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The aims of this study were (i) to evaluate the relationship between teicoplanin (TEIC) dosage and subsequent trough concentration, (ii) to investigate factors that affect TEIC serum concentration fluctuations and (iii) to examine the association between serum concentration of TEIC and adverse reactions in neonates. A total of 37 eligible neonates (<28 days of age) treated with TEIC from 2008–2012 were included in this study. The median trough concentration in the loading dose regimen of >12–16 mg/kg on Day 1, followed by >6–8 mg/kg every 24 h (q24 h) was 19.6 μg/mL on Day 3 or 4, and the median trough concentration in the maintenance dose regimen of >6–8 mg/kg q24 h was 18.5 μg/mL at steady-state. There were significant correlations between serum creatinine and concentration/dose ( C / D ) ratio ( r = 0.475, P = 0.019), body weight and C / D ratio ( r = −0.425, P = 0.038) and corrected gestational age and C / D ratio ( r = −0.482, P = 0.017) after administering the loading dose. The incidence of hepatic dysfunction, renal impairment and thrombocytopenia was 14.8%, 20.0% and 14.8%, respectively. There was no significant difference in the incidence of adverse reactions between the trough concentration <20 μg/mL and ≥20 μg/mL groups. These data suggest that the recommended TEIC dosage for neonates is appropriate to achieve and maintain a trough concentration range of 15–30 μg/mL, and it is possible to set the target trough concentration at ≥20 μg/mL for deep-seated infections such as endocarditis, bone and joint infections, and osteomyelitis. [ABSTRACT FROM AUTHOR]

A new length detection-micro fluidic device was developed using a sodium sulfite/hydrogen peroxide autocatalytic reaction system as a model reaction, and sub-ppm levels of horse radish peroxidase were determined with this device. Sodium sulfite solution containing bromo thymol blue as an indicator and hydrogen peroxide solution were pumped into a T-shaped mixer with the help of a microliter syringe pump and then mixed. The blue solution had changed to yellow beyond the midpoint of the fine pathway (micro channel). Furthermore, when horse radish peroxidase (POx) was pumped, a part of the blue solution in the micro channel (blue band) was shortened. Therefore, it was possible to determine the POx concentration by via the length of the blue band. The relationship between the blue band length ( y, mm) and the common logarithm of the POx concentration ( x, M) gave a straight line in the concentration range of 0.05–1 ppm. The equation for the straight line was as follows: y = −3.78 log( x) + 16.4. The correlation coefficient was γ = 0.995, the relative standard deviation was 5.7% ( n = 10), and the detection limits of the POx concentration was 0.029 ppm. [ABSTRACT FROM AUTHOR]

A flow analytical system using the sodium sulfite/hydrogen peroxide autocatalytic reaction system was developed. A sulfite solution containing a pH indicator and bromo thymol blue (BTB), and a hydrogen peroxide solution were pumped by a mechanical system, and then mixed while flowing. The blue‐colored solution changed to yellow in the mixing coil. Furthermore, when horseradish peroxidase (HRP) was mixed with them, the length of the blue‐colored band decreased. The relationship between the blue band length and logarithm value of the HRP concentration was linear in the concentration range of 1 to 50 ppm. [ABSTRACT FROM AUTHOR]

A powerful preconcentration method for nonylphenol (NP) has been developed for liquid-chromatography by combining the use of cellulose cotton (solid-phase extraction) with homogeneous liquid-liquid extraction. A 100 ml of sample solution was preconcentrated using cotton, and the eluate obtained (acetonitrile; 5 ml) was further preconcentrated to 50 µl within 10 min using a homogeneous liquid-liquid extraction method (volume ratio, 2,000-fold; 100 ml? 50 µl). The sample concentration increases from preconcentration was 1,599-fold, and NP was extracted into the sedimented phase at 80%. The proposed method was applied to high performance liquid chromatography with fluorescence detection (FL/HPLC); the lowest determination limit obtained was 1.0×10-9 mol l-1. [ABSTRACT FROM AUTHOR]

Hepatotoxicity is the major complaint during therapy with lipid-lowering agents such as statins, although the cellular mechanisms underlying the statin-induced liver injury are not fully understood. Using cultured human hepatocytes, we investigated the effects of lipophilic as well as hydrophilic statins on the cell viability. Lipophilic statins, including simvastatin, lovastatin, cerivastatin, fluvastatin and atorvastatin, reduced the viability of hepatocytes as assessed by the mitochondrial enzyme activity to reduce WST-8, however, a hydrophilic pravastatin did not cause cell injury. The simvastatin-induced loss of cell viability was attenuated by mevalonate or geranylgeranyl pyrophosphate. Simvastatin-induced DNA fragmentation and increased the number of cells stained with annexin V and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling, both of which were reversed by caspase inhibitors such as zDEVD-fmk, zLEHD-fmk and zIETD-fmk. Consistent with these data, the activities of caspase-3, caspase-9 and caspase-8 were elevated by simvastatin. Simvastatin reduced the protein content and mRNA expression for bcl-2 without affecting bax mRNA expression. On the other hand, both lipophilic and hydrophilic statins significantly reduced the content of endogenous cholesterol. These findings suggest that lipophilic statins cause an apoptotic injury in human hepatocytes by stimulating caspase-3 subsequent to the activation of caspase-9 and caspase-8, in which the inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase may be involved. [Copyright &y& Elsevier]

Studies the regulated initiator function of protein DnaA. Methodology; How a beta subunit of Pol lll inactivates DnaA; Details on the interaction of the initiator and replicase.

