Atomic structures of a liquid-phase bonded metal/nitride heterointerface.

Liquid-phase bonding is a technologically important method to fabricate high-performance metal/ceramic heterostructures used for power electronic devices. However, the atomic-scale mechanisms of how these two dissimilar crystals specifically bond at the interfaces are still not well understood. Here we analyse the atomically-resolved structure of a liquid-phase bonded heterointerface between Al alloy and AlN single crystal using aberration corrected scanning transmission electron microscopy (STEM). In addition, energy-dispersive X-ray microanalysis, using dual silicon drift X-ray detectors in STEM, was performed to analyze the local chemistry of the interface. We find that a monolayer of MgO is spontaneously formed on the AlN substrate surface and that a polarity-inverted monolayer of AlN is grown on top of it. Thus, the Al alloy is bonded with the polarity-inverted AlN monolayer, creating a complex atomic-scale layered structure, facilitating the bonding between the two dissimilar crystals during liquid-phase bonding processes. Density-functional-theory calculations confirm that the bonding stability is strongly dependent on the polarity and stacking of AlN and MgO monolayers. Understanding the spontaneous formation of layered transition structures at the heterointerface will be key in fabricating very stable Al alloy/AlN heterointerface required for high reliability power electronic devices.

Exome Sequencing Identification of EP300 Mutation in a Proband with Coloboma and Imperforate Anus: Possible Expansion of the Phenotypic Spectrum of Rubinstein-Taybi Syndrome.

Rubinstein-Taybi syndrome (RSTS) is a multisystem developmental disorder characterized by facial dysmorphisms, broad thumbs and halluces, growth retardation, and intellectual disability. In about 8% of RSTS cases, mutations are found in EP300. Previously, the EP300 mutation has been shown to cause the highly variable RSTS phenotype. Using exome sequencing, we identified a de novo EP300 frameshift mutation in a proband with coloboma, facial asymmetry and imperforate anus with minimal RSTS features. Previous molecular studies have demonstrated the importance of EP300 in oculogenesis, supporting the possibility that EP300 mutation may cause ocular coloboma. Since a wide phenotypic spectrum is well known in EP300-associated RSTS cases, the atypical phenotype identified in our proband may be an example of rare manifestations of RSTS.

Esco1 Acetylates Cohesin via a Mechanism Different from That of Esco2.

Sister chromatid cohesion is mediated by cohesin and is essential for accurate chromosome segregation. The cohesin subunits SMC1, SMC3, and Rad21 form a tripartite ring within which sister chromatids are thought to be entrapped. This event requires the acetylation of SMC3 and the association of sororin with cohesin by the acetyltransferases Esco1 and Esco2 in humans, but the functional mechanisms of these acetyltransferases remain elusive. Here, we showed that Esco1 requires Pds5, a cohesin regulatory subunit bound to Rad21, to form cohesion via SMC3 acetylation and the stabilization of the chromatin association of sororin, whereas Esco2 function was not affected by Pds5 depletion. Consistent with the functional link between Esco1 and Pds5, Pds5 interacted exclusively with Esco1, and this interaction was dependent on a unique and conserved Esco1 domain. Crucially, this interaction was essential for SMC3 acetylation and sister chromatid cohesion. Esco1 localized to cohesin localization sites on chromosomes throughout interphase in a manner that required the Esco1-Pds5 interaction, and it could acetylate SMC3 before and after DNA replication. These results indicate that Esco1 acetylates SMC3 via a mechanism different from that of Esco2. We propose that, by interacting with a unique domain of Esco1, Pds5 recruits Esco1 to chromatin-bound cohesin complexes to form cohesion. Furthermore, Esco1 acetylates SMC3 independently of DNA replication.

Identification of non-Ser/Thr-Pro consensus motifs for Cdk1 and their roles in mitotic regulation of C2H2 zinc finger proteins and Ect2.

