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We present a systematic review of the methods developed for the synthesis of the aromathecin family of compounds (benz[6,7]indolizino[1,2-b]quinolin-11(13H)-ones) and their derivatives. These methods can be broadly classified into four categories based on the construction of pentacyclic structures: Category 1: by constructing a pyridone moiety (D-ring) on the pyrroloquinoline ring (A/B/C-ring), Category 2: by constructing a pyridine moiety (B-ring) on the pyrroloisoquinolone ring (C/D/E-ring), Category 3: by constructing an indolizidinone moiety (C/D-ring) in a tandem reaction, and Category 4: by constructing a pyrrolidine moiety (C-ring) on the isoquinolone ring (D/E-ring). [ABSTRACT FROM AUTHOR]

Camptothecin-like compounds are actively employed as anticancer drugs in clinical treatments. The aromathecin family of compounds, which contains the same indazolidine core structure as the camptothecin family of compounds, is also expected to display promising anticancer activity. Therefore, the development of a suitable and scalable synthetic method of aromathecin synthesis is of great research interest. In this study, we report the development of a new synthetic approach for constructing the pentacyclic scaffold of the aromathecin family by forming the indolizidine moiety after synthesizing the isoquinolone moiety. Thermal cyclization of 2-alkynylbenzaldehyde oxime to the isoquinoline N-oxide, followed by a Reissert–Henze-type reaction, forms the key strategy in this isoquinolone synthesis. Under the optimum reaction conditions for the Reissert–Henze-type reaction step, microwave irradiation-assisted heating of the purified N-oxide in acetic anhydride at 50 °C reduced the formation of the 4-acetoxyisoquinoline byproduct to deliver the desired isoquinolone at a 73% yield after just 3.5 h. The eight-step sequence employed afforded rosettacin (simplest member of the aromathecin family) at a 23.8% overall yield. The synthesis of rosettacin analogs was achieved by applying the developed strategy and may be generally applicable to the production of other fused indolizidine compounds. [ABSTRACT FROM AUTHOR]

Melzer then presents an engaging study of knowledge transfer from the United States and Germany, concluding with a survey history of Japanese aviation after 1945 (epilogue). Vast scholarship, in English and even more so in Japanese, has often emphasized the successive stages of technology transfer within the aircraft industry, underscoring the French, British, and German influences on the shaping of Japanese aviation. This "new perspective", in the author's words (p. 1), provides fresh insights into the scholarship of Japan's aviation history and technology transfer at large. [Extracted from the article]

• Our HEV replication monitoring system uses Gaussia luciferase. • We validated candidates using cells robustly producing HEV. • We screened and evaluated anti-HEV drugs with an FDA-approved drug library. • Interferon λ1-3 inhibited HEV propagation in our new system. Hepatitis E, which is caused by hepatitis E virus (HEV), is generally a self-limiting, acute, and rarely fatal disease. It is sometimes fulminant and lethal, especially during pregnancy. Indeed, it occasionally takes a chronic course in immunocompromised individuals. To cure hepatitis E patients, the broad-spectrum antivirals (ribavirin and pegylated interferon α) are used. However, this treatment is insufficient and unsafe in some patients due to embryoteratogenic effects, leukopenia, and thrombocytopenia. In this study, we constructed an HEV replication reporter system with Gaussia luciferase for comprehensively screening anti-HEV drug candidates, and developed a cell-culture system using cells robustly producing HEV to validate the efficacy of anti-HEV drug candidates. We screened anti-HEV drug candidates from United States Food and Drug Administration-approved drugs using the established HEV replication reporter system, and investigated the selected candidates and type III interferons (interferon λ1-3) using the cell-culture system. In conclusion, we constructed an HEV replicon system for anti-HEV drug screening and a novel cell-culture system to strictly evaluate the replication-inhibitory activities of the obtained anti-HEV candidates. Our findings suggested that interferon λ1-3 might be effective for treating hepatitis E. [ABSTRACT FROM AUTHOR]

We developed a concise protocol for the synthesis of ellipticine quinone from the appropriate 3-iodoindole-2-carbaldehydes in four steps. The key step is the construction of carbazole-1,4-quinone through tandem Ring-Closing Metathesis (RCM) and dehydrogenation under oxygen atmosphere. Therefore, the ellipticine quinone analogs possessing substitution at the 8- and/or 9-positions were synthesized using this method. In total, 14 compounds were evaluated for antiproliferative activity against HCT-116 and HL-60 cell lines; 9-nitroellipticine quinone was found to have superior activity compared to calothrixin B. [ABSTRACT FROM AUTHOR]

The hepatitis E virus (HEV) is increasingly acknowledged as the primary cause of acute hepatitis. While most HEV infections are self-limiting, cases of chronic infection and fulminant hepatitis necessitate the administration of anti-HEV medications. However, there is a lack of specific antiviral drugs designed for HEV, and the currently available drug (ribavirin) has been associated with significant adverse effects. The development of innovative antiviral drugs involves targeting distinct steps within the viral life cycle: the early step (attachment and internalization), middle step (translation and RNA replication), and late step (virus particle formation and virion release). We recently established three HEV reporter systems, each covering one or two of these steps. Using these reporter systems, we identified various potential drug candidates that target different steps of the HEV life cycle. Through rigorous in vitro testing using our robust cell culture system with the genotype 3 HEV strain (JE03-1760F/P10), we confirmed the efficacy of these drugs, when used alone or in combination with existing anti-HEV drugs. This underscores their significance in the quest for an effective anti-HEV treatment. In the present review, we discuss the development of the three reporter systems, their applications in drug screening, and their potential to advance our understanding of the incompletely elucidated HEV life cycle. [ABSTRACT FROM AUTHOR]