Abstract: A novel direct polymer-transfer lithography (DPTL) technique is proposed for fabricating fine patterns having feature sizes ranging from ten to several tens of micrometers with extremely high throughput. By means of this technique, a homemade fluorine-containing polymer “ink”, which has good water repellency, was imprinted directly onto a Cu/polyimide sheet by using an elastomeric polydimethylsiloxane (PDMS) stamp; imprinting was followed by wet etching of the Cu layer, with the transferred polymer patterns serving as an etch mask. Under the optimized imprinting conditions, Cu lead patterns with a minimum line width of approximately 10μm were successfully fabricated with high accuracy and good reproducibility. The DPTL technique will be very useful for manufacturing flexible printed circuit boards (FPCs). [Copyright &y& Elsevier]

Abstract: Trace amounts of nickel(II) can function as a trigger (=reaction initiator) in an autocatalytic reaction with the sodium sulfite/hydrogen peroxide system. Based on this finding, sub-μgL−1 levels of nickel(II) were determined by a time measurement using the autocatalytic reaction. The detection range using the above method was 10−9–10−5 M, the detection limit (3σ) was 8.1×10−10 M (0.047μgL−1), and the relative standard deviation was 2.66% at nickel(II) concentration of 10−7 M (n =7). This method was applied to length detection-flow injection analysis. The detection range for the flow injection analysis was 2×10−9–2×10−3 M. The detection limit (3σ) was 1.4×10−9 M (0.082μgL−1), and the relative standard deviation was 1.86 at initial nickel(II) concentration of 10−6 M (n =7). [Copyright &y& Elsevier]

In Escherichia coli, the ATP-DnaA protein initiates chromosomal replication. After the DNA polymerase III holoenzyme is loaded on to DNA, DnaA-bound ATP is hydrolysed in a manner depending on Hda protein and the DNA-loaded form of the DNA polymerase III sliding clamp subunit, which yields ADP-DnaA, an inactivated form for initiation. This regulatory DnaA-inactivation represses extra initiation events. In this study, in vitro replication intermediates and structured DNA mimicking replicational intermediates were first used to identify structural prerequisites in the process of DnaA-ATP hydrolysis. Unlike duplex DNA loaded with sliding clamps, primer RNA-DNA heteroduplexes loaded with clamps were not associated with DnaA-ATP hydrolysis, and duplex DNA provided in trans did not rescue this defect. At least 40-bp duplex DNA is competent for the DnaA-ATP hydrolysis when a single clamp was loaded. The DnaA-ATP hydrolysis was inhibited when ATP-DnaA was tightly bound to a DnaA box-bearing oligonucleotide. These results imply that the DnaA-ATP hydrolysis involves the direct interaction of ATP-DnaA with duplex DNA flanking the sliding clamp. Furthermore, Hda protein formed a stable complex with the sliding clamp. Based on these, we suggest a mechanical basis in the DnaA-inactivation that ATP-DnaA interacts with the Hda-clamp complex with the aid of DNA binding. [ABSTRACT FROM AUTHOR]

Background: We previously reported that the apoptotic injury in a porcine renal tubular cell line LLC-PK1 cells induced by radiographic contrast media is attenuated by dibutyl cyclic adenosine monophosphate (cAMP) in a manner dependent on protein kinase A (PKA). The present study was designed to determine whether the elevation of endogenous cAMP with beraprost sodium, a prostacyclin analog, reduces the contrast material-induced renal tubular injury.Methods: The cell injury was induced by the exposure to ioversol for 30 minutes followed by further incubation for 24 hours in the absence of the contrast medium, and assessed by propidium iodide uptake and WST-8 assay. Apoptosis was determined by annexin V stain and DNA electrophoresis. Caspase activity was assessed by the enzymatic degradation of specific substrate peptides. Bax and bcl-2 mRNA expression were determined by reverse transcription-polymerase chain reaction (RT-PCR). The phosphorylation of cAMP-responsive element binding protein (CREB) was measured by an immunofluorescent method.Results: Beraprost sodium (10 to 1000 nmol/L) attenuated concentration dependently the ioversol-induced decrease in cell viability, in which the protective effect of beraprost sodium was dependent on the elevation of cellular cAMP content. The phosphorylation of CREB was enhanced by beraprost sodium in PKA-dependent manner. In addition, beraprost sodium reversed the ioversol-induced increase in bax mRNA with a concomitant decrease in bcl-2 mRNA and subsequent activation of caspase-3 and -9, thereby resulting in the inhibition of the nuclear damage.Conclusion: Beraprost sodium reversed the contrast media-induced renal tubular cells in culture by activating cAMP/protein kinase A-dependent phosphorylation of CREB and subsequent enhancement of bcl-2 expression. [ABSTRACT FROM AUTHOR]

A prostacyclin analog beraprost sodium attenuates radiocontrast media-induced LLC-PK1 cells injury. Background. We previously reported that the apoptotic injury in a porcine renal tubular cell line LLC-PK1 cells induced by radiographic contrast media is attenuated by dibutyl cyclic adenosine monophosphate (cAMP) in a manner dependent on protein kinase A (PKA). The present study was designed to determine whether the elevation of endogenous cAMP with beraprost sodium, a prostacyclin analog, reduces the contrast material-induced renal tubular injury. Methods. The cell injury was induced by the exposure to ioversol for 30 minutes followed by further incubation for 24 hours in the absence of the contrast medium, and assessed by propidium iodide uptake and WST-8 assay. Apoptosis was determined by annexin V stain and DNA electrophoresis. Caspase activity was assessed by the enzymatic degradation of specific substrate peptides. Bax and bcl-2 mRNA expression were determined by reverse transcription-polymerase chain reaction (RT-PCR). The phosphorylation of cAMP-responsive element binding protein (CREB) was measured by an immunofluorescent method. Results. Beraprost sodium (10 to 1000 nmol/L) attenuated concentration dependently the ioversol-induced decrease in cell viability, in which the protective effect of beraprost sodium was dependent on the elevation of cellular cAMP content. The phosphorylation of CREB was enhanced by beraprost sodium in PKA-dependent manner. In addition, beraprost sodium reversed the ioversol-induced increase in bax mRNA with a concomitant decrease in bcl-2 mRNA and subsequent activation of caspase-3 and -9, thereby resulting in the inhibition of the nuclear damage. Conclusion. Beraprost sodium reversed the contrast media-induced renal tubular cells in culture by activating cAMP/protein kinase A–dependent phosphorylation of CREB and subsequent enhancement of bcl-2 expression. [ABSTRACT FROM AUTHOR]

