Search

Mutations in IDH1, IDH2 , and TET2 are recurrently observed in myeloid neoplasms. IDH1 and IDH2 encode isocitrate dehydrogenase isoforms, which normally catalyze the conversion of isocitrate to α-ketoglutarate (α-KG). Oncogenic IDH1/2 mutations confer neomorphic activity, leading to the production of D-2-hydroxyglutarate (D-2-HG), a potent inhibitor of α-KG-dependent enzymes which include the TET methylcytosine dioxygenases. Given their mutual exclusivity in myeloid neoplasms, IDH1 , IDH2 , and TET2 mutations may converge on a common oncogenic mechanism. Contrary to this expectation, we observed that they have distinct, and even opposite, effects on hematopoietic stem and progenitor cells in genetically engineered mice. Epigenetic and single-cell transcriptomic analyses revealed that Idh2 R172K and Tet2 loss-of-function have divergent consequences on the expression and activity of key hematopoietic and leukemogenic regulators. Notably, chromatin accessibility and transcriptional deregulation in Idh2 R172K cells were partially disconnected from DNA methylation alterations. These results highlight unanticipated divergent effects of IDH1/2 and TET2 mutations, providing support for the optimization of genotype-specific therapies.

The molecular mechanisms contributing to the regulation of Th17-mediated inflammation remain underexplored. We here report a SUMO-specific protease (SENP)2-mediated pathway induced in pathogenic Th17 cells that restricts the pathogenesis of inflammatory colitis. SENP2 regulates the maturation of small ubiquitin-like modifiers (SUMO) and recycles SUMO from the substrate proteins. We found higher levels of SENP2 in pathogenic Th17 cells. By deleting Senp2 during T-cell development or in mature Th17 cells in mice, we demonstrated that the lack of Senp2 exacerbates the severity of experimental colitis, which is linked to elevated levels of GM-CSF+IL-17A+ pathogenic Th17 cells and more severe dysbiosis of the intestinal microbiome. Adoptive transfer experiments demonstrated the cell-autonomous effect of Senp2 in restraining Th17 differentiation and colitis. The enzymatic activity of SENP2 is important for deSUMOylation of Smad4, which prevents Smad4 nuclear entry and Rorc expression. Our findings reveal a SENP2-mediated regulatory axis in the pathogenicity of Th17 cells.

Mutations in IDH1, IDH2, and TET2 are recurrently observed in myeloid neoplasms. IDH1 and IDH2 encode isocitrate dehydrogenase isoforms, which normally catalyze the conversion of isocitrate to α-ketoglutarate (α-KG). Oncogenic IDH1/2 mutations confer neomorphic activity, leading to the production of D-2-hydroxyglutarate (D-2-HG), a potent inhibitor of α-KG-dependent enzymes which include the TET methylcytosine dioxygenases. Given their mutual exclusivity in myeloid neoplasms, IDH1, IDH2, and TET2 mutations may converge on a common oncogenic mechanism. Contrary to this expectation, we observed that they have distinct, and even opposite, effects on hematopoietic stem and progenitor cells in genetically engineered mice. Endogenous Idh2R172K caused much higher D-2-HG production compared to Idh1R132H and Idh2R140Q. This led to profound alterations in hematopoietic progenitor differentiation and to the development of myelodysplastic syndrome-like disease, with shorter survival compared to Tet2−/- mice. Epigenetic and single-cell transcriptomic analyses revealed that Idh2R172K and Tet2 loss-of-function have divergent and opposite effects on the expression and activity of key hematopoietic and leukemogenic regulators. Notably, chromatin accessibility and transcriptional deregulation in Idh2R172K cells were partially disconnected from DNA methylation alterations. These results highlight unanticipated divergent effects of IDH1/2 and TET2 mutations, which may inform the development of genotype-specific therapies. Citation Format: Jerome Fortin, Ming-Feng Chiang, Cem Meydan, Jonathan Foox, Parameswaran Ramachandran, Julie Leca, Francois Lemonnier, Wanda Y. Li, Miki S. Gams, Takashi Sakamoto, Mandy Chu, Chantal Tobin, Eric Laugesen, Troy M. Robinson, Annick You-Ten, Daniel J. Butler, Thorsten Berger, Mark D. Minden, Ross L. Levine, Cynthia J. Guidos, Ari M. Melnick, Christopher E. Mason, Tak W. Mak. Multi-omic analyses in genetically engineered mice reveal distinct and opposite effects of leukemogenic Idh and Tet2 mutations in hematopoietic stem and progenitor cells [abstract]. In: Proceedings of the AACR Special Conference: Acute Myeloid Leukemia and Myelodysplastic Syndrome; 2023 Jan 23-25; Austin, TX. Philadelphia (PA): AACR; Blood Cancer Discov 2023;4(3_Suppl):Abstract nr A16.

Purpose: Hepatocellular carcinoma (HCC) is a major malignancy and the common cause of cancer-related deaths. Surgical intervention provides superior long-term survival outcomes; however, perioperative mortality is a major concern for clinicians while making treatment decisions, especially for major hepatectomy. Scoring systems for predicting 90-day mortality in patients with HCC undergoing major hepatectomy are not available. Methods: This study used the Taiwan Cancer Registry Database that is linked to the National Health Insurance Research Database to analyze data of 60,250 patients with HCC who underwent major hepatectomy and determine risk factors to establish a novel predictive scoring system. By using the stepwise selection of the multivariate Cox proportional hazards model, we divided the patients with HCC undergoing major hepatectomy into four risk groups. Results: The Chang Gung-PohAi predictive scoring system exhibited significant differences in the 90-day mortality rate among the four risk groups (very low risk: 2.42%, low risk: 4.09%, intermittent risk: 17.1%, and high risk: 43.6%). Conclusion: The Chang Gung-PohAi predictive scoring system is a promising tool for predicting 90-day perioperative mortality in patients with HCC undergoing major hepatectomy.

