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1.
  • Wang, Zhaoming, et al. (creator_code:aut_t)
  • Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33
  • 2014
  • record:In_t: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:24, s. 6616-6633
  • swepub:Mat_article_t (swepub:level_refereed_t)abstract
    • Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
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2.
  • Machiela, Mitchell J., et al. (creator_code:aut_t)
  • Characterization of Large Structural Genetic Mosaicism in Human Autosomes
  • 2015
  • record:In_t: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 96:3, s. 487-497
  • swepub:Mat_article_t (swepub:level_refereed_t)abstract
    • Analyses of genome-wide association study (GWAS) data have revealed that detectable genetic mosaicism involving large (>2 Mb) structural autosomal alterations occurs in a fraction of individuals. We present results for a set of 24,849 genotyped individuals (total GWAS set II [TGSII]) in whom 341 large autosomal abnormalities were observed in 168 (0.68%) individuals. Merging data from the new TGSII set with data from two prior reports (the Gene-Environment Association Studies and the total GWAS set I) generated a large dataset of 127,179 individuals; we then conducted a meta-analysis to investigate the patterns of detectable autosomal mosaicism (n = 1,315 events in 925 [0.73%] individuals). Restricting to events >2 Mb in size, we observed an increase in event frequency as event size decreased. The combined results underscore that the rate of detectable mosaicism increases with age (p value = 5.5 x 3 10(-31)) and is higher in men (p value = 0.002) but lower in participants of African ancestry (p value = 0.003). In a subset of 47 individuals from whom serial samples were collected up to 6 years apart, complex changes were noted over time and showed an overall increase in the proportion of mosaic cells as age increased. Our large combined sample allowed for a unique ability to characterize detectable genetic mosaicism involving large structural events and strengthens the emerging evidence of non-random erosion of the genome in the aging population.
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3.
  • Machiela, Mitchell J, et al. (creator_code:aut_t)
  • Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome
  • 2016
  • record:In_t: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 7
  • swepub:Mat_article_t (swepub:level_refereed_t)abstract
    • To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events >2 Mb in 97 (0.25%) women. Here we show rates for X-chromosome mosaicism are four times higher than mean autosomal rates; X mosaic events more often include the entire chromosome and participants with X events more likely harbour autosomal mosaic events. X mosaicism frequency increases with age (0.11% in 50-year olds; 0.45% in 75-year olds), as reported for Y and autosomes. Methylation array analyses of 33 women with X mosaicism indicate events preferentially involve the inactive X chromosome. Our results provide further evidence that the sex chromosomes undergo mosaic events more frequently than autosomes, which could have implications for understanding the underlying mechanisms of mosaic events and their possible contribution to risk for chronic diseases.
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4.
  • Sampson, Joshua N., et al. (creator_code:aut_t)
  • Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types
  • 2015
  • record:In_t: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 107:12
  • swepub:Mat_article_t (swepub:level_refereed_t)abstract
    • Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, h(l)(2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (rho = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (rho = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (rho = 0.51, SE = 0.18), and bladder and lung (rho = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
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5.
  • Chi, Xiaoming, et al. (creator_code:aut_t)
  • Fractal superconducting nanowire single-photon detectors with reduced polarization sensitivity
  • 2018
  • record:In_t: Optics Letters. - : OPTICAL SOC AMER. - 0146-9592 .- 1539-4794. ; 43:20, s. 5017-5020
  • swepub:Mat_article_t (swepub:level_refereed_t)abstract
    • We demonstrate superconducting nanowire single-photon detectors (SNSPDs) based on a fractal design of the nanowires to reduce the polarization sensitivity of detection efficiency. We patterned niobium titanium nitride thin films into Peano curves with a linewidth of 100 nm and integrated the nanowires with optical microcavities to enhance their optical absorption. At a base temperature of 2.6 K, the fractal SNSPD exhibited a polarization-maximum device efficiency of 67% and a polarization-minimum device efficiency of 61% at a wavelength of 1550 nm. Therefore, the polarization sensitivity, defined as their ratio, was 1.1, lower than the polarization sensitivity of the SNSPDs in the meander design. The reduced polarization sensitivity of the detector could be maintained for higher-order spatial modes in multimode optical fibers and could tolerate misalignment between the optical mode and the detector. This fractal design is applicable to both amorphous and polycrystalline materials that are commonly used for making SNSPDs.
