Simulation of Deformation of Ni Twinned Nanocrystal Model by Molecular Dynamics

Molecular dynamics simulation of nickel crystal under uniaxial tensile and compressive deformation was performed for single nenocrystal model and twinned nanocrystal model composed of 1550 atoms using EAM (embedded atom method) potential with the object of investigating deformation induced phase tranformation (especially twin deformation). In the case of single nanocrystal model, the evolution and development of twin deformation, (111)[11(2)], is observed under compressive loading in [001] direction, whereas either slip or twin deformation is not recognized under tensile loading. In the case of twinned nanocrystal model, twin, (111)[11(2)], decreases and disappears under tensile loading, and develops under compressive loading, It is suggested from the difference of results between single nanocrystal model and twinned nanocrystal model that it is easy for twin to induce local deformation

Important parameters in the detection of left main trunk disease using stress myocardial perfusion imaging

SummaryObjectivesWe sought noninvasively to diagnose left main trunk (LMT) disease using myocardial perfusion imaging (MPI).MethodsFive hundred and eight patients with suspected coronary artery disease (CAD) underwent both stress MPI and coronary angiography. The extent and severity of perfusion abnormalities were assessed using a 20-segment model. In addition, perfusion defects in both left anterior descending and left circumflex arterial territories were defined as a left main (LM) pattern defect, and those in 3-coronary arterial territories as a 3-vessel pattern defect.ResultsIn 42 patients with LMT disease, a summed stress score (19.4±10.0 vs. 13.5±10.0; p<0.0001) and a summed rest score (12.1±9.7 vs. 7.0±7.8; p=0.002) were greater than in 466 patients without LMT disease, while a summed difference score was similar (7.3±7.7 vs. 6.5±6.1; p=NS). The prevalence of an LM-pattern defect was low in both groups (12% vs. 8%; p=NS). However, a 3-vessel pattern defect (33% vs. 7%; p<0.0001), lung uptake of radiotracers (38% vs. 11%; p<0.0001), and transient ischemic dilation (31% vs. 13%; p=0.003) were more frequently observed in patients with LMT disease than in those without. Logistic regression analysis showed that a 3-vessel pattern defect (OR=3.5, 95% CI=1.4–8.8; p=0.007), lung uptake of radiotracers (OR=2.5, 95% CI=1.1–5.7; p=0.03), and previous myocardial infarction (MI) (OR=2.4, 95% CI=1.0–5.7; p=0.05) were the most important parameters to detect LMT disease. After excluding 163 patients with previous MI, a repeat analysis revealed that lung uptake of radiotracers (OR=8.2, 95% CI=2.3–29.2; p=0.001) and an LM-pattern defect (OR=6.3, 95% CI=1.4–27.2; p<0.02) were independent predictors for LMT disease.ConclusionIn the identification of LMT disease, lung uptake of radiotracers was a single best parameter, which was independent of the presence or absence of previous MI

Delta-Function Bose Gas Picture of S=1 Antiferromagnetic Quantum Spin Chains Near Critical Fields

We study the zero-temperature magnetization curve (M-H curve) of the S=1 bilinear-biquadratic spin chain, whose Hamiltonian is given by $H=\sum_{i} S_i S_{i+1}+\beta (S_iS_{i+1})^2 with$0 \leq \beta <1$. We focus on validity of the delta-function bose-gas picture near the two critical fields: the saturation field$H_s$and the lower critical field$H_c$associated with the Haldane gap. Near$H_s$, we take ``low-energy effective S-matrix'' approach, which gives correct effective bose-gas coupling constant$c$, different from the spin-wave value. Comparing the M-H curve of the bose gas with the product-wavefunction renormalization group (PWFRG) calculation, excellent agreement is seen. Near$H_c$, comparing the PWFRG result with the bose-gas prediction, we find that there are two distinct regions of$\beta$separated by a critical value$\beta_c(\approx 0.41)$. In the region$0<\beta<\beta_c$, the effective coupling$c$is positive but rather small. The small value of$c$makes the ``critical region'' of the square-root behavior$M\sim \sqrt{H-H_c}$very narrow. Further, we find that in the$\beta \to \beta_c-0$, the square-root behavior transmutes to a different one,$M\sim (H-H_c)^{1/4}$. In the region$\beta_c<\beta <1$, the square-root behavior is rather distinct, but the effective coupling$c$ becomes negative.Comment: 6 pages, RevTeX, 8 ps figure

miR-1246 in tumor extracellular vesicles promotes metastasis via increased tumor cell adhesion and endothelial cell barrier destruction

