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MycG is a multifunctional P450 monooxygenase that catalyzes sequential hydroxylation and epoxidation or a single epoxidation in mycinamicin biosynthesis. In the mycinamicin-producing strain Micromonospora griseorubida A11725, very low-level accumulation of mycinamicin V generated by the initial C-14 allylic hydroxylation of MycG is observed due to its subsequent epoxidation to generate mycinamicin II, the terminal metabolite in this pathway. Herein, we investigated whether MycG can be engineered for production of the mycinamicin II intermediate as the predominant metabolite. Thus, mycG was subject to random mutagenesis and screening was conducted in Escherichia coli whole-cell assays. This enabled efficient identification of amino acid residues involved in reaction profile alterations, which included MycG R111Q/V358L, W44R, and V135G/E355K with enhanced monohydroxylation to accumulate mycinamicin V. The MycG V135G/E355K mutant generated 40-fold higher levels of mycinamicin V compared to wild-type M. griseorubida A11725. In addition, the E355K mutation showed improved ability to catalyze sequential hydroxylation and epoxidation with minimal mono-epoxidation product mycinamicin I compared to the wild-type enzyme. These approaches demonstrate the ability to selectively coordinate the catalytic activity of multifunctional P450s and efficiently produce the desired compounds.

The cytochrome P450 monooxygenase RosC catalyzes the three-step oxidation reactions, which leads to the formation of a hydroxy, formyl, and carboxy group at C-20 during rosamicin biosynthesis in Micromonospora rosaria IFO13697. To determine if amino acid substitutions in RosC could allow for the control of the multistep oxidation reactions, we screened RosC random mutants. The RosC mutant RM30, with five amino acid substitutions (P107S, L176Q, S254N, V277A, and I319N), catalyzed only the first step of the oxidation reaction. Whole-cell assays using Escherichia coli cells expressing RosC mutants with single and double amino acid substitutions derived from RM30 indicated that P107S/L176Q, P107S/V277A, P107S/I319N, L176Q/V277A, L176Q/I319N, and S254N/V277A significantly reduced the catalytic activity of the second reaction, which is alcohol oxidation. Of the previously mentioned mutants, double mutants containing L176Q, which was presumed to occur in the FG loop region, lost the total catalytic activity of the third reaction (aldehyde oxidation). Additionally, an engineered M. rosaria strain with rosC disruption, which introduced the gene encoding the RosC mutants P107S/L176Q and P107S/V277A preferentially produced 20-dihydrorosamicin, which is formed after the first oxidation reaction of RosC.

Quorum sensing (QS) is a microbial signaling system that regulates the expression of many virulence genes. Herein, we studied five compounds-No. 1: (E)-2-methyl-3- (4-nitro-phenyl)-acrylaldehyde; No. 29-2: pimprinine [5-(1H-indol-3-yl)-2-methyloxazole]; No. 48: (2E,4E)-2-methyl-5-phenyl-2,4-pentadienoic acid; No. 74: (3E,5E)-5-methyl-6-(4-nitrophenyl)-hexa-3,5-dien-2-ol; and No. 130: methyphenazine-1-carboxylate-derived from an actinomycete metabolite library. These compounds were confirmed to be QS inhibitors that reduced violacein production in Chromobacterium violaceum CV026. Additionally, compounds No. 1, No. 74, and No. 130 significantly reduced fluorescent pigment production in Pseudomonas aeruginosa ATCC 27853.

Objective The authors compared the occurrence of posterior wall puncture using the short-axis out-of-plane and long-axis in-plane approaches with that using the combined short-axis-and-long-axis approach that the authors previously showed to be effective in observational and manikin studies. Design Randomized controlled study. Setting Single tertiary institution. Participants One hundred twenty patients who underwent cardiac or vascular surgery under general anesthesia. Interventions The patients were divided randomly into combined short-axis-and-long-axis (n = 40), short-axis out-of-plane (SA-OOP) (n = 40), and long-axis in-plane (LA-IP) (n = 40) groups and received ultrasound-guided central venous catheterization at the right internal jugular vein. Measurements and Main Results Successful guidewire insertion without posterior wall puncture was performed in 40 patients (100%) in the combined short-axis-and-long-axis approach group, 28 (70%) in the short-axis out-of-plane approach group, and 38 (95%) in the LA-IP approach group (combined short-axis-and-long-axis v SA-OOP, p = 0.0002 [relative risk = 1.43; 95% CI: 1.17-1.75]; combined short-axis-and-long-axis v LA-IP, p = 0.49 [relative risk = 1.05; 95% CI: 0.98-1.13]). Procedure durations were 28.5 (24.1-36.4) seconds in the combined short-axis-and-long-axis group, 31.7 (24.4-40.6) seconds in the SA-OOP group, and 24.3 (20.8-32.1) seconds in the long-axis in-plane group (combined short-axis-and-long-axis v SA-OOP, p = 0.53; combined short-axis-and-long-axis v LA-IP, p = 0.044). Conclusion The combined short-axis-and-long-axis approach for ultrasound-guided central venous catheterization had a lower posterior wall puncture rate than the SA-OOP approach, but there was no significant difference with the long-axis in-plane approach.