Acute renal failure is a dose-limiting factor during cisplatin chemotherapy. We have previously shown in rats that the hydroxyl radical scavenger edaravone reverses cisplatin-induced in vivo renal damage. In the present study, the role of poly(ADP-ribose) polymerase (PARP) in cisplatin nephrotoxicity was investigated in porcine tubular cells LLC-PK1. Cell injury was elicited by transient exposure to 500 μM cisplatin for 1 h or continuous exposure to 30 μM cisplatin for 24 h. Various hydroxyl radical scavengers reversed cell damage in a transient but not permanent model. The cell injury seemed to be necrosis and apoptosis in transient and permanent models, respectively, as assessed by TUNEL method and Annexin V stain. PARP inhibitors such as 3-aminobenzamide and benzamide inhibited cell damage in transient but not permanent model. PARP-dependent cell injury was also observed after transient exposure to hydroxyl radical-generating solution. We demonstrated for the first time the activation of PARP in renal tubular cells by transient cisplatin exposure, as determined by immunofluorescent stain with anti-poly(ADP-ribose) antibody. Moreover, ATP was depleted by transient exposure to cisplatin or hydroxyl radical, both of which were reversed by PARP inhibitors. These findings suggest that hydroxyl radical generation followed by PARP activation contributes to the necrotic cell injury caused by a transient exposure to cisplatin. [Copyright &y& Elsevier]

Regioselective cobalt‐catalyzed [2+2+2] cycloaddition using fluorine‐containing diynes with nitriles was described. Cycloaddition of fluorinated diynes with nitriles under the influence of CoCl2(phen), zinc bromide, and zinc dust in dichloroethane at 80 °C for 3 h took place smoothly, exclusively affording the corresponding α‐fluoroalkylated pyridines in excellent yields. In addition, dinitriles as substrate were also found to be suitable for this reaction, giving the corresponding fluoroalkylated bipyridine derivatives in excellent yields. [ABSTRACT FROM AUTHOR]

Radioactive spent solvent waste containing U and Pu is generated from reprocessing process of spent nuclear fuel. The nuclear materials removal is important for safety storage or disposal. Imino diacetic acid (IDA) type chelating resin is promising adsorbent, and its characterization is performed by Particle Induced X-ray Emission (PIXE) and Extended X-ray Absorption Fine Structure (EXAFS) analyses on Zr in order to evaluate adsorption mechanism. PIXE succeeded in quantitative analysis on few microgram of adsorbed Zr, and EXAFS suggested that Zr in the aqueous solution and in the solvent can be trapped by IDA group with different mechanisms. [ABSTRACT FROM AUTHOR]

Background: Improvement in quality of life (QoL) of patients is one of the most important goals of palliative care, but evaluation of QoL of patients is difficult. Aim: To evaluate QoL of patients who died at home or in a hospital. Methods: We administered the Good Death Inventory (10 core and 8 optional domains) to the bereaved families of patients who died at home or in a hospital. A total of 107 bereaved families undertook a survey. Findings: If a bereaved family chose 'somewhat agree', 'agree' or 'absolutely agree', the answer was regarded as a 'satisfactory answer'. Regarding the 10 core domains, of patients who died in a hospital, <50% respondents gave a 'satisfactory answer' to three questions, whereas of patients who died at home, >60% of respondents gave a 'satisfactory answer' to seven questions. Regarding the eight optional domains, of patients who died in a hospital, <50% respondents gave a 'satisfactory answer' to five questions, whereas of patients who died at home, >60% of respondents gave a 'satisfactory answer' to four questions. Conclusions: QoL of patients who died at home appeared higher than that of those who died in a hospital. Patients prefer to remain at home rather than in a hospital, probably because at home they are surrounded by familiar things and can live according to their usual habits. [ABSTRACT FROM AUTHOR]

Helicenes fused with hexafluorocyclopentene (HFCP) were synthesized by oxidative photocyclization of stilbene derivatives (the Mallory reaction). Of the newly‐obtained fluorinated helicenes, the [7]helicenes bearing one‐ or three‐HFCP units were structurally characterized by X‐ray crystallographic analysis. The attempted synthesis of [9]helicene fused with three HFCP units resulted in the unexpected formation of a novel double helicene consisting of [4]‐ and [6]‐helicenes sharing peripheral benzene rings. Optical properties and chiral resolutions of the newly obtained HFCP‐substituted helicenes are also described. [ABSTRACT FROM AUTHOR]

Development of a new synthetic method for the construction of quaternary centers with a trifluoromethyl group was realized by way of 1,6-addition of various nucleophiles including active methylene compounds to highly reactive δ-trifluoromethylated p-quinone methides generated in situ from the corresponding tertiary carbonates with a catalytic amount of an appropriate base. [ABSTRACT FROM AUTHOR]

Herein, a series of 1,2‐disubstituted 3,3,4,4,5,5‐hexafluorocyclopentene derivatives is synthesized from the commercially available octafluorocyclopentene via addition‐elimination reactions, and their photophysical properties are investigated in detail. 1,2‐Bis[2‐(4‐alkoxyaryl)ethyn‐1‐yl]‐3,3,4,4,5,5‐hexafluorocyclopentene exhibits UV‐absorption at 345 nm in CH2Cl2 and deep blue photoluminescence (PL). The PL properties of these derivatives, including color and maximum wavelength (λPL), are strongly affected by the electron‐density distribution induced by the electronic characteristics of the alkoxy‐substituents at the 4‐position of the benzene ring, with more electron‐donating substituents resulting in a larger shift of λPL to longer wavelengths. Note that the present light‐emitting π‐conjugated luminophores also exhibit relatively strong PL in the crystalline state, where λPL shifts can be introduced by modulation of the terminal alkoxy‐chain length, resulting in different PL colors from light‐blue to orange. [ABSTRACT FROM AUTHOR]

