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Objectives: We aimed to determine the role of dihydroorotate dehydrogenase (DHODH) in pathogenesis of adult T‐cell leukemia (ATL) caused by human T‐cell leukemia virus type 1 (HTLV‐1) and the effects of its inhibition on the de novo pyrimidine biosynthesis pathway. Methods: Cell proliferation, viability, cycle, and apoptosis were analyzed using WST‐8 assays, flow cytometry, and Hoechst 33342 staining. To elucidate the molecular mechanisms involved in the anti‐ATL effects of DHODH knockdown and inhibition, RT‐PCR and immunoblotting were conducted. Results: HTLV‐1‐infected T‐cell lines aberrantly expressed DHODH. Viral infection and the oncoprotein, Tax, enhanced DHODH expression, while knockdown of DHODH decreased HTLV‐1‐infected T‐cell growth. In addition, BAY2402234, a DHODH inhibitor, exerted an anti‐proliferative effect, which was reversed by uridine supplementation. BAY2402234 induced DNA damage and S phase arrest by downregulating c‐Myc, CDK2, and cyclin A and upregulating p53 and cyclin E. It also induced caspase‐mediated apoptosis by the upregulation of pro‐apoptotic and downregulation of anti‐apoptotic proteins. Furthermore, BAY2402234 induced caspase‐independent ferroptosis and necroptosis. It decreased phosphorylation of IKK, IκBα, PTEN, Akt, and its downstream targets, suggesting that inhibition of NF‐κB and Akt signaling is involved in its anti‐ATL action. Conclusion: These findings highlight DHODH as a potential therapeutic target for treating ATL. [ABSTRACT FROM AUTHOR]

AbstractAdult T-cell leukemia (ATL), caused by HTLV-1, is the most lethal hematological malignancy. NEDD8-activating enzyme (NAE) is a component of the NEDD8 conjunction pathway that regulates cullin-RING ubiquitin ligase (CRL) activity. HTLV-1-infected T cells expressed higher levels of NAE catalytic subunit UBA3 than normal peripheral blood mononuclear cells. NAE1 knockdown inhibited proliferation of HTLV-1-infected T cells. The NAE1 inhibitor MLN4924 suppressed neddylation of cullin and inhibited the CRL-mediated turnover of tumor suppressor proteins. MLN4924 inhibited proliferation of HTLV-1-infected T cells by inducing DNA damage, leading to S phase arrest and caspase-dependent apoptosis. S phase arrest was associated with CDK2 and cyclin A downregulation. MLN4924-induced apoptosis was mediated by the upregulation of pro-apoptotic and downregulation of anti-apoptotic proteins. Furthermore, MLN4924 inhibited NF-κB, AP-1, and Akt signaling pathways and activated JNK. Therefore, neddylation inhibition is an attractive strategy for ATL therapy. Our findings support the use of MLN4924 in ATL clinical trials. [ABSTRACT FROM AUTHOR]

This retrospective cross-sectional study is aimed at investigating the prevalence and characteristics of behavioral and psychological symptoms (BPS) in subacute stroke patients with cognitive impairment. The Neuropsychiatric Inventory-Questionnaire (NPI-Q) was used to assess BPS. A total of 358 consecutive patients with first-ever stroke admitted to rehabilitation wards and with Mini-Mental State Examination (MMSE) scores < 24 on admission were included. BPS was defined as a total NPI-Q Severity or Distress score ≥ 1. Differences between the severity and presence of BPS among patients with severe cognitive impairment (MMSE scores 0–17) and those with mild cognitive impairment (MMSE scores 18–23) were analyzed using the Mann–Whitney U test and chi-squared test, respectively. Eighty-one patients (mean (standard deviation) age, 73.5 (13.1) years) were enrolled for analysis. BPS were observed in 69.1% and 74.1% of patients when assessed with NPI-Q Severity and NPI-Q Distress, respectively. The most frequently observed BPS was apathy, followed by depression (approximately 44% and 40%, respectively). The severity and frequency of delusions, euphoria, apathy, and disinhibition were significantly higher in the severe cognitive impairment group than in the mild cognitive impairment group. However, the severity, distress, and frequency of depression were not dependent on the severity of cognitive impairment. The presence of BPS, especially apathy and depression, in subacute stroke patients with cognitive impairment is high. The severity and frequency of some BPS are higher in patients with severe cognitive impairment than in those with mild cognitive impairment. However, depression is highly prevalent among the patients regardless of the severity of cognitive impairment. [ABSTRACT FROM AUTHOR]

Stress wave propagation in a metal–plastic bonded laminate immersed in a fluid is investigated based on linear viscoelastic theory. The reflection spectrum is theoretically derived for normal wave incidence. For the incidence from the plastic layer, the amplitude of the reflection spectrum is shown to have local minima at the resonance frequencies of every single layer. Resonance in the metal layer leads to the destructive interference of the reflected wave components, while resonance in the plastic layer appears due to its viscoelastic damping. Experimental results obtained for bonded specimens are discussed from the viewpoint of the characterization for dissimilar joints. [ABSTRACT FROM AUTHOR]

To elucidate the relevance of genetic alterations, we analysed 17 genes known to be involved in haematological neoplasms in patients with chronic leucocytosis and patients with persistent thrombocytosis. Mutations of the JAK2, SETBP1 and ASXL1 genes were found in 1/13, 1/13, and 2/13 patients with leucocytosis, respectively. Mutations of the JAK2, CALR, SETBP1 and ASXL1 genes were found in 1/5, 1/5, 1/5 and 2/5 patients with thrombocytosis, respectively. One leucocytosis patient with a JAK2 V617F mutation developed polycythaemia vera. Another leucocytosis patient developed Philadelphia chromosome-negative chronic myeloid leukaemia (Ph(−) CML) accompanied by t(9;12)(q34.1;p13.?3) (Mori et al. 2016). Another leucocytosis patient with mutations of the SETBP1 and ASXL1 genes progressed to blast crisis of Ph(−) CML accompanied by i(17)(q10). Chronic leucocytosis patients who had genetic alterations tended to develop haematological neoplasms, while thrombocytosis unexpectedly resolved in two persistent thrombocytosis patients with genetic alterations. [ABSTRACT FROM AUTHOR]