Objective Visualizing the needle tip using the short-axis out-of-plane (SA-OOP) ultrasound-guided central venous catheterization approach is difficult and results in posterior wall puncture (PWP). To improve needle tip visualization in the long-axis view, combining the SA-OOP and the long-axis in-plane approaches has been suggested. The authors, who previously reported on the utility of this technique using a manikin model, examined the feasibility of this novel method (referred to as the combined short-axis and long-axis [CSLA] approach) and compared the CSLA approach with the SA-OOP approach in humans for the present study. Design Prospective observational study. Setting Single institution, Rakuwakai Otowa Hospital. Participants Patients undergoing cardiac or vascular surgeries. Interventions The CSLA and SA-OOP approaches were used for ultrasound-guided right jugular venous puncture. The puncturing procedures were determined arbitrarily preoperatively without consideration of the patient's neck anatomy and were based on the operator's preference without randomization. Measurements and Main Results The study comprised 100 patients. Successful guidewire insertion without PWP was performed in 48 patients (96%) in the CSLA approach group and 33 (66%) in the SA-OOP approach group; the rate was significantly higher in the CSLA approach group (p = 0.0001). The procedural durations were 27.5 (range 17.0-122.0) seconds in the CSLA approach group and 25.0 (range 15.0-158.0) seconds in the SA-OOP approach group (p = 0.19). Conclusions This study showed that the CSLA approach to ultrasound-guided central venous catheterization might help prevent PWP.

Quorum sensing (QS) is an important microbial signaling system that controls the expression of many virulence genes. Combination treatment with QS inhibitors and antibiotics may be the new treatment option for infectious diseases in the future. Therefore, there is an increasing need to discover anti-QS compounds to prevent antimicrobial resistance. We isolated methyl-β-D-glucopyranoside from Scabiosa comosa and found that it exerts an anti-QS activity against Chromobacterium violaceum CV026 without exhibiting any antimicrobial activity.

A novel actinomycete, designated NUM-2625T, was isolated as an endophytic bacterium in aerial parts of Comarum salesowianum, an endemic species in the Altai, Himalaya mountain chain area, collected from Khasagt Khairkhan Mountain in Mongolia. The 16S rRNA gene sequence of strain NUM-2625T showed the highest similarity to Actinocatenispora thailandica TT2-10T (99.4 %), Actinocatenispora sera KV-744T (99.3 %), and Actinocatenispora rupis CS5-AC17T (97.7 %). Chemotaxonomic properties of strain NUM-2625T were essentially consistent with those of the genus Actinocatenispora, such as the presence of meso-diaminopimelic acid as the diagnostic diamino acid of the peptidoglycan, MK-9(H4) and MK-9(H6) as the major menaquinones, and iso-C16 : 0, iso-C15 : 0, iso-C14 : 0 3-OH, and anteiso-C17 : 0 as the major fatty acids. Meanwhile, digital DNA–DNA hybridization and average nucleotide identity values revealed a low relatedness between strain NUM-2625T and the other type strains of the genus Actinocatenispora . In addition, strain NUM-2625T exhibited several phenotypic properties that could be used to distinguish it from its closest relatives. Based on the results of polyphasic analyses, strain NUM-2625T represents a novel species in the genus Actinocatenispora , for which the name Actinocatenispora comari sp. nov. is proposed. The type strain is NUM-2625T (=NBRC 114660T=TBRC 13496T).

Optical correlation systems have been developed as hardware that is useful for high-speed and large-scale data analysis. Among them, our system using the disk-type hologram is promising because it can effectively utilize the control techniques of conventional optical disks. In previous work, however, we used a very simple disk structure consisting of a mirror substrate, photopolymer, and cover glass, and tracking control was not performed. Consequently, it was difficult to stably record a large amount of data in the long range of the circumference since the hologram recording position deviates from the disk circumference due to surface deflection and eccentricity attributed to rotation without tracking controls. In this study, we aim to stabilize the optical correlation system by introducing a new disk structure and conventional servo control. We confirmed that both sufficient correlation signal and servo control signals can be detected with the simple disk structure due to the signal detection principle of the optical correlation.

Background There is no large-scale study comparing postoperative mortality after aortic valve replacement (AVR) for asymptomatic severe aortic stenosis (AS) between initial treatment with AVR vs. eventual AVR after conservative management. Methods and Results: We analyzed data from a multicenter registry enrolling 3,815 consecutive patients with severe AS. Of 1,808 asymptomatic patients, 286 patients initially underwent AVR (initial AVR group), and 377 patients were initially managed conservatively and eventually underwent AVR (AVR after watchful waiting group). Mortality after AVR was compared between the 2 groups. Subgroup analysis according to peak aortic jet velocity (Vmax) at diagnosis was also conducted. There was no significant difference between the 2 groups in 5-year overall survival (OS; 86.0% vs. 84.1%, P=0.34) or cardiovascular death-free survival (DFS; 91.3% vs. 91.1%, P=0.61), but on subgroup analysis of patients with Vmax ≥4.5 m/s at diagnosis, the initial AVR group was superior to the AVR after watchful waiting group in both 5-year OS (88.4% vs. 70.6%, P=0.003) and cardiovascular DFS (91.9% vs. 81.7%, P=0.023). Conclusions Asymptomatic severe AS patients who underwent AVR after watchful waiting had a postoperative survival rate similar to those who initially underwent AVR. In a subgroup of patients with Vmax ≥4.5 m/s at diagnosis, however, the AVR after watchful waiting group had worse postoperative survival rate than the initial AVR group.

