Highly frequent promoter methylation and PIK3CA amplification in non-small cell lung cancer (NSCLC)

<p>Abstract</p> <p>Background</p> <p>Lung cancer is the leading cause of cancer-related death worldwide. Genetic and epigenetic alterations have been identified frequently in lung cancer, such as promoter methylation, gene mutations and genomic amplification. However, the interaction between genetic and epigenetic events and their significance in lung tumorigenesis remains poorly understood.</p> <p>Methods</p> <p>We determined the promoter methylation of 6 genes and <it>PIK3CA </it>amplification using quantitative methylation-specific PCR (Q-MSP) and real-time quantitative PCR, respectively, and explore the association of promoter methylation with <it>PIK3CA </it>amplification in a large cohort of clinically well-characterized non-small cell lung cancer (NSCLC).</p> <p>Results</p> <p>Highly frequent promoter methylation was observed in NSCLC. With 100% diagnostic specificity, excellent sensitivity, ranging from 45.8 to 84.1%, was found for each of the 6 genes. The promoter methylation was associated with histologic type. Methylation of <it>CALCA, CDH1, DAPK1</it>, and <it>EVX2 </it>was more common in squamous cell carcinomas (SCC) compared to adenocarcinomas (ADC). Conversely, there was a trend toward a higher frequency of <it>RASSF1A </it>methylation in ADC than SCC. In addition, <it>PIK3CA </it>amplification was frequently found in NSCLC, and was associated with certain clinicopathologic features, such as smoking history, histologic type and pleural indentation. Importantly, aberrant promoter methylation of certain genes was significantly associated with <it>PIK3CA </it>amplification.</p> <p>Conclusions</p> <p>Our data showed highly frequent promoter methylation and <it>PIK3CA </it>amplification in Chinese NSCLC population, and first demonstrated the associations of gene methylation with <it>PIK3CA </it>amplification, suggesting that these epigenetic events may be a consequence of overactivation of PI3K/Akt pathway.</p

Aqua­bis­(benzoato-κO)(1,10-phenanthroline-κ2 N,N′)zinc(II)

The Zn atom in the title compound, [Zn(C7H5O2)2(C12H8N2)(H2O)], is five-coordinate in a distorted trigonal–bipyramidal coordination environment involving two O atoms of two monodentate benzoates, two N atoms of a 1,10-phenanthroline mol­ecule and one O atom of a water mol­ecule. The axial positions are occupied by a carboxyl­ate O atom from the benzoate ligand and an N atom from the 1,10-phenanthroline ligand [N—Zn—O = 146.90 (7)°]. The water mol­ecule forms an intra­molecular O—H⋯O hydrogen bond; an inter­molecular O—H⋯O hydrogen bond gives rise to a dimer

Risk factors for high-altitude headache upon acute high-altitude exposure at 3700 m in young Chinese men: a cohort study.

BackgroundThis prospective and observational study aimed to identify demographic, physiological and psychological risk factors associated with high-altitude headache (HAH) upon acute high-altitude exposure.MethodsEight hundred fifty subjects ascended by plane to 3700 m above Chengdu (500 m) over a period of two hours. Structured Case Report Form (CRF) questionnaires were used to record demographic information, physiological examinations, psychological scale, and symptoms including headache and insomnia a week before ascending and within 24 hours after arrival at 3700 m. Binary logistic regression models were used to analyze the risk factors for HAH.ResultsThe incidence of HAH was 73.3%. Age (p =0.011), physical labor intensity (PLI) (p =0.044), primary headache history (p &lt;0.001), insomnia (p &lt;0.001), arterial oxygen saturation (SaO2) (p =0.001), heart rate (HR) (p =0.002), the Self-Rating Anxiety Scale (SAS) (p &lt;0.001), and the Epworth Sleepiness Scale (ESS) (p &lt;0.001) were significantly different between HAH and non-HAH groups. Logistic regression models identified primary headache history, insomnia, low SaO2, high HR and SAS as independent risk factors for HAH.ConclusionsInsomnia, primary headache history, low SaO2, high HR, and high SAS score are the risk factors for HAH. Our findings will provide novel avenues for the study, prevention and treatment of HAH