Chemical ecology is the highly interdisciplinary study of biochemicals that mediate the behavior of organisms and the regulation of physiological changes that alter intraspecific and/or interspecific interactions. Significant advances are often achieved through the collaboration of chemists and biologists working to understand organismal survival strategies with an eye on the development of targeted technologies for controlling agricultural, forestry, medical, and veterinary pests in a sustainable world. We highlight recent advances in chemical ecology from multiple viewpoints and discuss future prospects for applications. [ABSTRACT FROM AUTHOR]

Common wheat (Triticum aestivum L., AABBDD genome) is thought to have emerged through natural hybridization between Triticum turgidum L. (AABB genome) and Aegilops tauschii Coss. (DD genome). Hybridization barriers and doubling of the trihaploid F1 hybrids' genome (ABD) via unreduced gamete fusion had key roles in the process. However, how T. turgidum, the maternal progenitor, was involved in these mechanisms remains unknown. An artificial cross‐experiment using 46 cultivated and 31 wild T. turgidum accessions and a single Ae. tauschii tester with a very short genetic distance to the common wheat D genome was conducted. Cytological and quantitative trait locus analyses of F1 hybrid genome doubling were performed. The crossability and ability to cause hybrid inviability did not greatly differ between the cultivars and wild accessions. The ability to cause hybrid genome doubling was higher in the cultivars. Three novel T. turgidum loci for hybrid genome doubling, which influenced unreduced gamete production in F1 hybrids, were identified. Cultivated T. turgidum might have increased the probability of the emergence of common wheat through its enhanced ability to cause genome doubling in F1 hybrids with Ae. tauschii. The ability enhancement might have involved alterations at a relatively small number of loci. [ABSTRACT FROM AUTHOR]

Objectives: New effective therapeutic strategies for human T‐cell leukemia virus type 1 (HTLV‐1)‐driven adult T‐cell leukemia (ATL) are required because of resistance to chemotherapeutic agents. Here, we aimed to determine the therapeutic efficacy of a dual phosphoinositide 3 kinase (PI3K)/histone deacetylase (HDAC) inhibitor, CUDC‐907. Methods: Cell viability, cell cycle progression, and apoptotic events were examined by WST‐8 assay, flow cytometry, and Hoechst 33342 staining. Caspase activity was determined using Calorimetric Caspase Assay kits. Immunoblotting and electrophoretic mobility shift assay were used to assess the intracellular signaling cascades. Results: The combination of PI3K inhibitor BKM120 and HDAC inhibitor LBH589 resulted in a synergistic cytotoxic effect in HTLV‐1‐infected T cells. CUDC‐907 was more efficacious than BKM120 and LBH589. It induced G1 cell cycle arrest with downregulation of cyclin D1/D2, CDK4/6, c‐Myc, and phosphorylated retinoblastoma protein expression. Apoptosis was induced via caspase‐3/8/9 activation along with downregulation of Bcl‐XL, Bcl‐2, XIAP, survivin, and cIAP1/2, and upregulation of Bax and Bak. Histone H3 acetylation, H2AX activation, Hsp27 phosphorylation, and Hsp70 and Hsp27 upregulation were observed after treatment. CUDC‐907 suppressed Akt, NF‐κB, and AP‐1 by downregulating phosphorylated and/or total Akt, IKKα/β, RelA, JunB, and JunD. Conclusion: CUDC‐907 may be a potential therapeutic agent for ATL. [ABSTRACT FROM AUTHOR]

Objectives: T‐cell receptor (TCR) signaling‐induced activation of NF‐κB requires assembly of the CARD11‐BCL10‐MALT‐1 complex and IκB kinase (IKK). Gain‐of‐function alterations in this component of the TCR/NF‐κB pathway are associated with the development of HTLV‐1‐driven adult T‐cell leukemia (ATL). We aimed to determine whether inhibition of MALT‐1‐mediated NF‐κB activation could have anti‐ATL activity. Methods: RT‐PCR, immunoblotting, and electrophoretic mobility shift assays were performed to assess expression levels of MALT‐1 and the intracellular signaling cascades. Cell proliferation, cell cycle progression, and apoptotic events were examined using WST‐8 assays, flow cytometry, and Hoechst 33342 staining. Results: MALT‐1 expression was upregulated in ATL‐derived T‐cell lines compared to that in normal PBMCs and uninfected or HTLV‐1‐transformed T‐cell lines. Targeting MALT‐1 with siRNA decreased cell proliferation. A MALT‐1 inhibitor (MI‐2) suppressed cleavage of the MALT‐1‐target protein, CYLD, and inhibited proliferation via G1 phase arrest. MI‐2 induced apoptosis through caspase‐3/8/9 activation and inhibited the phosphorylation of IKKα/β and IκBα, resulting in the accumulation of IκBα and suppression of NF‐κB‐DNA binding. Additionally, MI‐2 inhibited the expression of apoptosis‐ and cell cycle‐related proteins regulated by NF‐κB. Conclusions: MALT‐1 plays an important regulatory role in NF‐κB signaling during ATL‐genesis, and targeting MALT‐1 is a promising therapeutic strategy for this disease. [ABSTRACT FROM AUTHOR]

A formal synthesis of pseudolaric acid B, a diterpene isolated from the root bark of Pseudolarix kaempferi Gordon (Pinaceae), to Trost's synthetic intermediate was achieved in 17 steps from a known ketone. Key features of this synthesis include a Claisen rearrangement and iodoetherification to construct quaternary stereocenters and ring-closing metathesis to form the seven-membered ring. [ABSTRACT FROM AUTHOR]

We report a case of an anomalous anastomosis formed between the external carotid artery (ECA) and the vertebrobasilar artery (VBA) and passing through the hypoglossal canal. A carotid–vertebrobasilar anastomosis of this kind is typically considered a variant of persistent primitive hypoglossal artery which usually originates from the internal carotid artery. However, the anastomotic vessel in this case had a common trunk with the occipital artery (OA), a remnant of the primitive proatlantal artery. The proximal and distal parts of the anastomotic vessel seemed to have been derived from the primitive proatlantal artery and the primitive hypoglossal artery, respectively. Thus, we propose that this ECA–VBA anastomosis, which passed through the hypoglossal canal and had a common trunk with the OA, be referred to as a dilated primitive hypoglossal–proatlantal anastomosis; that is, a dilated ascending pharyngeal artery rather than a variant of persistent primitive hypoglossal artery. [ABSTRACT FROM AUTHOR]