AIMS Tricuspid regurgitation (TR) has been reported to be associated with worse survival in various heart diseases, but there are few data in aortic stenosis (AS). METHODS AND RESULTS In the Contemporary Outcomes after Surgery and Medical Treatment in Patients with Severe Aortic Stenosis (CURRENT AS) Registry enrolling 3815 consecutive patients with severe AS, there were 628 patients with moderate or severe TR (TR group) and 3187 patients with no or mild TR (no TR group). The study patients were subdivided into the initial aortic valve replacement (AVR) stratum (n = 1197) and the conservative stratum (n = 2618) according to treatment strategy. The primary outcome measure was a composite of aortic valve-related death or hospitalization due to heart failure. The 5-year freedom rate from the primary outcome measure was significantly lower in the TR group than in the no TR group (49.1% vs. 67.3%, P

With the aim to find endophytic actinomycetes that synthesize bioactive compounds over 800 strains were isolated from 53 desert plants of the Gobi-Sumber, Umnugobi, Dundgobi, Dornogobi, Bayankhongor, and Gobi-Altai provinces of Mongolia. The HPLC study of strains with high anti-quorum sensing and antibacterial activities revealed that they produced flavonoids and phenolic compounds. Molecular diversity evaluated with 16S rRNA gene sequences of 123 strains showed that they belonged to 12 genera: Streptomyces, Promicromonospora, Micromonospora, Streptosporangium, Kribbella, Pseudonocardia, Nocardia, Micromonospora, Saccharothrix, Friedmanniella, Actinocatenispora, and Geodermatophilus, the latter two genera were registered in Mongolia for the first time. Moreover, the genus Actinocatenispora was isolated from plants for the first time.

Screening for circumventors of β-lactam resistance in methicillin-resistant Staphylococcus aureus (MRSA) led us to find 17 novel antibiotics, naphthacemycins A1–A11, B1–B4 and C1–C2. The naphthacemycins were isolated from a cultured broth of Streptomyces sp. KB-3346-5 by repeated silica gel column chromatography and HPLC. Naphthacemycins enhanced imipenem activity 100–500 times against MRSA at 0.5 μg ml−1, and naphthacemycins A4–A11 themselves showed MIC50 values of 1–4 μg ml−1 against 22 MRSA strains.

Quorum sensing (QS) is a microbial signaling system that regulates the expression of many virulence genes. Herein, we studied five compounds-No. 1: (E)-2-methyl-3- (4-nitro-phenyl)-acrylaldehyde; No. 29-2: pimprinine [5-(1H-indol-3-yl)-2-methyloxazole]; No. 48: (2E,4E)-2-methyl-5-phenyl-2,4-pentadienoic acid; No. 74: (3E,5E)-5-methyl-6-(4-nitrophenyl)-hexa-3,5-dien-2-ol; and No. 130: methyphenazine-1-carboxylate-derived from an actinomycete metabolite library. These compounds were confirmed to be QS inhibitors that reduced violacein production in Chromobacterium violaceum CV026. Additionally, compounds No. 1, No. 74, and No. 130 significantly reduced fluorescent pigment production in Pseudomonas aeruginosa ATCC 27853.

Background Data are scarce on the role of aortic valve area (AVA) to identify those patients with asymptomatic severe aortic stenosis (AS) who are at high risk of adverse events. We sought to explore the prognostic impact of AVA in asymptomatic patients with severe AS in a large observational database. Methods and Results Among 3815 consecutive patients with severe AS enrolled in the CURRENT AS (Contemporary Outcomes After Surgery and Medical Treatment in Patients With Severe Aortic Stenosis) registry, the present study included 1309 conservatively managed asymptomatic patients with left ventricular ejection fraction ≥50%. The study patients were subdivided into 3 groups based on AVA (group 1: AVA >0.80 cm2, N=645; group 2: 0.8 cm2 ≥AVA >0.6 cm2, N=465; and group 3: AVA ≤0.6 cm2, N=199). The prevalence of very severe AS patients (peak aortic jet velocity ≥5 m/s or mean aortic pressure gradient ≥60 mm Hg) was 2.0%, 5.8%, and 26.1% in groups 1, 2, and 3, respectively. The cumulative 5‐year incidence of AVR was not different across the 3 groups (39.7%, 43.7%, and 39.9%; P=0.43). The cumulative 5‐year incidence of the primary outcome measure (a composite of aortic valve–related death or heart failure hospitalization) was incrementally higher with decreasing AVA (24.1%, 29.1%, and 48.1%; P, See Editorial by Tribouilloy et al

There are various multiplexing methods in holographic data recording. A larger storage capacity is anticipated when combining two different multiplexing methods and then ensuring crosstalk-free recording. We have proposed a cross-shift multiplexing method that combines shift multiplexing and peristrophic multiplexing. Crosstalk-free conditions for shift multiplexing and peristrophic multiplexing were separately clarified. However, these conditions cannot be individually applied to cross-shift multiplexing. Then, we deduced the analytic formula of crosstalk for cross-shift multiplexing and verified its validity by comparing the theoretical and experimental results. Using this analytic formula, the shift pitch and rotation angle that attain crosstalk-free multiplexing can be determined.

Quorum sensing is an important microbial signaling system that controls the expression of many virulence genes. Maniwamycins C-F, new compounds and quorum-sensing inhibitors, were isolated from the culture broth of Streptomyces sp. TOHO-M025 using a silica gel column and preparative HPLC. The structures of maniwamycins were elucidated by spectroscopic analyses, including NMR. The compounds each have an azoxy moiety. All maniwamycins inhibited violacein synthesis, which is controlled by quorum sensing, in Chromobacterium violaceum CV026.