Three to eight percent of female carriers of Duchenne muscular dystrophy (DMD) develop dystrophic symptoms ranging from mild muscle weakness to a rapidly progressive DMD-like muscular dystrophy due to skewed inactivation of X chromosomes during early development. Here, we generated human induced pluripotent stem cells (hiPSCs) from a manifesting female carrier using retroviral or Sendai viral (SeV) vectors and determined their X-inactivation status. Although manifesting carrier-derived iPS cells showed normal expression of human embryonic stem cell markers and formed well-differentiated teratomas in vivo, many hiPS clones showed bi-allelic expression of the androgen receptor (AR) gene and loss of X-inactivation-specific transcript and trimethyl-histone H3 (Lys27) signals on X chromosomes, suggesting that both X chromosomes of the hiPS cells are in an active state. Importantly, normal dystrophin was expressed in multinucleated myotubes differentiated from a manifesting carrier of DMD-hiPS cells with XaXa pattern. AR transcripts were also equally transcribed from both alleles in induced myotubes. Our results indicated that the inactivated X chromosome in the patient’s fibroblasts was activated during reprogramming, and XCI occurred randomly during differentiation. [ABSTRACT FROM AUTHOR]

We report a convenient synthesis of carbazole-1,4-quinone alkaloid koeniginequinones A and B using a tandem ring-closing metathesis with the dehydrogenation reaction sequence under an O 2 atmosphere as an important step. Using this method, carbazole-1,4-quinones substituted at the 5-, 6-, 7-, and/or 8-positions have been synthesized. Moreover, 24 compounds, including koeniginequinones A and B, have been evaluated for their antiproliferative activity against HCT-116 and HL-60 cells, and the 6-nitro analog exhibited the most potent activity against both tumor cell types. [ABSTRACT FROM AUTHOR]

In this study, we achieved the total synthesis of carbazole alkaloid mukoenine A through a seven-step sequence involving the construction of a carbazole framework using the electrocyclization of a 6π-electron system including an allene intermediate as the key step. Subsequently, the synthesis of pyrano[3,2- a ]carbazole alkaloid girinimbine was achieved by the construction of the pyran ring via selenoetherification of the o-allylic phenol moiety of mukoenine A. [Display omitted] • The total synthesis of mukoenine A has been accomplished via a seven-step sequence. • Girinimbine was synthesized by the construction of the pyran ring via mukoenine A. • The carbazole framework was constructed by the allene-mediated electrocyclization. [ABSTRACT FROM AUTHOR]

Extracellular matrix (ECM) proteins are synthesized in the endoplasmic reticulum (ER), transported to the extracellular milieu through the secretory pathway, and assembled into an extracellular architecture. A previous study of ours showed that periostin, a secretory protein, interacts with fibronectin and is involved in ECM remodeling. Here we show that periostin played a role in fibronectin secretion from the ER. Co-immunoprecipitation and in situ proximity ligation assays revealed an interaction between periostin and fibronectin in the ER. Although accumulation of fibronectin was detected in the ER of fibroblastic C3H10T1/2 cells, forced expression of periostin in those cells decreased the accumulation of fibronectin in the ER, suggesting that periostin promoted the secretion of fibronectin. A substitution mutant of tryptophan at the position 65 to alanine in the EMI domain of periostin, which caused periostin to lose its ability to interact with fibronectin, did not decrease the accumulation. Furthermore, targeted disruption of periostin in mice caused the non-fibrillar and ectopic deposition of fibronectin in the periodontal ligament. Thus, these results demonstrate a subcellular role of periostin in promotion of fibronectin secretion from the ER. [ABSTRACT FROM AUTHOR]

Nanobubbles exist at solid–liquidinterfaces between purewater and hydrophobic surfaces with very high stability, lasting incertain cases up to several days. Not only semispherical but alsoother shapes, such as micropancakes, are known to exist at such interfaces.However, doubt has been raised as to whether or not the nanobubblesare gas-phase entities. In this study, surface nanobubbles at a purewater–highly ordered pyrolytic graphite (HOPG) interface wereinvestigated by peak force quantitative nanomechanics (PF-QNM). Multipleisolated nanobubbles generated by the solvent-exchange method werepresent on the terraced areas, avoiding the steps of the HOPG surface.Adjacent nanobubbles coalesced and formed metastable nanobubbles.Coalescence was enhanced by the PF-QNM measurement. We determinedthat nanobubbles can exist for a long time because of nanoscale contactangle hysteresis at the water–HOPG interface. Moreover, thehydrophilic steps of HOPG were avoided during coalescence, providingevidence that the nanobubbles are truly gas phase. [ABSTRACT FROM AUTHOR]

Abstract: A novel one-pot synthesis of carbazole-1,4-quinone by consecutive Pd-catalyzed cyclocarbonylation, desilylation, and oxidation reactions is described. We propose a possible mechanism of the cyclocarbonylation reaction between 3-iodo-2-propenylindole and CO (1 atm) in the presence of a tributyl(vinyl)tin and Pd-catalyst and the resulting acylpalladium species was directly coupled with a terminal alkene to produce the carbazole-1,4-quinone. To our knowledge, this is the first example of this type of reaction. A new formal total synthesis of a carbazole-1,4-quinone alkaloid, murrayaquinone A was established using this reaction. [Copyright &y& Elsevier]