The effect of interfacial properties on the reflection and transmission characteristics of ultrasonic waves at adhesively bonded joints is theoretically investigated. An adhesive joint is modeled as a double-interface model, namely, a homogeneous layer coupled to adherends by two spring-type interfaces with different interfacial stiffnesses. For the normal incidence of a one-dimensional longitudinal wave, theoretical results are obtained and validated by finite element simulation. When the thickness of the adhesive layer is sufficiently small compared to the wavelength, the amplitude reflection and transmission coefficients show monotonic dependence on frequency, which can be explained by the theoretical relation of the double-interface model to a single spring-type interface model. The reflection and transmission behavior is invariant if the values of the two interfacial stiffnesses are interchanged. For a relatively thick adhesive layer, on the other hand, the reflection coefficient shows local minima at multiple frequencies. As one interfacial stiffness decreases, the local minimum frequencies decrease and the local minima increase. If the values of the two interfacial stiffnesses are interchanged, the reflection coefficient remains invariant but the reflection waveform shows different features. The obtained reflection and transmission characteristics are discussed in light of the characterization of the interfacial adhesion. [ABSTRACT FROM AUTHOR]

The reflection and transmission characteristics of Lamb waves at an adhesive single lap joint of plates are examined theoretically by the hybrid finite element method. The adhesive joint is modeled by a linear spring-type interface, which is characterized by normal and tangential stiffnesses. For the incidence of the lowest-order antisymmetric (A0) Lamb mode in a low frequency range, it is shown that the reflection and transmission coefficients of the A0 mode take local maxima and minima at multiple frequencies. This behavior results from the interference of waves originating from the lowest-order antisymmetric guided wave mode in the overlap region. The peak frequencies of the transmission coefficient increase monotonically with increasing tangential stiffness, but are almost invariant with the normal stiffness of the adhesive joint. Furthermore, time-domain numerical simulation using the finite element method is carried out to discuss the theoretical results. As a result, for the A0 mode incidence, the reflection and transmission waveforms of the A0 mode from the lap joint are found to show long-oscillation tails. The spectral analysis for the obtained waveforms shows that these tails are necessary to identify the frequencies at which the reflection and transmission coefficients take local maxima and minima. [ABSTRACT FROM AUTHOR]

The monoterpene isolated from Mentha haplocalyx, 3,3,5-trimethyl-2-oxabicyclo[2.2.2]oct-5-en-4-ol, was synthesized according to its proposed structure. However, the NMR data of the synthetic sample were not in agreement with those reported for the natural product. After considerable efforts, the genuine structure was confirmed as (1R*,2R*)-4-(1′-hydroxy-1′-methylethyl)-1-methylycyclohex-3-ene-1,2-diol. [ABSTRACT FROM AUTHOR]

Highlights • Transmission ratios of the S0 and A0 Lamb waves across a closed crack are analyzed. • Spring-type interface model is applied to model a partially closed crack. • S0 and A0 modes show remarkably different interaction with a closed crack. • Experimental results are presented for a fatigue crack under variable tensile loading. Abstract The transmission characteristics of Lamb waves across a partially closed through-thickness crack in a plate are investigated numerically and experimentally. In the numerical analysis, the spectral element method is used to simulate the transmission of the lowest-order symmetric (S0) and antisymmetric (A0) Lamb modes across a crack in a low-frequency range. The analysis is carried out for an open crack with traction-free surfaces as well as for a partially closed crack modeled as a spring-type interface characterized by normal and tangential stiffnesses. The transmission ratios of both modes are obtained from the spectral amplitude of the simulated transmission waveforms for different crack lengths and interfacial stiffnesses. The numerical results show that the transmission ratio of the S0 mode increases monotonically with the interfacial stiffness, but that of the A0 mode depends on the interfacial stiffness in a non-monotonic manner depending on the frequency. The Lamb wave transmission measurements are carried out for aluminum alloy plates with artificial slits or a fatigue crack. The experimental results for the plates with slits show reasonable agreement with the numerical results for open cracks. The measured transmission ratio of the S0 mode is shown to decrease with the tensile load applied to the plate, but that of the A0 mode shows different load dependence for different frequencies. The qualitative features of the experimental results for the fatigue crack are discussed based on the numerical simulation for closed cracks. [ABSTRACT FROM AUTHOR]

Highlights • Damage localization method by the time-reversed Lamb waves is proposed for plates. • Mode conversion behavior of Lamb waves is considered in the time reversal process. • Localization of a notch-type defect in plates is numerically simulated. • Focused spots appear at the damage location by the proposed time reversal method. Abstract A damage localization method based on the time reversal focusing of the mode-converted scattered Lamb wave is proposed for plate structures with a non-symmetric defect in the thickness direction. Dual transducers are attached symmetrically on the upper and lower surfaces of the plate to selectively emit and receive the lowest-order symmetric (S0) and antisymmetric (A0) modes. The localization of damage is achieved by the numerical time-reversed (TR) simulation of the mode-converted Lamb wave generated at the defect. To investigate the validity of the proposed method, the signals of the Lamb waves in a plate with a partial-thickness notch are numerically simulated by the three-dimensional elastodynamic finite integration technique (EFIT). When the S0 mode is emitted in the damaged plate, not only the S0 mode is scattered but also the A0 mode is generated due to mode conversion at the notch. Similar mode conversion behavior is confirmed when the A0 mode is emitted. The time reversal of the mode-converted scattered Lamb waves creates focused spots at the damage location without using baseline data for the undamaged plate. The proposed method reduces the magnitude of the artifacts compared to the time reversal of the non-mode-converted Lamb wave, and yields the focused spot whose size is associated with the size of the notch and the half wavelength of the time-reversed wave mode. Furthermore, the proposed method is applied to a plate with a notch-type defect adjacent to an a priori known through-thickness hole, demonstrating the damage localization in a relatively complicated structure. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Synthesis of both enantiomers of conosilane A was achieved. • Conosilane A is an unprecedented sesquiterpene isolated from Conocybe siliginea. • Its highly oxygenated tetracyclic ring system was constructed stereoselectively. Abstract Conosilane A, an inhibitor of 11β-hydroxysteroid dehydrogenase type 1 isolated from Conocybe siliginea , is a tremulane sesquiterpene with highly oxygenated tetracyclic ring system. In this study, we report the synthesis of both enantiomers of conosilane A. The key steps of this synthesis involve asymmetric aldol reaction, furan-ring oxidation followed by transacetalization and intramolecular reductive Heck-type cyclization. [ABSTRACT FROM AUTHOR]

