Search

Bromodomain and extraterminal domain (BET) proteins are epigenetic readers that regulate gene expression. We investigated whether variants in BET genes are associated with survival outcomes for lung cancer. To do this, the associations between 77 variants in BET family genes and survival outcomes were analyzed in 773 non‐small‐cell lung cancer (NSCLC) patients who underwent surgery (349 and 424 patients in the discovery and validation cohorts, respectively). We found that six variants were significantly associated with overall survival (OS) in the discovery cohort, and one variant (rs2506711C>T) was replicated in the validation cohort. BRD3 rs2506711C>T is located in the repressed area and has a strong linkage disequilibrium with rs2427964C>T in the promoter region. BRD3 rs2427964C>T was significantly associated with worse OS in the discovery cohort, validation cohort, and combined analysis. In a luciferase assay, promoter activity in the BRD3 rs2427964 T allele was significantly higher than that in the BRD3 rs2427964 C allele, which selectively bound with the transcriptional repressor SIN3A. Knockdown of BRD3 with BRD3‐specific siRNA decreased the proliferation and migration of lung cancer cells while also increasing the rate of apoptosis. These results suggest that BRD3 rs2427964C>T increases BRD3 expression through increased promoter activity, which is associated with poor prognosis for lung cancer., In this study, we investigated the association of BET gene variants with survival of patients with non‐small‐cell lung cancer (NSCLC). We observed that the rs2427964C>T SNP in the BRD3 promoter region was associated with poorer survival outcome. BRD3 promoter activity was higher in rs2427964_T than in rs2427964_C, which selectively bound with the transcriptional repressor SIN3A. Additionally, BRD3 silencing decreased the proliferation and migration of NSCLC cells. Our data suggest that elevated BRD3 expression regulated by rs2427964C>T leads to reduced overall survival in patients with NSCLC.

BACKGROUND Achaete-scute homolog 1 (ASCL1) is a basic helix-loop-helix transcription factor and is essential in the differentiation of neuroendocrine cells and neural tissues. ASCL1 is frequently overexpressed in small cell lung cancer (SCLC) and plays a crucial role in the pathogenesis of SCLC. METHODS This study was conducted to identify the association between single nucleotide polymorphisms (SNPs) in ASCL1 target genes and clinical outcomes of patients with SCLC after chemotherapy. A total of 261 patients diagnosed with SCLC were enrolled in this study. The association between 103 SNPs in 58 ASCL1 target genes and the response to chemotherapy and survival of patients with SCLC were analyzed. RESULTS Among the 103 SNPs, 10 SNPs were significantly associated with the response to chemotherapy, and 19 SNPs were associated with OS in multivariate analyses. Among these, Dopa Decarboxylase (DDC) rs12666409A>T was significantly associated with both a worse response to chemotherapy and worse OS (adjusted odds ratio [aOR] = 0.40, 95% CI = 0.18-0.90, P = 0.03; adjusted hazard ratio [aHR] = 1.52, 95% CI = 1.10-2.10, P = 0.01, respectively, under a dominant model). In a stage-stratified analysis, the association was significant only in the extensive disease subgroup (aOR = 0.19, 95% CI = 0.06-0.60, P = 0.01; aHR = 1.73, 95% CI = 1.16-2.56, P = 0.01, respectively, under a dominant model), but not in the limited disease subgroup. CONCLUSION The results of our study suggest that DDC rs12666409A>T may be useful markers for predicting the clinical outcomes of patients with SCLC undergoing chemotherapy.

International audience; As the symbol of beauty, floral objects have been one of the most popular subjects of artistic drawing. However, designing 3D floral models is generally time-and resource-consuming, because of their structural and geometrical complexity. In this paper, we address the problem of reconstructing floral objects from sketch input. The user draws a relatively clean sketch of a flower and a few additional guide markings from an arbitrary view to rapidly create quality geometric models of flowers. Our system offers a novel modeling scheme compared to several existing flower modelers accepting sketch as input, where the user is required to work with different views, providing step-by-step sketch input. Given the silhouette and the guide strokes, an assumed, common botanical structure is estimated, i.e. a cone for each ring of petals. The cones and the silhouette sketch that we segment into elementary curves are used to retrieve model elements from the pre-constructed shape database. These elements are then placed together around the cone, where an additional, per-element deformation is performed so as to maximize the silhouette similarity between the user sketch and the 3D flower model from the chosen view. Our system has shown to robustly create a variety of flowers in various configurations, including flower models with several petal layers and various blooming degrees, drawn from different views.

