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Identification of cancer driver mutations is critical for advancing cancer research and personalized medicine. Due to inter-tumor genetic heterogeneity, many driver mutations occur at low frequencies, which make it challenging to distinguish them from passenger mutations. Here, we show that a novel Bayesian hierarchical modeling approach, named rDriver can achieve enhanced prediction accuracy by identifying mutations that not only have high functional impact scores but also are associated with systemic variation in gene expression levels. In examining 3,080 tumor samples from 8 cancer types in The Cancer Genome Atlas, rDriver predicted 1,389 driver mutations. Compared with existing tools, rDriver identified more low frequency mutations associated with lineage specific functional properties, timing of occurrence and patient survival. Evaluation of rDriver predictions using engineered cell-line models resulted in a positive predictive value of 0.94 in PIK3CA genes. Our study highlights the importance of integrating multi-omic data in predicting cancer driver mutations and provides a statistically rigorous solution for cancer target discovery and development.

Identifying molecular cancer drivers is critical for precision oncology. Multiple advanced algorithms to identify drivers now exist, but systematic attempts to combine and optimize them on large datasets are few. We report a PanCancer and PanSoftware analysis spanning 9,423 tumor exomes (comprising all 33 of The Cancer Genome Atlas projects) and using 26 computational tools to catalog driver genes and mutations. We identify 299 driver genes with implications regarding their anatomical sites and cancer/cell types. Sequence- and structure-based analyses identified >3,400 putative missense driver mutations supported by multiple lines of evidence. Experimental validation confirmed 60%-85% of predicted mutations as likely drivers. We found that >300 MSI tumors are associated with high PD-1/PD-L1, and 57% of tumors analyzed harbor putative clinically actionable events. Our study represents the most comprehensive discovery of cancer genes and mutations to date and will serve as a blueprint for future biological and clinical endeavors., (Published by Elsevier Inc.)

The functional impact of the vast majority of cancer somatic mutations remains unknown, representing a critical knowledge gap for implementing precision oncology. Here, we report the development of a moderate-throughput functional genomic platform consisting of efficient mutant generation, sensitive viability assays using two growth factor-dependent cell models, and functional proteomic profiling of signaling effects for select aberrations. We apply the platform to annotate >1,000 genomic aberrations, including gene amplifications, point mutations, indels, and gene fusions, potentially doubling the number of driver mutations characterized in clinically actionable genes. Further, the platform is sufficiently sensitive to identify weak drivers. Our data are accessible through a user-friendly, public data portal. Our study will facilitate biomarker discovery, prediction algorithm improvement, and drug development., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: Sarcomatoid renal cell carcinoma (SRCC) ranks among the most aggressive clinicopathologic phenotypes of RCC. However, the paucity of high-quality, genome-wide molecular examinations of SRCC has hindered our understanding of this entity. Experimental Design: We interrogated the mutational, copy number, and transcriptional characteristics of SRCC and compared these data with those of nonsarcomatoid RCC (RCC). We evaluated whole-exome sequencing, single-nucleotide polymorphism, and RNA sequencing data from patients with SRCC ( n = 65) and RCC ( n = 598) across different parent RCC subtypes, including clear-cell RCC, papillary RCC, and chromophobe RCC subtypes. Results: SRCC was molecularly discrete from RCC and clustered according to its parent RCC subtype, though with upregulation of TGFβ signaling across all subtypes. The epithelioid (E-) and spindled (S-) histologic components of SRCC did not show differences in mutational load among cancer-related genes despite a higher mutational burden in S-. Notably, sarcomatoid clear-cell RCC (SccRCC) showed significantly fewer deletions at 3p21-25, a lower rate of two-hit loss for VHL and PBRM1 , and more mutations in PTEN , TP53 , and RELN compared with ccRCC. A two-hit loss involving VHL predicted for ccRCC and a better prognosis, whereas mutations in PTEN , TP53 , or RELN predicted for SccRCC and worse prognosis. Conclusions: SRCC segregates by parent subtype, and SccRCC has a fundamentally different early molecular pathogenesis, usually lacking the classic 3p21-25 deletion and showing distinctive mutational and transcriptional profiles. These features prompt a more precise molecular classification of RCC, with diagnostic, prognostic, and therapeutic implications. Clin Cancer Res; 23(21); 6686-96. ©2017 AACR See related commentary by Bergerot et al., p. 6381 ., (©2017 American Association for Cancer Research.)

Ultrathin ceramic coatings are of high interest as protective coatings from aviation to biomedical applications. Here, a generic approach of making scalable ultrathin transition metal-carbide/boride/nitride using immiscibility of two metals is demonstrated. Ultrathin tantalum carbide, nitride, and boride are grown using chemical vapor deposition by heating a tantalum-copper bilayer with corresponding precursor (C 2 H 2 , B powder, and NH 3 ). The ultrathin crystals are found on the copper surface (opposite of the metal-metal junction). A detailed microscopy analysis followed by density functional theory based calculation demonstrates the migration mechanism, where Ta atoms prefer to stay in clusters in the Cu matrix. These ultrathin materials have good interface attachment with Cu, improving the scratch resistance and oxidation resistance of Cu. This metal-metal immiscibility system can be extended to other metals to synthesize metal carbide, boride, and nitride coatings., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Mortality outcomes in trials of low-dose computed tomography (CT) screening for lung cancer are inconsistent. This study aimed to evaluate whether CT screening in urban areas of China could reduce lung cancer mortality and to investigate the factors that associate with the screening effect., Methods: A decision tree model with three scenarios (low-dose CT screening, chest X-ray screening, and no screening) was developed to compare screening results in a simulated Chinese urban cohort (100,000 smokers aged 45-80 years). Data of participant characteristics were obtained from national registries and epidemiological surveys for estimating lung cancer prevalence. The selection of other tree variables such as sensitivities and specificities of low-dose CT and chest X-ray screening were based on literature research. Differences in lung cancer mortality (primary outcome), false diagnoses, and deaths due to false diagnosis were calculated. Sensitivity analyses were performed to identify the factors that associate with the screening results and to ascertain worst and optimal screening effects considering possible ranges of the variables., Results: Among the 100,000 subjects, there were 448, 541, and 591 lung cancer deaths in the low-dose CT, chest X-ray, and no screening scenarios, respectively (17.2% reduction in low-dose CT screening over chest X-ray screening and 24.2% over no screening). The costs of the two screening scenarios were 9387 and 2497 false diagnoses and 7 and 2 deaths due to false diagnosis among the 100,000 persons, respectively. The factors that most influenced death reduction with low-dose CT screening over no screening were lung cancer prevalence in the screened cohort, low-dose CT sensitivity, and proportion of early-stage cancers among low-dose CT detected lung cancers. Considering all possibilities, reduction in deaths (relative numbers) with low-dose CT screening in the worst and optimal cases were 16 (5.4%) and 288 (40.2%) over no screening, respectively., Conclusions: In terms of mortality outcomes, our findings favor conducting low-dose CT screening in urban China. However, approaches to reducing false diagnoses and optimizing important screening conditions such as enrollment criteria for screening are highly needed.

