In Situ Study of Twin Boundary Stability in Nanotwinned Copper Pillars under Different Strain Rates.

The nanoscopic deformation of ⟨111⟩ nanotwinned copper nanopillars under strain rates between 10-5/s and 5 × 10-4/s was studied by using in situ transmission electron microscopy. The correlation among dislocation activity, twin boundary instability due to incoherent twin boundary migration and corresponding mechanical responses was investigated. Dislocations piled up in the nanotwinned copper, giving rise to significant hardening at relatively high strain rates of 3-5 × 10-4/s. Lower strain rates resulted in detwinning and reduced hardening, while corresponding deformation mechanisms are proposed based on experimental results. At low/ultralow strain rates below 6 × 10-5/s, dislocation activity almost ceased operating, but the migration of twin boundaries via the 1/4 ⟨101¯ ⟩ kink-like motion of atoms is suggested as the detwinning mechanism. At medium strain rates of 1-2 × 10-4/s, detwinning was decelerated likely due to the interfered kink-like motion of atoms by activated partial dislocations, while dislocation climb may alternatively dominate detwinning. These results indicate that, even for the same nanoscale twin boundary spacing, different nanomechanical deformation mechanisms can operate at different strain rates.

Sofosbuvir-based direct-acting antivirals and changes in cholesterol and low density lipoprotein-cholesterol.

Worsened lipid profiles were observed in chronic hepatitis C (CHC) patients during direct-acting antivirals (DAAs) treatment, among which combination drugs confounded the effect of individual ingredient on lipid. Tenofovir alafenamide (TAF) also worsened lipid profiles in HIV patients. Structural similarity between sofosbuvir (SOF) and TAF prompted us to investigate rapid increase in total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in CHC patients treated with SOF-based DAAs. A retrospective study was performed to analyze 487 CHC patients receiving DAAs with SVR12. Relative risks on elevating TC and LDL-C were analyzed by logistic regression to determine SOF-based over non-SOF-based regimens. TC or LDL-C levels at baseline, week-4 and SVR12 were compared by Wilcoxon matched-pairs signed rank test. Week 4 or SVR12 to baseline ratios of serum TC or LDL-C between regimens were compared by Mann-Whitney's test. 487 patients were treated with Harvoni (SOF-based, 206 patients), Epclusa (SOF-based, 124 patients), Maviret (non-SOF-based, 122 patients), or Zepatier (non-SOF-based, 35 patients). At week 4 during drug treatment, Harvoni, Epclusa, and Maviret induced statistically significant elevation of TC and LDL-C, but Zepatier did not. SOF-based regimens had 2.72-fold higher relative risk (RR) causing 10% elevation of TC (95% CI 1.84-4.02, p < 0.001) and 2.04-fold higher RR causing 10% elevation of LDL-C (95% CI 1.39-3.01, p < 0.001) than non-SOF-based DAAs. SOF-based DAAs were associated with significantly larger amplitude of increases in TC and LDL-C than non-SOF-based DAAs during the initial 4 weeks of treatment, but the increases were not sustained to SVR12.

Differential H. pylori-Induced MAPK Responses Regulate Lewis Antigen Expression and Colonization Density on Gastric Epithelial Cells Between Children and Adults.

