Improved performance of pentacene OTFTs with HfLaO gate dielectric by using fluorination and nitridation

Pentacene organic thin-film transistors (OTFTs) with fluorinated high-κ HfLaO as gate insulator were fabricated. The dielectrics were prepared by sputtering method and then annealed in N 2 or NH 3 at 400 °C. Subsequently, the dielectrics were treated by fluorine plasma for different durations (100, 300, and 900 s). The N 2 and NH 3-annealed OTFTs with a 100-s plasma treatment achieve a carrier mobility of 0.62 and 0.66 cm 2V̇s, respectively, which are higher than those of the OTFTs without plasma treatment (0.22 and 0.41 cm 2V̇s). Moreover, the plasma-treated OTFTs realize better 1/f noise characteristics than those without plasma treatment. The improved performance is due to passivation of the dielectric surface by plasma-induced fluorine incorporation. However, for longer time (300 and 900 s) of plasma treatment, the performance of the OTFTs deteriorates in terms of carrier mobility and 1/f noise characteristics due to increased plasma-induced damage of the dielectric surface. The morphology of the pentacene film grown on the HfLaO gate insulator was characterized by SEM. It reveals that the pentacene film has larger grain size and smoother surface on the HfLaO dielectric (for both annealing gases) with 100-s plasma treatment than the others (0, 300, and 900 s). Finally, AFM characterization of the HfLaO film also confirms the damaging effect of excessive plasma treatment on the dielectric. © 2012 IEEE.published_or_final_versio

Effects of annealing temperature and gas on pentacene OTFTs with HfLaO as gate dielectric

Pentacene organic thin-film transistors (OTFTs) with high-κ HfLaO as gate insulator were fabricated. HfLaO film was prepared by sputtering method. To improve the film quality, the dielectric was annealed in N 2, NH 3, or O 2 at two temperatures, i.e., 200 °C and 400 °C, respectively. The I-V characteristics of the OTFTs and C-V characteristics of corresponding organic capacitors were measured. The OTFTs could operate at a low operating voltage of below 5 V, and the dielectric constant of the HfLaO film could be above ten. For all the annealing gases, the OTFTs annealed at 400 °C achieved higher carrier mobility than their counterparts annealed at 200 °C (with the one annealed in NH 3 at 400 °C showing the highest carrier mobility of 0.45 cm 2/ V·s), which could be supported by SEM images which indicate that pentacene tended to form larger grains on HfLaO annealed at 400 °C than on that annealed at 200 °C. The C-V measurement of the organic capacitors indicated that the localized charge density in the organic semiconductor/oxide was lower for the 400 °C annealing than for the 200 °C annealing. Furthermore, through the characterization of gate current leakage, HfLaO film annealed at 400 °C achieved much smaller leakage than that annealed at 200 °C. Since the maximum processing temperature of ITO glass substrates is around 400 °C , this study shows that 400 °C is suitable for the annealing of HfLaO film in high-performance OTFTs on glass substrate. © 2011 IEEE.published_or_final_versio

Pentacene thin-film transistors with HfO2 gate dielectric annealed in NH3 or N2O

Pentacene-based Organic Thin-Film Transistor (OTFT) with HfO 2 as gate dielectric is studied in this work. The HfO2 dielectric was prepared by RF sputtering at room temperature, and subsequently annealed in N 2O or NH 3 at 200 °C. The OTFTs were characterized by IV measurement and 1/f noise measurement. The OTFTs show small threshold voltage and can operate at as low as 3 V. Results indicate that the OTFT annealed in NH 3 shows higher carrier mobility, larger on/off current ratio, smaller sub-threshold swing and smaller Hooge parameter than the OTFT annealed in N 2O. Therefore, NH 3-annealed HfO 2 is a promising gate dielectric for the fabrication of high-performance OTFTs. © 2008 IEEE.published_or_final_versio

Epstein-barr virus-encoded latent membrane protein 1 impairs G2 checkpoint in human nasopharyngeal epithelial cells through defective Chk1 activation

Nasopharyngeal carcinoma (NPC) is a common cancer in Southeast Asia, particularly in southern regions of China. EBV infection is closely associated with NPC and has long been postulated to play an etiological role in the development of NPC. However, the role of EBV in malignant transformation of nasopharyngeal epithelial cells remains enigmatic. The current hypothesis of NPC development is that premalignant nasopharyngeal epithelial cells harboring genetic alterations support EBV infection and expression of EBV genes induces further genomic instability to facilitate the development of NPC. The latent membrane protein 1 (LMP1) is a well-documented EBV-encoded oncogene. The involvement of LMP1 in human epithelial malignancies has been implicated, but the mechanisms of oncogenic actions of LMP1, particularly in nasopharyngeal cells, are unclear. Here we observed that LMP1 expression in nasopharyngeal epithelial cells impaired G2 checkpoint, leading to formation of unrepaired chromatid breaks in metaphases after γ-ray irradiation. We further found that defective Chk1 activation was involved in the induction of G2 checkpoint defect in LMP1-expressing nasopharyngeal epithelial cells. Impairment of G2 checkpoint could result in loss of the acentrically broken chromatids and propagation of broken centric chromatids in daughter cells exiting mitosis, which facilitates chromosome instability. Our findings suggest that LMP1 expression facilitates genomic instability in cells under genotoxic stress. Elucidation of the mechanisms involved in LMP1-induced genomic instability in nasopharyngeal epithelial cells will shed lights on the understanding of role of EBV infection in NPC development. © 2012 Deng et al.published_or_final_versio