The application of exciplex energy has become a unique way to achieve organic light-emitting diodes (OLEDs) with high efficiencies, low turn-on voltage, and low roll-off. Novel δ-carboline derivatives with high triplet energy (T 1 ≈ 2.92 eV) and high glass transition temperature (T g ≈ 153 °C) were employed to manipulate exciplex emissions in this paper. Deep blue (peak at 436 nm) and pure blue (peak at 468 nm) thermally activated delayed fluorescence (TADF) of exciplex OLEDs were demonstrated by utilizing them as emitters with the maximum current efficiency (CE) of 4.64 cd A -1 , power efficiency (PE) of 2.91 lm W -1 , and external quantum efficiency (EQE) of 2.36%. Highly efficient blue phosphorescent OLEDs doped with FIrpic showed a maximum CE of 55.6 cd A -1 , PE of 52.9 lm W -1 , and EQE of 24.6% respectively with very low turn on voltage at 2.7 V. The devices still remain high CE of 46.5 cd A -1 at 100 cd m -2 , 45.4 cd A -1 at 1000 cd m -2 and 42.3 cd A -1 at 5000 cd m -2 with EQE close to 20% indicating low roll-off. Manipulating blue exciplex emissions by chemical structure gives an ideal strategy to fully utilize all exciton energies for lighting of OLEDs.

Introduction: Surgical safety has emerged as a crucial global health issue in the past two decades. Although several safety-enhancing tools are available, the pace of large-scale improvement remains slow, especially in developing countries such as China. The present project (Modern Surgery and Anesthesia Safety Management System Construction and Promotion) aims to develop and validate system-based integrated approaches for reducing perioperative deaths and complications using a multicentre, multistage design., Methods and Analysis: The project involves collection of clinical and outcome information for 1 20 000 surgical inpatients at four regionally representative academic/teaching general hospitals in China during three sequential stages: preparation and development, effectiveness validation and improvement of implementation for promotion. These big data will provide the evidence base for the formulation, validation and improvement processes of a system-based stratified safety intervention package covering the entire surgical pathway. Attention will be directed to managing inherent patient risks and regulating medical safety behaviour. Information technology will facilitate data collection and intervention implementation, provide supervision mechanisms and guarantee transfer of key patient safety messages between departments and personnel. Changes in rates of deaths, surgical complications during hospitalisation, length of stay, system adoption and implementation rates will be analysed to evaluate effectiveness and efficiency., Ethics and Dissemination: This study was approved by the institutional review boards of Peking Union Medical College Hospital, First Hospital of China Medical University, Qinghai Provincial People's Hospital, Xiangya Hospital Central South University and the Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences. Study findings will be disseminated via peer-reviewed journals, conference presentations and patent papers., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objectives: To explore the effect of interaction between ACE genotype and salt intake on hypertension among Chinese Kazakhs, and to compare applications of interactions between logistic model and generalised partially linear tree-based regression (GPLTR) model., Design: Population-based cross-sectional study., Setting: Hong Dun, North Xinjiang, China., Participants: Non-consanguineous Chinese Kazakh participants (n=916, 342 men and 574 women) aged ≥30 years., Main Outcome Measures: Association between ACE genotype and hypertension, association between salt intake and hypertension, and interaction of ACE genotype and salt intake on hypertension in two models., Results: Associations between salt intake and hypertension were different in ACE genotype of II and ID+DD. Under the logistic models, main and interaction effects were not observed for men, but effects were present in opposite directions for women (main effect of ACE: OR=0.20, p=0.003; interaction effect: OR=1.07, p=0.027). Under the GPLTR model, Bayesian information criterion trees included both salt intake and ACE genotype as split variables. Individuals with a salt intake ≥19.5 g/day and ID+DD genotypes had a 3.99-fold (p=0.004) higher risk of hypertension compared with the II genotype for men, whereas salt intake <20.1 g/day and ID+DD genotypes had an OR=0.55 (p=0.014) compared with the II genotype for women., Conclusions: An interaction of ACE genotype and salt intake on hypertension was observed among Chinese Kazakhs but in different ways according to sex. The GPLTR model appears to be more suitable for an exploration of interactions in complex diseases., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Mice and rats are the most commonly used animals for preclinical stroke studies, but it is unclear whether targets and mechanisms are always the same across different species. Here, we mapped the baseline expression of a chemokine/cytokine subnetwork and compared responses after oxygen-glucose deprivation in primary neurons, astrocytes, and microglia from mouse, rat, and human. Baseline profiles of chemokines (CX3CL1, CXCL12, CCL2, CCL3, and CXCL10) and cytokines (IL-1α, IL-1β, IL-6, IL-10, and TNFα) showed significant differences between human and rodents. The response of chemokines/cytokines to oxygen-glucose deprivation was also significantly different between species. After 4 h oxygen-glucose deprivation and 4 h reoxygenation, human and rat neurons showed similar changes with a downregulation in many chemokines, whereas mouse neurons showed a mixed response with up- and down-regulated genes. For astrocytes, subnetwork response patterns were more similar in rats and mice compared to humans. For microglia, rat cells showed an upregulation in all chemokines/cytokines, mouse cells had many down-regulated genes, and human cells showed a mixed response with up- and down-regulated genes. This study provides proof-of-concept that species differences exist in chemokine/cytokine subnetworks in brain cells that may be relevant to stroke pathophysiology. Further investigation of differential gene pathways across species is warranted.

An association between passive smoking and stroke is unclear in China, particularly the association with hemorrhagic stroke. This study included 16205 deaths due to stroke aged ≥30 years and 16205 non-stroke controls randomly selected and frequency-matched to cases on gender and age. Smoking of spouses, defined as ≥1 cigarette per day for up to 1 year, was taken as a measure of exposure to passive smoking of subjects that was retrospectively ascertained by interviewing surviving spouses. After adjustment for variables, passive smoking increased the risk of death by 10% (odds ratio (OR), 1.10; 95% confidence interval (CI), 1.05-1.16) for all strokes, by 10% (OR, 1.10; 95% CI, 1.04-1.16) for hemorrhagic stroke, and by 12% (OR, 1.12; 95% CI, 1.03-1.23) for ischemic stroke, compared with non-exposure. This finding was highly consistent in men or women and in smokers or non-smokers, and was generally consistent among zones of China despite geographic diversity. The risk significantly increased with exposure-years and quantity of cigarettes smoked daily by spouses. This study indicated that passive smoking is associated with deaths from all-type strokes. It is highly advisable for the government to promote strong tobacco prevention and cessation programs and smoke-free environments.