Abstract Litseaone A, isolated from the stem barks of Litsea rubescens and Litsea pedunculata , is a chalcone derivative with a novel spiro-epoxide moiety. The structural revision of litseaone A was achieved by the racemic synthesis of the proposed structure and the asymmetric synthesis of the revised structure. The major tautomeric structure of litseaone A and the relative stereochemistry at the epoxide carbon center were also clarified. Graphical abstract Image 1 Highlights • Litseaone A is a chalcone derivative with a novel spiro-epoxide moiety. • The structural revision of litseaone A was achieved. • The major tautomeric structure of litseaone A was clarified. [ABSTRACT FROM AUTHOR]

The first synthesis of myristicyclin A, which was isolated from the Papua New Guinean plant Horsfieldia spicata, is described. The synthesis features acid-mediated hydroarylation reaction to form a dihydrocoumarin moiety, construction of the 2,8-dioxabicyclo[3.3.1]nonane skeleton under acidic conditions, and regioselective Friedel-Crafts acylation at a later stage. [ABSTRACT FROM AUTHOR]

Abstract Callicarpenal, isolated from the leaves of American beautyberry ( Callicarpa americana ) and Japanese beautyberry ( Callicarpa japonica ), exhibits significant mosquito bite-deterring activity and repellent activity against ticks and fire ants. The mosquito bite-deterring activity level of callicarpenal was reported to be similar to that of N , N -diethyl- m -toluamide. The novel synthesis of (−)-callicarpenal reported herein was accomplished by starting from (+)-pulegone. In our original approach, a novel Prins-type cyclization based on Meyer–Schuster rearrangement was featured as a key step. Graphical abstract Image 1 Highlights • A novel synthesis of (−)-callicarpenal was achieved. • Callicarpenal is a tetranorditerpene aldehyde with a potent mosquito repellent activity. • Prins-type cyclization based on Meyer-Schuster rearrangement was featured as a key step. [ABSTRACT FROM AUTHOR]

The article provides an overview of organocatalysis and focuses on the use of diphenylprolinol silyl ether as a catalyst in reactions involving enamines and iminium ions. It discusses the challenges in synthesizing racemic molecules using this catalyst and suggests the potential use of inexpensive amines as alternatives. The article also presents a study on the reaction of isopropylidenemalononitrile and 3-phenyl-5-trimethylsilyl-pent-2-en-4-ynal, which resulted in the formation of substituted quinolines. It further explores the effectiveness of bis(2-ethylhexyl)amine (I) as an organocatalyst in reactions with α,β-unsaturated aldehydes, highlighting its unique characteristics and comparing it to other amine catalysts. While the catalyst shows promise, further research is needed to fully understand its potential. [Extracted from the article]

Pseudolaric acids A ( 1 ) and B ( 2 ) are diterpene acids isolated from the root bark of Pseudolarix kaempferi as the main biologically active constituents of tujinpi , a traditional Chinese medicinal herb. Studies toward the total synthesis of 2 are described. The unusual trans -fused [5–7] ring system in the core structure of 2 was successfully synthesized via Dieckmann condensation. [ABSTRACT FROM AUTHOR]

Lignans are a large class of naturally occurring secondary metabolites which are widely spread within the plant kingdom. Their diverse structures and variety of biological activities have fascinated organic chemists. For synthesizing optically active lignans, we have developed the novel asymmetric dimerization of cinnamic acid derivatives, and applied it to the enantioselective syntheses of furofuran lignans (yangambin, sesamin, eudesmin, caruilignan A) and diarylbutane lignans (sauriols A and B). This review summarizes the methodology of our asymmetric dimerization of cinnamic acid derivatives, and efficient total syntheses of furofuran and diarylbutane lignans reported by our and other groups. Optically active furofuran and diarylbutane lignans were synthesized in short steps employing the asymmetric dimerization of cinnamic acid derivatives. [ABSTRACT FROM PUBLISHER]

In order to gain basic insight into the interaction between ultrasonic guided waves and structural discontinuities with contacting surfaces, the transmission characteristics of Lamb waves at contacting edges of two plates are studied experimentally. The edges of two 2.5-mm thick aluminum alloy plates are mated together to constitute a contacting interface of plates and subjected to different levels of compressive loading. The transmission measurements of the lowest-order symmetric (S0) and antisymmetric (A0) Lamb modes across the contacting interface are performed in a frequency range below the cut-off frequencies of the higher-order modes. As a result, it is found that the transmission coefficient of the S0 mode increases monotonically with the applied contact pressure, but the transmission coefficient of the A0 mode exhibits non-monotonic dependence on the contact pressure and the frequency showing a local minimum. For the incidence of the S0 mode, the resonance at the contacting interface is observed as a long-time oscillation tail in the transmission waveform. The resonance frequency is found to increase with the contact pressure. The experimental results are discussed in the light of the theoretical results based on the spring-type interface model. The normal and tangential stiffnesses of the contacting interface are identified from the transmission coefficients as well as from the resonance frequency. The estimated interfacial stiffnesses increase monotonically with the contact pressure, and indicate their dependence on the frequency. Implications of the present results to the Lamb-wave based characterization of the plate contact condition are discussed briefly. [ABSTRACT FROM AUTHOR]