Helicobacter pylori causes gastrointestinal diseases, the manifestations of diseases are more serious in adults than in children. Lewis antigen expressions on the gastric epithelium serves as receptors targeted by H. pylori. Moreover, the MAPK signaling pathway involves glycoprotein synthesis of Lewis antigens. We aimed to investigate whether differences in H. pylori-induced MAPK responses mediate gastric Lewis antigens expression and colonization density differently in children and adults. We used human stomach fetal epithelium (HSFE) and SV40-immortalized human normal gastric epithelial (GES-1) cell lines to mimic primary gastric epithelium of children and adults, respectively. H. pylori colonization intensity and Lewis antigens were significantly higher in GES-1 than in HSFE cells, whereas IL-8 and IL-6 levels were significantly higher in HSFE than in GES-1 cells after infection. c-Jun N-terminal kinase (JNK) siRNA and inhibitor (SP600125) experiments showed that Lewis antigen expression and H. pylori colonization were reduced in GES-1 cells but increased in HSFE cells. Furthermore, p-p38 intensity was significantly higher in the superficial epithelium of the children than in the adults with/without H. pylori infection. The overexpression of p38 in GES-1 cells downregulated H. pylori-induced JNK activity mimicking H. pylori infection in children. In conclusion, a higher p38 expression in gastric epithelium counteracting JNK activity in children may contribute to lower Lewis antigen expression and colonization density than in adults after H. pylori infection.

Pd-Catalyzed sequential hydroarylation and olefination reactions of 3-allylchromones.

In this paper, a novel approach to regioselective α- or γ-hydroarylation of 3-allylchromones with electron-rich arenes has been presented. Results of this study indicated that the regioselectivity was dependent on the substituent at the γ-position of the allyl group. Hydrogen or alkyl substitution favored α-hydroarylation, whereas aryl substitution favored γ-hydroarylation. This methodology provides an efficient means to achieve the α- or γ-selective hydroarylation of 3-allylchromones. Application of α-hydroarylation to perform Pd-catalyzed one-pot sequential α-hydroarylation and π-chelation-assisted olefination has also been reported.

Correlation between the Microstructures of Bonding Interfaces and the Shear Strength of Cu-to-Cu Joints Using (111)-Oriented and Nanotwinned Cu.

Highly (111)-oriented Cu pillar-bumps were bonded to highly (111)-oriented Cu films at temperatures ranging from 200 °C/100 °C to 350 °C/100 °C in N2 ambient conditions. The microstructures of the bonded interfaces affected the shear strength performance of the bonded Cu joints. The bonded interfaces at 300 °C/100 °C and 350 °C/100 °C had far fewer voids than interfaces bonded at 200 °C/100 °C and 250 °C/100 °C. In addition, grain growth took place across the bonding interfaces at temperatures above 300 °C/100 °C. The corresponding orientation map (OIM) showed the preferred orientation of large grown grains to be <100>. Shear tests revealed that the fracture mode was brittle for joints bonded at 200 °C/100 °C, but became ductile after bonded above 300 °C/100 °C. Based on the results, we found that voids and grain growth behavior play import roles in the shear strength performance of bonded Cu joints.

Copper-to-copper direct bonding on highly (111)-oriented nanotwinned copper in no-vacuum ambient.

A vacuum-free Cu-to-Cu direct bonding by using (111)-oriented and nanotwinned Cu has been achieved. A fast bonding process occurs in 5 min under a temperature gradient between 450 and 100 °C. It is verified by grain growth across the bonded interface. To investigate the grain growth behavior, further annealing in the temperature gradient, as well as in a reversed temperature gradient, was performed. They showed similar recrystallization behavior with de-twinning. To analyze the de-twinning, we recall the classic model of annealing twin formation by Fullman and Fisher as comparison. Our case is opposite to the model of Fullman and Fisher. A mechanism of direct bonding by surface diffusion creep is proposed.

A new strategy for emergency department crowding: High-turnover utility bed intervention.

