Be Stars in the Open Cluster NGC 6830

We report the discovery of 2 new Be stars, and re-identify one known Be star in the open cluster NGC 6830. Eleven H-alpha emitters were discovered using the H-alpha imaging photometry of the Palomar Transient Factory Survey. Stellar membership of the candidates was verified with photometric and kinematic information using 2MASS data and proper motions. The spectroscopic confirmation was carried out by using the Shane 3-m telescope at Lick observatory. Based on their spectral types, three H-alpha emitters were confirmed as Be stars with H-alpha equivalent widths > -10 Angstrom. Two objects were also observed by the new spectrograph SED-Machine on the Palomar 60 inch Telescope. The SED-Machine results show strong H-alpha emission lines, which are consistent with the results of the Lick observations. The high efficiency of the SED-Machine can provide rapid observations for Be stars in a comprehensive survey in the future.Comment: 11 pages, 8 figures, AJ in pres

Magnetically Directed Two-Dimensional Crystallization of OmpF Membrane Proteins in Block Copolymers

Two-dimensional (2D) alignment and crystallization of membrane proteins (MPs) is increasingly important in characterizing their three-dimensional (3D) structure, in designing pharmacological agents, and in leveraging MPs for biomimetic devices. Large, highly ordered MP 2D crystals in block copolymer (BCP) matrices are challenging to fabricate, but a facile and scalable technique for aligning and crystallizing MPs in thin-film geometries would rapidly translate into applications. This work introduces a novel method to grow larger and potentially better ordered 2D crystals by performing the crystallization process in the presence of a strong magnetic field. We demonstrate the efficacy of this approach using a \u3b2-barrel MP, outer membrane protein F (OmpF), in short-chain polybutadiene-poly(ethylene oxide) (PB-PEO) membranes. Crystals grown in a magnetic field were up to 5 times larger than conventionally grown crystals, and a signal-to-noise (SNR) analysis of diffraction peaks in Fourier transforms of specimens imaged by negative-stain electron microscopy (EM) and cryo-EM showed twice as many high-SNR diffraction peaks, indicating that the magnetic field also improves crystal order

Afatinib versus gefitinib or erlotinib in first-line setting for Malaysia patients with EGFR mutant advanced lung adenocarcinoma

Abstract Background Afatinib is an irreversible second-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) while gefitinib or erlotinib are reversible first-generation EGFR-TKIs. Methods A retrospective analysis of patients with EGFR mutant advanced lung adenocarcinoma receiving first-line afatinib versus gefitinib or erlotinib at University Malaya Medical Centre from 1st January 2015 to 31th December 2018. Results Of 113 patients, 24 (21.2%) received afatinib, 63 (55.8%) received gefitinib and 26 (23.0%) received erlotinib in first-line setting. Their demographic and clinical characteristics are shown in the table. Afatinib was used significantly more frequently in patients with rare or complex EGFR mutations (p = 0.005), and more often in patients with symptomatic brain metastases. The median progression-free survival (mPFS) of patients treated with afatinib (13.1 months) was longer than that of patients treated with gefitinib (10.9 months) or erlotinib (7.8 months) (p = 0.479). Patients receiving afatinib had consistently longer PFS than patients receiving gefitinib for the first 17 months and erlotinib for the first 20 months. The overall response rate was higher in patients on afatinib (75.0%) than those on gefitinib (63.5%) or erlotinib (53.8%). There was no difference in the disease control rate. Three patients (2.7%) had severe side-effects while on EGFR-TKI. Of two patients on afatinib, one had grade-3 diarrhea while another had grade 3 stomatitis, rash and paronychia. One patient had grade 3 rash on gefitinib. Conclusions Patients receiving first-line afatinib demonstrated longer mPFS than those on first-line gefitinib or erlotinib. The lack of statistical significance in this study is because of the small number of patients treated with afatinib, more frequent rare or complex EGFR mutations and more symptomatic brain metastases among afatinib treated patients

OCIS codes: (230.5298) Photonic crystals; (140.3945) Nanocavities; (140.5960) Semiconductor lasers