The 3,6-O-(o-xylylene) bridge locks the conformation of glucopyranose to an axial-rich form. Although the conformational lock induces complete β-selectivity in a glycosylation reaction, the leaving group of the glycosyl donor is limited to fluorine. On the other hand, the bridge confers the furanose-preferred property to glucose, which makes synthesis of corresponding pyranosyl derivatives that equip various leaving groups difficult. This problem was solved through direct phenylthio glucosidation of 3,6-O-(o-xylylene)-1,2,4-O-orthoacetylglucose accompanying cleavage of the orthoester moiety. This paper describes the process of establishing direct thiophenylation. This process reduced the synthetic steps for the known glucopyranosyl fluoride and will expand application of conformationally locked glycosyl donors.

Background Although median sternotomy is standard during cardiac surgery, the procedure is associated with a risk of injury to mediastinal organs. Here, we discuss two cases of tracheal injury following median sternotomy during cardiac surgery. Case presentation Ventilation failure occurred in a 78-year-old Japanese man and a 71-year-old Japanese man after median sternotomy, and tracheal injury was identified. The sites of injury were directly repaired and covered with mediastinal fat tissue, following which ventilation was successful. The burn-like deposits observed at the site of tracheal injury and on the removed endotracheal tube support the notion that the injuries in our patients were caused by electrocautery prior to median sternotomy. In one case, short sternotracheal distance may have contributed to tracheal injury during post-sternal manipulation. In both cases, the relative inexperience of both surgeons also supports the suspected cause of injury. Conclusions Tracheal injury represents a potential complication following median sternotomy, especially when performed by inexperienced surgeons or in cases of short sternotracheal distance. Anesthesiologists should consider this rare yet potentially lethal complication.

The aim of this study was to evaluate the prognostic impact of left ventricular ejection fraction (LVEF) in patients with severe aortic stenosis (AS).The prognostic impact of LVEF in severe AS remains controversial.Among 3,815 consecutive patients with severe AS enrolled in the CURRENT AS (Contemporary Outcomes After Surgery and Medical Treatment in Patients With Severe Aortic Stenosis) registry, the present study population consisted of 3,794 patients after excluding 21 patients without LVEF data. Patients were divided into 4 groups according to LVEF at index echocardiography (50%, 50% to 59%, 60% to 69%, and ≥70%; conservative strategy: n = 388, n = 390, n = 1,025, and n = 800; initial aortic valve replacement strategy: n = 206, n = 170, n = 375, and n = 440). Echocardiographic data were site reported, and there was no echocardiography core laboratory.In the conservative group, the cumulative 5-year incidence of the primary outcome measure (a composite of aortic valve-related death or heart failure hospitalization) was significantly higher in patients with LVEFs 50% and 50% to 59% than in those with LVEFs 60% to 69% and ≥70% (72.3%, 58.4%, 38.7%, and 35.0%, respectively, p 0.001), whereas in the initial aortic valve replacement group, the negative effect of low LVEF was markedly attenuated (20.2%, 20.3%, 17.7%, and 12.4%, respectively, p = 0.03). After adjusting for confounders, LVEF 50% (hazard ratio: 1.82; 95% confidence interval: 1.44 to 2.28; p 0.001) and 50% to 59% (hazard ratio: 1.77; 95% confidence interval: 1.42 to 2.20; p 0.001) but not 60% to 69% (hazard ratio: 1.14; 95% confidence interval: 0.94 to 1.39; p = 0.17) were independently associated with poorer outcomes compared with LVEF ≥70% (reference) in the conservative group. In the initial aortic valve replacement group, the adjusted risk for the primary outcome measure was not significantly different across the 4 LVEF groups.This study demonstrates that survival in patients with severe AS is impaired when LVEF is 60%, and these findings have implications for decision making with regard to the timing of surgical intervention.

Background There are limited data regarding the risk stratification based on peak aortic jet velocity (Vmax) in patients with severe aortic stenosis ( AS ). Methods and Results Among 3815 consecutive patients with severe AS enrolled in the CURRENT AS (Contemporary Outcomes After Surgery and Medical Treatment in Patients With Severe Aortic Stenosis) registry, the study population consisted of 1075 conservatively managed patients with Vmax ≥4.0 m/s and left ventricular ejection fraction ≥50%. The study patients were subdivided into 3 groups based on Vmax (group 1, 4.0 ≤ Vmax AS ‐related events (aortic valve–related death or heart failure hospitalization) was incrementally higher with increasing Vmax (entire population; 38.0%, 49.4%, and 62.8%, P P =0.008; and asymptomatic patients; 29.4%, 38.9%, and 47.7%, P =0.005). After adjusting for confounders, the excess risk of group 2 and group 3 relative to group 1 for AS ‐related events remained significant (hazard ratio, 1.39; 95% CI , 1.07–1.81; P =0.02, and hazard ratio, 1.53; 95% CI , 1.17–2.00; P =0.002, respectively). The effect size of group 3 relative to group 1 for AS ‐related events in asymptomatic patients (N=479) was similar to that in symptomatic patients (N=596; hazard ratio, 1.59; 95% CI , 1.01–2.52; P =0.047, and hazard ratio, 1.67; 95% CI , 1.16–2.40, P =0.008, respectively), and there was no significant overall interaction between the symptomatic status and the effect of the Vmax categories on AS ‐related events (interaction, P =0.88). Conclusions In conservatively managed severe AS patients with preserved left ventricular ejection fraction, increasing Vmax was associated with incrementally higher risk for AS ‐related events. However, the cumulative 5‐year incidence of the AS ‐related events remained very high even in asymptomatic patients with less greater Vmax.