Abstract: A compositional gradient thin film of Fe/Si was fabricated by gravity-assisted pulsed laser ablation under a gravity field of 5.3×104 m/s2. Systematic experiments were conducted by varying the values of several parameters including the gravity, distance between the target and the substrate, and laser fluence. The atomic fraction of Fe was measured by scanning electron microscopy/energy dispersive X-ray spectroscopy. We found that the atomic fraction of Fe increases along the gravity direction, i.e., it exhibits an apparent spatial gradient. We also found the optimal laser fluence at which a thin film having the largest possible spatial compositional gradient is obtained. It is shown that the surface energy density on the substrate surface is the key parameter to control the compositional distribution. The relatively high laser fluence as well as the very narrow space between the target and the substrate are found to be essential to sputter the film material. A plausible model is presented to explain the experimental data. [Copyright &y& Elsevier]

Bacterial biofilm formation is an extremely widespread phenomenon involving the secretion of a protective exopolysaccharide matrix which helps the bacteria to attach to surfaces and to overcome a variety of stresses in different environments. This matrix may also include proteins, lipids, DNA and metal ions. Its composition depends on the bacterial species and growth conditions, but one of the most widely found components is polymeric β-1,6- N-acetyl-D-glucosamine (PGA). Several studies have suggested that PGA is an essential component of biofilm and it is produced by numerous bacteria, including Escherichia coli, Staphylococcus epidermis, Yersinia pestis, Bordetella spp. and Actinobacillus spp. In E. coli, PGA production and export are dependent on four genes that form a single operon, pgaABCD, which appears to have been transferred between various species. Biofilms themselves are recognized as environments in which such horizontal gene transfer may occur. The pga operon of E. coli, which is even found in innocuous laboratory strains, is highly homologous to that from the plague bacterium Yersinia pestis, and biofilm is believed to play an important role in the transmission of Yersinia. The crystal structure of the N-terminal domain of PgaB, which has deacetylase activity, is described and compared with models of other deacetylases. [ABSTRACT FROM AUTHOR]

This paper describes a decision model for an autonomous agent that provides an inhabitant with comfort based on information network technologies that connect home electric appliances with household equipment. The inhabitant enjoys the benefit of comfort, while he pays the cost for keeping that comfort. The autonomous agent should decide and control household equipment considering that cost from the inhabitant's viewpoint. Thus, we utilized a representation scheme called an 'influence diagram' that enabled us to model the decision-making process of the agent from the inhabitant's point of view. First, decision modeling using the influence diagram is presented via an example. The presented model consists of three information-processing modules: a module for estimating the situation of an inhabitant based on information from home networks, a module for evaluating comfort of the inhabitant, and a module for making decisions that maximize the utility of the inhabitant from both the viewpoints of comfort and the cost paid for that comfort. Next, an experiment for verifying whether the presented model is effective or not, and its results are described. Finally, our model of the agent is discussed in relation to social intelligence design by investigating the interactive processes between the agent and the inhabitant. [ABSTRACT FROM AUTHOR]

Background: Matricellular proteins, including periostin, are important for tissue regeneration. Methods and Findings: Presently we investigated the function of periostin in cutaneous wound healing by using periostindeficient (-/-) mice. Periostin mRNA was expressed in both the epidermis and hair follicles, and periostin protein was located at the basement membrane in the hair follicles together with fibronectin and laminin γ2. Periostin was associated with laminin γ2, and this association enhanced the proteolytic cleavage of the laminin γ2 long form to produce its short form. To address the role of periostin in wound healing, we employed a wound healing model using WT and periostin-/- mice and the scratch wound assay in vitro. We found that the wound closure was delayed in the periostin-/- mice coupled with a delay in re-epithelialization and with reduced proliferation of keratinocytes. Furthermore, keratinocyte proliferation was enhanced in periostin-overexpressing HaCaT cells along with up-regulation of phosphorylated NF-κB. Conclusion: These results indicate that periostin was essential for keratinocyte proliferation for re-epithelialization during cutaneous wound healing. [ABSTRACT FROM AUTHOR]

We carried out the thin film deposition of iron silicide by pulsed laser ablation (PLA) on a sapphire substrate, which was placed on a high-speed rotating titanium disk. The deposited thin film exhibited a continuous composition gradient. We investigated how the continuous composition gradient was attained, because the strength of the gravity field in our experiment was far below that in the experiment on bulk crystalline compounds. In the present study, we obtain the spatial distribution of several species in the PLA plume of FeSi by using an intensified charge-coupled device (ICCD) camera. We obtained the distribution of each species through high-speed imaging using narrow bandpass filters, whose wavelengths corresponded to the emission wavelengths of Fe, Fe, Si, Si, and neutral Fe. From the observed images, we could identify the particle species as well as determine the average velocity and the relative number density of each species. The Fe ions, Fe ions, and Fe atoms had quite different average velocities as a result of which they formed separate groups while moving toward the substrate. Species with the same valence value moves with the same velocity. We believe that the compositional gradient of FeSi attained under an appropriate gravity field may be explained by the movement of both the components driven by the acceleration field and the effect of selective etching. [ABSTRACT FROM AUTHOR]

compositionally graded thin film of FeSi was fabricated by a gravity-assisted pulsed laser ablation (GAPLA) system. By this method, a compositionally graded structure was successfully produced under a gravity field of 5400 G. We demonstrate that the atomic fraction of Fe, the heavier component of the thin film measured by scanning electron microscope/energy dispersive X-ray (SEM-EDX), showed increasing spatial distribution with the direction of gravity. We found that optimal laser fluence exists to give a thin film having the largest possible spatial compositional gradient. We found that surface energy density on the substrate surface is the key parameter to control the composition distribution. Furthermore, the ratio of Fe/Si of the film did not match that of the target. This result shows that the Si component is selectively etched during the film-forming process. Relatively high laser fluence as well as a very narrow space between the target and the substrate are essential to etch the film once it is deposited, in order to re-ionize and etch Si selectively while gravity accelerates both Fe and Si particles to the direction of gravity. We hypothesize that this process accounts for both the change in the stoichiometry and the formation of composition distribution. [ABSTRACT FROM AUTHOR]