Hypertension is a leading cause of death worldwide; data on hypertension among ethnic minorities in China are sparse. This study aimed to estimate hypertension prevalence, awareness, treatment, and control in a Kazakh population, and to assess the association between salt intake and the above measures. A cross-sectional survey was conducted among Kazakh adults (≥30 years old) in the town of Hongdun, Altay, Xinjiang. Survey procedures included a questionnaire, physical measurement, and laboratory tests. Of 1805 eligible individuals, 1668 (92.4%) were included in the analysis. After adjustment for gender, age, and occupation, prevalence of hypertension was 45.5%. The proportions with awareness, treatment, control, or medication-control were 61.0%, 28.8%, 2.9% and 10.1%, respectively. Higher prevalence was seen among nomads and farmers (50.7% and 44.6%, respectively). However, the proportions with treatment or control were lower than seen among urban citizens. Hypertension prevalence was higher in those with higher salt intake (p = 0.0008). In contrast, the proportions with awareness (p = 0.0389), treatment (p = 0.0010), control (p = 0.0503), and medication-control (p = 0.2012) reduced as salt intake increased. In conclusion, hypertension prevalence is high in this population, but the proportions with awareness, treatment, or control are sub-optimal. Public health interventions that improve hypertension prevention and control, particularly among nomads, is needed.

Background: The purpose of this study was to investigate whether ultra-low-dose chest computed tomography (CT) can be used for visual assessment of CT features in patients with pulmonary alveolar proteinosis (PAP) and to evaluate the relationship between the quantitative analysis of the ultra-low-dose CT scans and the pulmonary function tests (PFTs)., Methods: Thirty-eight patients (mean [SD] age, 44.47 [12.28] years; 29 males, 9 females) with PAP were enrolled and subjected to two scans each with low-dose CT (reference parameters: 120 kV and 50 mAs) and ultra-low-dose CT (reference parameters, 80 kV, 25 mAs). Images were reconstructed via filtered back projection (FBP) for low-dose CT and iterative reconstruction (IR) for ultra-low-dose CT. All patients underwent PFT. The Visual analysis for ground glass opacity (GGO) is performed. The quantitative CT and PFT results were analyzed by canonical correlations., Results: The mean body mass index (BMI) was 25.37±3.26 kg/m2. The effective radiation doses were 2.30±0.46 and 0.24±0.05 mSv for low-dose and ultra-low-dose CT, respectively. The size-specific dose estimates were 5.81±0.81 and 0.62±0.09 mSv for low-dose and ultra-low-dose CT. GGOs and interlobular septal thickening were observed bilaterally in all patients. The average visual GGO score was lower in the upper field (2.67±1.24) but higher in the middle and lower fields (3.08±1.32 and 3.08±0.97, respectively). The average score for the whole lung was 2.94±1.19. There is a significant correlation between PFTs and quantitative of ultra-low-dose CT (canonical loading = 0.78)., Conclusions: Ultra-low-dose CT has the potential to quantify the lung parenchyma changes of PAP. This technique could provide a sensitive and objective assessment of PAP and has good relation with PFTs. In addition, the radiation dose of ultra-low-dose CT was very low.

A novel bipolar hosting material, 11-(3-(4,6-diphenyl-1,3,5-triazin-2-yl)phenyl)-12,12-dimethyl-11,12-dihydroindeno[2,1- a ]carbazole (DPDDC), was designed, synthesized, and characterized for green phosphorescent organic light-emitting diodes (PhOLEDs). The DPDDC exhibits excellent hole and electron transport properties, superior thermal stability, a high glass-transition temperature and a small singlet-triplet energy gap for efficient reverse intersystem crossing from triplet to singlet, reducing the triplet density of the host for PhOLEDs. The electrophosphorescence properties of the devices using DPDDC as the host and three green phosphorescent iridium(iii) complexes, bis(2-(4-tolyl)pyridinato- N , C 2')iridium(iii) acetylacetonate, bis(2-phenylpyridine)iridium(iii) acetylacetonate, and bis(4-methyl-2,5-diphenylpyridine)iridium(iii) acetylacetonate [(mdppy) 2 Iracac] as the emitter were investigated. The green PhOLED with 5 wt% (mdppy) 2 Iracac presents an excellent performance, including a high power efficiency of 92.3 lm W -1 , high external quantum efficiency of 23.6%, current efficiency roll-off as low as 5.5% at 5000 cd m -2 and a twentyfold lifetime improvement (time to 90% of the 5000 cd m -2 initial luminance) over the reference electrophosphorescent device.

MicroRNAs (miRNAs) are small RNA molecules that play key regulatory roles in general biological processes and disease pathogenesis. These small RNA molecules interact with their target mRNAs to induce mRNA degradation and/or inhibit the translation of mRNAs into proteins. Therefore, identifying miRNA targets is an essential step to fully understand the regulatory effects of miRNAs. Here, we describe a regularized regression approach that integrates the sequence information with the miRNA and mRNA expression profiles for detecting miRNA targets. This method takes into account the full spectrum of gene sequence features of miRNA targets, including the thermodynamic stability, the accessibility energy, and the context features of the target sites,. Given these sequence features for each putative miRNA-mRNA interaction and their expression values, this model is able to quantify the down-regulation effect of each miRNA on its targets while simultaneously estimating the contribution of each sequence feature for predicting functional miRNA-mRNA interactions.

Objectives: To portray the stage characteristics of lung cancers detected in CT screenings, and explore whether there's universal stage superiority over other methods for various pathological types using available data worldwide in a meta-analysis approach., Materials and Methods: EMBASE and MEDLINE were searched for studies on lung cancer CT screening in natural populations through July 2015 without language or other filters. Twenty-four studies (8 trials and 16 cohorts) involving 1875 CT-detected lung cancer patients were enrolled and assessed by QUADAS-2. Pathology-confirmed stage information was carefully extracted by two reviewers. Stage I or limited stage proportions were pooled by random effect model with Freeman-Tukey double arcsine transformation., Results: Pooled stage I cancer proportion in CT screenings was 73.2% (95% confidence interval: 68.6%, 77.5%), with a significant rising trend (Ptrend<0.05) from baseline (64.7%) to ≥5 repeat rounds (87.1%). Relative to chest radiograph and usual care, the increased stage I proportions in CT were 12.2% (P>0.05), and 46.5% (P<0.05), respectively. Pathology-specifically, adenocarcinomas (66%) and squamous cell lung cancers (17%) composed the majority of CT-detected lung cancers, and had significantly higher stage I proportions relative to chest radiograph (bronchioloalveolar adenocarcinomas, 80.9% vs 51.4%; other adenocarcinomas, 58.8% vs 38.3%; squamous cell lung cancers, 52.3% vs 38.3%; all P<0.05). However, the percentage of small cell lung cancer was lower using CT than other detection routes, and no significant difference in limited stage proportion was observed (6.8% vs 10.8%, P>0.05)., Conclusion: CT screening can detect more early stage non-small cell lung cancers, but not all of them could be beneficial as there are a considerable number of indolent ones such as bronchioloalveolar adenocarcinomas. Still, current evidence is lacking regarding small cell lung cancers., Competing Interests: The authors have declared that no competing interests exist.