• Wave interference in bilayer laminates is studied theoretically and experimentally. • Critical attenuation is shown to occur in metal-plastic bilayer laminates. • Approximate conditions for wave resonance and critical attenuation are derived. • Critical attenuation lowers the amplitude of the reflection spectrum at resonance. • Results of ultrasonic measurement are well reproduced by theoretical predictions. The resonance of ultrasonic waves in a metal-plastic bilayer laminate placed in an infinite medium is theoretically investigated, and critical attenuation is shown to occur under specific conditions. The bilayer laminate is subjected to normal wave incidence from the side of the plastic layer. Based on a linear viscoelastic model, the amplitude of the reflection spectrum for the laminate is formulated to obtain the exact results for wave resonance and critical attenuation by numerical calculations. Furthermore, the approximate formulae for the conditions of the resonance and critical attenuation are derived explicitly by Taylor expansions with respect to the loss factor of the plastic. As a result, the exact solution shows that the resonance frequencies of the plastic layer slightly increase with increasing loss factor. Their variation with the loss factor agrees well with the second-order approximation result but is insignificant in the cases of common plastics with relatively low loss factors. The exact results also show that the amplitude at each order resonance depends on the loss factor and has a minimum at a critical loss factor. The obtained critical loss factor decreases with increasing resonance order and is well reproduced by the zeroth-order approximation. Experiments are performed on two types of metal-plastic bonded laminates, demonstrating that the measured reflection spectra are in good agreement with the theoretical predictions. In particular, the amplitude of the measured reflection spectrum decreases significantly at a resonance frequency, which is theoretically predicted to satisfy the critical attenuation condition. [ABSTRACT FROM AUTHOR]

Substituted quinolines, tricyclic and tetracyclic molecules with a quinoline moiety are synthesized by a domino reaction from dicyanoalkenes and 3‐aryl‐pent‐2‐en‐4‐ynals in one pot. We established two methods: one is catalyzed by chiral diphenylprolinol silyl ether, and the other is catalyzed by di(2‐ethyl)hexylamine, in combination with p‐nitrophenol. A wide variety of dicyanoalkenes can be employed. As the catalysts are secondary amines, and water is the only by‐product, this is an environmentally benign synthetic method for the preparation of substituted quinolines. [ABSTRACT FROM AUTHOR]

Objectives We previously reported loss of heterozygosity on 1p in chronic myelogenous leukemia ( CML). We analyzed promoter methylation and mutation of tumor suppressor genes on 1p36 in CML. Methods We performed methylation-specific PCR ( MS- PCR) analysis of the PRDM2, RUNX3, and TP73 genes in 61 patients with CML (43 chronic phase, CP; two accelerated phase; and 16 blast crisis, BC). Oxidative MS- PCR, PCR-single-strand conformation polymorphism, and real-time reverse transcriptase PCR were also analyzed. K-562 cells were grown in the presence of 5-Aza- dC and trichostatin A. Results Methylation of the PRDM2, RUNX3, and TP73 genes was detected in 24/60 (40%), 21/61 (34%), and 28/60 (47%) patients, respectively. Methylation of all three genes was detected in 19/59 (32%) patients. Methylation was more frequent in BC than in CP. Oxidative MS- PCR analysis detected 5- mC in the PRDM2, RUNX3, and TP73 genes in 10/22 (45%), 15/21 (71%), and 16/26 (62%) samples with methylation detected by MS- PCR, respectively. Decreased expression was observed in several samples with methylation, while no mutations were found in the genes. Treatment of K-562 cells induced growth suppression, demethylation, and reexpression of the PRDM2 and RUNX3 genes. Conclusion Multiple tumor suppressor genes on 1p were inactivated in CML by methylation. [ABSTRACT FROM AUTHOR]

A new electrochemical method for the asymmetric oxidative dimerization of cinnamic acid derivatives has been developed. This method enabled the enantioselective syntheses of furofuran lignans, yangambin, sesamin and eudesmin. [ABSTRACT FROM AUTHOR]

The transmission behavior of Lamb waves and the possible occurrence of resonance at an adhesive butt joint of plates are studied experimentally. To this purpose, two 2.5-mm thick aluminum alloy plates are bonded at their edges using cyanoacrylate-based adhesive. Bonded plate specimens with different joint conditions are prepared by changing the bonding procedure. The measurements are performed for the transmission characteristics of the lowest-order symmetric (S0) and antisymmetric (A0) Lamb modes for the frequency range of 0.4–0.6 MHz below the cut-off frequency of the higher-order modes. The experimental results show that the transmission coefficients of the S0 and A0 modes exhibit different frequency-dependent characteristics depending on the joint condition. Furthermore, for the incidence of the S0 mode at the center frequency of 1 MHz, the transmitted S0 mode in weakly bonded specimens shows a long oscillation tail due to the resonance effect. The experimental results are discussed in the light of the theoretical results based on the spring-type interface model. The interfacial stiffnesses identified from the transmission coefficients are shown to be correlated with the bonding condition of the joint and give reasonable estimates of the resonance frequencies of weakly bonded specimens. [ABSTRACT FROM AUTHOR]

A concise synthesis of litseaones A and B, which were isolated from the stem barks of Litsea rubescens and L. pedunculata, is described in this study. Litseaone A was synthesized in just three steps from a known phloroglucinol derivative. The direct conversion of litseaone A into litseaone B was also achieved. The concise synthesis of (±)-litseaones A and B was accomplished. [ABSTRACT FROM AUTHOR]

Pseudohygrophorones A 12 and B 12 are cyclohexenone derivatives isolated from Hygrophorus abieticola (Basidiomycete) as anti-phytopathogenic compounds. In this study, the first synthesis of (±)-pseudohygrophorones A 12 is reported, utilizing Michael–aldol cascade reaction for constructing the 3,3-dimethyl-2,4-dioxabicyclo[3.1.1]nonan-9-one skeleton and the diastereoselective addition of alkyllithium to the one-side blocked ketone as the key steps. [ABSTRACT FROM AUTHOR]

An asymmetric formal synthesis of azadirachtin, a potent insect antifeedant, was accomplished in 30 steps to LeyÏs synthetic intermediate (longest linear sequence). The synthesis features: 1) rapid access to the optically active righthand segment starting from the known 5-hydroxymethyl-2- cyclopentenone scaffold; 2) construction of the B and E rings by a key intramolecular tandem radical cyclization; 3) formation of the hemiacetal moiety in the C ring through the aoxidation of the six-membered lactone followed by methanolysis. [ABSTRACT FROM AUTHOR]

An asymmetric formal synthesis of azadirachtin, a potent insect antifeedant, was accomplished in 30 steps to Ley's synthetic intermediate (longest linear sequence). The synthesis features: 1) rapid access to the optically active right-hand segment starting from the known 5-hydroxymethyl-2-cyclopentenone scaffold; 2) construction of the B and E rings by a key intramolecular tandem radical cyclization; 3) formation of the hemiacetal moiety in the C ring through the a-oxidation of the six-membered lactone followed by methanolysis. [ABSTRACT FROM AUTHOR]