Abstract: Deposition processes of ultrananocrystalline diamond/hydrogenated amorphous carbon composite (UNCD/a-C:H) films in a hydrogen atmosphere using a coaxial arc plasma gun were spectroscopically investigated with an intensified charge-coupled device (ICCD) camera equipped with narrow-bandpass filters. Strong emissions lasted for more than 100μs. From the emission time and deposition rate, a supersaturated condition should be strongly realized. This might contribute to the formation of UNCD crystallites. A UNCD crystallite size was estimated to be 2.3nm from an X-ray diffraction peak. The extremely small value implies that nuclei are repeatedly generated without the subsequent growth. A probable reason is as follows: since the number of carbon species caused using the arc plasma gun is so large as compared to that of hydrogen atoms, which generate from ambient hydrogen molecules by the collision with carbon species, the hydrogen atoms do not effectively contribute to the UNCD crystallite formation. This consideration does not contradict the fact that a coaxial arc plasma gun makes possible UNCD crystallite formation even in vacuum. [Copyright &y& Elsevier]

Extracellular matrix (ECM) underlies a complicated multicellular architecture that is subjected to significant forces from mechanical environment. Although various components of the ECM have been enumerated, mechanisms that evolve the sophisticated ECM architecture remain to be addressed. Here we show that periostin, a matricellular protein, promotes incorporation of tenascin-C into the ECM and organizes a meshwork architecture of the ECM. We found that both periostin null mice and tenascin-C null mice exhibited a similar phenotype, confined tibial periostitis, which possibly corresponds to medial tibial stress syndrome in human sports injuries. Periostin possessed adjacent domains that bind to tenascin-C and the other ECM protein: fibronectin and type I collagen, respectively. These adjacent domains functioned as a bridge between tenascm-C and the ECM, which increased deposition of tenascin-C on the ECM. The deposition of hexabrachions of tenascin-C may stabilize bifurcations of the ECM fibrils, which is integrated into the extracellular meshwork architecture. This study suggests a role for periostin in adaptation of the ECM architecture in the mechanical environment. [ABSTRACT FROM AUTHOR]

Optical emission spectroscopy was used to study pulsed laser ablation of graphite in a hydrogen atmosphere wherein ultrananocrystalline diamond (UNCD)/hydrogenated amorphous carbon (a-C:H) composite films were grown on heated substrates. Time-resolved photographs of a plume that expanded from a laser-irradiation spot toward a substrate were taken using a high-speed ICCD camera equipped with narrow-bandpass filters.While the emissions from C atoms and C2 dimers lasted above the laser-irradiation spot on the target, the emission from C+ ions lasted above the substrate surface for approximately 7 microseconds, although the emission lifetime of species is generally approximately 10 nanoseconds. This implies that C+ ions actively collided with each other above the substrate surface for such a long time. We believe that the keys to UNCD growth in PLD are the supply of highly energetic carbon species at a high density to the substrate and existence of atomic hydrogen during the growth. [ABSTRACT FROM AUTHOR]

A hydroxylamine oxidoreductase (HAO) was purified from anammox sludge in which an anammox bacterium, strain KSU-1, was dominant. The enzyme was a 118-kDa homodimer composed of a 53-kDa subunit. With phenazine methosulfate and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide as electron acceptors, the V max and K m for hydroxylamine were determined as 9.6±0.2 μmol/min·mg and 33±2 μM, while those for hydrazine were 0.54±0.0 μmol/min·mg and 25±2 μM, respectively. The HAO had a P468 chromophore. These enzymatic properties were different from those of the hydrazine-oxidizing enzyme (HZO), a multiheme protein abundantly produced by the KSU-1 strain, but were similar to those of the HAO purified from Candidatus Brocadia anammoxidans. The hao gene exists upstream of the hzoB gene, which codes for the HZO. The sequence deduced from the hao gene indicated eight c-type heme binding motifs and showed 87% identity with a polypeptide encoded by an open reading frame (kustc1061) in the genome of an anammox bacterium Candidatus Kuenenia stuttgartiensis. These suggested that the HAO is an indispensable enzyme and well conserved in anammox bacteria, similar to the HZO. This enzyme might therefore be a specific hydroxylamine oxidoreductase for anammox bacteria. [Copyright &y& Elsevier]

The article discusses the shift from wood to steel and the influence of war and peace in the development of all-steel construction of railcars in Japan from the 1880s to the 1950s. Wooden construction of railcars dominated Japan before the 1920s since wood was cheap and readily available. But safety concerns led to half-wood, half-steel railcars. The demands for steel in World War II meant less steel for railcars despite the safety issues. By war's end, only 47% of coaches were functional.