Anthrax, a bacteriogenic fatal infectious disease against human beings, demands early and ready detection of its bacterial endospores. We disclose here poly(diacetylene acid) derived liposomes functionalized with Eu(III)-EDTA complexes as a novel ratiometric fluorescence detection system for dipicolinate, an anthrax biomarker and the major component of the endospores. The red fluorescence of the polymerized liposomes offers a biult-in reference signal, allowing us to monitor the relative change of europium luminescence sensitized by the bound dipicolinate with respect to the reference liposome emission. The liposome based integrated sensing system shows reasonable sensitivity as well as remarkable selectivity toward dipicolinate over other structurally related analytes. We also show paper stripe sensors based on the polymerized liposome for the detection of dipicolinate by naked eyes.

Background and objective Few studies have analysed a large number of patients with necrotizing pneumonia (NP) diagnosed based on computed tomography (CT) scans. The aim of the present study was to document the incidence and clinical features of NP in patients with community-acquired pneumonia (CAP). Methods This retrospective study was conducted on CAP patients who had been admitted to a tertiary referral centre and who had available enhanced CT scan images. Patients were allocated into NP and non-NP groups, and they were compared with respect to various clinical variables. Results Of the 830 patients included in the present study, necrotizing change was observed in 103 patients (12%). Patients with NP experienced more symptoms of pneumonia, had higher blood levels of inflammatory markers and more often required pleural drainage compared to patients with non-NP. Although the use of mechanical ventilation, vasopressor infusion, 30-day mortality, in-hospital mortality and clinical deterioration did not differ between the NP and non-NP groups, the median length of hospital stay (LOS) was significantly longer in the NP group. Multivariate analysis using Cox proportional hazards model showed that necrotizing change independently predicted LOS in patients with CAP. Conclusion NP affects approximately one-tenth of hospitalized CAP patients. It may be associated with more severe clinical manifestations and may increase the need for pleural drainage. NP was found to be an independent predictor of LOS, but not of mortality in CAP patients.

A method for determining a novel phosphodiesterase-4 inhibitor, 3-[1-(3cyclopropylmethoxy-4-difluoromethoxybenzyl)-1H-pyrazol-3-yl]-benzoic acid (PDE-423), in rat plasma was developed and validated using liquid chromatography–tandem mass spectrometry for further pharmacokinetic study for development as a novel anti-asthmatic drug. PDE-423 in the concentration range of 0.02–10 µg/mL was linear with a correlation coefficient of >0.99, and the mean intra- and inter-assay precisions of the assay were 7.50 and 3.86%, respectively. The validated method was used successfully for a pharmacokinetic study of PDE-423 in rats. Copyright © 2014 John Wiley & Sons, Ltd.

We describe a compression method for three-dimensional animation sequences that has notable advantages over existing techniques. We first aggregate the frame data by similarity and reorganize them into clusters, which results in the sequence split into several motion fragments of varying lengths. To minimize the number of clusters and obtain optimal clustering, we perform frame alignment, which eliminates the “global” rigid transformation from each frame data and use only “pose” when evaluating the similarity between frames. We then apply principal component analysis for each cluster, from which we get coordinates of corresponding frames in a reduced dimension. Because similar frames are considered, the number of coefficients required for each frame becomes smaller; thus, we obtain better dimension reduction for a given reconstruction error. Further, we perform intracluster compression based on linear coding. Because every motion fragment presents similar frames, conventional linear predictive coding can be replaced by key frame-based linear coding to achieve minimal reconstruction error. Results show that our method can obtain a high compression ratio, with a limited reconstruction error. Copyright © 2013 John Wiley & Sons, Ltd.