BackgroundTumor blood vessels play a key role in tumor metastasis. We have previously reported that tumor endothelial cells (TECs) exhibit abnormalities compared to normal endothelial cells. However, it is unclear how TECs acquire these abnormalities. Tumor cells secrete extracellular vesicles (EVs) to create a suitable environment for themselves. We have previously identified miR-1246 to be more abundant in high metastatic melanoma EVs than in low metastatic melanoma EVs. In the current study, we focused on miR-1246 as primarily responsible for acquiring abnormalities in TECs and examined whether the alteration of endothelial cell (EC) character by miR-1246 promotes cancer metastasis.MethodsWe analyzed the effect of miR-1246 in metastatic melanoma, A375SM-EVs, in vivo metastasis. The role of tumor EV-miR-1246 in the adhesion between ECs and tumor cells and the EC barrier was addressed. Changes in the expression of adhesion molecule and endothelial permeability were examined.ResultsIntravenous administration of A375SM-EVs induced tumor cell colonization in the lung resulting in lung metastasis. In contrast, miR-1246 knockdown in A375SM decreased lung metastasis in vivo. miR-1246 transfection in ECs increased the expression of adhesion molecule ICAM-1 via activation of STAT3, followed by increased tumor cell adhesion to ECs. Furthermore, the expression of VE-Cadherin was downregulated in miR-1246 overexpressed EC. A375SM-EV treatment enhanced endothelial permeability. VE-Cadherin was validated as the potential target gene of miR-1246 via the target gene prediction database and 3′ UTR assay.ConclusionmiR-1246 in high metastatic tumor EVs promotes lung metastasis by inducing the adhesion of tumor cells to ECs and destroying the EC barrier

Plasma angiotensin-converting enzyme 2 (ACE2) is a marker for renal outcome of diabetic kidney disease (DKD) (U-CARE study 3)

Introduction ACE cleaves angiotensin I (Ang I) to angiotensin II (Ang II) inducing vasoconstriction via Ang II type 1 (AT1) receptor, while ACE2 cleaves Ang II to Ang (1-7) causing vasodilatation by acting on the Mas receptor. In diabetic kidney disease (DKD), it is still unclear whether plasma or urine ACE2 levels predict renal outcomes or not. Research design and methods Among 777 participants with diabetes enrolled in the Urinary biomarker for Continuous And Rapid progression of diabetic nEphropathy study, the 296 patients followed up for 9 years were investigated. Plasma and urinary ACE2 levels were measured by the ELISA. The primary end point was a composite of a decrease of estimated glomerular filtration rate (eGFR) by at least 30% from baseline or initiation of hemodialysis or peritoneal dialysis. The secondary end points were a 30% increase or a 30% decrease in albumin-to-creatinine ratio from baseline to 1 year. Results The cumulative incidence of the renal composite outcome was significantly higher in group 1 with lowest tertile of plasma ACE2 (p=0.040). Group 2 with middle and highest tertile was associated with better renal outcomes in the crude Cox regression model adjusted by age and sex (HR 0.56, 95% CI 0.31 to 0.99, p=0.047). Plasma ACE2 levels demonstrated a significant association with 30% decrease in ACR (OR 1.46, 95% CI 1.044 to 2.035, p=0.027) after adjusting for age, sex, systolic blood pressure, hemoglobin A1c, and eGFR. Conclusions Higher baseline plasma ACE2 levels in DKD were protective for development and progression of albuminuria and associated with fewer renal end points, suggesting plasma ACE2 may be used as a prognosis marker of DKD.Trial registration number UMIN000011525

Tumor-Derived Microvesicles Induce Proangiogenic Phenotype in Endothelial Cells via Endocytosis

Background: Increasing evidence indicates that tumor endothelial cells (TEC) differ from normal endothelial cells (NEC). Our previous reports also showed that TEC were different from NEC. For example, TEC have chromosomal abnormality and proangiogenic properties such as high motility and proliferative activity. However, the mechanism by which TEC acquire a specific character remains unclear. To investigate this mechanism, we focused on tumor-derived microvesicles (TMV). Recent studies have shown that TMV contain numerous types of bioactive molecules and affect normal stromal cells in the tumor microenvironment. However, most of the functional mechanisms of TMV remain unclear. Methodology/Principal Findings: Here we showed that TMV isolated from tumor cells were taken up by NEC through endocytosis. In addition, we found that TMV promoted random motility and tube formation through the activation of the phosphoinositide 3-kinase/Akt pathway in NEC. Moreover, the effects induced by TMV were inhibited by the endocytosis inhibitor dynasore. Our results indicate that TMV could confer proangiogenic properties to NEC partly via endocytosis. Conclusion: We for the first time showed that endocytosis of TMV contributes to tumor angiogenesis. These findings offer new insights into cancer therapies and the crosstalk between tumor and endothelial cells mediated by TMV in the tumor microenvironment