PURPOSE: To investigate the effects of pre-existing sleep disorders on the survival outcomes of women receiving standard treatments for breast invasive ductal carcinoma (IDC). METHODS: We recruited patients from the Taiwan Cancer Registry Database who had received surgery for clinical stage I–III breast IDC. The Cox proportional hazards model was used to analyze all-cause mortality. We categorized the patients into those with and without sleep disorders (Groups 1 and 2, respectively) through propensity score matching. RESULTS: In the multivariate Cox regression analysis, the adjusted hazard ratio for all-cause mortality for Group 1 compared with Group 2 was 1.51 (95% confidence interval: 1.19, 1.91; p < 0.001). CONCLUSION: Our study demonstrated that the sleep disorder group had poorer survival rates than the non-sleep disorder group in breast cancer. Therefore, patients should be screened and evaluated for pre-existing sleep disorders prior to breast surgery, with such disorders serving as a predictor of survival in patients with breast cancer. Future studies may investigate the survival benefits of pharmacological and behavioral treatments for sleep problems in patients with breast cancer.

This study is the first to examine the effect of adjuvant whole-breast radiotherapy (WBRT) on oncologic outcomes such as all-cause death, locoregional recurrence (LRR), and distant metastasis (DM) in old (aged ≥80 years) and very old (aged ≥90 years) women with breast invasive ductal carcinoma (IDC) receiving breast-conserving surgery. After propensity score matching, adjuvant WBRT was associated with decreases in all-cause death, LRR, and DM in old and very old women with IDC compared with no use of adjuvant WBRT. Background: To date, no data on the effect of adjuvant whole-breast radiotherapy (WBRT) on oncologic outcomes, such as all-cause death, locoregional recurrence (LRR), and distant metastasis (DM), are available for old (aged ≥80 years) and very old (≥90 years) women with breast invasive ductal carcinoma (IDC) receiving breast-conserving conservative surgery (BCS). Patients and Methods: We enrolled old (≥80 years old) and very old (≥90 years old) women with breast IDC who had received BCS followed by adjuvant WBRT or no adjuvant WBRT. We grouped them based on adjuvant WBRT status and compared their overall survival (OS), LRR, and DM outcomes. To reduce the effects of potential confounders when comparing all-cause mortality between the groups, propensity score matching was performed. Results: Overall, 752 older women with IDC received BCS followed by adjuvant WBRT, and 752 with IDC received BCS with no adjuvant WBRT. In multivariable Cox regression analysis, the adjusted hazard ratio (aHR) and 95% confidence interval (95% CI) of all-cause death for adjuvant WBRT compared with no adjuvant WBRT in older women with IDC receiving BCS was 0.56 (0.44–0.70). The aHRs (95% CIs) of LRR and DM for adjuvant WBRT were 0.29 (0.19–0.45) and 0.45 (0.32–0.62), respectively, compared with no adjuvant WBRT. Conclusions: Adjuvant WBRT was associated with decreases in all-cause death, LRR, and DM in old (aged ≥80 years) and very old (aged ≥90 years) women with IDC compared with no adjuvant WBRT.

BACKGROUND: To date,no data on the effect of adjuvant whole-breast radiotherapy (WBRT) on oncologic outcomes, such as all-cause death, locoregional recurrence (LRR), and distant metastasis (DM), are available forold (aged ≥80 years) and very old (≥90 years) women with breast invasive ductal carcinoma (IDC) receiving breast-conserving conservative surgery (BCS).PATIENTS AND METHODS: We enrolled old (≥80 yearsold) and very old (≥90 yearsold) women with breast IDC who had received BCS followed by adjuvant WBRT or no adjuvant WBRT. We groupedthem based on adjuvant WBRT status and compared their overall survival (OS), LRR, and DM outcomes. To reduce the effects of potential confounders when comparing all-cause mortality between the groups, propensity score matching was performed.RESULTS:Overall, 752 older women with IDC received BCS followed by adjuvant WBRT, and 752 with IDC received BCS with no adjuvant WBRT.In multivariable Cox regression analysis, the adjusted hazard ratio (aHR) and 95% confidence interval (95% CI) of all-cause death for adjuvant WBRT compared with no adjuvant WBRT in older women with IDC receiving BCS was 0.56 (0.44-0.70). The aHRs (95% CIs) of LRR and DM foradjuvant WBRT were 0.29 (0.19-0.45) and 0.45 (0.32-0.62), respectively, compared with no adjuvant WBRT.CONCLUSION: Adjuvant WBRT was associated with decreases in all-cause death, LRR, and DM in old (aged ≥80 years) and very old (aged ≥90 years) women with IDC compared with no adjuvant WBRT.Condensed Abstract: This study is the first to examine the effect of adjuvant whole-breast radiotherapy (WBRT) on oncologic outcomes such as all-cause death, locoregional recurrence (LRR), and distant metastasis (DM) in old (aged ≥80 years) and very old (aged ≥90 years) women with breast invasive ductal carcinoma (IDC) receiving breast-conserving surgery. After propensity score matching, adjuvant WBRT was associated with decreases in all-cause death, LRR, and DM in old and very old women with IDC compared with no use of adjuvant WBRT.