The cyclin B-dependent protein kinase Cdk1 is a master regulator of mitosis and phosphorylates numerous proteins on the minimal consensus motif Ser/Thr-Pro (S/T-P). At least in several proteins, however, not well-defined motifs lacking a Pro in the +1 position, referred herein to as non-S/T-P motifs, have been shown to be phosphorylated by Cdk1. Here we show that non-S/T-P motifs in fact form consensus sequences for Cdk1 and probably play roles in mitotic regulation of physiologically important proteins. First, we show, by in vitro kinase assays, that previously identified non-S/T-P motifs all harbour one or more C-terminal Arg/Lys residues essential for their phosphorylation by Cdk1. Second, using Arg/Lys-scanning oriented peptide libraries, we demonstrate that Cdk1 phosphorylates a minimal sequence S/T-X-X-R/K and more favorable sequences (P)-X-S/T-X-[R/K](2-5) as its non-S/T-P consensus motifs. Third, on the basis of these results, we find that highly conserved linkers (typically, T-G-E-K-P) of C2H2 zinc finger proteins and a nuclear localization signal-containing sequence (matching P-X-S-X-[R/K]5) of the cytokinesis regulator Ect2 are inhibitorily phosphorylated by Cdk1, well accounting for the known mitotic regulation and function of the respective proteins. We suggest that non-S/T-P Cdk1 consensus motifs identified here may function to regulate many other proteins during mitosis.

The Effects of Percutaneous Endoscopic Gastrostomy on Quality of Life in Patients With Dementia.

BACKGROUND: To examine the effects of percutaneous endoscopic gastrostomy (PEG) on quality of life (QOL) in patients with dementia. METHODS: We retrospectively included 53 Japanese community and tertiary hospitals to investigate the relationship between the newly developed PEG and consecutive dementia patients with swallowing difficulty between Jan 1st 2006 and Dec 31st 2008. We set improvements in 1) the level of independent living, 2) pneumonia, 3) peroral intake as outcome measures of QOL and explored the factors associated with these improvements. RESULTS: Till October 31st 2010, 1,353 patients with Alzheimer's dementia (33.1%), vascular dementia (61.7%), dementia with Lewy body disease (2.0%), Pick disease (0.6%) and others were followed-up for a median of 847 days (mean 805 ± 542 days). A total of 509 deaths were observed (mortality 59%) in full-followed patients. After multivariate adjustments, improvement in the level of independent living was observed in milder dementia, or those who can live independently with someone, compared with advanced dementia, characterized by those who need care by someone: Odds Ratio (OR), 3.90, 95% confidence interval (95%CI), 1.59 - 9.39, P = 0.003. Similarly, improvement of peroral intake was noticed in milder dementia: OR, 2.69, 95%CI, 1.17 - 6.17, P = 0.02. Such significant associations were not observed in improvement of pneumonia. CONCLUSIONS: These results suggest that improvement of QOL after PEG insertion may be expected more in milder dementia than in advanced dementia.

Randomised controlled trial evaluating the efficacy of wrap therapy for wound healing acceleration in patients with NPUAP stage II and III pressure ulcer.

Objectives To evaluate if 'wrap therapy' using food wraps, which is widely used in Japanese clinical sites, is not inferior when compared to guideline adhesion treatments. Design Multicentre, prospective, randomised, open, blinded endpoint clinical trial. Setting 15 hospitals in Japan. Patients 66 older patients with new National Pressure Ulcer Advisory Panel stage II or III pressure ulcers. Interventions Of these 66 patients, 31 were divided into the conventional treatment guidelines group and 35 into the wrap therapy group. Main outcome measures The primary end point was the period until the pressure ulcers were cured. The secondary end point was a comparison of the speed of change in the Pressure Ulcer Scale for Healing score. Results 64 of the 66 patients were analysed. The estimated mean period until healing was 57.5 days (95% CI 45.2 to 69.8) in the control group as opposed to 59.8 days (95% CI 49.7 to 69.9) in the wrap therapy group. By the extent of pressure ulcer infiltration, the mean period until healing was 16.0 days (95% CI 8.1 to 23.9) in the control group as opposed to 18.8 days (95% CI 10.3 to 27.2) in the wrap therapy group with National Pressure Ulcer Advisory Panel stage II ulcers, and 71.8 days (95% CI 61.4 to 82.3) as opposed to 63.2 days (95% CI 53.0 to 73.4), respectively, with stage III ulcers. There is no statistical significance in difference in Pressure Ulcer Scale for Healing scores. Conclusions It might be possible to consider wrap therapy as an alternative choice in primary care settings as a simple and inexpensive dressing care. Clinical Trial registration UMIN Clinical Trials Registry UMIN000002658. Summary protocol is available on https://upload.umin.ac.jp/cgi-bin/ctr/ctr.cgi?function=brows&action=brows&type=detail&recptno=R000003235&admin=0&language=J.