The first enantioselective synthesis of (3 S ,4a R ,8a R )- 1 (the enantiomer of natural okundoperoxide) has been accomplished. The synthesis features: 1) stereoselective installation of the peroxy functionality ( 16 → 17 ); 2) ring opening of peroxyacetal and subsequent intramolecular reaction between the hydroperoxide and the vinyl epoxide to form the peroxy six-membered ring ( 5 → 1 ). The absolute configuration of okundoperoxide was determined to be 3 R ,4a S ,8a S by comparing specific rotations of the synthetic sample and the natural product. [ABSTRACT FROM AUTHOR]

Background and Aims: Differentiation of gallbladder (GB) carcinoma from benign GB wall thickening is challenging. The recent introduction of second-generation ultrasonic contrast agents has made contrast harmonic imaging with EUS possible. The aim of our study was to evaluate the utility of contrast-enhanced harmonic EUS (CH-EUS) for the differential diagnosis of GB wall thickening. Methods: Thirty-six consecutive patients with GB wall thickening imaged by CH-EUS and then underwent surgery were enrolled in this study. After the lesions were observed with conventional harmonic EUS (H-EUS), CH-EUS was performed with intravenous injection of 0.015 ml/kg of Sonazoid. Three reviewers with various levels of experience of EUS (Reviewer A: experienced endosonographer, B: EUS trainee, C: experienced gastroenterologist with expertise in transabdominal ultrasound but no EUS experience) were blinded to findings of recorded video of H-EUS and CH-EUS. The diagnostic accuracy of H-EUS and CH-EUS for malignant GB wall thickening was compared. Results: Final diagnoses based on surgical histology were GB carcinoma in 16, cholecystitis in 11, adenomyomatosis in 6 and cholesterolosis in 3. Overall sensitivity, specificity and accuracy for diagnosing malignant GB wall thickening of H-EUS and CH-EUS were 83.3 versus 89.6, 65 versus 98 % ( p < 0.001) and 73.1 versus 94.4 % ( p < 0.001). The inter-observer agreement for H-EUS was moderate ( κ = 0.51), whereas that for CH-EUS was substantial ( κ = 0.77). The inhomogeneous enhanced pattern on CH-EUS was a strong predictive factor of malignant GB wall thickening. Conclusion: CH-EUS has the potential to improve the preoperative diagnostic accuracy and inter-observer agreement in the differential diagnosis of GB wall thickening. [ABSTRACT FROM AUTHOR]

Transmission spectra of the lowest-order antisymmetric (A0) Lamb wave for adhesively bonded single lap joints are experimentally investigated in a frequency range below 0.4 MHz. Based on the theoretical results of the wave interference, a tangential bond stiffness evaluation method is proposed for the lap joints. Aluminum alloy plates bonded with epoxy adhesive on different conditions were prepared as bonded specimens. An air-coupled ultrasonic transducer was used to generate the A0 mode in the specimens, and the signals of the transmitted waves across the joints were measured with a pin-type piezoelectric transducer. Spectral analysis was performed for the measured waveforms, and the transmission coefficient was calculated for each specimen as a function of frequency. The experimental results showed that the transmission coefficient has local maxima and minima at multiple frequencies, called peak and notch frequencies, respectively. The sets of the peak and notch frequencies were different among the bonded specimens. Based on the peak and notch frequencies, the tangential bond stiffness was estimated for each bonded specimen. As a result, the bond stiffnesses obtained for the specimens with the same nominal bond thickness and adherend pretreatment were almost equal even if the bond lengths were different. Furthermore, the evaluation results showed that pretreatments such as sanding and contamination of adherend surfaces affect the bond stiffness due to the change in the interfacial stiffness. [ABSTRACT FROM AUTHOR]

• Subsurface defects are visualized using a scanning laser source. • The defect images are significantly affected by local defect resonant frequency. • This imaging technique is useful for in-situ testing of additive manufacturing. The quality of additive manufacturing (AM) components must be guaranteed to ensure wide applicability, and a nondestructive inspection technology is required in this regard. Therefore, this study examined a method for detecting subsurface defects using ultrasonic waves excited by a laser. Fundamental experiments showed that wideband ultrasonic waves can be excited with a suitable signal-to-noise ratio using high-repetition laser pulses. Images of subsurface defects were appropriately obtained using a scanning laser source (SLS) with broadband waves for an aluminum alloy flat plate with artificial defects. The imaging experiments showed that the acquisition condition depends on the local defect resonant (LDR) frequency in the defective part. The imaging technique also enabled to detect subsurface circular defects created by AM with the diameter below 1.0 mm that were undetectably small in our previous study using the SLS. Based on results of these experiments and a finite element analysis, the following guideline is proposed: the LDR frequencies of targeted defects must be included in the tested frequency range. [ABSTRACT FROM AUTHOR]

Left ventricular (LV) twist can be evaluated using two-dimensional speckle tracking echocardiography (2DSTE) by analyzing difference between apical and basal rotation. However, it is unable to evaluate global rotational dyssynchrony because it cannot assess mid-wall rotation. Recently developed three-dimensional STE (3DSTE) can investigate LV global rotational dyssynchrony. In this study, we investigated the role of torsion on the long-term effects of cardiac resynchronization therapy ( CRT) using 3DSTE. We evaluated 43 patients by 3DSTE: 12 CRT responders, 14 CRT nonresponders, and 17 healthy normal controls. Regional torsion and rotation were assessed using 3DSTE across 16 segments during CRT-off (native conduction) and CRT-on. The following parameters were calculated: global peak twist, Δ global peak twist (difference between CRT-on and CRT-off), and torsion delay index. The torsion delay index was considered to be the rotational energy lost by rotational dyssynchrony. Global peak twist did not show significant differences between the responders and nonresponders during CRT-off (4.0 ± 3.4° vs. 2.8 ± 2.3°, P = 0.295), but it significantly improved in responders compared to nonresponders after CRT-on (5.4 ± 3.5° vs. 2.6 ± 2.6°, P = 0.029). The torsion delay index during CRT-off was significantly higher in responders compared to nonresponders and normal controls (18.5 ± 11.3 vs. 8.6 ± 3.8 and 7.8 ± 5.5, P = 0.010 and P = 0.004, respectively). The torsion delay index during CRT-off significantly correlated with the Δ global peak twist (r = 0.503, P = 0.009). Improvement in LV global peak twist, which is one of the mechanisms for the long-term effects of CRT correlated with the torsion delay index during native conduction that can only be calculated by 3DSTE. [ABSTRACT FROM AUTHOR]