BACKGROUND To date, no data on the effect of adjuvant whole breast radiotherapy (WBRT) on oncologic outcomes, such as all-cause death, locoregional recurrence (LRR), and distant metastasis (DM), are available in women with left-side breast intraductal carcinoma (IDC) and heart failure with reduced ejection fraction (HFrEF). PATIENTS AND METHODS : We enrolled 294 women with left-breast IDC at clinical stages IA–IIIC and HFrEF receiving breast-conserving surgery (BCS) followed by adjuvant WBRT or non-adjuvant WBRT. We categorized them into two groups based on their adjuvant WBRT status and compared their overall survival (OS), LRR, and DM outcomes. We calculated the propensity score and applied inverse probability of treatment weighting (IPTW) to create a pseudo-study cohort. Furthermore, we performed a multivariate analysis of the propensity score–weighted population to obtain hazard ratios (HRs). RESULTS In the IPTW-adjusted model, adjuvant WBRT (adjusted HR [aHR]: 0.60; 95% confidence interval [CI]: 0.44–0.94) was a significant independent prognostic factor for all-cause death (P = 0.0424), and the aHR (95% CI) of LRR and DM for adjuvant WBRT was 0.33 (0.24–0.71; P = 0.0017) and 0.37 (0.22–0.63; P = 0.0004), respectively, compared with the no adjuvant WBRT group. The aHR (95% CI) of breast cancer death for adjuvant WBRT was 0.54 (0.44–0.85; P = 0.0201) compared with no adjuvant WBRT group. CONCLUSION Adjuvant WBRT was associated with a decrease in all-cause death, breast cancer death, LRR, and DM in women with left IDC and HFrEF compared with no adjuvant WBRT.

BACKGROUND: To date, no data on the effect of adjuvant whole breast radiotherapy (WBRT) on oncologic outcomes, such as all-cause death, locoregional recurrence (LRR), and distant metastasis (DM), are available in women with left-side breast intraductal carcinoma (IDC) and heart failure with reduced ejection fraction (HFrEF). PATIENTS AND METHODS: We enrolled 294 women with left-breast IDC at clinical stages IA–IIIC and HFrEF receiving breast-conserving surgery (BCS) followed by adjuvant WBRT or non-adjuvant WBRT. We categorized them into two groups based on their adjuvant WBRT status and compared their overall survival (OS), LRR, and DM outcomes. We calculated the propensity score and applied inverse probability of treatment weighting (IPTW) to create a pseudo-study cohort. Furthermore, we performed a multivariate analysis of the propensity score–weighted population to obtain hazard ratios (HRs).RESULTS: In the IPTW-adjusted model, adjuvant WBRT (adjusted HR [aHR]: 0.58; 95% confidence interval [CI]: 0.33–1.00) was a significant independent prognostic factor for all-cause death (P = 0.0494), and the aHR (95% CI) of LRR and DM for adjuvant WBRT was 0.25 (0.10–0.62; P = 0.0028) and 0.29 (0.14–0.60; P = 0.0007), respectively, compared with the nonadjuvant WBRT group. CONCLUSION: Adjuvant WBRT was associated with a decrease in all-cause death, LRR, and DM in women with left IDC and HFrEF compared with nonadjuvant WBRT.

Background To date, no data on the effect of adjuvant postmastectomy radiotherapy (PMRT) on oncologic outcomes, such as all-cause death, locoregional recurrence (LRR), and distant metastasis (DM), are available in women with left-side breast invasive ductal carcinoma (IDC) and heart failure with reduced ejection fraction (HFrEF). Patients and methods We enrolled 646 women with left-breast IDC at clinical stages I–IIIC and HFrEF receiving radical total mastectomy (TM) followed by adjuvant PMRT or non-adjuvant PMRT. We categorized them into two groups based on their adjuvant PMRT status and compared their overall survival (OS), LRR, and DM outcomes. We calculated the propensity score and applied inverse probability of treatment weighting (IPTW) to create a pseudo-study cohort. Furthermore, we performed a multivariate analysis of the propensity score–weighted population to obtain hazard ratios (HRs). Results In the IPTW-adjusted model, adjuvant PMRT (adjusted HR [aHR]: 0.52; 95% confidence interval [CI]: 0.37–0.74) was a significant independent prognostic factor for all-cause death (P = 0.0003), and the aHR (95% CI) of LRR and DM for adjuvant PMRT was 0.90 (0.79–0.96; P = 0.0356) and 0.89 (0.54–1.50; P = 0.6854), respectively, compared with the nonadjuvant PMRT group. Conclusion Adjuvant PMRT was associated with a decrease in all-cause death, and LRR in women with left IDC and HFrEF compared with nonadjuvant PMRT.

H1-antihistamines (AHs) may exert protective effects against cancer. We investigated the association of AH use with hepatocellular carcinoma (HCC) risk in type 2 diabetes mellitus (T2DM) patients without hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.The data of patients with T2DM enrolled from Taiwan's National Health Insurance Research Database were examined for the period of January 1, 2008, to December 31, 2018. We used the Kaplan-Meier method and Cox proportional hazards regression to evaluate the AH use-HCC risk association.After 1:1 propensity score matching was performed, the two cohorts were each divided into AH users (n = 47,990) and nonusers (n = 47,990). The risk of HCC was significantly lower in AH users than in AH nonusers (adjusted hazard ratio [aHR]: 0.55 95% confidence interval [95% CI], 0.46 to 0.67; IRR: 0.70; 95% CI, 0.60 to 0.84), respectively. The dose-response relationship between AH use and HCC risk was also observed (aHRs: 0.58, 0.56, 0.50, and 0.41 for 28-35, 36-49, 50-77, and77 cumulative defined daily doses of AH, respectively).AH use can reduce HCC risk in T2DM patients without HBV or HCV infection in a dose-dependent manner.