[2 + 3] Cycloaddition reaction of fluorine-containing alkynes with various 2-iodoaryl ketones in the presence of CoCl 2 (dppf) catalyst proceeded very smoothly to give the corresponding 2- or 3-fluoroalkylated indenols in 57–98% yields. These regioisomers could be successfully separated and obtained in a pure form. From X-ray crystallographic and NOESY analyses, major or minor regioisomers were determined as 3- or 2-fluoroalkylated indenols, respectively. Image 1 [ABSTRACT FROM AUTHOR]

Background: Magnesium oxide (MgO) is often co-prescribed with L-dopa/carbidopa (LDCD) to improve constipation in Parkinson's disease patients. The mixing of L-dopa and MgO has been shown to degrade L-dopa; however, there is no interaction study on humans. We proposed mechanisms for the interaction between LDCD and MgO and conducted pharmacokinetic studies on rats and humans. To assess pharmacodynamic changes with the MgO treatment, we applied a model-based meta-analysis (MBMA).Methods: The effects of MgO on the stabilities of L-dopa and carbidopa were evaluated in in vitro studies. We conducted pharmacokinetic interaction studies of MgO and LDCD on rats and healthy volunteers. A clinical study was conducted with an open-label, non-randomized, single-arm, and two-phase study. In MBMA, we constructed a population pharmacokinetic/pharmacodynamic model of L-dopa and predicted the effects of the MgO treatment on the pharmacodynamics of L-dopa.Results: In vitro results suggested that carbidopa was unstable under alkaline pH conditions. Reductions in plasma LDCD concentrations were observed after oral-MgO/oral-LDCD, but not in oral-MgO/i.v.-LDCD treatments in rats, suggesting that the gastrointestinal tract is an interaction site. A healthy volunteer study showed that MgO was also associated with significant decreases of 35.3 and 80.9% in the AUC0-12 of L-dopa and carbidopa, respectively. A model-based simulation suggested that the MgO treatment was undesirable for the effectiveness of L-dopa.Conclusions: This is the first study to show a clear pharmacokinetic interaction between LDCD and MgO in humans. Further investigations to confirm the effects of MgO on the pharmacodynamics of L-dopa are required. [ABSTRACT FROM AUTHOR]

Graphical abstract R N H 2 : 12 examples including bifunctional reagents. *R 2 N H: only cyclic sec -amines, and no reactions for the corresponding acyclic counterpart. Highlights • Facile construction of CF 3 -containing γ-lactams starting from primary amines. • Further cyclization from the product using 2-aminoethanol. • Net substitution reactions from cyclic secondary amines. Abstract Unprecedented isobenzofuran-1-ones (phthalides) with CF 3 and ethoxy groups both at the 3-position were readily synthesized from the corresponding aromatic 1,2-diesters and reacted with a variety of primary amines to find out convenient conversion to the corresponding γ-lactams, while secondary amines behaved in a totally different manner to affect the net substitution reactions for the EtO moiety, where characteristics of the strongly electron-withdrawing CF 3 group was considered to play a significantly important role. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Fluorine-containing diarylethene with hydroxyl groups was prepared from available octafluorocyclopentene and bromophenol. • Mallory reaction of the prepared diarylethene afforded fluorine-containing phenanthrene bearing hydroxyl groups. • The fluorine-containing phenanthrene copolymerized with acid dichlorides to give fluorine-containing polyesters. Abstract Mallory reaction of 1,2-bis(4-hydroxyphenyl)-3,3,4,4,5,5-hexafluorocyclopentene under light irradiation (λ = 356 nm) in the presence of iodine as an oxidant proceeded to give fluorine-containing phenanthrene bearing hydroxyl groups, 6,9-bis(4-hydroxyphenyl)-1,1,2,2,3,3-hexafluoro-2,3-dihydro-1 H -cyclopenta[ l ]phenanthrene. Polycondensation of the prepared fluorine-containing phenanthrene with various acid dichlorides afforded the phenanthrene-type polyesters. For comparison, diarylethene-type polyesters were also prepared analogously. Diarylethene-type polyesters consisting m -phenylene unit showed good solubility in typical organic solvents such as CHCl 3. Tetramethylene-linked diarylethene-type polyesters with M n = 4100 (M n = number average molecular weight) was isolated as oil. Other diarylethene-type and all phenanthrene-type polyesters were insoluble in organic solvents. The phenanthrene-type polyesters had high thermal stability revealed by TGA analysis. [ABSTRACT FROM AUTHOR]

We have demonstrated that reactions of aromatic 1,2‐diesters and the Ruppert–Prakash reagent (TMSCF3) afforded hitherto unknown phthalides 1 with both trifluoromethyl (CF3) and alkoxy groups at the 3 position, and their unique transformation was also investigated in detail to attain construction of a variety of very rare types of compounds, such as 1,3‐dihydroisobenzofurans 8 as well as indanones 9 with a CF3 moiety, whose behavior was completely different from the structurally similar compound 2a. A variety of transformation of unprecedented phthalides readily formed by the reaction of TMSCF3 and aromatic 1,2‐diesters resulted in obtaining different types of CF3‐containing compounds, which were almost inaccessible by previously developed methods. [ABSTRACT FROM AUTHOR]