Background: An important step towards personalizing cancer treatment is to integrate heterogeneous evidences to catalog mutational hotspots that are biologically and therapeutically relevant and thus represent where targeted therapy would likely be beneficial. However, existing methods do not sufficiently delineate varying functionality of individual mutations within the same genes., Results: We observed a large discordancy of mutation rates across different mutation subtypes and tumor types, and nominated 702 hotspot mutations in 549 genes in the Catalog of Somatic Mutations in Cancer (COSMIC) by considering context specific mutation characteristics such as genes, cancer types, mutation rates, mutation subtypes and sequence contexts. We observed that hotspot mutations were highly prevalent in Non CpG-island C/G transition and transversion sequence contexts in 10 tumor types, and specific insertion hotspot mutations were enriched in breast cancer and deletion hotspot mutations in colorectal cancer. We found that the hotspot mutations nominated by our approach were significantly more conserved than non-hotspot mutations in the corresponding cancer genes. We also examined the biological significance and pharmacogenomics properties of these hotspot mutations using data in the Cancer Genome Atlas (TCGA) and the Cancer Cell-Line Encyclopedia (CCLE), and found that 53 hotspot mutations are independently associated with diverse functional evidences in 1) mRNA and protein expression, 2) pathway activity, or 3) drug sensitivity and 82 were highly enriched in specific tumor types. We highlighted the distinct functional indications of hotspot mutations under different contexts and nominated novel hotspot mutations such as MAP3K4 A1199 deletion, NR1H2 Q175 insertion, and GATA3 P409 insertion as potential biomarkers or drug targets., Conclusion: We identified a set of hotspot mutations across 17 tumor types by considering the background mutation rate variations among genes, tumor subtypes, mutation subtypes, and sequence contexts. We illustrated the common and distinct mutational signatures of hotspot mutations among different tumor types and investigated their variable functional relevance under different contexts, which could potentially serve as a resource for explicitly selecting targets for diagnosis, drug development, and patient management.

Background: A relationship of blood uric acid (UA) with hypertension and cardiovascular risk is under debate thus salt intake is hypothesized to contribute to such associations., Methods: In this cross-sectional study, stratified cluster random sampling elicited a sample of 1805 Kazakhs with 92.4% compliance. Hypertension and moderate-or-high total cardiovascular risk (mTCR) were defined according to guidelines. Sodium intake was assessed by urinary sodium excretion. Prevalence ratios (PRs) were used to express associations of UA with hypertension and mTCR., Results: In the highest tertile of sodium intake in women, the adjusted PRs (95% confidence intervals) of low to high quartiles compared with the lowest quartile of UA, were 1.22(0.78-1.91), 1.18(0.75-1.85), and 1.65(1.09-2.51) for hypertension and 1.19(0.74-1.90), 1.39(0.91-2.11), and 1.65(1.10-2.47) for mTCR (P for trend <0.05). However, these findings were not shown for other sodium intake levels. There were similar results in men. PRs markedly increased with a concomitant increase in UA and sodium intake and there was a significant interaction (P = 0.010) for mTCR with PRs of 1.69(1.10-2.60) for men and 3.70(2.09-6.52) for women in those with the highest compared with the lowest quartile of UA and tertile of sodium intake. Similar findings were shown for hypertension., Conclusions: This study implied that a high salt intake may enhance the associations of UA with hypertension and cardiovascular risk.

Background: In this study, the accuracy of ultra-low-dose computed tomography (CT) with iterative reconstruction (IR) for detection and measurement of pulmonary nodules was evaluated., Methods: Eighty-four individuals referred for lung cancer screening (mean age: 54.5±10.8 years) underwent low-dose computed tomography (LDCT) and ultra-low-dose CT. CT examinations were performed with attenuation-based tube current modulation. Reference tube voltage and current were set to 120kV/25mÅs for LDCT and 80kV/4mÅs for ultra-low-dose CT. CT images were reconstructed with filtered back projection (FBP) for LDCT, and with FBP and IR for ultra-low-dose CT datasets. A reference standard was established by a consensus panel of 2 different radiologists on LDCT. Volume and diameter of the solid nodules were measured on LDCT with FBP and ultra-low dose CT with FBP and IR. Interobserver and interscan variability were analyzed and compared by the Bland-Altman method., Results: A total of 127 nodules were identified, including 105 solid nodules, 15 part solid nodules, 7 ground glass nodules. On ultra-low-dose CT scans, the effective radiation dose was 0.13±0.11mSv. A total of 113 (88.9%) and 110 (86.6%) true-positive nodules with FBP versus 117 (92.1%) and 118(92.9%) with IR were detected by two observers, respectively. The volume and size of the 105 solid nodules were measured, with mean volume/diameter of 46.5±46.6 mm(3)/5.1±1.6mm. There was no significant difference in nodule volume or diameter measurements between ultra-low-dose CT and LDCT protocols for solid nodules., Conclusions: Ultra-low-dose CT with iterative reconstruction has high sensitivity for lung nodule detection without significant difference in nodule size and volume measurement compared to LDCT., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Smoking increases the risk of numerous cancers; however, an association of smoking with adult gliomas has not been found in a population., Methods: This case-control study included 4556 glioma cases (ICD-9 code 191.0-191.9) aged ≥ 30 years and 9112 controls from a national survey of smoking and mortality in China in 1989-1991. Controls from 325 255 surviving spouses of all-cause deaths were randomly assigned to cases in each of 103 areas according to sex and age groups at a ratio of 2:1. Smoking information was ascertained retrospectively by interviewing surviving spouses., Results: After adjustment for confounders, smoking increased the risk of glioma deaths by 11% (odds ratio [OR] = 1.11; 95% confidence interval [CI]: 1.03-1.21). Compared with non-smokers; the increased risk was 9% (OR = 1.09; 95% CI: 0.99-1.20) in men and 16% (OR = 1.16; 95% CI: 1.00-1.36) in women. The risk increased with age and doses. For individuals aged ≥ 50 years, smoking was associated with higher risk of glioma death by 25% (OR = 1.25; 95% CI: 1.15-1.38); this increased risk for smokers who smoked ≥ 20 cigarettes daily for ≥ 30 years was 53% (OR = 1.53; 95% CI: 1.34-1.74). There were similar findings in both men and women and with either pathology-based or non-pathology-based comparisons., Conclusions: This study indicates that smoking is associated with glioma deaths in the Chinese population. Long-term heavy smoking could be a factor for risk stratification in individuals attending brain tumor clinics., (© The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Motivation: MicroRNAs (miRNAs) play important roles in general biological processes and diseases pathogenesis. Identifying miRNA target genes is an essential step to fully understand the regulatory effects of miRNAs. Many computational methods based on the sequence complementary rules and the miRNA and mRNA expression profiles have been developed for this purpose. It is noted that there have been many sequence features of miRNA targets available, including the context features of the target sites, the thermodynamic stability and the accessibility energy for miRNA-mRNA interaction. However, most of current computational methods that combine sequence and expression information do not effectively integrate full spectrum of these features; instead, they perceive putative miRNA-mRNA interactions from sequence-based prediction as equally meaningful. Therefore, these sequence features have not been fully utilized for improving miRNA target prediction., Results: We propose a novel regularized regression approach that is based on the adaptive Lasso procedure for detecting functional miRNA-mRNA interactions. Our method fully takes into account the gene sequence features and the miRNA and mRNA expression profiles. Given a set of sequence features for each putative miRNA-mRNA interaction and their expression values, our model quantifies the down-regulation effect of each miRNA on its targets while simultaneously estimating the contribution of each sequence feature to predicting functional miRNA-mRNA interactions. By applying our model to the expression datasets from two cancer studies, we have demonstrated our prediction results have achieved better sensitivity and specificity and are more biologically meaningful compared with those based on other methods., Availability and Implementation: The source code is available at: http://nba.uth.tmc.edu/homepage/liu/miRNALasso., Supplementary Information: Supplementary data are available at Bioinformatics online., Contact: Yin.Liu@uth.tmc.edu., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

