Expression of the mismatch repair gene hMLH1 is enhanced in non-small cell lung cancer with EGFR mutations

Mismatch repair (MMR) plays a pivotal role in keeping the genome stable. MMR dysfunction can lead to carcinogenesis by gene mutation accumulation. HMSH2 and hMLH1 are two key components of MMR. High or low expression of them often mark the status of MMR function. Mutations (EGFR, KRAS, etc) are common in non-small cell lung cancer (NSCLC). However, it is not clear what role MMR plays in NSCLC gene mutations. The expression of MMR proteins hMSH2 and hMLH1, and the proliferation markers PCNA and Ki67 were measured by immunohistochemistry in 181 NSCLCs. EGFR and KRAS mutations were identified by high resolution melting analysis. Stronger hMLH1 expression correlated to a higher frequency of EGFR mutations in exon 19 and 21 (p<0.0005). Overexpression of hMLH1 and the adenocarcinoma subtype were both independent factors that related to EGFR mutations in NSCLCs (p=0.013 and p<0.0005). The expression of hMLH1, hMSH2 and PCNA increased, while Ki67 expression significantly decreased (p=0.030) in NSCLCs with EGFR mutations. Overexpression of hMLH1 could be a new molecular marker to predict the response to EGFR-TKIs in NSCLCs. Furthermore, EGFR mutations might be an early event of NSCLC that occur before MMR dysfunction.This work was supported by the National Nature Science Funds in China (Fund No. 81071805; URL: http://isisn.nsfc.gov.cn/egrantweb/), and Dalian Merricon Gene Diagnosis Technology Co., Ltd. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Full-sky ray-tracing simulation of weak lensing using ELUCID simulations: exploring galaxy intrinsic alignment and cosmic shear correlations

The intrinsic alignment of galaxies is an important systematic effect in weak-lensing surveys, which can affect the derived cosmological parameters. One direct way to distinguish different alignment models and quantify their effects on the measurement is to produce mocked weak-lensing surveys. In this work, we use full-sky ray-tracing technique to produce mock images of galaxies from the ELUCID $N$-body simulation run with the WMAP9 cosmology. In our model we assume that the shape of central elliptical galaxy follows that of the dark matter halo, and spiral galaxy follows the halo spin. Using the mocked galaxy images, a combination of galaxy intrinsic shape and the gravitational shear, we compare the predicted tomographic shear correlations to the results of KiDS and DLS. It is found that our predictions stay between the KiDS and DLS results. We rule out a model in which the satellite galaxies are radially aligned with the center galaxy, otherwise the shear-correlations on small scales are too high. Most important, we find that although the intrinsic alignment of spiral galaxies is very weak, they induce a positive correlation between the gravitational shear signal and the intrinsic galaxy orientation (GI). This is because the spiral galaxy is tangentially aligned with the nearby large-scale overdensity, contrary to the radial alignment of elliptical galaxy. Our results explain the origin of detected positive GI term from the weak-lensing surveys. We conclude that in future analysis, the GI model must include the dependence on galaxy types in more detail.Comment: 23 pages, 13 figures, published in ApJ. Our mock galaxy catalog is available upon request by email to the author ([email protected], [email protected]

Genomic and Transcriptomic Evidence for Carbohydrate Consumption among Microorganisms in a Cold Seep Brine Pool

The detailed lifestyle of microorganisms in deep-sea brine environments remains largely unexplored. Using a carefully calibrated genome binning approach, we reconstructed partial to nearly-complete genomes of 51 microorganisms in biofilms from the Thuwal cold seep brine pool of the Red Sea. The recovered metagenome-assembled genomes (MAGs) belong to six different phyla: Actinobacteria, Proteobacteria, Candidatus Cloacimonetes, Candidatus Marinimicrobia, Bathyarchaeota and Thaumarchaeota. By comparison with close relatives of these microorganisms, we identified a number of unique genes associated with organic carbon metabolism and energy generation. These genes included various glycoside hydrolases, nitrate and sulfate reductases, putative bacterial microcompartment biosynthetic clusters (BMC), and F420H2 dehydrogenases. Phylogenetic analysis suggested that the acquisition of these genes probably occurred through horizontal gene transfer (HGT). Metatranscriptomics illustrated that glycoside hydrolases are among the most highly expressed genes. Our results suggest that the microbial inhabitants are well adapted to this brine environment, and anaerobic carbohydrate consumption mediated by glycoside hydrolases and electron transport systems (ETSs) is a dominant process performed by microorganisms from various phyla within this ecosystem