Background: Mechanical reperfusion has proven to be an unquestionably superior treatment strategy over that of thrombolytic therapy in patients with acute coronary syndrome (ACS). Excimer laser coronary angioplasty (ELCA) is a unique revascularization device that has a lytic effect on thrombus, in addition to its debulking effect on the atherosclerotic plaque beneath the thrombus. Methods and Results: This single-center retrospective analysis consisted of consecutive ACS patients treated with ELCA (n=50) and age- and sex-matched ACS patients treated with manual aspiration (n=48) without use of a distal protection device. Success rate was judged by lesion crossability, procedure complications, and significant reduction of stenosis. Tissue-level perfusion was assessed on antegrade Thrombolysis In Myocardial Infarction (TIMI) flow grade, myocardial blush grade (MBG), and ST-segment elevation resolution (STR). Short-term outcome was evaluated according to occurrence of in-hospital major adverse cardiac events (MACE; myocardial infarction, target lesion revascularization, coronary artery bypass graft, and death). Lesion crossability was higher in the ELCA group than in the aspiration group (96.2% vs. 82.6%, P=0.04). Attainment of TIMI 3 flow (86.0% vs. 68.8%, P=0.04) and MBG 3 (76.0% vs. 54.2%, P=0.02) was also higher in the ELCA group than in the aspiration group. Complete STR was similar between the 2 groups. In-hospital MACE were significantly more frequent in the aspiration group. Conclusions: ELCA is feasible, safe, and effective for the treatment of patients with ACS and appears to be useful as an adjunctive lesion preparation device. (Circ J 2013; 77: 1445–1452)

Piericidin A1, 3’-rhamnopiericidin A1, and a novel compound piericidin E, a new quorum-sensing (QS) inhibitor against Chromobacterium violaceum CV026, were isolated from the culture broth of Streptomyces sp. QS is well known as a microbial signaling system and controls certain types of gene expression resulting in bioluminescence, biofilm formation, swarming motility, antibiotic biosynthesis, and virulence factor production. C. violaceum CV026 is commonly used to determine qualitative and quantitative QS activity. The structures of piericidin derivatives were characterized, and their QS activities were determined.

The cytochrome P450 enzyme RosC catalyzes a two-step, hydroxylation and alcohol oxidation, oxidation reaction to form the C-20 formyl group in the biosynthesis of a 16-membered macrolide antibiotic rosamicin produced by Micromonospora rosaria IFO13697. RosC is presumed to be involved in the formation of 20-carboxyrosamicin because it has been isolated from the culture broth of M. rosaria. Here, we confirmed that RosC has catalytic activity, with E. coli expressing RosC converting rosamicin into 20-carboxyrosamicin. Therefore, it was revealed that RosC is a multifunctional P450 that catalyzes a three-step oxidation reaction that leads to the formation of the hydroxyl group, formyl group and carboxyl group at C-20 on the macrolactone ring in the rosamicin biosynthetic pathway. Moreover, the cytochrome P450 enzyme TylI, which is involved in formation of the formyl group of a 16-membered macrolide antibiotic tylosin produced by Streptomyces fradiae ATCC 19609, also converted rosamicin into 20-carboxyrosamicin.

Seventeen new compounds, naphthacemycins A1–A11, B1–B4 and C1–C2, were isolated from a cultured broth of Streptomyces sp. KB-3346-5 during screening for circumventors of β-lactam resistance in methicillin-resistant Staphylococcus aureus. Their structures were elucidated by spectroscopic studies, including NMR and X-ray crystallographic analysis. The naphthacemycin A series has a new skeleton displaying a 7-phenylnaphthacene-5,6,11(12H)-trione. In contrast, the quinone moiety of the A series is changed to dehydroxyquinol in the B series and to a semiquinone-like structure in the C series.

To evaluate real-world outcomes of PCI in unselected individuals using sirolimus-eluting (SESs) or paclitaxel-eluting stents (PESs) in a single-center randomized trial. Eight hundred consecutive patients (919 lesions) with coronary artery disease were randomized to receive SES or PES implantation. In-hospital, mid-term, and 1-year clinical and angiographical outcomes in both groups were compared. MACEs were defined as cardiac death, myocardial infarction, CABG and target vessel revascularization (TLR). Follow-up angiography was performed in 80.7% of patients. The baseline clinical characteristics were similar in both groups. Pre- and postprocedural reference vessel diameter, minimum length diameter, and diameter stenosis (%DS) were similar in both groups, as was incidence of in-hospital and mid-term MACEs. SESs significantly reduced the risk of TLR, compared with PESs (SES = 5.5%, PES = 10.5%). The superiority of SESs for TLR was also demonstrated with regard to small vessel lesions (stent diameter2.5 mm) (SES = 6.0%, PES = 15.9%), whereas larger vessel (stent diameter2.5 mm) lesions did not differ between groups (SES = 5.3%, PES = 8.4%). The safety and efficacy of both DESs were nearly equivalent. SESs, however, were superior to PESs in reducing mid-term TLR, particularly in the small vessel lesion subsets.

A multiscale simulation model is developed for optimizing the parameters of SiO2 plasma-enhanced atomic layer deposition of high-aspect-ratio hole patterns in three-dimensional (3D) stacked memory. This model takes into account the diffusion of a precursor in a reactor, that in holes, and the adsorption onto the wafer. It is found that the change in the aperture ratio of the holes on the wafer affects the concentration of the precursor near the top of the wafer surface, hence the deposition profile in the hole. The simulation results reproduced well the experimental results of the deposition thickness for the various hole aperture ratios. By this multiscale simulation, we can predict the deposition profile in a high-aspect-ratio hole pattern in 3D stacked memory. The atomic layer deposition parameters for conformal deposition such as precursor feeding time and partial pressure of precursor for wafers with various hole aperture ratios can be estimated.