Crossed aldol reactions of the CF3-containing pseudo C2 symmetric cyclic imide 3 were carried out by way of the corresponding boron bisenolate to stereoselectively furnish the desired products 4 and this procedure allowed the preferential construction of the diastereomers of the compounds previously obtained from the acyclic counterpart 1. [ABSTRACT FROM AUTHOR]

Novel cobalt-catalyzed [2+2+2] cycloaddition using fluorine-containing alkynes was described. Cyclotrimerization of fluorinated alkynes under the influence of CoCl 2 (dppb) in acetonitrile at 80 °C for 3 h took place smoothly, affording the corresponding benzene derivatives in excellent yields with high regioselectivity. Additionally, intermolecular cycloaddition of fluorinated alkynes with non-fluorinated diynes also proceeded in the presence of a catalytic amount of CoCl 2 (( S )-BINAP) and ZnI 2 to give various bicyclic aromatic compounds in high yields. [ABSTRACT FROM AUTHOR]

The dehydrofluorination of 2 H ,3 H -decafluoropentane (HFC-4310mee) using 1,8-diazabicyclo[5.4.0]-7-undecene (DBU) selectively gave ( Z )-2 H -nonafluoropent-2-ene as a bench-stable volatile liquid. Nucleophilic substitution reactions of ( Z )-2 H -nonafluoropent-2-ene with allylic alcohols gave the corresponding polyfluorinated allylic vinyl ether derivatives. The Claisen rearrangement of the polyfluorinated allylic vinyl ethers smoothly proceeded under ambient conditions to give polyfluorinated homoallylic ketones quantitatively. These results indicate the potential of 2 H ,3 H -decafluoropentane as an inexpensive and easy-to-handle chemical feedstock for the syntheses of densely functionalized polyfluorinated organic compounds. [ABSTRACT FROM AUTHOR]

Dihydroxylation of 3,3,4,4,5,5-hexafluorocyclopentene by KMnO 4 afforded a highly-fluorinated 1,2-cycloalkanediol, 3,3,4,4,5,5-hexafluoro- cis -1,2-cyclopentanediol, as a colorless crystalline solid. The cis -configuration of the two hydroxy groups was elucidated by the X-ray crystallographic analysis on the dibenzoate of the 1,2-diol. Treatment of the 1,2-diol with several diacid chlorides afforded the corresponding oligoesters in good yields. [ABSTRACT FROM AUTHOR]

An asymmetric carbon center with a tetrafluoroethylene fragment can be efficiently constructed via a highly enantioselective conjugate addition reaction of various arylboronic acids with β-(bromotetrafluoroethyl)-α,β-unsaturated ketones. This system can be successfully applied to an enantiomerically enriched tetrafluoroethylenated liquid crystalline molecule. [ABSTRACT FROM AUTHOR]

The synthetic protocols for symmetrical/unsymmetrical 3,6-disubstituted 1,1,2,2-tetrafluorocyclohexane molecules were successfully established for the first time. Some of thus obtained tetrafluorinated cyclohexanes underwent recrystallization to afford trans -configured products preferentially. One of the unsymmetrical trans -disubstituted tetrafluorocyclohexanes, trans -1-ethyl-2,2,3,3-tetrafluoro-4-[4-( trans -4- n -propylcyclohex-1-yl)phenyl]cyclohexane, was found to possess a low birefringence Δ n (0.073) and a large negative dielectric anisotropy Δ ε (–9.4) in a binary mixture system, which were very prominent as characteristics of LC molecules in VA-mode driving LC displays. [ABSTRACT FROM AUTHOR]

Solid-phase extraction was used for on-site speciation and preconcentration of inorganic arsenic in groundwater involving the retention of molybdoarsenate on activated carbon. A total of 0.25 µg of As(V) in 50-500 mL of sample was selectively retained on 100 mg of activated carbon in a mini-column as molybdoarsenate at pH 2. A total of 0.1 mL of 0.26 mol/L ammonium molybdate was introduced for every 50 mL of the sample. As(III) was quantitatively retained with As(V) by adding 0.01 mL of 0.02 mol/L KMnO4 solution for every 50 mL of the sample prior to the addition of ammonium molybdate. The retained As(V) was quantitatively eluted by circularly passing 3 mL of 1 mol/L NH4OH through the column for at least 5 min with determination by graphite furnace atomic absorption spectrometry. A palladium chemical modifier was used to provide a detection limit and blank equivalent concentration of 0.047 and 0.19 µg/L, respectively (n 6, sample volume of 50 mL). Concomitant ions in seawater or river water did not cause interferences. The method was used for the preconcentration of arsenic in groundwater from Chiba, Japan. The recoveries of fortified As(V) (2 µg/L) were from 89 to 98%. Concentrations of 0.35-1.6 µg/L of As(V) were determined with a relative standard deviation less than 3.7% for five replicates. The recoveries of 2 µg/L fortified As(III) were from 92 to 103%. [ABSTRACT FROM AUTHOR]

Novel photoinduced double perfluoroalkylation of methylacenes has been described. The reaction proceeded with appropriately substituted methylacenes to produce a mixture of the expected aromatic compounds with Rf groups both at the methyl and its para position as well as the corresponding nonaromatic tautomers. Steric repulsive interaction of fluorine atoms in perfluoroalkyl groups with hydrogen atoms at the peri positions would be the most significant factor for control of ratios of these products. [ABSTRACT FROM AUTHOR]

Abstract: We have succeeded in establishment of a novel route for the construction of optically active CF3-containing carboxylic acids in a stereochemically predictable manner starting from easily available mandelic acid by convenient combination of the copper-mediated anti-SN2′ type substitution and Ireland-Claisen rearrangement. [Copyright &y& Elsevier]