DIGAP - a Database of Improved Gene Annotation for Phytopathogens

<p>Abstract</p> <p>Background</p> <p>Bacterial plant pathogens are very harmful to their host plants, which can cause devastating agricultural losses in the world. With the development of microbial genome sequencing, many strains of phytopathogens have been sequenced. However, some misannotations exist in these phytopathogen genomes. Our objective is to improve these annotations and store them in a central database DIGAP.</p> <p>Description</p> <p>DIGAP includes the following improved information on phytopathogen genomes. (i) All the 'hypothetical proteins' were checked, and non-coding ORFs recognized by the Z curve method were removed. (ii) The translation initiation sites (TISs) of 20% ~ 25% of all the protein-coding genes have been corrected based on the NCBI RefSeq, ProTISA database and an <it>ab initio </it>program, GS-Finder. (iii) Potential functions of about 10% 'hypothetical proteins' have been predicted using sequence alignment tools. (iv) Two theoretical gene expression indices, the codon adaptation index (CAI) and the <it>E</it>(<it>g</it>) index, were calculated to predict the gene expression levels. (v) Potential agricultural bactericide targets and their homology-modeled 3D structures are provided in the database, which is of significance for agricultural antibiotic discovery.</p> <p>Conclusion</p> <p>The results in DIGAP provide useful information for understanding the pathogenetic mechanisms of phytopathogens and for finding agricultural bactericides. DIGAP is freely available at <url>http://ibi.hzau.edu.cn/digap/</url>.</p

Rethink Baseline of Integrated Gradients from the Perspective of Shapley Value

Numerous approaches have attempted to interpret deep neural networks (DNNs) by attributing the prediction of DNN to its input features. One of the well-studied attribution methods is Integrated Gradients (IG). Specifically, the choice of baselines for IG is a critical consideration for generating meaningful and unbiased explanations for model predictions in different scenarios. However, current practice of exploiting a single baseline fails to fulfill this ambition, thus demanding multiple baselines. Fortunately, the inherent connection between IG and Aumann-Shapley Value forms a unique perspective to rethink the design of baselines. Under certain hypothesis, we theoretically analyse that a set of baseline aligns with the coalitions in Shapley Value. Thus, we propose a novel baseline construction method called Shapley Integrated Gradients (SIG) that searches for a set of baselines by proportional sampling to partly simulate the computation path of Shapley Value. Simulations on GridWorld show that SIG approximates the proportion of Shapley Values. Furthermore, experiments conducted on various image tasks demonstrate that compared to IG using other baseline methods, SIG exhibits an improved estimation of feature's contribution, offers more consistent explanations across diverse applications, and is generic to distinct data types or instances with insignificant computational overhead.Comment: 12 page

Optimal coherent control of CARS: signal enhancement and background elimination

The ability to enhance resonant signals and eliminate the non-resonant background is analyzed for Coherent Anti-Stokes Raman Scattering (CARS). The analysis is done at a specific frequency as well as for broadband excitation using femtosecond pulse-shaping techniques. An appropriate objective functional is employed to balance resonant signal enhancement against non-resonant background suppression. Optimal enhancement of the signal and minimization of the background can be achieved by shaping the probe pulse alone while keeping the pump and Stokes pulses in transform-limited-form (TLF). In some cases analytical forms for the probe pulse can be found, and numerical simulations are carried out for other circumstances. It is found that a good approximate solution for the optimal pulse in the two-pulse CARS is a superposition of linear and arctangent type phases for the pump. The well-known probe delay method is shown to be a quasi-optimal scheme for background suppression. The results should provide a basis to improve the performance of CARS spectroscopy and microscopy.Comment: 11 pages,10 figures, JC