Effects of different annealing gases on pentacene OTFT with HfLaO gate dielectric

Pentacene organic thin-film transistors (OTFTs) with HfLaO high-kappa gate dielectric were fabricated. The dielectric was prepared by a sputtering method and then annealed in N2,NH3,O2, or NO at 400°C. The carrier mobility of the NH3-annealed OTFT could reach 0.59 cm2/V̇s, which is higher than those of the other three devices. Moreover, the NH3-annealed OTFT obtained the smallest subthreshold swing of 0.26 V/dec among them. Furthermore,1/f noise measurement indicated that the NH3-annealed OTFT achieved the smallest 1/f noise. All these should be attributed to the improved interface between the gate dielectric and the organic semiconductor associated with the passivation effects of the NH3 annealing on the dielectric surface. © 2010 IEEE.published_or_final_versio

β-TrCP-mediated ubiquitination and degradation of liver-enriched transcription factor CREB-H

CREB-H is an endoplasmic reticulum-resident bZIP transcription factor which critically regulates lipid homeostasis and gluconeogenesis in the liver. CREB-H is proteolytically activated by regulated intramembrane proteolysis to generate a C-terminally truncated form known as CREB-H-ΔTC, which translocates to the nucleus to activate target gene expression. CREB-H-ΔTC is a fast turnover protein but the mechanism governing its destruction was not well understood. In this study, we report on β-TrCP-dependent ubiquitination and proteasomal degradation of CREB-H-ΔTC. The degradation of CREB-H-ΔTC was mediated by lysine 48-linked polyubiquitination and could be inhibited by proteasome inhibitor. CREB-H-ΔTC physically interacted with β-TrCP, a substrate recognition subunit of the SCFβ-TrCP E3 ubiquitin ligase. Forced expression of β-TrCP increased the polyubiquitination and decreased the stability of CREB-H-ΔTC, whereas knockdown of β-TrCP had the opposite effect. An evolutionarily conserved sequence, SDSGIS, was identified in CREB-H-ΔTC, which functioned as the β-TrCP-binding motif. CREB-H-ΔTC lacking this motif was stabilized and resistant to β-TrCP-induced polyubiquitination. This motif was a phosphodegron and its phosphorylation was required for β-TrCP recognition. Furthermore, two inhibitory phosphorylation sites close to the phosphodegron were identified. Taken together, our work revealed a new intracellular signaling pathway that controls ubiquitination and degradation of the active form of CREB-H transcription factor.published_or_final_versio

Combination of angiotensin converting enzyme inhibitor and irbesartan for the treatment of heart failure

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Impact of G 2 checkpoint defect on centromeric instability

Centromeric instability is characterized by dynamic formation of centromeric breaks, deletions, isochromosomes and translocations, which are commonly observed in cancer. So far, however, the mechanisms of centromeric instability in cancer cells are still poorly understood. In this study, we tested the hypothesis that G 2 checkpoint defect promotes centromeric instability. Our observations from multiple approaches consistently support this hypothesis. We found that overexpression of cyclin B1, one of the pivotal genes driving G 2 to M phase transition, impaired G 2 checkpoint and promoted the formation of centromeric aberrations in telomerase-immortalized cell lines. Conversely, centromeric instability in cancer cells was ameliorated through reinforcement of G 2 checkpoint by cyclin B1 knockdown. Remarkably, treatment with KU55933 for only 2.5 h, which abrogated G 2 checkpoint, was sufficient to produce centromeric aberrations. Moreover, centromeric aberrations constituted the major form of structural abnormalities in G 2 checkpoint-defective ataxia telangiectasia cells. Statistical analysis showed that the frequencies of centromeric aberrations in G 2 checkpoint-defective cells were always significantly overrepresented compared with random assumption. As there are multiple pathways leading to G 2 checkpoint defect, our finding offers a broad explanation for the common occurrence of centromeric aberrations in cancer cells. © 2011 Macmillan Publishers Limited All rights reserved.postprin

β2 integrin LFA1 mediates airway damage following neutrophil trans-epithelial migration during RSV infection

RSV bronchiolitis is the most common cause of infant hospital admissions, but there is limited understanding of the mechanisms of disease and no specific anti-viral treatment. Using a novel in vitro primary trans-epithelial neutrophil migration model and innovative imaging methods, we show that RSV infection of nasal airway epithelium increased neutrophil trans-epithelial migration and adhesion to infected epithelial cells, which is associated with epithelial cell damage, reduced ciliary beat frequency, but also a reduction in infectious viral load. Following migration, RSV infection results in greater neutrophil activation, degranulation and release of neutrophil elastase into the airway surface media compared to neutrophils that migrated across mock-infected nasal epithelial cells. Blocking of the interaction between the ligand on neutrophils (the β2 integrin LFA-1) for intracellular adhesion molecule-1 (ICAM-1) on epithelial cells reduced neutrophil adherence to RSV infected cells and epithelial cell damage to pre-infection levels, but did not reduce the numbers of neutrophils which migrated or prevent the reduction in infectious viral load. These findings have provided important insights into the contribution of neutrophils to airway damage and viral clearance, which are relevant to pathophysiology of RSV bronchiolitis. This model is a convenient, quantitative pre-clinical model that will further elucidate mechanisms that drive disease severity and has utility in anti-viral drug discovery