Purpose: To identify novel radiological features and clinical characteristics to improve diagnostic criteria for early detection of small hepatocellular carcinoma (HCC). Patients and Methods: We retrospectively recruited asymptomatic patients with no history of HCC but a high risk of HCC in whom a new, solitary, well-defined, solid nodule between 10 and 20 mm was detected through a screening ultrasound. We retrospectively collected all clinical data, and patients were examined using dynamic contrast-enhanced computed tomography or magnetic resonance imaging; subsequently, fine-needle biopsy was performed. A multivariate analysis of the predictors of small HCCs was performed by fitting a multiple logistic regression model with the stepwise variable selection method. Results: In total, 392 and 347 patients with a small liver nodule received a final pathologic confirmation of HCC and non-HCC, respectively. The estimated odds ratios and 95% confidence intervals of tumor size > 12.45 mm, age > 56.61 years, liver cirrhosis, hepatitis C virus (HCV) carrier status, ln alpha-fetoprotein (AFP) > 1.954, arterial phase enhancement, and portal or venous phase washout appearance without arterial phase enhancement were 2.0735 (1.4746-2.9155), 1.8878 (1.2949-2.7521), 1.6927 (1.1294-2.5369), 1.6186 (1.0347-2.5321), 2.0297 (1.3342-3.0876), 3.7451 (2.3845-5.8821), and 2.0327 (1.3500-3.0608), respectively. The area under the receiver operating characteristic curves for the diagnosis of small HCCs was 0.79 for arterial phase enhancement and 0.75 for portal or venous phase washout appearance without arterial phase enhancement. Conclusion: Clinical and contrast-enhanced image features are valuable in the prediction model for the detection and early diagnosis of small HCCs in patients with a high risk of HCC. In addition to negative portal or venous washout and negative arterial enhancement in images, age > 56.61 years, tumor size > 12.45 mm, HCV carrier status, and ln(AFP) > 1.954, are useful indicators for the early detection of small HCCs.

High-power disk laser welding a steel plate using the Inconel 82 (IN82) filler wire with a 1.2 and 3.0 m/min feeding rate has been investigated in the experiment. The rapid thermal cycle combined with convection induced by the keyhole mechanism in laser welding results in the rapid solidification of the fusion zone (FZ). However, the microstructure of the FZ is not homogeneous at the macroscopic scale. The dilution of the FZ is important in determining the final microstructure of the weldment. For the specimen with a 1.2 m/min wire feeding rate, a lower amount of Ni-based IN82 filler is introduced into the weld pool, and the dilution of the FZ is between 65% and 100%. The BCC structure with high density boundaries dominates the entire FZ. For the specimen with a 3.0 m/min wire feeding rate, part of the filler melt is trapped on the top of the weld pool, and solidified into austenite alloyed with a Ni concentration above 15 at%. The range of dilution in the FZ with a 3.0 m/min wire feeding rate is decreased to 50–90%. There are hot cracks initiated/propagated along interdendritic austenite and in the austenite free of boundaries. Boundaries, especially for high-angle ones, in the BCC structure retard hot crack propagation in the FZ. The application of quantitative chemical analyses of Fe or Ni concentrations in the weldment provides a good approximation in evaluating the dilution of the FZ in laser welding. The methodology proposed in this study shows potential to obtain the dilution of any specific location in the FZ for industrial application in the future.

PURPOSE: The survival effect of smoking-related chronic obstructive pulmonary disease (COPD) and COPD with acute exacerbation (COPDAE) on patients with muscle-invasive bladder urothelial carcinoma (MIBUC) receiving concurrent chemoradiotherapy (CCRT) for bladder preservation is unclear. METHODS: We recruited patients with MIBUC, clinical stages IIA–IVB, who had received maximal transurethral resection of bladder tumor (TURBT) followed by CCRT from the Taiwan Cancer Registry Database. The Cox proportional hazards model was used to analyze all-cause mortality. We categorized the patients into two groups by using propensity score matching based on the preexisting COPD status (within 1 year before CCRT) to compare overall survival outcomes: Group 1 (never smokers without COPD) and Group 2 (current smokers with COPD). RESULTS: In multivariate Cox regression analyses, the adjusted hazard ratio (aHR, 95% confidence interval (CI)) of all-cause mortality in Group 2 compared with Group 1 was 1.89 (1.12–3.18), p = 0.017. The aHRs (95% CIs) of all-cause mortality for ≥1 and ≥2 hospitalizations for COPDAE within 1 year before CCRT for bladder preservation were 3.26 (1.95–5.46) and 6.33 (3.55–11.281) compared with non-COPDAE patients with MIBUC undergoing CCRT for bladder preservation. CONCLUSIONS: Among patients with MIBUC undergoing TURBT followed by CCRT for bladder preservation, current smokers with smoking-related COPD had worse survival outcomes than did nonsmokers without COPD. Condensed Abstract: This was the first study to estimate the survival impact of smoking-related chronic obstructive pulmonary disease (COPD) on patients with muscle-invasive bladder urothelial carcinoma (MIBUC) receiving maximal transurethral resection of bladder tumor (TURBT) followed by concurrent chemoradiotherapy (CCRT) for bladder preservation. Smoking-related COPD was a significant independent risk factor for all-cause mortality in patients with clinical stages IIA–IVB receiving TURBT followed by CCRT. Hospitalization frequency for COPD with at least one acute exacerbation within 1 year before CCRT was highly associated with high mortality for patients with MIBUC receiving CCRT for bladder preservation. Not only all-cause death but also bladder cancer death and COPD death were significantly higher in the current-smoking COPD group than in the never-smoking non-COPD group.