It has been reported that a major cause of coronary vasospastic angina (VSA) is endothelial dysfunction of the coronary artery. On the other hand, some studies showed that serum uric acid and lipoprotein(a) are correlated with endothelial dysfunction. Thus, we examined whether uric acid and lipoprotein(a), are correlated with VSA. Four hundred forty-one patients with suspected VSA who underwent a coronary angiogram with acetylcholine provocation (ACh test) during an 8-year period were enrolled. We divided them into a VSA group, who showed coronary spasm by the ACh test, and an atypical chest pain (ACP) group, who showed negative ACh test. We compared serum markers between the two groups, including low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, high-sensitivity C-reactive protein (hs-CRP), lipoprotein(a), fibrinogen, total plasminogen activator inhibitor-1, and uric acid. Uric acid, hs-CRP, and lipoprotein(a) were significantly higher in the VSA group than in the ACP group (all P < 0.05) while there were no significant differences in the other parameters. Multivariate analyses identified uric acid and lipoprotein(a) as significant independent markers for VSA. Uric acid and lipoprotein(a) are correlated with VSA, and medical intervention to decrease uric acid and lipoprotein(a) might be effective in controlling VSA. [ABSTRACT FROM AUTHOR]

Patients with adult T-cell leukemia (ATL), caused by the human T-cell leukemia virus type 1 (HTLV-1), exhibit poor prognosis owing to drug resistance. Pimozide is a dopamine D2 receptor antagonist and antipsychotic shown to exhibit anticancer activity. Herein, we investigated whether pimozide exerts anti-ATL effects and explored the mechanisms underlying these effects. Pimozide inhibited cell growth and survival in HTLV-1-infected T cells but not in the uninfected T cells. The dopamine D2 receptor subfamily mRNA expression levels in HTLV-1-infected T cells were high. Pimozide induced G1 cell cycle arrest concomitant with the upregulation of p21/p27/p53, and suppression of cyclin D2/E, cyclin-dependent kinase 2/4/6 and c-Myc expression, and pRb phosphorylation. Pimozide also induced apoptosis by activating caspases, upregulating pro-apoptotic proteins and downregulating anti-apoptotic proteins. Additionally, it promoted reactive oxygen species (ROS) generation and increased the expression of the endoplasmic reticulum stress marker activating transcription factor 4 and the DNA damage-inducible protein GADD45α and the phosphorylation of the DNA damage marker H2AX. Furthermore, pimozide-induced cytotoxicity was partially inhibited by a ROS scavenger, and pan-caspase and necroptosis inhibitors, indicating the involvement of caspase-dependent and -independent lethal pathways. The activities of the nuclear factor-κB, Akt, STAT3/5 and AP-1 signaling pathways were inhibited via the dephosphorylation of IκBα, IκB kinase α/β, Akt and STAT3/5, in addition to reduced JunB and JunD expression in HTLV-1-infected T cells. Pimozide also exhibited potent anti-ATL activity in the xenograft mouse model. These findings demonstrated the efficacy of pimozide as a potential therapeutic agent for ATL. [ABSTRACT FROM AUTHOR]

In wheat ( Triticum) and Aegilops, chloroplast and mitochondrial genomes have been studied for over three decades to clarify the phylogenetic relationships among species, and most of the maternal lineages of polyploid species have been clarified. Mitochondrial genomes of Emmer (tetraploid with nuclear genome AABB) and Dinkel (hexaploid with AABBDD) wheat are classified into two different types, VIIa and VIIb, by the presence-absence of the third largest HindIII fragment (named H3) in the mitochondrial DNA. Although the mitochondrial genome in the genera often provides useful information to clarify the phylogenetic relationship among closely related species, the phylogenetic significance of this dimorphism has yet not been clarified. In this study, to facilitate analysis using a large number of accessions, a sequence characterized amplified region (SCAR) marker that distinguishes the type VIIb mitochondrial genome from type VIIa was first developed. Mitochondrial genome type was determined for each of 30 accessions of wild and cultivated Emmer wheat and 25 accessions of Dinkel wheat. The mitochondrial genome type for each accession was compared with the plastogroup that had been determined using chloroplast microsatellite markers. Unexpectedly, the distribution of mitochondrial genome type was not in accordance with that of the plastogroups, suggesting occasional paternal leakage of either the mitochondrial or chloroplast genome during speciation and differentiation of Emmer and Dinkel wheat. An alternative possibility that substoichiometric shifting is involved in the observed dimorphism of the mitochondrial genome is also discussed. [ABSTRACT FROM AUTHOR]

Retinoblastoma protein-interacting zinc finger, RIZ1, is a tumor suppressor gene that is inactivated in various solid tumors. However, the role of the RIZ1 gene has not been well examined in adult acute lymphoblastic leukemia (ALL). We analyzed the expression and promoter methylation status of the RIZ1 gene in patients with newly diagnosed ALL by quantitative real-time reverse transcription polymerase chain reaction (PCR) and methylation-specific PCR, respectively. RIZ1 expression in 67 cases of ALL (mean 1.043) was decreased compared with that in normal bone marrow (mean 1.471) ( p = 0.030). Methylation was detected in 11 of 71 patients (15.5%) but not in healthy controls. Methylation was associated with decreased RIZ1 expression in many ALL cases examined, but this was not statistically significant. In T-ALL, RIZ1 methylation was more frequent (63.6%) than in B-ALL (6.7%) ( p < 0.0001) and the decrease of RIZ1 expression was more significant than in B-ALL ( p = 0.045). 5-Aza-2′-deoxycytidine treatment of MOLT-4 cells with RIZ1 methylation induced demethylation of RIZ1 and restoration of expression. Forced RIZ1 expression in T-ALL cell lines suppressed cell growth accompanied by G2/M arrest and apoptosis. No mutations were found by PCR-single strand conformation polymorphism analysis in hotspots of the gene. These results suggest that RIZ1 is inactivated in adult ALL, and this inactivation is associated with methylation in T-ALL. [ABSTRACT FROM AUTHOR]