The dependence of the morphology of neat chloroaluminum phthalocyanine (ClAlPc) films on substrate temperature (Tsub) during deposition is investigated by variable angle spectroscopic ellipsometry (VASE), x-ray diffraction (XRD), and atomic force microscopy (AFM) to obtain detailed information about the molecular orientation, phase separation, and crystallinity. AFM images indicate that both grain size and root mean square (RMS) roughness noticeably increase with Tsub both in neat and blend films. Increasing Tsub from room temperature to 420 K increases the horizontal orientation of the ClAlPc molecules with an increase of the mean molecular tilt angle from 60.13° (300 K) to 65.86° (420 K). The UV-vis absorption band of the corresponding films increases and the peak wavelength slightly red shifts with the Tsub increase. XRD patterns show a clear diffraction peak at Tsub over 390 K, implying the π-stacking of interconnected ClAlPc molecules at high Tsub. Planar and bulk heterojunction (BHJ) photovoltaic cells containing pristine ClAlPc films and ClAlPc:C60 blend films fabricated at Tsub of 390 K show increases in the power conversion efficiency (ηPCE) of 28% (ηPCE = 3.12%) and 36% (ηPCE = 3.58%), respectively, relative to devices as-deposited at room temperature. The maximum short circuit current in BHJs is obtained at 390 K in the Tsub range from 300 K to 450 K.

Purpose: To determine whether smoking, in any form, is a risk factor in the development of cervical cancer (CC) among urban Chinese women., Methods: We ascertained retrospectively the smoking habits of 1,865 women (aged 35+) who had died from CC (cases) and 48,781 who had died from causes unrelated to smoking (controls) in 24 cities using data from a large national survey of smoking and mortality in 1989-1991. We assessed the risk of smoking on CC mortality with and without considering passive smoke exposure from a spouse using a proportional mortality study design., Results: Overall, there was a 51.0 % excess risk of death from CC among smokers. When the spouse's exposure was further considered, the RR (95 % CI) for exposed versus unexposed women was 1.28 (1.04-1.57) for passive smokers, 1.49 (1.02-2.20) for active smokers, and 1.69 (1.27-2.26) for women with both exposures (all p < 0.001). Significant dose-response associations were observed between smoking and CC for all categories of exposure. For example, individuals with both smoking exposure had the highest risk of CC mortality with moderate [RR = 1.67 (1.18-2.38)] and high [RR = 1.88 (1.04-3.41)] daily cigarette consumption, and they also had the highest risk with ≤15 years exposure [RR = 1.73 (1.19-2.52)] and >15 years exposure [RR = 1.95 (1.15-3.32)], compared with the active and passive groups (p for trend <0.001)., Conclusions: Younger trend of CC death and the rapid increase in smoking among young women may have a profound impact on future incidence of CC. Our findings emphasize the need for preventive efforts among both women and men in China.

Purpose: Widely used (18)F 2'-deoxy-2'-fluoro-d-glucose (FDG) positron emission tomography (PET) can be problematic with false positives in cancer imaging. This study aims to investigate the diagnostic accuracy of a candidate PET tracer, (18)F 2',3'-dideoxy-3'-fluoro-2-thiothymidine (FLT), in diagnosing pulmonary lesions compared with FDG., Materials and Methods: After comprehensive search and study selection, a meta-analysis was performed on data from 548 patients pooled from 17 studies for evaluating FLT accuracy, in which data from 351 patients pooled from ten double-tracer studies was used for direct comparison with FDG. Weighted sensitivity and specificity were used as main indicators of test performance. Individual data was extracted and patient subgroup analyses were performed., Results: Overall, direct comparisons showed lower sensitivity (0.80 vs. 0.89) yet higher specificity (0.82 vs. 0.66) for FLT compared with FDG (both p<0.01). Patient subgroup analysis showed FLT was less sensitive than FDG in detecting lung cancers staged as T1 or T2, and those ≤2.0 cm in diameter (0.81 vs. 0.93, and 0.53 vs. 0.78, respectively, both p<0.05), but was comparable for cancers staged as T3 or T4, and those >2.0 cm in diameter (0.95 vs. 1.00, 0.96 vs. 0.88, both p>0.05). For benignities, FLT performed better compared with FDG in ruling out inflammation-based lesions (0.57 vs. 0.32, p<0.05), and demonstrated greater specificity regardless of lesion sizes., Conclusions: Although FLT cannot replace FDG in detecting small and early lung cancers, it may help to prevent patients with larger or inflammatory lesions from cancer misdiagnosis or even over-treatment., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Hybrid porous carbon fibers with strong anion-exchangeable functional groups (HACAX) were synthesized by alkylation of pyrolyzed polyacrylonitrile. HACAX exhibits generic stable positively charged functional groups. This expands the applications of porous carbon media for interacting with anions without adjusting pH, such as Cr(vi) adsorption at natural pH.

