCC panel assay. In the test, discorhabdins could have a novel mode of action with the tumor cells.

Discorhabdin A (1) exhibits a strong cytotoxic activity in vitro, but it is difficult to synthesize and handle due to the instability of its highly strained N,S-acetal structure. We then designed the analogues of discorhabdin A which also have strong cytotoxic activity and stability. The synthesis and examination of the biological activity of various types of stable discorhabdin A oxa analogues (2) were achieved.

Mutation in the X-chromosomal adrenoleukodystrophy gene (ALD; ABCD1) leads to X-linked adrenoleukodystrophy (X-ALD), a severe neurodegenerative disorder. The encoded adrenoleukodystrophy protein (ALDP/ABCD1) is a half-size peroxisomal ATP-binding cassette protein of 745 amino acids in humans. In this study, we chose nine arbitrary mutant human ALDP forms (R104C, G116R, Y174C, S342P, Q544R, S606P, S606L, R617H, and H667D) with naturally occurring missense mutations and examined the intracellular behavior. When expressed in X-ALD fibroblasts lacking ALDP, the expression level of mutant His-ALDPs (S606L, R617H, and H667D) was lower than that of wild type and other mutant ALDPs. Furthermore, mutant ALDP-green fluorescence proteins (S606L and H667D) stably expressed in CHO cells were not detected due to rapid degradation. Interestingly, the wild type ALDP co-expressed in these cells also disappeared. In the case of X-ALD fibroblasts from an ALD patient (R617H), the mutant ALDP was not detected in the cells, but appeared upon incubation with a proteasome inhibitor. When CHO cells expressing mutant ALDP-green fluorescence protein (H667D) were cultured in the presence of a proteasome inhibitor, both the mutant and wild type ALDP reappeared. In addition, mutant His-ALDP (Y174C), which has a mutation between transmembrane domain 2 and 3, did not exhibit peroxisomal localization by immunofluorescense study. These results suggest that mutant ALDPs, which have a mutation in the COOH-terminal half of ALDP, including S606L, R617H, and H667D, were degraded by proteasomes after dimerization. Further, the region between transmembrane domain 2 and 3 is important for the targeting of ALDP to the peroxisome.

Hypervalent iodine(III) reagents are readily available, easy to handle, and have a low toxicity and similar reactivities to those of heavy metal reagents, and hence they are used for various oxidative reactions. The oxidative cleavage of alkynes or carbonyl compounds by using bis(trifluoroacetoxy)iodo(III) pentafluorobenzene (C(6)F(5)I(OCOCF(3))(2)) has been reported. Herein, the efficient direct synthesis of N,O-acetal compounds as key intermediates of discorhabdin A, by the oxidative fragmentation reaction of alpha-amino acids or beta-amino alcohols by using C(6)F(5)I(OCOCF(3))(2), is described.

The use of hypervalent iodine(III) reagents allowed us to develop the novel and efficient direct synthesis of N,O-acetal compounds via the oxidative fragmentation reaction of alpha-amino acids or alpha-amino alcohols; furthermore, we succeeded in developing an improved synthesis of the key intermediate of discorhabdins.

The first stereoselective total synthesis of a potent antitumor alkaloid, discorhabdin A (1), which is a unique sulfur-containing pyrroloiminoquinone alkaloid, is described. The key step in the stereocontrolled total synthesis of 1 involves both a diastereoselective oxidative spirocyclization using a hypervalent iodine(III) reagent and an efficient construction of the labile and highly strained N,S-acetal skeleton. These methodologies provide a breakthrough in the total syntheses of these promising new antitumor agents, discorhabdins and their analogues, which should serve as valuable probes for structure-activity studies.