Abstract: Zinc 31-hydroxy-131-oxo-chlorins possessing various perfluorooctyl groups in the 17-propionate were prepared by modifying naturally occurring chlorophyll-a. The synthetic compound having four perfluorooctyl groups readily self-assembled to form large J-aggregates, which were dissolved in fluorous phases with more ordered supramolecular structures than in a hydrocarbon solvent. [Copyright &y& Elsevier]

A multiheme protein having hydrazine-oxidizing activity was purified from enriched culture from a reactor in which an anammox bacterium, strain KSU-1, was dominant. The enzyme has oxidizing activity toward hydrazine but not hydroxylamine and is a 130-kDa homodimer composed of a 62-kDa polypeptide containing eight hemes. It was therefore named hydrazine-oxidizing enzyme (HZO). With cytochrome c as an electron acceptor, the Vmax and Km for hydrazine are 6.2 ± 0.3 μmol/min · mg and 5.5 ± 0.6 μM, respectively. Hydrazine (25 μM) induced an increase in the proportion of reduced form in the spectrum, whereas hydroxylamine (500 μM) did not. Two genes coding for HZO, hzoA and hzoB, were identified within the metagenomic DNA from the culture. The genes encode the same amino acid sequence except for two residues. The sequences deduced from these genes showed low-level identities (<30%) to those of all of the hydroxylamine oxidoreductases reported but are highly homologous to two hao genes found by sequencing the genome of ‘Candidatus Kuenenia stuttgartiensis’ (88% and 89% identities). The purified enzyme might therefore be a novel hydrazine-oxidizing enzyme having a critical role in anaerobic ammonium oxidation. [ABSTRACT FROM AUTHOR]

An amino-terminal methionine corresponding to a recombinant AUG initiation codon sometimes affects the functions of proteins. To test the performance of translation mediated by a dicistroviral internal ribosome entry site (IRES), which initiates protein synthesis with elongator tRNAs, we optimized the conditions for cell-free translation. Although the IRES is 188 nucleotides long, a further 50 nucleotides of the upstream sequence stabilized translation efficiency. Optimal ion concentrations were affected by the sequences of the constructs. In a wheat-germ system, IRES-mediated translation produced 78 µg/ml of firefly luciferase from the AUG-deleted sequence, suggesting that dicistroviral IRESs will be able to yield polypeptides with a specific N-terminal amino acid other than methionine. [ABSTRACT FROM PUBLISHER]

The positive-stranded RNA genome of Plautia stali intestine virus (PSIV) has an internal ribosome entry site (IRES) in an intergenic region (IGR). The IGR-IRES of PSIV initiates translation of the capsid protein by using CAA, the codon for glutamine. It was previously reported (J. Sasaki and N. Nakashima, J. Virol. 73:1219-1226, 1999) that IGR-IRES extended by several nucleotides into the capsid open reading frame (ORF). Despite the fact that the secondary structure model of the IGR-IRES is highly conserved, we were unable to find structural similarities in the 5' region of the capsid ORFs in related viruses. Therefore, we reevaluated the role of the capsid ORE in IGR-IRES-mediated translation in PSIV. Mutation of the CAA codon with various triplets did not inhibit IGR-IRES-mediated translation. N-terminal amino acid analyses of mutated products showed that the IGR-IRES could initiate translation by using various elongator tRNAs. By replacement of the capsid ORF with exogenous coding sequences having AUG deleted, translation products were produced in most cases, but capsid-exogenous fusion proteins were produced more efficiently than were the translation products. These data indicate that the 5' part of the capsid ORF is not an absolute requirement for the IGR-IRES-mediated translation. RNA structure probing analyses showed that the 5' part of the capsid ORF was a single strand, while that of exogenous reading frames was structured. Exogenous sequences also caused structural distortion in the 3' part of the IGR-IRES. We hypothesize that the single-stranded capsid ORE helps to form the tertiary structure of the IGR-IRES and facilitates precise positioning of ribosomes. [ABSTRACT FROM AUTHOR]

The behavior of a granite subject to a triaxial compression test ranging from the prefailure stage to the postfailure stage was studied using a fluorescent technique from the geological point of view. Microscopic observations of the specimens at different stages showed changes in the failure process. The start of formation of new microcracks paralleled the compression direction through their propagation until the onset of faulting and ended with the failure of shear zones after the strength failure point. Pores chiefly identified in the feldspar increased in length and width in the early stages, but not in number. It seems that the effect of pore spaces did not have any effect of failure. The microcracks generated on angular edges of quartz or feldspar grains and around biotite grains with increasing compression force. The phenomenon appearing on the crystal boundaries among biotite and quartz or feldspar agrees with the result calculated based on the theory on stress fields with ellipsoidal inhomogeneity suggested by Eshelby. [Copyright &y& Elsevier]

Diamond thin films were grown on diamond (1 0 0) substrates in oxygen atmospheres by pulsed laser deposition (PLD) using a graphite target. In the optimum oxygen pressure of 5×10–2 Torr, the sp2 bonding fractions can be etched away preferentially and the sp3 bonding fractions remain predominantly on the substrate. At substrate temperatures lower than 400 °C, amorphous carbon generates. At higher than 400 °C, diamond crystallites begin to generate in the amorphous carbon. At the suitable substrate temperatures between 550 and 650 °C, single-phase diamond films consisting of diamond crystal with diameters of 1–5 μm could be grown. Based on the results, the growth process of diamond thin film by PLD is considered. [Copyright &y& Elsevier]

Diamond thin films were grown on diamond (100) substrates in oxygen atmospheres by pulsed laser deposition (PLD) using an ArF excimer laser. The suitable oxygen atmosphere of 5×10[sup -2] Torr can etch the sp² bonding fractions preferentially. At substrate temperatures between 550°C and 650°C, single-phase diamond films consisting of diamond crystal with diameters of 1 - 5 µm could be grown. The results demonstrated that the diamond thin films can be grown homoepitaxially using PLD by controlling the deposition parameters, such as the oxygen pressure and the substrate temperature. [ABSTRACT FROM AUTHOR]

Abstract: A tandem ring-closing metathesis and dehydrogenation reaction under oxygen atmosphere was newly developed to the synthesis of carbazole-1,4-quinones. This new tandem reaction was applied to the synthesis of murrayaquinone A in four steps. [Copyright &y& Elsevier]