Abstract: We propose a point-shifted nanocavity based on square lattice photonic crystal, which sustains a lowest-order whispering-gallery (WG) mode. In simulation, the optimized WG mode (quality (Q) factor ~14,000) in point-shifted nanocavity can be with smaller mode volume (~5.5(λ/2n) 3 ) but larger nano-post tolerance than those in single-defect cavity design. From well-fabricated device, single WG mode lasing with measured Q factor of 4,100 and low threshold of 160 µW is obtained. Besides, we also observe the changed polarization of WG mode due to modal symmetry breaking caused by the presence of a nearby dielectric nano-particle, which would be useful in sensing molecule binding or attaching for bio-chemical applications. (C ©2010 Optical Society of Americ

Comparison of pattern of disease progression and prevalence of acquired T790M mutation in Malaysia patients with EGFR mutant lung adenocarcinoma upon failure of first-line afatinib, gefitinib and erlotinib

Abstract Background Patients receiving first-line afatinib, gefitinib or erlotinib for epidermal growth factor receptor (EGFR) mutant advanced non-small cell lung cancer develop progression of disease (PD) after an average of 9-13 months. Methods A retrospective analysis of PD pattern and prevalence of acquired T790M mutation among patients failing first-line afatinib versus gefitinib or erlotinib at University Malaya Medical Centre from 1st January 2015 to 31th December 2018. Results Of 87 patients who developed PD while on first-line EGFR-tyrosine kinase inhibitor (TKI) treatment, 19 (21.8%) were on afatinib, 49 (56.3%) were on gefitinib, and 19 (21.8%) were on erlotinib. The median progression-free survival (mPFS) of these patients is as shown in the table. Of 20 patients (23.0%) who developed new symptomatic brain metastases, one (5.0%) had new leptomeningeal metastases, three (15.0%) had both new leptomeningeal metastases and solid brain metastases, and the remaining 16 (80.0%) had new solid brain metastases only. New leptomeningeal metastases occurred in one patient treated with afatinib and three patients treated with gefitinib. Forty-nine patients (56.3%) were investigated for acquired T790M mutation either by plasma biopsy or tissue biopsy or both. The prevalence of acquired T790M mutation was 61.2%. There was no difference in the pattern of PD or prevalence of acquired T790M mutation among patients treated with afatinib, gefitinib or erlotinib. Conclusions New leptomeningeal metastases were uncommon in patients receiving first-line EGFR-TKI. The choice of first-line first- or second generation EGFR-TKI did not influence the pattern of PD and prevalence of acquired T790M mutation. However, patients receiving afatinib appeared to have longer mPFS than those on gefitinib or erlotinib

Androgen-Regulated Expression of Arginase 1, Arginase 2 and Interleukin-8 in Human Prostate Cancer

BACKGROUND: Prostate cancer (PCa) is the most frequently diagnosed cancer in North American men. Androgen-deprivation therapy (ADT) accentuates the infiltration of immune cells within the prostate. However, the immunosuppressive pathways regulated by androgens in PCa are not well characterized. Arginase 2 (ARG2) expression by PCa cells leads to a reduced activation of tumor-specific T cells. Our hypothesis was that androgens could regulate the expression of ARG2 by PCa cells. METHODOLOGY/PRINCIPAL FINDINGS: In this report, we demonstrate that both ARG1 and ARG2 are expressed by hormone-sensitive (HS) and hormone-refractory (HR) PCa cell lines, with the LNCaP cells having the highest arginase activity. In prostate tissue samples, ARG2 was more expressed in normal and non-malignant prostatic tissues compared to tumor tissues. Following androgen stimulation of LNCaP cells with 10 nM R1881, both ARG1 and ARG2 were overexpressed. The regulation of arginase expression following androgen stimulation was dependent on the androgen receptor (AR), as a siRNA treatment targeting the AR inhibited both ARG1 and ARG2 overexpression. This observation was correlated in vivo in patients by immunohistochemistry. Patients treated by ADT prior to surgery had lower ARG2 expression in both non-malignant and malignant tissues. Furthermore, ARG1 and ARG2 were enzymatically active and their decreased expression by siRNA resulted in reduced overall arginase activity and l-arginine metabolism. The decreased ARG1 and ARG2 expression also translated with diminished LNCaP cells cell growth and increased PBMC activation following exposure to LNCaP cells conditioned media. Finally, we found that interleukin-8 (IL-8) was also upregulated following androgen stimulation and that it directly increased the expression of ARG1 and ARG2 in the absence of androgens. CONCLUSION/SIGNIFICANCE: Our data provides the first detailed in vitro and in vivo account of an androgen-regulated immunosuppressive pathway in human PCa through the expression of ARG1, ARG2 and IL-8