An asymmetric Michael reaction of malononitrile and α,β-unsaturated aldehydes catalyzed by a diarylprolinol silyl ether was developed. Michael products were obtained in good yields and with excellent enantioselectivities without the formation of overreaction products. As a malononitrile moiety can be transformed into an alkoxy or amino carbonyl moiety by oxidative transformation, α-chiral esters or amides with all-carbon quaternary centers can be synthesized with excellent enantioselectivities. [ABSTRACT FROM AUTHOR]

The asymmetric cross‐aldol reaction of two different aldehydes is a synthetically relevant reaction. Diarylprolinol catalyst with trifluoromethyl substituents and sulfonamide catalyst derived from diphenylprolinol are organocatalysts for the cross‐aldol reaction. The reactivity and stereoselectivity of these two catalysts were compared in the asymmetric cross‐aldol reactions of propanal and acetaldehyde as nucleophilic aldehydes and several electrophilic aldehydes. Depending on the electrophilic aldehydes, the preferable catalyst differs. By the proper selection of these two catalysts, potentially synthetically useful chiral building blocks can be synthesized with diastereoselectivities of anti:syn=2.6:1∼>20:1 and enantioselectivities of 60∼>98% ee. [ABSTRACT FROM AUTHOR]

Behavioral analysis revealed that S-(+)-isopiperitenone [( S)-3-methyl-6-isopropenyl-2-cyclohexen-1-one], previously identified as an alarm pheromone, is also the female sex pheromone of Tyrophagus similis (Astigmata: Acaridae), showing maximum male attraction at a dose of 0.1 female equivalent. Although the antipode, R-(−)-isopiperitenone, was not detectable in the mite extract, this synthetic optical isomer (80% e.e.) also induced activity at a dose of 100 ng, a response indicative of S-(+)-isopiperitenone being the active compound. The average content was determined to be 38.5 ng per female and 19.8 ng per male. This is the first example of an astigmatid mite species possessing a compound that functions as an alarm as well as a sex pheromone. [ABSTRACT FROM AUTHOR]

Larvae of a swallowtail butterfly, Papilio xuthus L., feed exclusively on plants of the family Rutaceae, including various Citrus crops. Larvae were strongly stimulated to feed on paper strips impregnated with ethanolic extracts of host-plant leaves. Stimulation of feeding on extracts of Citrus unshiu leaves required a mixture of chemicals including sugars ( d-glucose, d-fructose, and d-sucrose), a betaine [(−)-stachydrine], a cyclic peptide (citrusin I), a polymethoxyflavone (isosinensetin), and the lipids 1-linolenoylglycerol, 1-linoleoylglycerol, 1-octadecenoylglycerol, 1-stearoylglycerol, and 1,2-dilinolenoyl-3-galactosyl-sn-glycerol. When these compounds were assayed individually, few larvae consumed test strips. However, larvae readily chewed the test strips treated with a mixture of all compounds, indicating that host recognition by P. xuthus larvae is mediated by a specific combination of both primary and secondary substances. Comparison of 11 stimulant components with 10 compounds from C. unshiu leaves previously reported as stimulant components for oviposition by P. xuthus adult females revealed only one compound, stachydrine, as an ingredient in common. While the larval feeding-stimulant mixture is dominated by nutrients and other compounds of general significance for primary metabolism, the component oviposition stimulants are mostly secondary substances, including flavonoid glycosides, protoalkaloids, a cyclitol, and a betaine, that have restricted distributions in plants. Reliance by adult females on unique profiles of secondary compounds presumably reflects the need to locate and recognize specific host-plant species within a diverse flora. Since the initial host choice for the larvae is made typically by the ovipositing female, however, unique secondary compounds may be less important for larval feeding than are compounds useful for indicating food and microhabitat quality once on the host plant. [ABSTRACT FROM AUTHOR]

Background: The relation with SNF5 mutation and chromosome 22 abnormalities is not clear in hematological neoplasms. Methods: To elucidate the relevance of the SNF5 gene on 22q11.2, karyotypes were reviewed in 283 hematological neoplasms. Loss of heterozygosity (LOH) on 22q was analyzed in 21 plasma cell myelomas without chromosome 22 abnormalities. Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) on the SNF5 gene was analyzed in 8 hematological neoplasms with 22q- or -22, and 8 chronic myelogenous leukemias (CMLs) in blast crisis. Fluorescence in situ hybridization (FISH) was performed in 1 myelodysplastic syndrome (MDS) case with -22,del(22)(q11.2 q13). Results: 22q- or -22 was observed in 36 patients. LOH on 22q was detected in 1 of the 21 myelomas. Mobility shifts were found by PCR-SSCP analysis in 2 CMLs, whereas sequence analysis showed polymorphisms. FISH analysis revealed the SNF5 gene was not deleted in the MDS case. Conclusion: These results suggest that alterations of the SNF5 gene are rare in hematological neoplasms with chromosome 22 abnormalities. Haploinsufficiency may contribute to the development of these neoplasms. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Common wheat (Triticum aestivum) evolved through hybridization between cultivated tetraploid emmer wheat (T. turgidum), which has A and B genomes, and the wild diploid species, Aegilops tauschii, which has the D genome. Although the evolution of common wheat is generally understood, specific details remain unclear. For example, the phylogenetic relationships and origins of the six wheat subspecies (ssp. spelta, macha, vavilovi, aestivum, compactum, and sphaerococcum) have not yet been thoroughly resolved. To clarify the origin of ssp. sphaerococcum, we employed comparative sequence analysis of the D genome-specific sequence-tagged-site (STS) locus A1 in common wheat accessions, including sphaerococcum. Only the two known alleles, type A and type B were found among the accessions. Of the two sphaerococcum accessions, both possessed the type A allele. Four aestivum accessions also possessed the type A allele, while the remaining three accessions possessed the type B allele. Conversely, the accessions of the four remaining subspecies possessed the type B allele. Since sphaerococcum has morphological traits that differ from aestivum and which are pleiotropically regulated by a single recessive gene designated s, sphaerococcum most likely originated from aestivum, with the type A allele at the A1 locus arising through a spontaneous mutation at the s locus. [ABSTRACT FROM AUTHOR]