In this study, the total syntheses of 1,3,4-trisubstituted carbazole alkaloid clausamine E was accomplished via an eight-step sequence using construction of the 1,4-dioxygenated carbazole framework based on the cyclocarbonylation between 3-iodo-2-(prop-2-enyl)indole and CO (1 atm) in the presence of tributyl(vinyl)tin and a Pd catalyst. Image 1 • The total synthesis of clausamine E has been accomplished via an eight-step sequence. • Synthesis of 1,4-dioxygenated carbazoles by Pd-catalyzed cyclocarbonylation. • This method could be used as a versatile method to synthesize substituted carbazoles. [ABSTRACT FROM AUTHOR]

• The enantioselective total synthesis of (+)-asiaticumine A has been accomplished. • The construction of phenanthridine framework by MW-assisted electrocyclization. • The synthesis of 1,2-dihydroxyethyl moiety by Sharpless asymmetric dihydroxylation. • Its absolute configuration was determined to be S by Mosher's method. In this study, the first asymmetric enantioselective total syntheses of (+)-asiaticumine A (2) and its enantiomer were accomplished through a seven-step sequence using the bond formation between the C4a and N5 positions of the phenanthridine framework based on the microwave-assisted electrocyclization of cyclohexenylbenzaldoxime methyl ether as an aza 6π-hexatriene system followed by the Sharpless asymmetric dihydroxylation as the key step. In addition, the absolute configuration of natural (+)- 2 was determined to be S by Mosher's method. [ABSTRACT FROM AUTHOR]

Hepatitis E is a global public health problem. Ribavirin (RBV) and pegylated interferon alpha are currently administered to cure hepatitis E. Recently, in combination with RBV, sofosbuvir (SOF), an anti-hepatitis C virus nucleotide analog, is also given to patients with chronic hepatitis E. However, this combinatorial therapy sometimes fails to achieve a sustained virological response. In this study, we used 27 antiviral compounds, including 15 nucleos(t)ide analogs, for in vitro screening against a genotype 3 HEV strain containing a Gaussia luciferase reporter. RBV, SOF, 2′- C -methyladenosine, 2′- C -methylcytidine (2CMC), 2′- C -methylguanosine (2CMG), and two 4′-azido nucleoside analogs (R-1479 and RO-9187) suppressed replication of the reporter genome, while only RBV, SOF, 2CMC and 2CMG inhibited the growth of genotype 3 HEV in cultured cells. Although 2CMG and RBV (2CMG/RBV) exhibited a synergistic effect while SOF/RBV and 2CMC/RBV showed antagonistic effects on the reporter assay, these three nucleos(t)ide analogs acted additively with RBV in inhibiting HEV growth in cultured cells. Furthermore, SOF and 2CMG, with four interferons (IFN-α2b, IFN-λ1, IFN-λ2 and IFN-λ3), inhibited HEV growth efficiently and cleared HEV in cultured cells. These results suggest that, in combination with RBV or interferons, SOF and 2CMG would be promising bases for developing anti-HEV nucleos(t)ide analogs. • We tested inhibitory effects of 27 compounds on replication of an HEV reporter genome and growth of HEV in cultured cells. • 2′- C -methylguanosine (2CMG), 2′- C -methylcytidine (2CMC) and sofosbuvir (SOF) robustly suppressed HEV growth in cultured cells. • Ribavirin (RBV) with 2CMG suppressed replication of the reporter genome synergistically but antagonistically with 2CMC or SOF. • RBV with SOF, 2CMG, or 2CMC inhibited HEV growth additively and cleared HEV in cultured cells. • SOF or 2CMG with interferon-α2b, -λ1, -λ2, or -λ3 inhibited HEV growth additively and cleared HEV in cultured cells. [ABSTRACT FROM AUTHOR]

3-Iodo-2-propenylindoles (I) are easily prepared from corresponding indole-2-carbaldehydes and vinyl Grignard reagents. [ABSTRACT FROM AUTHOR]

Liquid cell electron microscopy is a useful technique for the observation of chemical, biological, and mechanical processes in liquids at nanometer-scale resolution. This study investigated the generation and growth of nanobubbles using the Fresnel fringe method, which enabled us to determine the location of bubble interface; the nanobubbles were induced in the 600-nm-thick water sample in the cell, by the electron beam. Nucleation occurred first at the solid–liquid interface in the upstream side of electron beam, and this was followed by second-group nucleation at the downstream-side interface; all of the stable nucleations occurred on the solid surfaces. The size of the nucleated bubbles at the moment they became visible depended on the magnification used in the electron microscope, and a higher-energy density in the electron beam induced larger bubbles. The underlying mechanism was also considered in this study. [ABSTRACT FROM AUTHOR]

The effect of the high order structure of an isotactic polypropylene (PP) composite on the resistivity of composites containing magnetically aligned Ni particles was studied. Only a small amount of particles needed to be added for the composite material to become conducting after heating while in a magnetic field. The Ni columns formed on applying the field were distorted by the formation of large PP spherulites. Changes to the crystallization process due to the addition of a nucleating agent gave rise to changes in the columnar structure, resulting in large changes in the resistivity of the composite material. Controlling the high order structure of the polymer matrix including its morphology is very important in order to be able to control the magnetically aligned Ni structure. [ABSTRACT FROM AUTHOR]