In this study, we developed a method for the determination of PF-04620110 (2-{(1r,4r)-4-[4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)phenyl]cyclohexyl}acetic acid), a novel diacylglycerol acyltransferase 1 (DGAT-1) inhibitor, in rat plasma and validated it using liquid chromatography–tandem mass spectrometry (LC-MS/MS). Rat plasma samples were processed following a protein precipitation method by using acetonitrile and were then injected into an LC-MS/MS system for quantification. PF-04620110 and imipramine (internal standard) were separated using a Hypersil Gold C18 column, with a mixture of acetonitrile and 10 mm ammonium formate (90:10, v/v) as the mobile phase. The ion transitions monitored in positive-ion mode [M + H]+ of multiple-reaction monitoring were m/z 397.0 260.2 for PF-04620110 and m/z 280.8 86.0 for imipramine. The detector response was specific and linear for PF-04620110 at concentrations within the range 0.05–50 µg/mL and the signal-to-noise ratios for the samples were ≥10. The intra- and inter-day precision and accuracy of the method matched the acceptance criteria for assay validation. PF-04620110 was stable under various processing and/or handling conditions. PF-04620110 concentrations in the rat plasma samples could be measured up to 24 h after intravenous or oral administration of PF-04620110, suggesting that the assay is useful for pharmacokinetic studies in rats. Copyright © 2013 John Wiley & Sons, Ltd.

Vinylgold intermediates involved in various gold-catalyzedreactions are known to undergo proto-deauration in thepresence of a proton source. The unexpected result drew ourattention on the chemistry of vinylgold intermediatesinvolved and thus prompted us to investigate the gold-mediated cyclization in detail with simple substrates, N-(propargyl)benzamides. Described herein is identification ofthe vinylgold(III) intermediates involved and their reactionpathways, all of which expands our present understanding onthe vinylgold intermediates.The treatment of N-(propargyl)benzamide (1) with anequimolar amount of AuCl

We introduce in this paper a new method for smooth foldover-free warping of images. It allows users to specify the constraints in two different ways: positional constraints to constrain the position of points in the image and gradient constraints to constrain the orientation and scaling of some parts of the image. We then show how our method is used for texture mapping with hard constraints. We start with an unconstrained planar embedding of the target mesh calculated with conventional methods. In order to obtain a mapping that satisfies the user-defined constraints, we use our warping method to align the features of the texture image with those of the unconstrained embedding. Compared to previous work, our method generates a smoother texture mapping and offers higher level of control for defining the constraints.

**************** **************** **************** **************** **************** ************* The advent of 3D scanning technology has allowed effective measurement and analysis of breast size and shape, attracting interests by plastic surgeons, brassier designers, etc. Much work remains, however, before 3D scanning systems can be successfully used in automated analysis and synthesis of the breast—filtering noise, filling holes, and, in case a statistical analysis is desired, finding correspondence among each scan data. Moreover, analysis of a sagged breast is difficult to obtain, due to occlusions. In this paper, we address the problems and specific issues of using 3D scan data for the analysis and synthesis of breast models. The goal of our work is to build a breast modeler which can help both surgeons and garment designers in analyzing breast volume and surface measurements. Given enough samples of scanned breasts, our modeler can generate highly realistic breast shape, with some expected and consistent variability. Copyright # 2007 John Wiley & Sons, Ltd.

Background and objective ‘Focal necrotizing pneumonia’ was defined as a localized type of necrotizing pneumonia characterized by a single or few cavities of low density without rim enhancement on computed tomography (CT) scan. The purpose of this study was to investigate the clinical features and course of patients with focal necrotizing pneumonia, thereby elucidating its clinical relevance. Methods The present study was conducted retrospectively in patients who had been interpreted as having lung abscess or necrotizing pneumonia on CT scan. Clinical and radiological characteristics were compared between the focal necrotizing pneumonia and lung abscess groups. Results Overall, 68 patients with focal necrotizing pneumonia (n = 35) or lung abscess (n = 33) were included in the present study. The frequency of risk factors for aspiration was significantly lower in the focal necrotizing group, compared with the lung abscess group (14.3% vs 45.5%, P = 0.005). Compared with lung abscess, focal necrotizing pneumonia was observed more commonly in non-gravity-dependent segments (66% vs 36%, P