O-linked N-acetylglucosamine (O-GlcNAc) transferase (Ogt) catalyzes O-GlcNAc modification. O-GlcNAcylation is increased after cross-linking of the B-cell receptor (BCR), but the physiological function of this reaction is unknown. Here we show that lack of Ogt in B-cell development not only causes severe defects in the activation of BCR signaling, but also perturbs B-cell homeostasis by enhancing apoptosis of mature B cells, partly as a result of impaired response to B-cell activating factor. O-GlcNAcylation of Lyn at serine 19 is crucial for efficient Lyn activation and Syk interaction in BCR-mediated B-cell activation and expansion. Ogt deficiency in germinal center (GC) B cells also results in enhanced apoptosis of GC B cells and memory B cells in an immune response, consequently causing a reduction of antibody levels. Together, these results demonstrate that B cells rely on O-GlcNAcylation to maintain homeostasis, transduce BCR-mediated activation signals and activate humoral immunity., Post-translational modification has a variety of regulatory functions for important immune molecules. Here the authors use B-cell specific knockout mice to show how O-GlcNAcylation is required for functional B cell responses and humoral immunity.

The novel Cu–Ni–Si–Cr alloy (Cu-6.7Ni-1.6Si-0.3Cr) has good prospects for substitution with toxic Be–Cu alloy. This study used a Nd: YAG laser process with a variety of heat treatment processes and repair welding parameters to investigate the effects of heat treatment and repair welding parameters on the microstructure and properties of the Cu–Ni–Si–Cr mold alloy. To eliminate the disadvantages of the laser welding process for the Cu–Ni–Si–Cr mold alloy, such as high thermal conductivity and high thermal expansion coefficients, many improved approaches have been used, including pre-weld heat treatments (expected to reduce thermal conductivity), control of the laser shape, and preheating (to slow down the cooling rate and avoid excessive expansion and contraction). The results showed that after the pre-weld heat treatment and preheating, deeper penetration and defect-free welds were obtained. However, continuous Ni/Si phase precipitates were observed along the grain boundaries in the welding fusion zone (WFZ), which may have harmful effects on the mechanical properties of the welds. This problem was improved by post-weld heat treatment (PWHT). The repair welds (including WFZ and HAZ) after PWHT showed a good combination of hardness, tensile strength, and thermal properties. The high hardness or tensile strength in the weld was attributed to the formation of a nano-sized Ni/Si phase, which was identified via a transmission electron microscope.

Organic thin-film transistor (OTFT) with solution-process, low process temperature (< 120°C), high performance, good uniformity and excellent stability is achieved. Also, a systematic comparison of device performance and reliability of OTFT and a-Si:H TFT is performed in this research. Due to the excellent device characteristics, especially of the bias stability, the OTFT technology nowadays is comparable even overwhelming to the mass production a-Si:H TFT technology. The commercialization of organic electronics driven by OTFT backplane is expected.

In this paper, the electrical stability of organic thin-film transistors (OTFTs) were investigated. Solution and photolithography technologies were used for organic thin film formation and patterning. All stacks were constructed with organic materials. However, the polymer-type organic semiconductor material was used for active layer. Also, all process temperatures taken place below 120D. In addition, the OTFTs exhibit a good process uniformity and high stability. Furthermore, the OTFTs integrated with 6-inch active matrix organic light emitting diodes (AMOLEDs) was realized.

In this work, RXA cladding tubes were hydrogen-charged to target hydrogen content levels between 150 and 800 wppm (part per million by weight). The strings of zirconium hydrides observed in the cross sections are mostly oriented in the circumferential direction. The fracture toughness of hydrided RXA Zircaloy-4 cladding was measured to evaluate its hydride embrittlement susceptibility. With increasing hydrogen content, the fracture toughness of hydrided RXA cladding decreases at both 25 °C and 300 °C. Moreover, highly localized hydrides (forming a hydride rim) aggravate the degradation of the fracture properties of RXA Zircaloy-4 cladding at both 25 °C and 300 °C. Brittle features in the form of quasi-cleavages and secondary cracks were observed on the fracture surface of the hydride rim, even for RXA cladding tested at 300 °C.

The organic thin film transistors (OTFTs) were fabricated and investigated in this study. Solution and photography technology were used for organic thin film formation and patterning. Also, the process temperatures were kept below 120 degree C for low temperature process development. Furthermore, the performances of OTFTs were investigated in this study, including electrical characteristics and reliability.