This study is the first to demonstrate the startup of a pilot-scale single-stage nitrogen removal using anammox and partial nitritation (SNAP) reactor utilizing marine anammox bacteria. A complete mixing type reactor, continuously fed with waste brine obtained from a natural gas plant (salinity 3%, NH 4 +-N 130–180 mg/L) and having an effective volume of 2 m3, achieved stable operation at temperatures of 20–30°C with a maximum nitrogen removal rate of 1.43 kg-N/m3/day. During the startup process, along with a small amount of seed sludge, granular sludge was additionally inoculated as a biomass carrier for the enrichment of ammonia oxidizing bacteria (AOB), followed by the enrichment of anammox bacteria. A mesh screen equipped at the outlet of the reactor facilitated the successful sludge retention in the reactor. Analysis of bacterial community composition indicated that Candidatus Scalindua was successfully enriched in the pilot SNAP reactor. These methods for stable sludge retention in the reactor greatly contributed to the startup of the first pilot-scale SNAP reactor using marine anammox bacteria. • Pilot scale SNAP reactor to treat waste brine was successfully started up for the first time. • Marine anammox bacteria affiliated to Candidatus Scalindua was enriched. • AOB granule formed precedingly provided favorable growth condition for anammox bacteria and worked as biomass carrier. • Application of mesh-screen contributed to the retention of SNAP sludge in the reactor. [ABSTRACT FROM AUTHOR]

The pulse laser ablation of a liquid surface in air when induced by laser irradiation through a liquid medium has been experimentally investigated. A supersonic liquid jet is observed at the liquid-air interface. The liquid surface layer is driven by a plasma plume that is produced by laser ablation at the layer, resulting in a liquid jet. This phenomenon occurs only when an Nd:YAG laser pulse (wavelength: 1064 nm) is focused from the liquid onto air at a low fluence of 20 J/cm. In this case, as Fresnel's law shows, the incident and reflected electric fields near the liquid surface layer are superposed constructively. In contrast, when the incident laser is focused from air onto the liquid, a liquid jet is produced only at an extremely high fluence, several times larger than that in the former case. The similarities and differences in the liquid jets and atomization processes are studied for several liquid samples, including water, ethanol, and vacuum oil. The laser ablation of the liquid surface is found to depend on the incident laser energy and laser fluence. A pulse laser light source and high-resolution film are required to observe the detailed structure of a liquid jet. [ABSTRACT FROM AUTHOR]

Background: Matricellular proteins, including periostin, modulate cell-matrix interactions and cell functions by acting outside of cells. Methods and Findings: In this study, however, we reported that periostin physically associates with the Notch1 precursor at its EGF repeats in the inside of cells. Moreover, by using the periodontal ligament of molar from periostin-deficient adult mice (Pn-/- molar PDL), which is a constitutively mechanically stressed tissue, we found that periostin maintained the site-1 cleaved 120-kDa transmembrane domain of Notch1 (N1™) level without regulating Notch1 mRNA expression. N1™ maintenance in vitro was also observed under such a stress condition as heat and H2O2 treatment in periostin overexpressed cells. Furthermore, we found that the expression of a downstream effector of Notch signaling, Bcl-xL was decreased in the Pn-/- molar PDL, and in the molar movement, cell death was enhanced in the pressure side of Pn-/- molar PDL. Conclusion: These results suggest the possibility that periostin inhibits cell death through up-regulation of Bcl-xL expression by maintaining the Notch1 protein level under the stress condition, which is caused by its physical association with the Notch1 precursor. [ABSTRACT FROM AUTHOR]

We studied a new pulse laser ablation phenomenon on a liquid surface layer, which is caused by the difference between the refractive indices of the two materials involved. The present study was motivated by our previous study, which showed that laser ablation can occur at the interface between a transparent material and a gas or liquid medium when the laser pulse is focused through the transparent material. In this case, the ablation threshold fluence is reduced remarkably. In the present study, experiments were conducted in water and air in order to confirm this phenomenon for a combination of two fluid media with different refractive indices. This phenomenon was observed in detail by pulse laser shadowgraphy. A high-resolution film was used to record the phenomenon with a Nd:YAG pulse laser with 10-ns duration as a light source. The laser ablation phenomenon on the liquid surface layer caused by a focused Nd:YAG laser pulse with 1064-nm wavelength was found to be followed by the splashing of the liquid surface, inducing a liquid jet with many ligaments. The liquid jet extension velocity was around 1000 m/s in a typical case. The liquid jet decelerated drastically due to rapid atomization at the tips of the ligaments. The liquid jet phenomenon was found to depend on the pulse laser parameters such as the laser fluence on the liquid surface, laser energy, and laser beam pattern. The threshold laser fluence for the generation of a liquid jet was 20 J/cm2. By increasing the incident laser energy with a fixed laser fluence, the laser focused area increased, which eventually led to an increase in the size of the plasma column. The larger the laser energy, the larger the jet size and the longer the temporal behavior. The laser beam pattern was found to have significant effects on the liquid jet’s velocity, shape, and history. [ABSTRACT FROM AUTHOR]

Abstract: This study investigated partial nitrification treatment of methane fermentation digester liquor effluent from magnesium ammonium phosphate precipitation process in a swim-bed reactor. The reactor was operated at a temperature of 35 °C and pH between 7.5 and 7.8. Partial nitrification was achieved at the onset of the experiments even though conventional activated sludge was used as seed sludge. The maximum nitrite production rate was 1.0 kg NO2-N/m3/d at a nitrogen loading rate of 2.0 kg-N/m3/d. The average effluent NO2-N/NH4-N ratio and the effluent NO3-N concentration were 1.04±0.34 and 5.7 mg/l, respectively, during the stable experiment periods. After 150 days of operation, the sludge volume index value decreased to 15 ml/g and the mean particle size of suspended sludge increased by approximately 3 times from 80 to 260 μm. Comparison of mineral analysis between the seed sludge and the partial nitrification sludge demonstrated that the mineral content of the latter increased approximately three-fold in comparison to that of the former. High Ca concentration was considered to be closely related to dense floc formation and superior settleability of the sludge. Both DGGE and DNA clone analysis verified that there were significant microbiological differences between the samples taken at different time periods. Nitrosomonas was confirmed to be the predominant species after stable partial nitrification performance was obtained. The overall results of this study validated our previous results that swim-bed reactor technology could be successfully used as a pre-treatment technology for anammox treatment. [Copyright &y& Elsevier]