Phenol and nitrogenous heterocyclic compounds (NHCs) are typical organic pollutants in coal gasification wastewater which are difficult to deal with. Unlike phenol, the stable molecular structure of NHCs make them nearly impossible to degrade under aerobic or anaerobic condition. In this paper, biodegradation of phenol and NHCs as carbon sources for denitrification was studied in a laboratory-scale anoxic reactor. Denitrifiers could degrade 490 mg/L phenol and 321.5 mg/L NO3(-)-N within 12 hours with removal efficiencies of 99.8% and 99.6%, respectively. The inhibition of pyridine on the microbes could be reduced by adding phenol into influent and the experimental results showed that pyridine could be degraded as the sole carbon source with the maximum organic loading rate of 4.38 mg/(g MLSS·h) (MLSS: mixed liquor suspended solids). When phenol was included as a growth substrate, the degradation performance of quinoline and pyrrole was improved due to co-degradation, and removal rate of NHCs increased according with increment of phenol in influent.

MicroRNAs (miRNAs) are small regulatory RNAs that play key gene-regulatory roles in diverse biological processes, particularly in cancer development. Therefore, inferring miRNA targets is an essential step to fully understanding the functional properties of miRNA actions in regulating tumorigenesis. Bayesian linear regression modeling has been proposed for identifying the interactions between miRNAs and mRNAs on the basis of the integrated sequence information and matched miRNA and mRNA expression data; however, this approach does not use the full spectrum of available features of putative miRNA targets. In this study, we integrated four important sequence and structural features of miRNA targeting with paired miRNA and mRNA expression data to improve miRNA-target prediction in a Bayesian framework. We have applied this approach to a gene-expression study of liver cancer patients and examined the posterior probability of each miRNA-mRNA interaction being functional in the development of liver cancer. Our method achieved better performance, in terms of the number of true targets identified, than did other methods.

MicroRNAs (miRNAs) are small RNA molecules that play important roles in gene regulation and translational repression. The mechanisms that facilitate miRNA target binding and recognition have been extensively studied in recent years. However, it is still not well known how the miRNA regulation is affected by the location and the flanking sequences of miRNA target sites. In this study, we systematically quantify the contribution of a wide spectrum of target sites on miRNA-mediated gene expression regulation. Our study investigates target sites located in four different gene regions, including 3' untranslated regions, coding sequences, 5' untranslated regions and promoter regions. We have also introduced four additional non-canonical types of seed matches beyond the canonical seed matches, and included them in our study. Computational analysis of quantitative proteomic data has demonstrated that target sites located in different regions impact the miRNA-mediated repression differently but synergistically. In addition, we have shown the synergistic effects among non-canonical seed matches and canonical ones that enhance the miRNA regulatory effects. Further systematic analysis on the site accessibility near the target regions and the secondary structure of the mRNA sequences have demonstrated substantial variations among target sites of different locations and of different types of seed matches, suggesting the mRNA secondary structure could explain some of the difference in the miRNA regulatory effects impacted by these different target sites. Our study implies miRNAs might regulate their targets under different mechanisms when target sites vary in both their locations and the types of seed matches they contain.

Background: Many variable selection techniques have been proposed for the clustering of gene expression data. While these methods tend to filter out irrelevant genes and identify informative genes that contribute to a clustering solution, they are based on criteria that do not consider the potential interactive influence among individual genes. Motivated by ensemble clustering, there is a strong interest in leveraging the structure of gene networks for gene selection, so that the relationship information between genes can be effectively utilized, while the selected genes are expected to preserve all the possible clustering structures in the data., Results: We present a new filter method that uses the gene connectivity in the gene co-expression network as the evaluation criteria for variable selection. The gene connectivity measures the importance of the genes in term of their expression similarity with others in the co-expression network. The hard threshold and soft threshold transformations are employed to construct the gene co-expression networks. Both simulation studies and real data analysis have shown that the network based on soft thresholding is more effective in selecting relevant variables and provides better clustering results compared to the hard thresholding transformation and two other canonical filter methods for variable selection. Furthermore, a new module analysis approach is proposed to reveal the higher order organization of the gene space, where the genes of a module share significant topological similarity and are associated with a consensus partition of the sample space. We demonstrate that the identified modules can lead to biologically meaningful sample partitions that might be missed by other methods., Conclusions: By leveraging the structure of gene co-expression network, first we propose a variable selection method that selects individual genes with top connectivity. Both simulation studies and real data application have demonstrated that our method has better performance in terms of the reliability of the selected genes and sample clustering results. In addition, we propose a module recovery method that can help discover novel sample partitions that might be hidden when performing clustering analyses using all available genes. The source code of our program is available at http://nba.uth.tmc.edu/homepage/liu/netVar/.

Background: Currently available microRNA (miRNA) target prediction algorithms require the presence of a conserved seed match to the 5' end of the miRNA and limit the target sites to the 3' untranslated regions of mRNAs. However, it has been noted that these requirements may be too stringent, leading to a substantial number of missing targets., Results: We have developed TargetS, a novel computational approach for predicting miRNA targets with the target sites located along entire gene sequences, which permits finding additional targets that are not located in the 3' un-translated regions. Our model is based on both canonical seed matching and non-canonical seed pairing, which discovers targets that allow one bit GU wobble. It does not rely on evolutionary conservation, so it allows the detection of species-specific miRNA-mRNA interactions and makes it suitable for analyzing un-conserved gene sequences. To test the performance of our approach, we have imported the widely used benchmark dataset revealing fold-changes in protein production corresponding to each of the five selected microRNAs. Compared to well-known miRNA target prediction tools, including TargetScanS, PicTar and MicroT&#95;CDS, our method yields the highest sensitivity, while achieving a comparable level of accuracy. Human miRNA target predictions using our computational approach are available online at http://liubioinfolab.org/targetS/mirna.html, Conclusions: A simple but powerful computational miRNA target prediction method is developed that is solely based on canonical and non-canonical seed matches without requiring evolutionary conservation of the target sites. Our method also expands the target search space to different gene regions, rather than limiting to 3'UTR only. This improves the sensitivity of miRNA target identification, while achieving a comparable accuracy with existing methods.

Motivation: A major goal in genomic research is to identify genes that may jointly influence a biological response. From many years of intensive biomedical research, a large body of biological knowledge, or pathway information, has accumulated in available databases. There is a strong interest in leveraging these pathways to improve the statistical power and interpretability in studying gene networks associated with complex phenotypes. This prior information is a valuable complement to large-scale genomic data such as gene expression data generated from microarrays. However, it is a non-trivial task to effectively integrate available biological knowledge into gene expression data when reconstructing gene networks., Results: In this article, we developed and applied a Lasso method from a Bayesian perspective, a method we call prior Lasso (pLasso), for the reconstruction of gene networks. In this method, we partition edges between genes into two subsets: one subset of edges is present in known pathways, whereas the other has no prior information associated. Our method assigns different prior distributions to each subset according to a modified Bayesian information criterion that incorporates prior knowledge on both the network structure and the pathway information. Simulation studies have indicated that the method is more effective in recovering the underlying network than a traditional Lasso method that does not use the prior information. We applied pLasso to microarray gene expression datasets, where we used information from the Pathway Commons (PC) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) as prior information for the network reconstruction, and successfully identified network hub genes associated with clinical outcome in cancer patients., Availability: The source code is available at http://nba.uth.tmc.edu/homepage/liu/pLasso.