A novel semiconducting polymer, PDPP3T, with alternating diketopyrrolopyrrole and terthiophene units is presented in this study. Due to PDPP3T has a small band gap of 1.3 eV, and high hole mobility of 0.04 cm(2) V(-1) s(-1), it can be used for organic photo sensor to absorb the near infrared (NIR) parts of the spectrum. The photo sensor are fabricated from Poly (diketopyrrolopyrrole-terthiophene) (PDPP3T) and [6,6]-phenyl C61-butylric acid methyl ester (PCBM) using a solution-based, temperature assisted deposition protocol. Devices made by this protocol lead to photo and dark current of around 4.6µA/cm2 and 2.1nA/cm2 at -1V. The device yields a good linear response of photocurrent to the near infrared exposure (from 50-400µW/cm2) for a range of operating biases

B lymphocyte-induced maturation protein-1 (Blimp-1) is a transcriptional repressor important for the differentiation and function of several types of immune cells. Because skin serves as a physical barrier and acts as an immune sentinel, we investigated whether Blimp-1 is involved in epidermal immune function. We show that Blimp-1 expression is reduced in skin lesions of some human eczema samples and in stimulated primary keratinocytes. Epidermal-specific deletion of PR domain containing 1, with ZNF domain ( Prdm1 ), the gene encoding Blimp-1, in adult mice caused spontaneously inflamed skin characterized by massive dermal infiltration of neutrophils/macrophages and development of chronic inflammation associated with higher levels of cytokines/chemokines, including granulocyte colony-stimulating factor (G-CSF), and enhanced myelopoiesis in bone marrow. Deletion of Prdm1 in the epidermis of adult mice also led to stronger inflammatory reactions in a tape-stripping test and in a disease model of contact dermatitis. The elevated G-CSF produced by keratinocytes after deletion of Prdm1 in vitro was mediated by the transcriptional activation of FBJ osteosarcoma oncogene ( Fos ) and fos-like antigen 1 ( Fosl1 ). Systemic increases in G-CSF contributed to the inflammatory responses, because deletion of the G-CSF gene [colony stimulating factor 3, ( Csf3 )] prevented neutrophilia and partially ameliorated the inflamed skin in Prdm1- deficient mice. Our findings indicate a previously unreported function for Blimp-1 in restraining steady-state epidermal barrier immunity.

Crosslinking of B-cell receptor (BCR) sets off an apoptosis programme, but the underlying pathways remain obscure. Here we decipher the molecular mechanisms bridging B-cell activation and apoptosis mediated by post-translational modification (PTM). We find that O-GlcNAcase inhibition enhances B-cell activation and apoptosis induced by BCR crosslinking. This proteome-scale analysis of the functional interplay between protein O-GlcNAcylation and phosphorylation in stimulated mouse primary B cells identifies 313 O-GlcNAcylation-dependent phosphosites on 224 phosphoproteins. Among these phosphoproteins, temporal regulation of the O-GlcNAcylation and phosphorylation of lymphocyte-specific protein-1 (Lsp1) is a key switch that triggers apoptosis in activated B cells. O-GlcNAcylation at S209 of Lsp1 is a prerequisite for the recruitment of its kinase, PKC-β1, to induce S243 phosphorylation, leading to ERK activation and downregulation of BCL-2 and BCL-xL. Thus, we demonstrate the critical PTM interplay of Lsp1 that transmits signals for initiating apoptosis after BCR ligation., B cell receptor (BCR) activation can trigger signalling causing apoptosis in order to eliminate auto-reactive B cells. Here the authors show that the O-GlcNAcylation and phosphorylation of lymphocyte-specific protein-1 are involved in a switch that regulates the initiation of apoptosis induced by BCR cross-linking.

This work reports the fabrication and physical properties of biodegradable poly( l -lactide) (PLLA) composites containing a fraction of unmodified layered double hydroxides (LDH–NO3) and γ-polyglutamate-modified layered double hydroxides (γ-LDH) by melt blending process. The X-ray diffraction (XRD) and transmission electron microscopy (TEM) experimental results showed that the original LDH–NO3 with the certain amount of aggregates was unevenly dispersed throughout the PLLA matrix. Conversely, γ-LDH allows the formation of an intercalated nanocomposite. Although the water vapor permeability of the PLLA/LDH systems was decreased with increasing the loading of LDH, the barrier property of PLLA reinforced with γ-LDH is superior to that of PLLA-L composites. The effects of both LDHs on mechanical and thermal properties of PLLA were also investigated.

This study reports the preparation and physical properties of biodegradable nanocomposites fabricated using poly( l -lactide) (PLLA) and γ-polyglutamate-modified magnesium/aluminum layered double hydroxide (γ-LDH) by solution mixing process. Both X-ray diffraction data and transmission electron microscopy images of PLLA/γ-LDH nanocomposites indicate that most of the swellable γ-LDHs were disorderedly distributed into the PLLA matrix. Mechanical properties of the fabricated 5 wt% PLLA/γ-LDH nanocomposites show significant enhancements in the storage modulus when compared to neat PLLA. Adding more γ-LDH into PLLA matrix induced a slight decrease in the storage modulus of PLLA/γ-LDH nanocomposites, probably due to the excessive content of γ-PGA moleculars with low mechanical properties. The effect of γ-LDH on thermal degradability of PLLA was also investigated.

We report the controllable UV-Visible-to-NIR Si-nanocrystals photonic sensor, photo-spectrum band-gap engineering technology, and integrated in TFT-LCD as multi-function intelligent display. Photonic Sensor using Si-nanocrystals as sensitizer sandwiched between two electrodes structure is proposed to integrate optical input function for new application in next generation mobile devices. The optical input function, used for image scanner, fingerprint recognition, and touch-input application, are achieved by integrating these image sensor elements within each display pixel. A 2-transistor (2T) active pixel sensor (APS) is used to integrate a VGA (> 250 dpi) image sensor within an LCD panel.