Abstract: Effect of high salt concentration on the anammox treatment was investigated to establish an acclimation strategy under high salt concentration conditions. An anammox fixed-bed reactor with non-woven biomass carrier was used and the salt concentration was gradually increased from 2.5 g L−1 to 33 g L−1. The anammox reactor demonstrated stable nitrogen removal rate (NRR) of 1.7 kg-N m−3 d−1 for 65 days under a salt concentration of 30 g L−1. However, the NRR sharply declined at a salt concentration of greater than 30 g L−1. The bacterial community was examined by 16S rRNA gene analysis and DGGE after the acclimation of the anammox sludge to high salt conditions. Although the salt concentration was almost sea level, the freshwater anammox bacteria, KU2, were detected. In addition, the unidentified bacteria which perhaps belong to candidate division OP10 and Lysobacter sp. were found to coexist with anammox bacteria at a salt concentration of 30 g L−1. [Copyright &y& Elsevier]

Anisotropy of heat conduction in multi-walled carbon nanotubes (MWNTs) is investigated by measuring heat flows in a pristine MWNT and in a MWNT with defects. The in- and out-of-shell thermal conductivities of each MWNT graphite shell are determined, and differences of more than four orders of magnitude are obtained because of the inter-shell gaps. This enhanced anisotropy reduces the conductance by 74% compared with that of the pristine MWNT because of the presence of outer shell defects, which comprise only 2.8% volume ratio. Furthermore, the anisotropy-assisted length dependence of thermal conductivity is demonstrated, even though there is no ballistic phonon transport. [ABSTRACT FROM AUTHOR]

Abstract: Endotoxemia has been reported as a mechanism for the fatal sequela after heatstroke. Subsequent disseminated fungal infection in a heatstroke patient has been also described. Beta-d-glucan, a constituent of the fungal cell wall, is an early diagnostic measure for fungal infection. In a heatstroke case, we examined for the first time levels of serum beta-d-glucan and endotoxin. A 34-year-old man with a body temperature of 43.5°C was admitted in a state of shock. Prior to the development of disseminated intravascular coagulopathy (DIC), a remarkable elevation of serum beta-d-glucan level to 116pg/mL (normal level<6.0pg/mL) was revealed on the first day of admission. However, serum endotoxin was not detected when using a method that excluded beta-d-glucan contamination from endotoxin measurement (normal level<1.0pg/mL). This change of beta-d-glucan level was accompanied by a depressed neutrophil function, especially in phagocytosis of 34% (normal range 70–90%) but not in bacterocidal function (81% versus a normal range of 70–100%). After intensive care including continuous hemodiafiltration, the patient regained consciousness but remained ataxic due to cerebellar infarction, which might have resulted from DIC, and subsequent bilateral fungal oculitis were revealed 45 days after admission. This case report demonstrates the elevation of serum beta-d-glucan but normal endotoxin levels after heatstroke, which may prompt further study to re-examine the serum levels of endotoxin in such catastrophic insults. [Copyright &y& Elsevier]

Abstract Neutrophils are recruited to infection sites and kill bacteria by phagocytosis and reactive oxygen species (ROS) production. It has been reported that vacuoles are present in neutrophils that produce ROS and are present in large numbers in blood smears of patients with bacterial infections. The leukocyte differentiation function on the Sysmex automated hematology analyzer classifies leukocytes by flow cytometry. Particularly, side-scattered light is known to reflect the quantity of organelles. This study investigated the possibility of detecting vacuoles or invagination of cell membrane in neutrophils producing ROS using a hematology analyzer. Whole blood and polymorphonuclear (PMN) cell fractions were activated with phorbol myristate acetate (PMA) or formylmethionylleucylphenylalanine (fMLP) and analyzed using the Sysmex XE-2100 automated hematology analyzer. PMN fractions were morphologically analyzed with a confocal laser scanning microscope (CLSM), electron microscope (EM), and general-purpose conventional flow cytometer. In the white blood cell differentiation scattergram obtained in this analysis, a new cluster separate from the original neutrophil cluster appeared in the eosinophil area in an area of higher side-scattering (SSC) intensity. Flow cytometry analysis of the PMN fractions revealed that the cells in this new cluster were CD16b- and APF-positive, indicating that the cells were activated neutrophils that produced ROS. CLSM and EM findings revealed that ROS production occurred in the cytoplasm and that the activated neutrophils contained some vacuole-like structures of vacuoles or invagination of cell membrane. Vacuole-like S structures were found within the cytoplasm of neutrophils producing ROS. These neutrophils were detected as an independent cluster in the eosinophil area with higher SSC intensity than that shown by neutrophils in the traditional cluster on the white blood cell differentiation scattergram, likely because the vacuole-like structures increased the SSC intensity. Highlights • Neutrophils produce vacuoles in their cytoplasm during ROS production. • Vacuoles increase the side-scattering light intensity of neutrophils in flow cytometry. • Neutrophils producing ROS are detectable using a hematology analyzer. [ABSTRACT FROM AUTHOR]