The isothiocyanate sulforaphane [SF; 1-isothiocyanato-4(R)-methylsulfinylbutane] is abundant in broccoli sprouts in the form of its glucosinolate precursor (glucoraphanin). SF is powerfully bactericidal against Helicobacter pylori infections, which are strongly associated with the worldwide pandemic of gastric cancer. Oral treatment with SF-rich broccoli sprouts of C57BL/6 female mice infected with H. pylori Sydney strain 1 and maintained on a high-salt (7.5% NaCl) diet reduced gastric bacterial colonization, attenuated mucosal expression of tumor necrosis factor-α and interleukin-1β, mitigated corpus inflammation, and prevented expression of high salt-induced gastric corpus atrophy. This therapeutic effect was not observed in mice in which the nrf2 gene was deleted, strongly implicating the important role of Nrf2-dependent antioxidant and anti-inflammatory proteins in SF-dependent protection. Forty-eight H. pylori–infected patients were randomly assigned to feeding of broccoli sprouts (70 g/d; containing 420 μmol of SF precursor) for 8 weeks or to consumption of an equal weight of alfalfa sprouts (not containing SF) as placebo. Intervention with broccoli sprouts, but not with placebo, decreased the levels of urease measured by the urea breath test and H. pylori stool antigen (both biomarkers of H. pylori colonization) and serum pepsinogens I and II (biomarkers of gastric inflammation). Values recovered to their original levels 2 months after treatment was discontinued. Daily intake of sulforaphane-rich broccoli sprouts for 2 months reduces H. pylori colonization in mice and improves the sequelae of infection in infected mice and in humans. This treatment seems to enhance chemoprotection of the gastric mucosa against H. pylori–induced oxidative stress.

Reaction of Mo(2)(pyphos)(4) (1) (pyphos = 6-diphenylphosphino-2-pyridonate) with Pd(dba)(2) (dba = dibenzylideneacetone) afforded the Pd(0) complex Mo(2)Pd(2)(pyphos)(4) (2) which has two Pd(0) centers at both axial positions of the Mo(2) core. The unsaturated Pd(0) centers of 2 were coordinated with donor molecules such as olefins, acetylenes, isonitriles, carbon monoxide, and triphenylphosphine to give the corresponding adducts, Mo(2)Pd(2)(pyphos)(4)(L)(2) (3a: L = acrylonitrile, 3b: L = fumaronitrile, 3c: L = tetracyanoethylene, 3d: L = diisopropyl fumarate, 3e: L = diethyl fumarate, 3f: L = dimethyl fumarate, 3g: L = dimethyl maleate, 3h: L = 2,6-xylylisocyanide, 3i: L = tert-butylisocyanide, 3j: L = dimethyl acetylenedicarboxylate, 3k: L = 1,4-benzoquinone, 3l: L = 1,4-naphthoquinone, 3m: L = carbon monooxide, and 3n: L = triphenylphosphine). Oxidative 1,4-addition of ArSSAr and benzoyl peroxide to the Pd(0) centers of 2 afforded the corresponding Pd(I) complexes Mo(2)Pd(2)(SAr)(2)(pyphos)(4) (7a: Ar = C(6)H(5), 7b: Ar = 4-Me(3)CC(6)H(4), 7c: Ar = 4-MeC(6)H(4), 7d: 4-NO(2)C(6)H(4)) and Mo(2)Pd(2)(OCOPh)(2)(pyphos)(4) (9). Chemical oxidation of 2 with [Cp(2)Fe][BF(4)] in CH(3)CN afforded a dicationic Pd(I) complex [Mo(2)Pd(2)(pyphos)(4)(CH(3)CN)(2)][BF(4)](2) (10a). Similarly, the reaction of 2 with [Cp(2)Fe][BF(4)] in the presence of excess amounts of various donor molecules in THF gave rise to corresponding dicationic Pd(I) complexes [Mo(2)Pd(2)(pyphos)(4)(L')(2)][BF(4)](2) (10b; L' = dimethylsulfoxide, 10c: L' = THF, 10d: L' = benzonitrile, 10e: L' = p-methoxyphenylnitrile, 10f: L' = p-trifluoromethylphenylnitrile, 10g: L' = pyridine, and 10h: L' = p-dimethylaminopyridine), whereas complexes [Mo(2)Pd(2)(pyphos)(4)(CNXyl)(2)][BF(4)](2) (10i) and [Mo(2)Pd(2)(pyphos)(4)(CN(t)Bu)(2)][BF(4)](2) (10j) were prepared by oxidation of the corresponding isonitrile-Pd(0) complexes 3h and 3i. Cyclic voltammetry of 10aj displayed two different oxidation profiles of Pd(0) depending on the donor molecules: complexes 10af showed two waves ascribed to electron communication through monocationic species as intermediates, whereas complexes 10gj showed one wave due to two-electron process. Furthermore, the oxidative addition of alkyl and aryl halides to 2 gave rise to two different reaction patterns: excess amounts of benzyl halides BnX (X = Cl, Br, I), PhCl, and PhBr, and 2 equiv of PhI reacted with 2 to give Pd(I) complexes Mo(2)Pd(2)(X)(2)(pyphos)(4) (4a: X = Cl, 4b: X = Br, 4c: X = I), and the reactions of 2 with excess amounts of PhI and MeI afforded Pd(II) complexes Mo(2)Pd(2)(Ph)(2)I(2)(pyphos)(4) (11) and Mo(2)Pd(2)(CH(3))(2)I(2)(pyphos)(4) (13) bearing two "Pd(Ph)I" and "Pd(CH(3))I" moieties.