γ-Poly(glutamic acid) (γ-PGA), an anionic, hydrophilic and biodegradable polymer, was selected to modify the magnesium/aluminum (Mg/Al) layered double hydroxide (LDH) using the anion exchange method. The wide-angle X-ray diffraction (WAXD) and Fourier transform infrared (FTIR) methods were used to identify the incorporation behavior of γ-PGA within the inorganic nanolayers of LDH. The thermal decompositions of original and γ-PGA-modified LDHs, including dehydration and dehydroxylation together with decomposition of intercalated anions, were investigated by thermogravimetric analyses (TGA). In addition, the effect of temperature on the real-time structural and dehydration behavior of γ-PGA intercalated LDH was investigated in detail by means of in situ WAXD and in situ FTIR. The results clearly indicated that the dehydration of organically-modified LDH has resulted in the contraction of the interlayer spacing from 15.0 A to 11.5 A as temperature increases from 30 to 130 °C. This behavior might be ascribable to the elimination of interlayer constitution water, which has resulted in the destruction of hydrogen bonding among of hydroxide sheets, intercalated anions and water molecules. However, the layered structure of the dehydrated LDH remains unchanged up to 250 °C.

This study elucidates the thermal degradation behavior of biodegradable poly( l -lactide) (PLLA)/layered double hydroxide (LDH) nanocomposites was explored using thermogravimetric analysis (TGA) and pyrolysis-gas chromatography/mass spectroscopy (Py-GC/MS) in an inert atmosphere. PLLA/LDH nanocomposites were fabricated using PLLA and organically-modified magnesium/aluminum layered double hydroxide (P-LDH) in tetrahydrofuran solution. According to the TGA results, the thermal stability of PLLA/P-LDH nanocomposites was significantly lower than that of pure PLLA matrix, perhaps because P-LDH provides thermal acceleration of the degradation of the underlying polymer from the heat source. The identification of the thermal degradation products by Py-GC/MS evidently shows that introducing P-LDH into PLLA leads to a remarkable change during the thermal degradation process. The main reaction route of neat PLLA was through inter- and intra-transesterification to generate lactides and oligomer. The primary volatile products obtained from PLLA/P-LDH nanocomposites were lactides regardless of the temperature of degradation. These results suggest that the thermal degradation behavior of PLLA/P-LDH nanocomposites is governed by the preferential formation of lactide by the unzipping depolymerization reaction, which is catalyzed by Mg and Al components in P-LDH.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT Reflux oesophagitis is a common clinical disorder associated with significant morbidity. Proton pump inhibitors are the current pharmacotherapy of choice, but not all treated patients achieve symptom relief. Little is known about the efficacy of mosapride, a prokinetic agent which decreases episodes of gastro-oesophageal reflux, as an adjunct to proton pump inhibitors in improving the symptoms of reflux oesophagitis. WHAT THIS STUDY ADDS Mosapride was generally not more effective than placebo as an adjunct therapy to a standard dose of lansoprazole in decreasing the symptom burden of patients with reflux oesophagitis. However, in a subgroup with more severe symptoms, combination therapy with lansoprazole and mosapride was possibly superior to monotherapy with lansoprazole. AIMS To investigate if mosapride, a prokinetic agent, was an effective adjunct to acid suppression in improving the symptoms of reflux oesophagitis. METHODS Patients (n= 96) with reflux oesophagitis were randomly assigned to either mosapride (5 mg three times daily) or placebo for 4 weeks. Symptom severity was assessed by a validated questionnaire at enrolment, 4 and 8 weeks after medication. The primary outcome for the first 4 weeks was decrease in symptom scores. After a 3 day washout period, patients initially allocated to mosapride crossed over to placebo and vice versa for the next 4 weeks. The outcome of the second phase was maintenance of symptom control. All patients received lansoprazole (30 mg once daily) throughout study. RESULTS The decreased symptom score after 4 weeks of treatment with lansoprazole and mosapride (n= 50) was 13.42 +/- 1.16 (mean +/- SEM), similar to that of lansoprazole plus placebo (10.85 +/- 1.03, n= 46), with an insignificant difference of 2.57 (95% CI -0.53, 5.67, P= 0.103). However, a sub-group analysis for patients with pre-treatment scores of >18 points (n= 48) revealed that lansoprazole plus mosapride achieved a greater reduction of symptom score than lansoprazole plus placebo (18.22 +/- 1.91 vs. 12.88 +/- 1.65; mean difference of 5.34, 95% CI 0.28, 10.40, P= 0.039). In the second phase, there was no difference between lansoprazole with mosapride or placebo in maintaining symptom control (39/44 or 86.64% vs. 41/50 or 82%, P= 0.401). Subgroup analysis for those with substantial residual symptoms revealed similar results. CONCLUSION Compared with placebo, mosapride generally does not provide additional benefit to a standard dose of lansoprazole in patients with reflux oesophagitis, except possibly in the subgroup of severely symptomatic patients.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • An adjunct to endoscopy, proton pump inhibitor (PPI) is effective pharmacotherapy in high-risk patients with peptic ulcer bleeding (PUB). • An intravenous 80-mg bolus and 192 mg day−1 successive infusion for 3 days is the currently recommended dosing modality in administering PPI. WHAT THIS STUDY ADDS • Clinical outcomes are not different in PUB patients receiving infusional pantoprazole at either 192 mg or 160 mg day−1 for 3 days. • The effective dosage of PPI may not be as high as currently recommended. • In view of cost-effectiveness, a lower dosage (160 mg day−1) of infusional PPI may be adopted in the management of PUB. AIM The optimal dosage of proton pump inhibitor in bleeding peptic ulcers remains controversial. The aim was to compare the clinical effectiveness of two doses of infusional pantoprazole in peptic ulcer bleeding. METHODS Peptic ulcer patients (n= 120) with bleeding stigmata were enrolled after successful endoscopic therapy. After an initial bolus injection of 80 mg pantoprazole, patients were randomized to receive continuously infused pantoprazole at either 192 mg day−1 or 40 mg every 6 h (i.e. 160 mg day−1) for 3 days. Clinical outcomes between the two groups within 14 days were compared, with 14-day recurrent bleeding regarded as the primary end-point. RESULTS Both groups (n= 60 each) were well matched in demographic and clinical factors upon entry. Bleeding totally recurred in 11 (9.2%) patients, with six (10%) in the 192 mg day−1 group and five (8.3%) in the 160 mg day−1 group (relative risk of bleeding recurrence between two treatments 1.2; 95% CI 0.39, 3.72). All secondary outcomes between the two groups were similar, including the amount of blood transfusion (mean 1179 ml vs. 1203 ml, P > 0.1), hospital stay (mean 9.5 days vs. 9.9 days, P > 0.1), need for surgery (n= 1 vs. n= 0, P > 0.1), and mortality (n= 1 vs. n= 0, P > 0.1). CONCLUSIONS Following endoscopic haemostasis, infusional pantoprazole at either 192 mg day−1 or 40 mg every 6 h appear similar.