The performance of small molecular organic photovoltaic materials is typically limited by their low exciton diffusion lengths, poor solubility, and poor energy level alignment with fullerenes so that the design and synthesis of new materials remain a top priority. To overcome these limitations, we explored the use of an iridium complex as a donor material with the potential for compatibility with solution processing, long exciton diffusion length and easy molecular modification for tunable optical or electrical properties. A bilayer device with a cyclometalated iridium complex and C60 resulted in a power conversion efficiency as high as 2.8%. Furthermore, a VOC of 1 V was achieved in the bilayer device despite an estimated exciton energy of only 1.55 eV, and the device showed minimal temperature and light intensity dependence.

A white OLED with a maximum EQE of 20.1%, CIE coordinates of (0.33, 0.33) and CRI of 80 is fabricated based on platinum(II) bis(N-methyl-imidazolyl)benzene chloride (Pt-16). The device emission spectrum and the chemical structure of Pt-16 are shown in the inset of the efficiency versus luminance graph., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

In Drosophila melanogaster, combinatorial activities of four death genes, head involution defective (hid), reaper (rpr), grim, and sickle (skl), have been known to play crucial roles in the developmentally regulated programmed cell death (PCD) of various tissues. However, different expression patterns of the death genes also suggest distinct functions played by each. During early metamorphosis, a great number of larval neurons unfit for adult life style are removed by PCD. Among them are eight pairs of corazonin-expressing larval peptidergic neurons in the ventral nerve cord (vCrz). To reveal death genes responsible for the PCD of vCrz neurons, we examined extant and recently available mutations as well as RNA interference that disrupt functions of single or multiple death genes. We found grim as a chief proapoptotic gene and skl and rpr as minor ones. The function of grim is also required for PCD of the mitotic sibling cells of the vCrz neuronal precursors (EW3-sib) during embryonic neurogenesis. An intergenic region between grim and rpr, which, it has been suggested, may enhance expression of three death genes in embryonic neuroblasts, appears to play a role for the vCrz PCD, but not for the EW3-sib cell death. The death of vCrz neurons and EW3-sib is triggered by ecdysone and the Notch signaling pathway, respectively, suggesting distinct regulatory mechanisms of grim expression in a cell- and developmental stage-specific manner.

As a typical industrial wastewater, coal gasification wastewater has poor biodegradability and high toxicity. In this paper, a laboratory-scale anaerobic-anoxic-oxic membrane reactor (A(2)O-MBR) system was developed to investigate the treatment ability of coal gasification wastewater. The removal capacity of each pollutants used in this system were determined at different hydraulic residence times (HRT) and mixed liquor recycle ratios (R). The experimental results showed that this system could effectively deal with COD and phenol removal and remain in a stable level when the operational parameters altered, while the nitrification was sensitive to operational conditions. The best performance was obtained at HRT of 48 h and R of 3. The maximum removal efficiencies of COD, NH(4)(+)-N and phenols were 97.4%, 92.8% and 99.7%, with final concentrations in the effluent of 71 mg/L, 9.6 mg/L and 3 mg/L, respectively. Organics degradation and transformation were analyzed by GC/MS and it was found that anaerobic process played an important role in degradation of refractory compounds., (Copyright © 2012. Published by Elsevier B.V.)

A great number of obsolete larval neurons in the Drosophila central nervous system are eliminated by developmentally programmed cell death (PCD) during early metamorphosis. To elucidate the mechanisms of neuronal PCD occurring during this period, we undertook genetic dissection of seven currently known Drosophila caspases in the PCD of a group of interneurons (vCrz) that produce corazonin (Crz) neuropeptide in the ventral nerve cord. The molecular death program in the vCrz neurons initiates within 1 hour after pupariation, as demonstrated by the cytological signs of cell death and caspase activation. PCD was significantly suppressed in dronc-null mutants, but not in null mutants of either dredd or strica. A double mutation lacking both dronc and strica impaired PCD phenotype more severely than did a dronc mutation alone, but comparably to a triple dredd/strica/dronc mutation, indicating that dronc is a main initiator caspase, while strica plays a minor role that overlaps with dronc's. As for effector caspases, vCrz PCD requires both ice and dcp-1 functions, as they work cooperatively for a timely removal of the vCrz neurons. Interestingly, the activation of the Ice and Dcp-1 is not solely dependent on Dronc and Strica, implying an alternative pathway to activate the effectors. Two remaining effector caspase genes, decay and damm, found no apparent functions in the neuronal PCD, at least during early metamorphosis. Overall, our work revealed that vCrz PCD utilizes dronc, strica, dcp-1, and ice wherein the activation of Ice and Dcp-1 requires a novel pathway in addition to the initiator caspases.

N-ethyl-N-nitrosourea (ENU)-induced mutagenesis is an important approach in the study of gene function and the establishment of human disease models. Here we report an ENU-induced mutation, Elfin, as a mouse model with hearing loss. Homozygous mutants were deaf and displayed severe ataxia, while heterozygous mice had a significant hearing loss. Histological analysis of the inner ear revealed that Elfin had progressive degeneration of the organ of Corti, spiral ganglion cells and an absence of otoconia in the vestibular system. The new mutation was mapped to chromosome 6 between microsatellite markers D6Mit39 and D6Mit254, where the Ca(2+)-ATPase type 2 (Atp2b2) gene resides. Sequence analysis revealed a unique T-to-A transition mutation at amino acid 655 resulting in Ile-to-Asn substitution. These results for the Elfin mutant confirm the role of ATP2B2 in balance, hearing and formation of otoconia and suggest it may serve as a new model of human hereditary hearing loss.