A holographic data storage channel is normally a nonlinear channel; however, it can be made linear. Using coherent addition of DC components in the reproduction process and calculating the square root of intensity, we can retrieve a linearly reproduced signal. Our simulation results revealed that a conventional equalizer works well to suppress interpixel interference so that a higher recording density can be achieved.

An improvement of the recording density in a coaxial holographic recording system is described. We employ a new optical setup into our coaxial system, where the numerical aperture (NA) of an objective lens and the data capacity in one page increase up to 0.85 and 135 kbits, respectively. The recording performances are evaluated experimentally and numerically. The obtained results demonstrate that implemented techniques successfully improve the recording density by a factor of 1.5, achieving a raw data density of 270 Gbit/in.2.

Cyslabdan, a new potentiator of imipenem activity against methicillin-resistant Staphylococcus aureus, was isolated from the culture broth of Streptomyces sp. K04-0144 by Diaion HP-20 and ODS column chromatographies and preparative HPLC. The structure of cyslabdan was elucidated by spectroscopic analyses including NMR. The compound has a labdane-type diterpene skeleton connecting with an N-acetylcysteine via thioether linkage.

We describe a simple and effective technique for acute aortic dissection using a combination of polyester fabric and a fibrin sealant patch (FSP) to achieve effective reinforcement and haemostasis of the aortic stump. Firstly, the 0.61mm thick knitted polyester fabric sheet was cut to half of the size of the FSP. Next, fibrin glue was sprayed onto the collagen layer of the FSP. Subsequently, a fabric sheet was placed upon it, and the FSP was put together with the irrigated collagen layer, and then completely dried to bind the patch. As a result, the dry fibrinogen/thrombin layers, as an adhesive surface, faced outward. This patch was trimmed to a 10-15-mm-wide strip. The composite patch was inserted into the false lumen. The stump was gently pressed to fix the aortic intima and adventitia. There are several advantages: the combined patch can be prepared during systemic cooling, and therefore can minimise the circulatory arrest time; secondly, the false lumen is not directly exposed to fibrin glue and so the risk of embolism is extremely low; thirdly, the expected haemostatic effect is greater as FSP lines the exterior of the intima, achieving haemostasis for suture holes.

In this paper, we evaluate photopolymer media using a polycarbonate (PC) substrate. In holographic data storage medium, substrates that sandwich the photopolymer material are needed to protect the photopolymer material against exogenous shock and open air. An optical glass such as BK-7 is normally used as a substrate, but a PC substrate has a cost advantage and is easy to fabricate compared with optical glass. For holographic recording and reading, however, the high birefringence and high thermal expansion of a PC substrate are significant problems. First, we analyze the degree of degradation of output power by the polarization change and estimate the threshold value of birefringence to record hologram normally. Next, we estimate the temperature tolerance of hologram readout with polycarbonate substrate hologram medium. These analyses results indicate the possible usage of the PC substrate as holographic recording media.

The Pt0···MoII dative bond of linear tetrametal Pt0–MoII–MoII–Pt0 complexes, Mo2Pt2(pyphos)4(L)2 [4a: L = PPh3; 4b: L = PMe3; 4c: L = PMe2Ph; 4d: L = PMePh2; 4e: L = P(OMe)3], was characterized by means of spectroscopic analysis and X-ray crystallographic studies. Complex 4a reacted with diaryl disulfides to give dithiolate PtI complexes, Mo2Pt2(SAr)2(pyphos)4 [5a: Ar = C6H4Me-4; 5b: C6H4OMe-4; 5c: C6H3Me2-2,6; 5d: C6H5], which are unique 1,4-oxidative addition products.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

We investigated the capability and tolerance of the optical collinear system by numerical simulation. Using Fourier optics, the simulation can calculate the hologram pixel image intensity distribution, the corresponding signal-to-noise-ratio and its histogram. For holographic data storage using the optical collinear system, we presented and we discussed the medium position and the medium thickness dependency, the medium displacement in the x-, and the z-directions during the hologram recording process, and the recording wavelength shift.

Mushrooms and soils samples collected from a sub-alpine forest of Mt. Fuji in Japan were measured for 137Cs and stable Cs. The ranges of 137Cs specific activities and stable Cs concentrations in the mushrooms were 291-7950 Bq kg(-1) dry weight and 4.69-58.1 mg kg(-1) dry weight, respectively. Both 137Cs specific activities and stable Cs concentrations in the mushrooms were higher than those in common agricultural plants. The 137Cs specific activities and stable Cs concentrations in the soils were 3.18-149 Bq kg(-1) dry weight and 0.618-2.18 mg kg(-1) dry weight, respectively. The appearance frequencies of filamentous actinomycetes and planktonic bacteria from the soils decreased according to increasing Cs contents in the medium. No relationship was observed between the appearance frequencies of those and the stable Cs concentrations in the soils. The filamentous actinomycetes from any soil sample could not grow in the presence of 25 mM Cs, although the planktonic bacteria from the soil samples could grow with up to 50 mM Cs in YM agar. In addition, the planktonic bacteria from approximately 70% of the soil samples could grow even in the presence of 100 mM Cs. Filamentous actinomycetes were more sensitive to Cs than planktonic bacteria. In in vitro experiments, Cs uptake by these strains of filamentous actinomycetes and planktonic bacteria was high in the presence of 5 mM CsCl and the strains accumulated Cs, the same as in mushrooms. Our results indicate that filamentous actinomycetes in the soils have higher sensitivity to Cs than planktonic bacteria, and several strains of filamentous actinomycetes have a high Cs accumulation in the presence of 5 mM Cs.