Survival of geriatric patients after percutaneous endoscopic gastrostomy in Japan.

AIM: To examine the long term survival of geriatric patients treated with percutaneous endoscopic gastrostomy (PEG) in Japan. METHODS: We retrospectively included 46 Japanese community and tertiary hospitals to investigate 931 consecutive geriatric patients (≥ 65 years old) with swallowing difficulty and newly performed PEG between Jan 1st 2005 and Dec 31st 2008. We set death as an outcome and explored the associations among patient's characteristics at PEG using log-rank tests and Cox proportional hazard models. RESULTS: Nine hundred and thirty one patients were followed up for a median of 468 d. A total of 502 deaths were observed (mortality 53%). However, 99%, 95%, 88%, 75% and 66% of 931 patients survived more than 7, 30, 60 d, a half year and one year, respectively. In addition, 50% and 25% of the patients survived 753 and 1647 d, respectively. Eight deaths were considered as PEG-related, and were associated with lower serum albumin levels (P = 0.002). On the other hand, among 28 surviving patients (6.5%), PEG was removed. In a multivariate hazard model, older age [hazard ratio (HR), 1.02; 95% confidence interval (CI), 1.00-1.03; P = 0.009], higher C-reactive protein (HR, 1.04; 95% CI: 1.01-1.07; P = 0.005), and higher blood urea nitrogen (HR, 1.01; 95% CI: 1.00-1.02; P = 0.003) were significant poor prognostic factors, whereas higher albumin (HR, 0.67; 95% CI: 0.52-0.85; P = 0.001), female gender (HR, 0.60; 95% CI: 0.48-0.75; P < 0.001) and no previous history of ischemic heart disease (HR, 0.69; 95% CI: 0.54-0.88, P = 0.003) were markedly better prognostic factors. CONCLUSION: These results suggest that more than half of geriatric patients with PEG may survive longer than 2 years. The analysis elucidated prognostic factors.

Effects of lacquer polysaccharides, glycoproteins and isoenzymes on the activity of free and immobilised laccase from Rhus vernicifera.

The purified polysaccharides, glycoproteins, and isoenzymes of Rhus laccase, and crude enzymes, from Chinese lacquer (Rhus vernicifera sap) were used to determine their influence on the enzymic activity of Rhus laccase on several substrates (4-phenylenediamine, isoeugenol and coniferyl alcohol). No product identity changes were observed when these components were added singularly or in combination to the enzymic reactions (only relative product yields varied significantly), however, the polysaccharides (GP1 and GP2) and glycoprotein (stellacyanin, St) exhibited negative effects, and the two isoenzymes (L1 and L2) exhibited positive synergistic effects, on the activity of Rhus laccase. With respect to the activity of the crude enzymes, the negative effects of GP1, GP2 and St were greater than the positive effects of L1 and L2, compared with free Rhus laccase on its own (using 4-phenylenediamine as substrate), the estimated inhibitory effect (of GP1, GP2 and St) being by at least a factor of 50 (even with the positive effect of L1 and L2). This contributes to understanding of lacquer storage stability and drying rates. Immobilisation of crude enzymes using a variety of techniques (using natural and modified polysaccharides, and an inorganic support) where evaluated using isoeugenol as substrate. Agar embedding and zirconium chloride chelation methods resulted in the highest substrate conversion levels. The yields and products of isoeugenol catalysis using Vietnamese crude enzymes/purified Rhus laccase and commercial Denilite laccase were also compared and contrasted with their Chinese lacquer sap equivalents.

Sinusoidal-wavelength-scanning interferometer with double feedback control for real-time distance measurement.

In addition to a conventional phase a the interference signal of a sinusoidal-wavelength-scanning interferometer has a phase-modulation amplitude Zb that is proportional to the optical path difference L and amplitude b of the wavelength scan. L and b are controlled by a double feedback system so that the phase alpha and the amplitude Zb are kept at 3pi/2 and pi, respectively. The voltage applied to a device that displaces a reference mirror to change the optical path difference becomes a ruler with scales smaller than a wavelength. Voltage applied to a device that determines the amplitude of the wavelength scan becomes a ruler marking every wavelength. These two rulers enable one to measure an absolute distance longer than a wavelength in real time.