ELUCID IV: Galaxy Quenching and its Relation to Halo Mass, Environment, and Assembly Bias

We examine the quenched fraction of central and satellite galaxies as a function of galaxy stellar mass, halo mass, and the matter density of their large scale environment. Matter densities are inferred from our ELUCID simulation, a constrained simulation of local Universe sampled by SDSS, while halo masses and central/satellite classification are taken from the galaxy group catalog of Yang et al. The quenched fraction for the total population increases systematically with the three quantities. We find that the `environmental quenching efficiency', which quantifies the quenched fraction as function of halo mass, is independent of stellar mass. And this independence is the origin of the stellar mass-independence of density-based quenching efficiency, found in previous studies. Considering centrals and satellites separately, we find that the two populations follow similar correlations of quenching efficiency with halo mass and stellar mass, suggesting that they have experienced similar quenching processes in their host halo. We demonstrate that satellite quenching alone cannot account for the environmental quenching efficiency of the total galaxy population and the difference between the two populations found previously mainly arises from the fact that centrals and satellites of the same stellar mass reside, on average, in halos of different mass. After removing these halo-mass and stellar-mass effects, there remains a weak, but significant, residual dependence on environmental density, which is eliminated when halo assembly bias is taken into account. Our results therefore indicate that halo mass is the prime environmental parameter that regulates the quenching of both centrals and satellites.Comment: 21 pages, 16 figures, submitted to Ap

Spatially resolved Spectro-photometry of M81: Age, Metallicity and Reddening Maps

In this paper, we present a multi-color photometric study of the nearby spiral galaxy M81, using images obtained with the Beijing Astronomical Observatory 60/90 cm Schmidt Telescope in 13 intermediate-band filters from 3800 to 10000{\AA}. The observations cover the whole area of M81 with a total integration of 51 hours from February 1995 to February 1997. This provides a multi-color map of M81 in pixels of 1\arcsec.7 \times 1\arcsec.7. Using theoretical stellar population synthesis models, we demonstrate that some BATC colors and color indices can be used to disentangle the age and metallicity effect. We compare in detail the observed properties of M81 with the predictions from population synthesis models and quantify the relative chemical abundance, age and reddening distributions for different components of M81. We find that the metallicity of M81 is about $Z=0.03$ with no significant difference over the whole galaxy. In contrast, an age gradient is found between stellar populations of the central regions and of the bulge and disk regions of M81: the stellar population in its central regions is older than 8 Gyr while the disk stars are considerably younger, $\sim 2$ Gyr. We also give the reddening distribution in M81. Some dust lanes are found in the galaxy bulge region and the reddening in the outer disk is higher than that in the central regions.Comment: Accepted for publication in AJ (May 2000 issue). 27 pages including 6 figures. Uses AASTeX aasms4 styl

Explicit Topology Optimization of Conforming Voronoi Foams

Topology optimization is able to maximally leverage the high DOFs and mechanical potentiality of porous foams but faces three fundamental challenges: conforming to free-form outer shapes, maintaining geometric connectivity between adjacent cells, and achieving high simulation accuracy. To resolve the issues, borrowing the concept from Voronoi tessellation, we propose to use the site (or seed) positions and radii of the beams as the DOFs for open-cell foam design. Such DOFs cover extensive design space and have clear geometrical meaning, which makes it easy to provide explicit controls (e.g. granularity). During the gradient-based optimization, the foam topology can change freely, and some seeds may even be pushed out of the shape, which greatly alleviates the challenges of prescribing a fixed underlying grid. The mechanical property of our foam is computed from its highly heterogeneous density field counterpart discretized on a background mesh, with a much improved accuracy via a new material-aware numerical coarsening method. We also explore the differentiability of the open-cell Voronoi foams w.r.t. its seed locations, and propose a local finite difference method to estimate the derivatives efficiently. We do not only show the improved foam performance of our Voronoi foam in comparison with classical topology optimization approaches, but also demonstrate its advantages in various settings, especially when the target volume fraction is extremely low

Constraints on Spin-Spin-Velocity-Dependent Interaction

The existence of exotic spin-dependent forces may shine light on new physics beyond the Standard Model. We utilize two iron shielded SmCo$_5$ electron-spin sources and two optically pumped magnetometers to search for exotic long-range spin-spin-velocity-dependent force. The orientations of spin sources and magnetometers are optimized such that the exotic force is enhanced and common-mode noise is effectively subtracted. We set direct limit on proton-electron interaction in the force range from 1\,cm to 1\,km. Our experiment represents more than ten orders of magnitude improvement than previous works