Structural disjoining potential for grain boundary premelting and grain coalescence from molecular-dynamics simulations

We describe a molecular dynamics framework for the direct calculation of the short-ranged structural forces underlying grain-boundary premelting and grain-coalescence in solidification. The method is applied in a comparative study of (i) a Sigma 9 120 degress twist and (ii) a Sigma 9 {411} symmetric tilt boundary in a classical embedded-atom model of elemental Ni. Although both boundaries feature highly disordered structures near the melting point, the nature of the temperature dependence of the width of the disordered regions in these boundaries is qualitatively different. The former boundary displays behavior consistent with a logarithmically diverging premelted layer thickness as the melting temperature is approached from below, while the latter displays behavior featuring a finite grain-boundary width at the melting point. It is demonstrated that both types of behavior can be quantitatively described within a sharp-interface thermodynamic formalism involving a width-dependent interfacial free energy, referred to as the disjoining potential. The disjoining potential for boundary (i) is calculated to display a monotonic exponential dependence on width, while that of boundary (ii) features a weak attractive minimum. The results of this work are discussed in relation to recent simulation and theoretical studies of the thermodynamic forces underlying grain-boundary premelting.Comment: 24 pages, 8 figures, 1 tabl

Major histocompatibility complex (Mhc) class Ib gene duplications, organization and expression patterns in mouse strain C57BL/6

<p>Abstract</p> <p>Background</p> <p>The mouse has more than 30 <it>Major histocompatibility complex </it>(<it>Mhc</it>) class Ib genes, most of which exist in the <it>H2 </it>region of chromosome 17 in distinct gene clusters. Although recent progress in <it>Mhc </it>research has revealed the unique roles of several <it>Mhc </it>class Ib genes in the immune and non-immune systems, the functions of many class Ib genes have still to be elucidated. To better understand the roles of class Ib molecules, we have characterized their gene duplication, organization and expression patterns within the <it>H2 </it>region of the mouse strain C57BL/6.</p> <p>Results</p> <p>The genomic organization of the <it>H2-Q</it>, -<it>T </it>and -<it>M </it>regions was analyzed and 21 transcribed <it>Mhc </it>class Ib genes were identified within these regions. Dot-plot and phylogenetic analyses implied that the genes were generated by monogenic and/or multigenic duplicated events. To investigate the adult tissue, embryonic and placental expressions of these genes, we performed RT-PCR gene expression profiling using gene-specific primers. Both tissue-wide and tissue-specific gene expression patterns were obtained that suggest that the variations in the gene expression may depend on the genomic location of the duplicated genes as well as locus specific mechanisms. The genes located in the <it>H2-T </it>region at the centromeric end of the cluster were expressed more widely than those at the telomeric end, which showed tissue-restricted expression in spite of nucleotide sequence similarities among gene paralogs.</p> <p>Conclusion</p> <p>Duplicated <it>Mhc </it>class Ib genes located in the <it>H2-Q</it>, -<it>T </it>and -<it>M </it>regions are differentially expressed in a variety of developing and adult tissues. Our findings form the basis for further functional validation studies of the <it>Mhc </it>class Ib gene expression profiles in specific tissues, such as the brain. The duplicated gene expression results in combination with the genome analysis suggest the possibility of long-range regulation of <it>H2-T </it>gene expression and/or important, but as yet unidentified nucleotide changes in the promoter or enhancer regions of the genes. Since the <it>Mhc </it>genomic region has diversified among mouse strains, it should be a useful model region for comparative analyses of the relationships between duplicated gene organization, evolution and the regulation of expression patterns.</p

Single nucleotide polymorphism detection by polymerase chain reaction-restriction fragment length polymorphism

ArticleNATURE PROTOCOLS. 2(11): 2857-2864 (2007)journal articl

Lack of association of Toll-like receptor 9 gene polymorphism with Behcet's disease in Japanese patients

The definitive version is available at www.blackwell-synergy.com.ArticleTISSUE ANTIGENS. 70(1-5) 423-426 (2007)journal articl

Clinical impact of left and right axis deviations with narrow QRS complex on 3-year outcomes in a hospital-based population in Japan