BACKGROUND: This study applied a new strategy, termed high-turnover utility bed intervention, to offer early admission chances for emergency department (ED) patients and alleviate ED crowding. METHODS: This before-and-after observational cohort study was conducted at the ED of an urban tertiary hospital. On January 1, 2012, 14 utility beds were prepared exclusively for ED patient use. A strict 48-hour course limit for each patient was formulated to govern these high-turnover beds. The primary outcome measure for this study was ED length of stay. Secondary outcome measures were the number of ED admissions, patients who left without being seen, and revisits within 72 hours of discharge, as well as the outcomes of cardiac arrest management and ambulance diversion hours. RESULTS: There were 70,515 adult ED visits enrolled during the preintervention period (January-December 2011), and 69,706 during the postintervention period (July 2012-June 2013). In the postintervention period, this new strategy offered 1401 early admission opportunities. The ambulance diversion hours decreased prominently from 5.4 hours to 1.6 hours per day. A shortening in ED length of stay from 9.7 hours to 8.0 hours was achieved, mainly in cases of nontrauma. More patients (31.2% vs. 29.7%) were admitted to the wards with a lower discharge rate in the postintervention period. Additionally, there was no difference in ED revisit within 72 hours and cardiac arrest management. CONCLUSION: The high-turnover ED utility bed intervention offered improved admission chance and alleviated ED crowding output. ED efficiency improved, with shortened ED length of stay and fewer ambulance diversion hours.

Effect of grain orientations of Cu seed layers on the growth of <111>-oriented nanotwinned Cu.

We investigate the growth of Cu films on two different Cu seed layers: one with regular <111>-oriented grains and the other with very strong <111>-preferred orientation. It is found that densely-packed nanotwinned Cu (nt-Cu) can be grown by pulsed electroplating on the strong <111>-oriented Cu seed layer without a randomly-oriented transition layer between the nt-Cu and the Cu seed layer. The electroplated nt-Cu grow almost epitaxially on the seed layer and formed <111>-oriented columnar structures. However, with the regular <111>-oriented Cu seed, there is a randomly-oriented transition layer between the nt-Cu and the regular <111>-oriented Cu seed. The results indicate that the seed layer plays a crucial role on the regularity of <111>-oriented nanotwinned Cu.

Unidirectional growth of microbumps on (111)-oriented and nanotwinned copper.

Highly oriented [111] Cu grains with densely packed nanotwins have been fabricated by direct-current electroplating with a high stirring rate. The [111]-oriented and nanotwinned Cu (nt-Cu) allow for the unidirectional growth of Cu(6)Sn(5) intermetallics in the microbumps of three-dimensional integrated-circuit packaging; a uniform microstructure in a large number of microbumps of controlled orientation can be obtained. The high-density twin boundaries in the nt-Cu serve as vacancy sinks during the solid-state reaction between Pb-free solder and Cu and greatly reduce the formation of Kirkendall (or Frenkel) voids.

Risk factors associated with non-alcoholic fatty liver disease in Chinese patients and the role of tumor necrosis factor-alpha.

BACKGROUND/AIMS: Tumor necrosis factor-alpha (TNFalpha) has been reported to be associated with insulin resistance and induce inflammatory cytokines formation. Previous studies in human and animals showed inhibition of TNF-alpha improved severity of non-alcoholic fatty liver disease (NAFLD). The aims of this study were to measure plasma levels of TNFalpha in NAFLD and healthy subjects and investigate potential risk factors. METHODOLOGY: A total of 144 patients (90 NAFLD, 50 controls) were enrolled. Clinical and laboratory data of each patient were collected. Plasma levels of TNF-alpha were measured with a commercially available solid phase sandwich enzyme-linked immunosorbent assay (R&D systems, USA). The lower detection limit of this assay was 0.12 pg/mL. RESULTS: Multivariate analyses showed elevated triglyceride (odds ratio: 7.30, p<0.001) and BMI >25 kg/m2 (odds ratio: 3.57, p<0.005) were the two factors associated with NAFLD. Mean plasma level of TNF-alpha was significantly higher in NAFLD patients with abnormal ALT than controls (2.63+/-0.44 pg/mL vs. 1.56+/-0.10 pg/mL, p=0.016). Modest correlations were noted between plasma levels of TNF-alpha with ALT (r=0.25, p<0.005) and triglyceride (r=0.40, p<0.001). CONCLUSIONS: TNF-alpha may participate in the pathogenesis of NAFLD. Inhibition of TNF-alpha activity by drugs or antibodies may be a potential approach to treat NAFLD patients.