Abstract: The reaction of β-fluoroalkylated α,β-unsaturated ketones with various enamines gave 4-fluoroalkylated 3,4-dihydro-2H-pyrans as a major product in good yields by a one-pot operation, and these products display the high diastereoselection just after single recrystallization. This unexpected result is rationalized by the unique reactivity of β-fluoroalkylated α,β-unsaturated ketones. As the synthetic application, 4-trifluoromethyl tetrahydropyran was synthesized in moderate isolated yield with high diastereoselectivity. [Copyright &y& Elsevier]

Abstract: 2-Chloro-1,1,1,2-tetrafluoroethane 1 (HCFC-124) obtained as one of the major byproducts of tetrafluoroethylene synthesis were successfully employed for the stereodivergent construction of tetrafluorinated enamides 4 just by selection of a base for affecting the removal of HCl. [Copyright &y& Elsevier]

Abstract: The purpose of this study was (i) to determine the optimal dosage of teicoplanin for each patient group stratified by renal function and weight based on a population pharmacokinetic model and observed distribution of patient characteristics and (ii) to develop new simplified dosing regimens designed to achieve 15–30μg/mL. Patient data were collected retrospectively from routine therapeutic drug monitoring files of adult patients who were given the standard loading dose regimen of teicoplanin (400mg twice on Day 1, followed by 400mg once daily for 2 days) and whose trough concentration was measured just before administration on Day 4. Monte Carlo simulation was conducted to estimate the trough concentration at 72h after the initial loading dose (C min 72h) and at steady state (C ss min). The percentage of observed C min 72h in patients who received the standard loading dose regimen outside the non-parametric 90% prediction interval (from 5th to 95th percentile) of the simulated C min 72h was <10%. Simplified loading dose and maintenance dose regimens for each group stratified by renal function and weight were created to achieve C min 72h and C ss min of 15μg/mL and 20–25μg/mL, respectively. The percentage of C min 72h and C ss min in the range 15–30μg/mL was 43–65% and 61–82% across each renal function and weight strata, respectively. These new simplified dosing regimens of teicoplanin could be helpful in individual adjustment of the loading and maintenance doses to achieve 15–30μg/mL. [Copyright &y& Elsevier]

Abstract: This paper presented a novel thermal imprinting technique for forming through holes in polymers with high quality and extremely high throughput. By using an array of out-of-plane, hollow silicon dioxide (SiO2) microneedles, we successfully fabricated through holes with a diameter of approximately 30μm in polypropylene films (thickness: 35μm) and polyimide films (thickness: 37.5μm). No burr was observed on the entrance and exit of the through holes, and the inner surface of these holes was very smooth. Moreover, the entrance and exit diameters were almost the same, indicating that the through holes had an almost perfectly vertical sidewall. The results indicate that our proposed technique has the potential of enabling high-throughput and low-cost fabrication of through holes with a minimum feature of a few tens of micrometers in a wide variety of polymers. [Copyright &y& Elsevier]

Abstract: Objective: Hepatotoxicity is one of the major complaints that occur during lipid-lowering therapy with 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitors, known as statins. We reported earlier that lipophilic but not hydrophilic statins induce apoptosis through inhibition of mevalonate biosynthesis cascade in Chang liver cells. The present study was designed to determine the role for small G protein RhoA in the hepatocytotoxicity of statins. Methods: Statin-induced hepatocytotoxicity in HepG2 cells were assessed by WST-8 cell viability assay, JC-1 mitochondrial membrane potential assay and caspase-3/7 activity assay. Cytosolic RhoA was detected by Western blotting and RhoA activation was measured by ELISA. Results: The lipophilic atorvastatin but not the hydrophilic pravastatin induced the mitochondrial membrane depolarization and the activation of caspase-3/7, which led to cell injury. Supplementation of mevalonate or geranylgeranyl pyrophosphate (GGPP) but not farnesyl pyrophosphate (FPP) reversed these cellular events and cell death induced by atorvastatin. Atorvastatin induced a translocation of RhoA protein into the cytosol and inhibited the activity of the protein. In addition, atorvastatin reduced mitochondrial membrane potential, which was mimicked by GGTase inhibitor GGTI-2147 or the specific RhoA inhibitor such as toxin B and C3 exoenzyme. However, only a few cells revealed mitochondrial membrane depolarization and a loss of viability after exposure to the Rho-kinase inhibitors such as Y-27632 and hydroxy fasudil. Conclusions: RhoA inactivation and to a lesser extent Rho-kinase inhibition after depletion of GGPP is implicated in the etiology of mitochondrial membrane depolarization and subsequent caspase-dependent cell death induced by the lipophilic statin in HepG2 cells. [Copyright &y& Elsevier]

Abstract: Adsorption behaviors of the high-valence metal ions Zr(IV), Hf(IV), Ti(IV), V(V), Nb(V), Ta(V), and Mo(IV) on desferrioxamine B (DFB) immobilization nylon 6,6 chelate fiber was investigated under highly acidic conditions. Though the complexes of DFB and the high-valence metal ions were extracted without selectivity by solvent extraction, the only zirconium ions showed higher adsorption percentages than that of other high-valence metal ions on the DFB immobilization nylon 6,6 chelate fiber. Adsorption properties were caused that limited the freedom of DFB by chemical immobilization. Especially, hafnium ions and zirconium ions, which have similar chemical properties, showed different adsorption behavior in highly acidic aqueous solutions. Zirconium ions were quantitatively adsorbed up to 13.5 μmol/g. [Copyright &y& Elsevier]

The DIBAL reduction of 2-phenylethyl 3,3,3-trifluoro-2-methylpropionate 2 at -78 °C afforded the aluminum acetal 3, and this intermediate, on worming up to 0 °C, was found to slowly decompose into the corresponding aldehyde 4, which smoothly reacted with appropriate nucleophiles in a one-pot manner in good to excellent yields with up to 93% diastereoselectivity. [ABSTRACT FROM AUTHOR]