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6.
  • Chi, Xiaoming, et al. (creator_code:aut_t)
  • RF-amplifier-free superconducting nanowire single-photon detector system
  • 2018
  • record:In_t: 2018 ASIA COMMUNICATIONS AND PHOTONICS CONFERENCE (ACP). - : IEEE. - 9781538661581
  • swepub:Mat_conferencepaper_t (swepub:level_refereed_t)abstract
    • We used a superconducting nanowire single photon detector integrated th a current reservoir in a closed-cycle cryocooler to demonstrate
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7.
  • Feng, Yifan, et al. (creator_code:aut_t)
  • Fractal Superconducting Nanowire Single-Photon Detectors and Their Applications in Imaging
  • 2022
  • record:In_t: Proceedings of the 2022 Conference on Lasers and Electro-Optics Pacific Rim, CLEO/PR 2022. - : Optica Publishing Group.
  • swepub:Mat_conferencepaper_t (swepub:level_refereed_t)abstract
    • We present our research on fractal superconducting nanowire single-photon detectors and their applications in light detection and ranging (LiDAR), full-Stokes polarimetric imaging, and non-line-of-sight imaging.
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8.
  • Hao, Zifan, et al. (creator_code:aut_t)
  • Fractal superconducting nanowire single-photon detector at 1540 nm with 91% system detection efficiency
  • 2023
  • record:In_t: 2023 Conference on Lasers and Electro-Optics, CLEO 2023. - : Institute of Electrical and Electronics Engineers Inc..
  • swepub:Mat_conferencepaper_t (swepub:level_refereed_t)abstract
    • We demonstrate a fiber-coupled f ractal s uperconducting n anowire single-photon detector working in dual bands, with 91% system detection efficiency (SDE) at the wavelength of 1540 nm and with 61% SDE at 520 nm.
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9.
  • Hu, Nan, et al. (creator_code:aut_t)
  • Full-Stokes polarimetric measurements and imaging using a fractal superconducting nanowire single-photon detector
  • 2022
  • record:In_t: Optica. - : Optica Publishing Group. - 2334-2536. ; 9:4, s. 346-351
  • swepub:Mat_article_t (swepub:level_refereed_t)abstract
    • Measuring the states of polarization (SoP) of light is fundamentally important for applications ranging from communication, sensing, spectroscopy, imaging, to navigation. Superconducting nanowire single-photon detectors (SNSPDs) are ideal detectors of choice for faint-light detection and measurements, but SNSPDs themselves cannot resolve the SoP of photons. Here, based on a fractal SNSPD, we demonstrate a full-Stokes polarimetric measurement system that can measure arbitrary SoP of faint light. The measured SoPs are in excellent agreement with those of a state-of-the-art commercial polarimeter, but the sensitivity of our system reaches -86.6 dBm, which is 26.6 dB better than that of the commercial counterpart. As a direct application, we further demonstrate remote polarimetric imaging (i.e., polarimetric LiDAR) with a complete set of polarimetric contrast.
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10.
  • Hu, Nan, et al. (creator_code:aut_t)
  • Photon-Counting LIDAR Based on a Fractal SNSPD
  • 2021
  • record:In_t: 2021 OPTICAL FIBER COMMUNICATIONS CONFERENCE AND EXPOSITION (OFC). - : IEEE.
  • swepub:Mat_conferencepaper_t (swepub:level_refereed_t)abstract
    • We report on a photon-counting LIDAR system based on a polarization-insensitive fractal SNSPD with high detection efficiency and high timing resolution, and showcase depth imaging of an object at 1560 nm with millimeter depth resolution.
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