In order to investigate the ground state and excited state properties of Pt(N(∧)C(∧)N)X, we have prepared a series of Pt complexes, where N(∧)C(∧)N aromatic chelates are derivatives of m-di(2-pyridinyl)benzene (dpb) and X are monoanionic and monodentate ancillary ligands including halide and phenoxide. Facile synthesis of platinum m-di(2-pyridinyl)benzene chloride and its derivatives, using controlled microwave heating, was reported. This method not only shortened the reaction time but also improved the reaction yield for most of the Pt complexes. Two Pt(N(∧)C(∧)N)X complexes have been structurally characterized by X-ray crystallography. The change of functional group does not affect the structure of the core Pt(N(∧)C(∧)N)Cl fragment. Both molecules pack as head-to-tail dimers, each molecule of the dimer related to the other by a center of inversion. The electrochemical studies of all Pt complexes demonstrate that the oxidation process occurs on the metal-phenyl fragment and the reduction process is associated with the electron accepting groups like pyridinyl groups and their derivatives. The maximum emission wavelength of the Pt(N(∧)C(∧)N)X complexes ranges between 471 and 610 nm, crossing the spectrum of visible light. Most of the Pt complexes are strongly luminescent (Φ = 0.32-0.63) and have short luminescence lifetimes (τ = 4-7 μs) at room temperature. The lowest excited state of the Pt(N(∧)C(∧)N)X complexes is identified as a dominant ligand-centered (3)π-π* state with some (1)MLCT/(3)MLCT character, which appears to have a larger (1)MLCT component than their bidentate and tridentate analogs. This results in a high radiative decay rate and high quantum yield for Pt(dpb)Cl and its analogs. However, the excited state properties of the Pt(N(∧)C(∧)N)X complexes are strongly dependent on the nature of the electron-accepting groups and substituents to the metal-phenyl fragment. A rational design will be needed to tune the emission energies of the Pt(N(∧)C(∧)N)X complexes over a wide range while maintaining their high luminescent efficiency.

Two parallel membrane bioreactors (MBRs) were operated under different calcium dosages (168.5, 27 mg/L) to gain a better understanding of the mechanism of retarding membrane fouling by adding calcium. The results showed that the particle size of sludge flocs increased and the particle size distribution tended to be narrow at the optimum dosage (168.5 mg/L). Calcium was effective in decreasing loosely bound extracellular polymeric substances (LB-EPS) in microbial flocs and soluble microbial products (SMP) in the supernatant at the dosage of 168.5 mg/L by strengthening the neutralization and bridging of EPS with flocs. Furthermore, the amount of CODs and CODc decreased in both the mixed liquor and the fouling cake layer on the membrane surface. In order to compare the filtration characteristics of cake layers from the MBRs with the two calcium dosages, the specific cake resistance and the compressibility coefficient were measured. The specific cake resistance from the MBR with optimum dosage (168.5 mg/L) was distinctly lower than that with low dosage (27 mg/L). The compressibility coefficient of the cake layers under two dosages were respectively attained as 0.65, 0.91. Scanning electron microscopy (SEM) and three-dimensional confocal scanning laser microscope analysis (CLSM) images were utilized to observe the gel layer directly.

Here we report two unrelated Chinese families with congenital missing teeth inherited in an X-linked manner. We mapped the affected locus to chromosome Xp11-Xq21 in one family. In the defined region, both families were found to have novel missense mutations in the ectodysplasin-A (EDA) gene. The mutation of c.947A>G caused the D316G substitution of the EDA protein. The mutation of c.1013C>T found in the other family resulted in the Thr to Met mutation at position 338 of EDA. The EDA gene has been reported responsible for X-linked hypohidrotic ectodermal dysplasia (XLHED) in humans characterized by impaired development of hair, eccrine sweat glands, and teeth. In contrast, all the affected individuals in the two families that we studied here had normal hair and skin. Structural analysis suggests that these two novel mutants may account for the milder phenotype by affecting the stability of EDA trimers. Our results indicate that these novel missense mutations in EDA are associated with the isolated tooth agenesis and provide preliminary explanation for the abnormal clinical phenotype at a molecular structural level.

Although the corazonin gene (Crz) has been molecularly characterized, little is known concerning the function of this neuropeptide in Drosophila melanogaster. To gain insight into Crz function in Drosophila, we have investigated the developmental regulation of Crz expression and the morphology of corazonergic neurons. From late embryo to larva, Crz expression is consistently detected in three neuronal groups: dorso-lateral Crz neurons (DL), dorso-medial Crz neurons (DM), and Crz neurons in the ventral nerve cord (vCrz). Both the vCrz and DM groups die via programmed cell death during metamorphosis, whereas the DL neurons persist to adulthood. In adults, Crz is expressed in a cluster of six to eight neurons per lobe in the pars lateralis (DLP), in numerous neuronal cells in the optic lobes, and in a novel group of four abdominal ganglionic neurons present only in males (ms-aCrz). The DLP group consists of two subsets of cells having different developmental origins: embryo and pupa. In the optic lobes, we have detected both Crz transcripts and Crz promoter activity, but no Crz-immunoreactive products, suggesting a post-transcriptional regulation of Crz mRNA. Projections of the ms-aCrz neurons terminate within the ventral nerve cord, implying a role as interneurons. Terminals of the DLP neurons are found in the retrocerebral complex that produces juvenile hormone and adipokinetic hormone. Significant reduction of trehalose levels in adults lacking DLP neurons suggests that DLP neurons are involved in the regulation of trehalose metabolism. Thus, the tissue-, stage-, and sex-specific expression of Crz and the association of Crz with the function of the retrocerebral complex suggest diverse roles for this neuropeptide in Drosophila.

A series of pi-conjugated compounds (1-23) were successfully synthesized by the Sonogashira, Suzuki, and Wittig-Horner reactions. The structure-property relationship about photoluminescence based on these synthesized compounds was systematically discussed in detail. In addition, energy gaps between ground and excited states of these compounds, which were in good agreement with the experimental observation, were calculated by the semiempirical parametrized PM3 method. It was revealed that emission efficiency largely depends on molecular structure, aggregation type, and size of nanoaggregates.

A dual-fluorescent donor-acceptor (D-A) dyad with tercarbazole (donor) and 2,3-dithienylmaleimide (acceptor) was synthesized and characterized. The emission intensity of long wavelength could be regulated by either bistable structures of the dyad or the polarities of solvents. By mimicking the function of an integrated logic gate, a 2-input AND logic operation is established. [reaction: see text].

A series of pi-conjugated compounds ending with dibenzosuberenylidene were synthesized efficiently. Their luminescence efficiencies were well-tuned by structural modification. Moreover, relative emission intensities were strongly affected by their existing appearances and exhibited aggregation-induced emission (AIE) behavior. Thus, emissions from nanoparticles, films, or powders were found to be more efficient than those from solutions. It demonstrated that these synthesized compounds might be practically used as fluorescent materials for potential optoelectronic applications.

2,7-Bis(4-dimethylaminophenyl)-9-(cycloheptatrienylidene)fluorene (1) was synthesized and characterized. 1 could be used as a fluorescent sensor either for pH or for pyridinium halide. Integrated with the ratiometric method and an NOR logic gate, a tunable two-input/multi-output system was presented on the basis of this single molecule. [structure: see text]

A series of 9-(cycloheptatrienylidene)fluorene derivatives were synthesized in good yields through the Suzuki or Sonogashira cross-coupling reactions. Fluorescence "off-on" behaviors of these compounds were investigated on the basis of variable acid concentrations. These compounds were shown to be acid-sensing fluorophores with utility as indicators in acidic environments.