Abstract: The effect of fluoromethyl groups on the diastereoselectivity in the electrophilic alkylation is described. In particular, the electrophilic alkylation of enolates with a trifluoromethyl group was proceeded with highly diastereofacial selectivity based on the steric and/or electrostatic effect of substituent with strong electron withdrawing. [Copyright &y& Elsevier]

The DnaA protein is the initiator of Escherichia coli chromosomal replication. In this study, we identify a novel DnaA-associating protein, DiaA, that is required for the timely initiation of replication during the cell cycle. DiaA promotes the growth of specific temperature-sensitive dnaA mutants and ensures stable minichromosome maintenance, whereas DiaA does not decrease the cellular DnaA content. A diaA::Tn5 mutation suppresses the cold-sensitive growth of an overinitiation type dnaA mutant independently of SeqA, a negative modulator of initiation. Flow cytometry analyses revealed that the timing of replication initiation is disrupted in the diaA mutant cells as well as wild-type cells with pBR322 expressing the diaA gene. Gel filtration and chemical cross-linking experiments showed that purified DiaA forms a stable homodimer. Immunoblotting analysis indicated that a single cell contains about 280 DiaA dimers. DiaA stimulates minichromosome replication in an in vitro system especially when the level of DnaA included is limited. Moreover, specific and direct binding between DnaA and DiaA was observed, which requires a DnaA N-terminal region. DiaA binds to both ATP- and ADP-bound forms of DnaA with a similar affinity. Thus, we conclude that DiaA is a novel DnaA-associating factor that is crucial to ensure the timely initiation of chromosomal replication. [ABSTRACT FROM AUTHOR]

Background: Radiographic contrast material is one of agents that are prone to cause nephropathy, although little is known about cellular mechanisms underlying contrast media-induced renal failure. The present study was designed to determine the role of caspase in contrast media-induced renal injury. The modulation by cyclic adenosine monophosphate (cAMP) of cell injury was subsequently examined.Methods: LLC-PK1 cells (a proximal renal tubular cell line of porcine origin) were exposed to diverse contrast media for 30 minutes followed by incubation for 24 hours in normal medium. Cell viability was assessed by mitochondrial enzyme activity and propidium iodide stain. Apoptosis was determined by DNA electrophoresis and annexin V stain. Caspase activity was measured fluorometrically. The mRNA for bax and bcl-2 was determined by reverse transcription-polymerase chain reaction (RT-PCR).Results: Iodinated and magnetic resonance contrast media reduced cell viability due to apoptosis. The cell damage induced by a non-ionic contrast medium ioversol was inhibited by specific inhibitors for caspase-3 and -9 but not caspase-8. Ioversol enhanced the activities of caspase-3 and -9, but to a lesser extent, caspase-8. The bax mRNA was enhanced, while bcl-2 mRNA was reduced, after exposure to ioversol. All of these actions of ioversol were reversed by dibutyl cAMP in the manner sensitive to a protein kinase A inhibitor H89 and a phosphatidylinositol 3 (PI3) kinase inhibitor wortmannin.Conclusion: We demonstrated for the first time that cAMP reversed caspase-dependent apoptotic renal cell damage caused by contrast media. Both protein kinase A and PI3 kinase might be involved in protective effect of cAMP. [ABSTRACT FROM AUTHOR]

Focuses on the DNA replication-coupled inactivation of Dna protein in vitro. Initiation of chromosomal replication in Escherichia coli; Outcome of enhanced clamp formation; Conservation of arginine residue among Dna homologues.

In this study, unprecedented polyacrylates with vinylene-bridged fluoroalkyl side chains (–(CF 2) 6 –CH CH-(CF 2) 5 CF 3) were successfully synthesized. These polyacrylates comprise short perfluoroalkyl groups, thus allowing to prevent the formation of bioaccumulative polyfluorinated compounds including perfluorooctanoic acid (PFOA). The bulk organization and surface properties of these polymers were investigated by differential scanning calorimetry, X-ray diffraction analysis, and contact angle measurements. Thin films of the novel polyacrylates bearing the –(CF 2) 6 –CH CH-(CF 2) 5 CF 3 groups exhibited excellent water and oil repellency comparable to those made by conventional polyacrylates bearing C 8 F 17 groups. A novel polymethacrylate bearing the –(CF 2) 6 –CH CH-(CF 2) 5 CF 3 group showed low surface energy and low contact angle hysteresis despite of its amorphousness in the bulk state, which is very different from conventional polymethacrylates bearing a C 6 F 13 group. Therefore, these polyacrylates bearing vinylene-bridged fluoroalkyl side chains are promising alternatives to conventional analogues containing long perfluoroalkyl side chains. Image 1 • Poly(meth)acrylates bearing a vinylene-intercepted polyfluorinated side chain have been synthesized. • The newly obtained poly(meth)acrylates exhibited good surface properties, e.g. , high water and oil repellency. • The new polymethacrylate showed a remarkably low contact angle hysteresis despite of its amorphous nature in the solid state. [ABSTRACT FROM AUTHOR]

• α,ω-Diynes bearing a perfluoroalkylene linker were readily prepared from the corresponding dienes in three steps. • Co-catalyzed [2+2+2] cycloaddition of HC≡C(CF 2) 4 C≡CH with alkynes afforded benzene derivatives bearing a perfluorobutan-1,4-diyl group. • HC≡C(CF 2) 6 C≡CH underwent aromatization polymerization by a Rh catalyst to give an insoluble network polymer. α,ω-Diynes bearing a perfluoroalkylene linker HC≡C(CF 2) n C≡H (n = 4,6) were obtained from commercially available α,ω-dienes H 2 C=CH(CF 2) n CH=CH 2 via bromination and dehydrobromination. In the presence of CoCl 2 -Zn-ZnI 2 catalyst, the diyne HC≡C(CF 2) 4 C≡H underwent [2+2+2] cycloaddition reactions with terminal alkynes to afford benzene derivatives fused with an octafluorocyclohexene moiety. In this reaction, trimerization of the diyne was observed as a major side reaction. Rh-catalyzed aromatization polymerization of the diyne HC≡C(CF 2) 6 C≡H afforded an insoluble polymer consisting of a densely cross-linked, aromatic skeleton, which was characterized by solid-state CP-MAS 13C NMR and IR spectroscopy. This insoluble polymer exhibited high thermal stability, and engineering applications of the product polymer are being evaluated. [ABSTRACT FROM AUTHOR]

