| 1. |
- Sampson, Joshua N., et al.
(författare)
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Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types
- 2015
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 107:12
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Tidskriftsartikel (refereegranskat)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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| 2. |
- Feng, Ruizhi, et al.
(författare)
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Mutations in TUBB8 and Human Oocyte Meiotic Arrest.
- 2016
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Ingår i: The New England journal of medicine. - 1533-4406. ; 374:3, s. 223-232
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Tidskriftsartikel (refereegranskat)abstract
- Background Human reproduction depends on the fusion of a mature oocyte with a sperm cell to form a fertilized egg. The genetic events that lead to the arrest of human oocyte maturation are unknown. Methods We sequenced the exomes of five members of a four-generation family, three of whom had infertility due to oocyte meiosis I arrest. We performed Sanger sequencing of a candidate gene, TUBB8, in DNA samples from these members, additional family members, and members of 23 other affected families. The expression of TUBB8 and all other β-tubulin isotypes was assessed in human oocytes, early embryos, sperm cells, and several somatic tissues by means of a quantitative reverse-transcriptase-polymerase-chain-reaction assay. We evaluated the effect of the TUBB8 mutations on the assembly of the heterodimer consisting of one α-tubulin polypeptide and one β-tubulin polypeptide (α/β-tubulin heterodimer) in vitro, on microtubule architecture in HeLa cells, on microtubule dynamics in yeast cells, and on spindle assembly in mouse and human oocytes. Results We identified seven mutations in the primate-specific gene TUBB8 that were responsible for oocyte meiosis I arrest in 7 of the 24 families. TUBB8 expression is unique to oocytes and the early embryo, in which this gene accounts for almost all the expressed β-tubulin. The mutations affect chaperone-dependent folding and assembly of the α/β-tubulin heterodimer, disrupt microtubule behavior on expression in cultured cells, alter microtubule dynamics in vivo, and cause catastrophic spindle-assembly defects and maturation arrest on expression in mouse and human oocytes. Conclusions TUBB8 mutations have dominant-negative effects that disrupt microtubule behavior and oocyte meiotic spindle assembly and maturation, causing female infertility. (Funded by the National Basic Research Program of China and others.).
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| 3. |
- Wu, Xiuchen, et al.
(författare)
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Exposures to temperature beyond threshold disproportionately reduce vegetation growth in the northern hemisphere
- 2019
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Ingår i: National Science Review. - : Oxford University Press (OUP). - 2095-5138 .- 2053-714X. ; 6:4, s. 786-795
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Tidskriftsartikel (refereegranskat)abstract
- In recent decades, terrestrial vegetation in the northern hemisphere (NH) has been exposed to warming and more extremely high temperatures. However, the consequences of these changes for terrestrial vegetation growth remain poorly quantified and understood. By examining a satellite-based vegetation index, tree-ring measurements and land-surface model simulations, we discovered a consistent convex pattern in the responses of vegetation growth to temperature exposure (TE) for forest, shrub and grass in both the temperate (30°−50° N) and boreal (50°−70° N) NH during the period of 1982−2012. The response of vegetation growth to TE for the three vegetation types in both the temperate and boreal NH increased convergently with increasing temperature, until vegetation type-dependent temperature thresholds were reached. A TE beyond these temperature thresholds resulted in disproportionately weak positive or even strong negative responses. Vegetation growth in the boreal NH was more vulnerable to extremely high-temperature events than vegetation growth in the temporal NH. The non-linear responses discovered here provide new insights into the dynamics of northern terrestrial ecosystems in a warmer world.
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| 4. |
- Yang, Huiqing, et al.
(författare)
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Protic Quaternary Ammonium Ionic Liquids for Catalytic Conversion of CO2 into Cyclic Carbonates : A Combined Ab Initio and MD Study
- 2018
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Ingår i: Industrial & Engineering Chemistry Research. - : AMER CHEMICAL SOC. - 0888-5885 .- 1520-5045. ; 57:21, s. 7121-7129
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Tidskriftsartikel (refereegranskat)abstract
- The mechanism of CO2 fixation catalyzed by protic hydroxyl-functionalized quaternary ammonium ionic liquids (ILs) is investigated by two different models, the Single-IL model and the Double-IL model. The relative sequence of catalytic activity calculated by the Single-IL model is contradictory with the experimental result. The situation is totally varied when the Double-IL model is utilized. In this system, ILs are not limited to the catalyst but solvent. The ILs are incorporated into the catalytic system to consider the solvent effect rather than by the existing solvent model. When the solvent effect is included, it is better to distinguish the catalytic activity of three ILs. According to the noncovalent interaction and the atoms in molecules analysis, the highest catalytic activity of tris(2-hydroxyethyl)ammonium bromide ([HTEA]Br) is attributed to its strongest nucleophilic attack and moderate hydrogen bond interaction between IL and reactant. It is necessary to consider the interaction between ILs to get a reliable result. Moreover, the solvent effect aroused by ILs should be carefully considered.