This study reports the preparation and physical properties of biodegradable nanocomposites fabricated using poly( l -lactide) (PLLA) and magnesium/aluminum layered double hydroxide (MgAl-LDH). The MgAl-LDH with molar ratio of Mg/Al = 2 were synthesized by the co-precipitation method. In order to improve the chemical compatibility between PLLA and LDH, the surface of LDH was organically-modified by polylactide with carboxyl end group (PLA–COOH) using ion-exchange process. Then, the PLLA/LDH nanocomposites were prepared by solution intercalation of PLLA into the galleries of PLA–COOH modified LDH (P-LDH) in tetrahydrofuran solution. Both X-ray diffraction data and Transmission electron microscopy images of PLLA/P-LDH nanocomposites indicate that the P-LDHs are randomly dispersed and exfoliated into the PLLA matrix. Mechanical properties of the fabricated 1.2 wt.% PLLA/P-LDH nanocomposites show significant enhancements in the storage modulus when compared to that of neat PLLA. Adding more P-LDH into PLLA matrix induced a decrease in the storage modulus of PLLA/P-LDH nanocomposites, probably due to the excessive content of PLA–COOH moleculars with low mechanical properties. The thermal stability and degradation activation energies of the PLLA and PLLA/P-LDH nanocomposites can also be discussed.

This study describes the preparation of polycarbonate (PC)/multiwalled carbon nanotube (MWCNT) composites by melt processing the PC and PC/MWCNT master batch at 260°C. The PC/MWCNT master batch was prepared using ultrasonic mixing the carboxylic acid containing MWCNT and PC in a tetrahydrofuran (THF) solution. The HRTEM images of PC/MWCNT master batch and PC/MWCNT nanocomposites show that the MWCNT is well separated and uniformly distributed in the PC matrices. Mechanical properties of the fabricated nanocomposites measured by dynamic mechanical analysis indicate significant improvements in the storage modulus when compared with that of pure PC matrix. The conductivities of 2 and 5 wt% PC/MWCNT nanocomposites are more than four and seven orders in magnitude higher than that of PC without MWCNT, respectively. POLYM. ENG. SCI., 2008. © 2008 Society of Plastics Engineers

In this article, we report the fabrication of novel poly(L-lactide) (PLLA) nanocomposites based on PLLA and magnesium-aluminium layered double hydroxides (MgAl-LDH) which were mixed the polylactide with carboxyl end group (PLA-COOH) in acetone . Both the X-ray diffraction data and transmission electron microscopy images of the PLLA/LDH nanocomposites indicate that most of the LDH layers were disorderly exfoliated into the PLLA matrix. The thermal degradation behaviors of PLLA and its nanocomposites were studied using thermal gravimetric analysis (TGA) under nitrogen atmosphere at heating rates from 5 to 40 °C/min. The TGA profiles of the PLLA/LDH nanocomposites show less thermal stability than that of neat PLLA due to the presence of Mg and Al which has a drastic influence on thermal stability of PLLA. The activation energy of PLLA, 1 wt% and 3 wt% PLLA/LDH nanocomposites were 158, 140 and 130 kJ/mol, respectively.

In this study biocompatible/biodegradable poly(lactic acid) (PLA)/layered silicate nanocomposites (PLSNs) were successfully prepared by the intercalation of PLA polymer into organically modified layered silicate through the solution mixing process. Both X-ray diffraction data and transmission electron microscopy images of PLSNs indicate most of the swellable silicate layers were disorderedly intercalated into the PLA matrix. Mechanical properties of the 0.1 wt% silicate-containing fabricated nanocomposites performed by dynamic mechanical analysis have significant improvements in the storage modulus when compared to that of neat PLA matrix. Adding more layered silicates into PLA matrix induced a decrease in the mechanical properties of PLSNs, probably due to the presence of a large dimension of porosity in the fabricated nanocomposites. POLYM. ENG. SCI., 45: 1615–1621, 2005. © 2005 Society of Plastics Engineers