While the prognostic impact of QRS axis deviation has been assessed, it has never been investigated in patients without conduction block. Thus, we evaluated the prognostic impact of QRS-axis deviation in patients without conduction block. We retrospectively analyzed 3353 patients who had undergone both scheduled transthoracic echocardiography and electrocardiography in 2013 in a hospital-based population, after excluding patients with a QRS duration of ≥ 110 ms, pacemaker placement, and an QRS-axis - 90° to - 180° (northwest axis). The study population was categorized into three groups depending on the mean frontal plane QRS axis as follows: patients with left axis deviation (N = 171), those with right axis deviation (N = 94), and those with normal axis (N = 3088). The primary outcome was a composite of all-cause death and major adverse cardiovascular events. The cumulative 3-year incidence of the primary outcome measure was significantly higher in the left axis deviation group (26.4% in the left axis deviation, 22.7% in the right axis deviation, and 18.4% in the normal axis groups, log-rank P = 0.004). After adjusting for confounders, the excess risk of primary outcome measure remained significant in the left axis deviation group (hazard ratio [HR] 1.44; 95% confidence interval [CI] 1.07-1.95; P = 0.02), while the excess risk of primary outcome measure was not significant in the right axis deviation group (HR 1.22; 95% CI 0.76-1.96; P = 0.41). Left axis deviation was associated with a higher risk of a composite of all-cause death and major adverse cardiovascular events in hospital-based patients without conduction block in Japan

Discrepancy between left ventricular hypertrophy by echocardiography and electrocardiographic hypertrophy: clinical characteristics and outcomes

[Background] The clinical significance of the discrepancy between left ventricular hypertrophy (LVH) by echocardiography and ECG remains to be elucidated. [Methods] After excluding patients who presented with pacemaker placement, QRS duration ≥120 ms and cardiomyopathy and moderate to severe valvular disease, we retrospectively analysed 3212 patients who had undergone both scheduled transthoracic echocardiography (echo) and ECG in a hospital-based population. Cornell product >2440 mm · ms was defined as ECG-based LVH; left ventricular mass index >115 g/m2 for men and >95 g/m2 for women was defined as echo-based LVH. The study population was categorised into four groups: patients with both ECG-based and echo-based LVH (N=131, 4.1%), those with only echo-based LVH (N=156, 4.9%), those with only ECG-based LVH (N=409, 12.7%) and those with no LVH (N=2516, 78.3%). [Results] The cumulative 3-year incidences of a composite of all-cause death and major adverse cardiovascular events were 32.0%, 33.8%, 19.2% and 15.7%, respectively. After adjusting for confounders, the HRs relative to that in no LVH were 1.63 (95% CI 1.16 to 2.28), 1.68 (95% CI 1.23 to 2.30) and 1.09 (95% CI 0.85 to 1.41) in patients with both ECG-based and echo-based LVH, those with only echo-based LVH, and those with only ECG-based LVH, respectively. [Conclusions] Echo-based LVH without ECG-based LVH was associated with a significant risk of adverse clinical events, and the risk was comparable to that in patients with both echo-based and ECG-based LVH

Assessment of Artificial MiRNA Architectures for Higher Knockdown Efficiencies without the Undesired Effects in Mice.

RNAi-based strategies have been used for hypomorphic analyses. However, there are technical challenges to achieve robust, reproducible knockdown effect. Here we examined the artificial microRNA (amiRNA) architectures that could provide higher knockdown efficiencies. Using transient and stable transfection assays in cells, we found that simple amiRNA-expression cassettes, that did not contain a marker gene (-MG), displayed higher amiRNA expression and more efficient knockdown than those that contained a marker gene (+MG). Further, we tested this phenomenon in vivo, by analyzing amiRNA-expressing mice that were produced by the pronuclear injection-based targeted transgenesis (PITT) method. While we observed significant silencing of the target gene (eGFP) in +MG hemizygous mice, obtaining -MG amiRNA expression mice, even hemizygotes, was difficult and the animals died perinatally. We obtained only mosaic mice having both -MG amiRNA cells and amiRNA low-expression cells but they exhibited growth retardation and cataracts, and they could not transmit the -MG amiRNA allele to the next generation. Furthermore, +MG amiRNA homozygotes could not be obtained. These results suggested that excessive amiRNAs transcribed by -MG expression cassettes cause deleterious effects in mice, and the amiRNA expression level in hemizygous +MG amiRNA mice is near the upper limit, where mice can develop normally. In conclusion, the PITT-(+MG amiRNA) system demonstrated here can generate knockdown mouse models that reliably express highest and tolerable levels of amiRNAs