Background: There is no standardized brain computed tomography (CT) reference line that can be determined on both scout and reformatted sagittal CT images. Here, a tangential line from the anterior edge of the lower eyelid to the inner table of the occipital base (LEL/O line) appears nearly parallel to the Talairach–Tournoux (T/T) line, which shows a consistent intracranial anatomical relationship among subjects, and acts as a standard reference line for magnetic resonance (MR) imaging. Purpose: To quantitatively validate the LEL/O line as a new standard brain CT reference line. Material and Methods: We measured: angle 1 = the LEL/O line on scout images from the LEL/O line on parasagittal CT images (n=93); and angle 2 = the LEL/O line on scout images from the T/T line on high resolution midsagittal MR images (n=97). Angles in a clockwise direction were defined as positive and were expressed as mean±SD with the 95% confidence interval (CI) of the SD. Angle 2 was measured independently by two observers and intraclass correlation coefficients (ICCs) were calculated. Results: Angle 1 was –0.4°±1.2° (95% CI of SD 1.1°–1.5°); angle 2 was –0.4°±2.0° (95% CI of SD, 1.8°–2.4°). The ICC in the angle 2 measurement was 0.780 (P <0.001), which indicated high inter-observer reliability. Conclusion: The LEL/O lines on scout and parasagittal CT images show practically the same gradient, and these LEL/O lines are almost parallel to the T/T line. Use of the LEL/O line either for direct scanning or reformation can minimize intra- and inter-subject variations on CT images and mismatch between CT and MR images. [ABSTRACT FROM AUTHOR]

The introduction of perfluoroalkyl (Rf) groups into polycyclic aromatic hydrocarbons (PAHs) is a potential strategy for developing air-stable electron-acceptors that are useful for manufacturing novel n-type organic semiconductors. This paper describes a facile synthetic method for 9,13-bis[(triisopropylsilyl)ethynyl]pentacene ("TIPS-pentacene") derivatives bearing two or four Rf groups at peripheral regions. The molecular structures of newly synthesized TIPS pentacenes bearing four Rf groups were established by single-crystal X-ray analysis. The Rf-substituted TIPS-pentacenes are stable both in solutions and in the solid state under ambient conditions, probably because of the combination of the TIPS-ethynyl and Rf groups. The Rf groups stabilize the π-orbitals of the TIPS-pentacene framework and improve the electron-accepting properties, as evidenced by electrochemical measurements and photoelectron yield spectroscopy (PYS). Image 1 • TIPS-pentacenes bearing two or four perfluoroalkyl (Rf) groups were synthesized. • The molecular structures of the Rf-substituted TIPS-pentacenes were established by the single crystal X-ray diffraction measurements. • The Rf-substituted TIPS-pentacenes exhibited good thermal- and photo-stability under ambient conditions. • Electron-withdrawing Rf groups stabilized the π-orbitals of the Rf-substituted pentacenes. [ABSTRACT FROM AUTHOR]

A new collaborative research project for systematic treatments of radioactive liquid wastes containing various reagents generating in nuclear facilities was started from 2018 initiated by Japan Atomic Energy Agency. The project was named as STRAD (Systematic Treatments of RAdioactive liquid wastes for Decommissioning) project. Tentative targets to be studied under the project are aqueous and organic liquid wastes which have been generated by experiments and analyses in a reprocessing experimental laboratory of JAEA. Currently fundamental studies for treatments of the liquid wastes with complicated compositions are underway. In the STRAD project, process flow for treatment of ammonium ion involved in aqueous waste was designed though the inactive experiments, and decomposition of ammonium ion using catalysis will be carried out soon. Adsorbents for recovery of U and Pu from spent solvent were also developed. Demonstration experiments on genuine spent solvent is under planning. • JAEA started treatment of legacy radioactive liquid waste. • Treatment of several liquids has been carried out inside hot cells or glove boxes. • A new study project named STRAD for the treatment was started. • STRAD project has already shown some achievements. [ABSTRACT FROM AUTHOR]

Intramolecular photocyclization of stilbene derivatives (Mallory reaction) is one of the efficient methods for building polycyclic aromatic hydrocarbon (PAH) frameworks, and is also expected to be applicable to synthesis of fluorine-containing PAHs (F-PAHs). In this study, dibenzoanthracene-type (4a) and benzoperylene-type (4b) F-PAHs were synthesized using the Mallory reaction of the 1,4-distyrylbenzene-type π-conjugated molecule (3a), which was prepared by addition-defluorination of available octafluorocyclopentene (OFCP) and aryllithium in three steps. The structure of 4a originating from π–π interaction was characterized by X-ray crystallographic analysis. The absorption maxima of UV-Vis spectra and emission maxima of photoluminescence spectra of the PAHs were positioned at a longer wavelength compared to those of the corresponding unsubstituted PAHs, presumably due to the electron-withdrawing nature of perfluorocyclopentene (PFCP) units. The effect of PFCP units in F-PAHs was also studied by time-dependent density functional theory (TD-DFT) calculation. [ABSTRACT FROM AUTHOR]

An abstract of the article "Photoinduced Double Perfluoroalkylation of Methylacenes" by Emiko Nogami and colleagues is presented.