慢性透析患者の冠動脈バイパス術(CABG)症例においては,その周術期管理のさまざまな問題により,合併症発症頻度,早期死亡率とも依然高いのが現状である.そこでわれわれは,慢性透析患者に対し,手術リスクを下げ,かつ周術期合併症を予防する目的で,off-pump CABG (OPCAB)の術中に血液濾過透析(HDF)を施行した.手術開始時よりHDFを開始し,OPCAB(LITA-#8～#10)を施行した.吻合中は,血行動態への影響を軽減するため,透析装置の血液流量を下げ,除水を中断した.吻合終了後は,ヘマトクリット30～35%,中心静脈圧3～5mmHg,血清K+濃度3.0～3.5mEq/lを目標に,開胸のまま,輸血を十分行いながらHDFを続行した.目標達成後,HDFを終了し,術野の出血がないことを十分確認したのちに閉胸を行い,手術を終了した.ICU入室後90分で抜管,翌朝より食事を開始し,術後2日目に一般病室へ転室した.術後3日目から透析室にて週3回の維持透析を再開し,合併症もなく術後11日目に退院となった.OPCABの術中にHDFを施行したことにより,早期抜管,早期離床が可能となり,術後経過がきわめて良好であった慢性透析患者の1例を経験した.

Angiotensin-converting enzyme (ACE) inhibitors have cardioprotective effects in animals, but whether that occurs in humans is still controversial. The effect of myocardial ACE activity on coronary vascular resistance during coronary artery bypass surgery and on serum brain natriuretic peptide (BNP) concentration after surgery was studied in myocardial tissue sampled from the right atrium of patients during cardiac surgery (n=20). Tissue enzyme activity (nmol/min per mg protein) was measured using a photometric technique, and the flow rate and pressure upon antegrade infusion of a crystalloid cardioplegic solution was measured for calculating the coronary vascular resistance (mmHg. ml(-1). min(-1)). Serum BNP concentration (pg/ml) was measured on days 0 and 5 after the surgery. Linear regression between tissue ACE activity and coronary vascular resistance (y = 0.46x + 0.56, r=0.85) as well as serum BNP concentration on days 0 (y = 129x + 30, r=0.59) and 5 (y = 347x + 180, r=0.73) after the surgery was significant (x: ACE activity; y: coronary vascular resistance/serum BNP concentration). The results indicate that inhibition of myocardial ACE activity might improve coronary circulation during surgery and hence, cardiac function after surgery.

Genetic engineering of post-polyketide synthase-tailoring genes can be used to generate new macrolide analogs through manipulation of the genes involved in their biosynthesis. Rosamicin, a 16-member macrolide antibiotic produced by Micromonospora rosaria IFO13697, contains a formyl group and an epoxide at C-20 and C-12/13 positions which are formed by the cytochrome P450 enzymes RosC and RosD, respectively. The d-mycinose biosynthesis genes in mycinamicin II biosynthesis gene cluster of Micomonospora guriseorubida A11725 were introduced into the rosC and rosD disruption mutants of M. rosaria IFO13697. The resulting engineered strains, M. rosaria TPMA0054 and TPMA0069, produced mycinosyl rosamicin derivatives, IZIV and IZV, respectively. IZIV was identified as a novel mycinosyl rosamicin derivative, 23-O-mycinosyl-20-deoxo-20-dihydrorosamicin.

We fabricated strained-Si n-channel metal-oxide-semiconductor field-effect transistors (MOSFETs) on very thin SiGe buffer layers. The ion implantation technique was successfully employed and the Si 0.83 Ge 0.17 relaxed layer with the thickness as small as 100 nm was obtained. As a result, 2.0 times drive current, 2.6 times transconductance and 1.6 times mobility enhancements over the control Si device were obtained, indicating that the ion implantation technique is very promising for realization of high performance strained-Si devices on very thin SiGe virtual substrates.

Thermal stability of strained SOI fabricated by Smart Cut technique was found to be high enough for the current Si process, particularly with SiO2 protection films. The strain states, in-plane and out-of-plane lattice constants, were found not to change after annealing up to 1150 °C with SiO2 films though those of thinner sSOI without the protection film gradually changed due to strain relaxation. It was also found that 3D correction of the orientation mismatch between the Si substrate and the strained Si was essential for precise evaluation of strain states.

As a fabrication method for high quality SiGe relaxed thin layers we developed the ion implantation technique, where SiGe layers were grown on pre-ion-implanted Si substrates, followed by post-anneal for promoting strain relaxation. In this study, Ar+, Ge+ or Si+ ion was employed for implantation and properties of SiGe layers were precisely compared. It was found that the strain relaxation was well enhanced and very uniform in-plane strain-field distribution was obtained by the implantation irrespective of ion elements, but optimized conditions were quite different, implying that the defects properties were different among ions. In the case of Si+ and Ge+ implantation, the surface smoothness was highly improved presumably as a result of higher compatibility of Si+ and Ge+ to the Si substrate than Ar+. Rms roughness as low as 0.2 nm was achieved by Si+ implantation. These results indicate that this ion implantation technique especially with Si+ and Ge+ ions is very promising for high performance strained Si/Ge device applications.

The surgical treatment of constrictive pericarditis often requires extensive pericardial dissection under cardiopulmonary bypass. We performed a pericardiectomy in a patient with constrictive pericarditis without cardiopulmonary bypass, with assistance of a sternal retractor and a suction heart positioner. The severely calcified pericardium, which adhered tightly to the epicardium, was dissected with an ultrasonic scalpel. The operation was completed without blood transfusion. There was no malignant arrhythmia.