Decreased Circulating Endothelial Progenitor Cell Levels and Function in Patients with Nonalcoholic Fatty Liver Disease

OBJECTIVES: Nonalcoholic fatty liver disease (NAFLD) is associated with advanced atherosclerosis and a higher risk of cardiovascular disease. Increasing evidence suggests that injured endothelial monolayer is regenerated by circulating bone marrow derived-endothelial progenitor cells (EPCs), and levels of circulating EPCs reflect vascular repair capacity. However, the relation between NAFLD and EPC remains unclear. Here, we tested the hypothesis that patients with nonalcoholic fatty liver disease (NAFLD) might have decreased endothelial progenitor cell (EPC) levels and attenuated EPC function. METHODS AND RESULTS: A total of 312 consecutive patients undergoing elective coronary angiography because of suspected coronary artery disease were screened and received examinations of abdominal ultrasonography between July 2009 and November 2010. Finally, 34 patients with an ultrasonographic diagnosis of NAFLD, and 68 age- and sex-matched controls without NAFLD were enrolled. Flow cytometry with quantification of EPC markers (defined as CD34(+), CD34(+)KDR(+), and CD34(+)KDR(+)CD133(+)) in peripheral blood samples was used to assess circulating EPC numbers. The adhesive function, and migration, and tube formation capacities of EPCs were also determined in NAFLD patients and controls. Patients with NAFLD had a significantly higher incidence of metabolic syndrome, previous myocardial infarction, hyperuricemia, and higher waist circumference, body mass index, fasting glucose and triglyceride levels. In addition, patients with NAFLD had significantly decreased circulating EPC levels (all P<0.05), attenuated EPC functions, and enhanced systemic inflammation compared to controls. Multivariate logistic regression analysis showed that circulating EPC level (CD34(+)KDR(+) [cells/10(5) events]) was an independent reverse predictor of NAFLD (Odds ratio: 0.78; 95% confidence interval: 0.69-0.89, P<0.001). CONCLUSIONS: NAFLD patients have decreased circulating EPC numbers and functions than those without NAFLD, which may be one of the mechanisms to explain atherosclerotic disease progression and enhanced cardiovascular risk in patients with NAFLD

Significance of Aurora B overexpression in hepatocellular carcinoma. Aurora B Overexpression in HCC

<p>Abstract</p> <p>Background</p> <p>To investigate the significance of Aurora B expression in hepatocellular carcinoma (HCC).</p> <p>Methods</p> <p>The <it>Aurora B </it>and <it>Aurora A </it>mRNA level was measured in 160 HCCs and the paired nontumorous liver tissues by reverse transcription-polymerase chain reaction. Mutations of the <it>p53 </it>and <it>β-catenin </it>genes were analyzed in 134 and 150 tumors, respectively, by direct sequencing of exon 2 to exon 11 of <it>p53 </it>and exon 3 of <it>β-catenin</it>. Anticancer effects of AZD1152-HQPA, an Aurora B kinase selective inhibitor, were examined in Huh-7 and Hep3B cell lines.</p> <p>Results</p> <p><it>Aurora B </it>was overexpressed in 98 (61%) of 160 HCCs and in all 7 HCC cell lines examined. The overexpression of <it>Aurora B </it>was associated with <it>Aurora A </it>overexpression (<it>P </it>= 0.0003) and <it>p53 </it>mutation (<it>P </it>= 0.002) and was inversely associated with <it>β</it>-<it>catenin </it>mutation (<it>P </it>= 0.002). <it>Aurora B </it>overexpression correlated with worse clinicopathologic characteristics. Multivariate analysis confirmed that <it>Aurora B </it>overexpression was an independent poor prognostic factor, despite its interaction with Aurora A overexpression and mutations of <it>p53 </it>and <it>β</it>-<it>catenin</it>. In Huh-7 and Hep3B cells, AZD1152-HQPA induced proliferation blockade, histone H3 (Ser10) dephosphorylation, cell cycle disturbance, and apoptosis.</p> <p>Conclusion</p> <p><it>Aurora B </it>overexpression is an independent molecular marker predicting tumor invasiveness and poor prognosis of HCC. Aurora B kinase selective inhibitors are potential therapeutic agents for HCC treatment.</p