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| 5. |
- Feng, Zhenhua, et al.
(författare)
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Multicore-Fiber-Enabled WSDM Optical Access Network With Centralized Carrier Delivery and RSOA-Based Adaptive Modulation
- 2015
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Ingår i: IEEE PHOTONICS JOURNAL. - : Institute of Electrical and Electronics Engineers (IEEE). - 1943-0655. ; 7:4
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Tidskriftsartikel (refereegranskat)abstract
- We proposed and experimentally demonstrated a wavelength-space division multiplexing (WSDM) optical access network architecture with centralized optical carrier delivery utilizing multicore fibers (MCFs) and adaptive modulation based on reflective semiconductor amplifier (RSOA). In our experiment, five of the outer cores are used for undirectional downstream (DS) transmission only, whereas the remaining outer core is utilized as a dedicated channel to transmit upstream (US) signals. Optical carriers for US are delivered from the optical line terminal (OLT) to the optical network unit (ONU) via the inner core and then transmitted back to the OLT after amplification and modulation by the RSOA in the colorless ONU side. The mobile backhaul (MB) service is also supported by the inner core. Wavelengths used in US transmission should be different from that of the MB in order to avoid the Rayleigh backscattering effect in bidirectional transmission. With quadrature phase-shift keying-orthogonal frequency-division multiplexing (QPSK-OFDM) modulation format, the aggregation DS capacity reaches 250 Gb/s using five outer cores and ten wavelengths, and it can be further scaled to 1 Tb/s using 20 wavelengths modulated with 16 QAM-OFDM. For US transmission, 2.5 Gb/s QPSK-OFDM transmission can be achieved just using a low-bandwidth RSOA, and adaptive modulation is applied to the RSOA to further enhance the US data rate to 3.12 Gb/s. As an emulation of high-speed MB transmission, 48 Gb/s inphase and quadrature (IQ) modulated popularization division multiplexing (PDM)-QPSK signal is transmitted in the inner core of MCF and coherently detected in the OLT side. Both DS and US optical signals exhibit acceptable performance with sufficient power budget.
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| 6. |
- Marand, Ata Jalili, et al.
(författare)
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Quandary of service logistics: Fast or reliable?
- 2019
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Ingår i: European Journal of Operational Research. - : ELSEVIER SCIENCE BV. - 0377-2217 .- 1872-6860. ; 275:3, s. 983-996
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Tidskriftsartikel (refereegranskat)abstract
- Delivery time and delivery reliability are two top-level measures of delivery performance, and they both influence customers perception of service value. However, the classic queue-pricing literature emphasizes the former and ignores the latter. In order to bridge the gap between research and practice, this study addresses the interactive impact of price, delivery time, and delivery-reliability level on the equilibrium behaviour of rational customers and the optimal decisions of a revenue-maximizing service provider. We assume that the customers sensitivity to the delivery-reliability level is characterized by an increasing concave service value function. We model the operations of the service provider as an M/M/1 queue. Two cases are investigated: homogeneous customers and heterogeneous customers. For the homogeneous customers case, we analytically characterize the service providers optimal price, delivery time, and delivery reliability level decisions. We show how the service providers decisions on whether to provide faster or more reliable service are affected when different problem parameters are subject to variation. For instance, when customers become more sensitive to the delivery-reliability level, the service provider increases the delivery-reliability level at the expense of a longer delivery time. However, the optimal price may either increase or decrease depending on a benchmark value for the delivery-reliability level. For the heterogeneous customers case, our results suggest that when the potential arrival rate is sufficiently high, the service provider always benefits from markets with higher levels of customer heterogeneity. (C) 2018 Elsevier B.V. All rights reserved.
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| 7. |
- Parsons, Michael T, et al.
(författare)
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Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants : An ENIGMA resource to support clinical variant classification
- 2019
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Ingår i: Human Mutation. - : Hindawi Limited. - 1059-7794 .- 1098-1004. ; , s. 1557-1578
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Tidskriftsartikel (refereegranskat)abstract
- The multifactorial likelihood analysis method has demonstrated utility for quantitative assessment of variant pathogenicity for multiple cancer syndrome genes. Independent data types currently incorporated in the model for assessing BRCA1 and BRCA2 variants include clinically calibrated prior probability of pathogenicity based on variant location and bioinformatic prediction of variant effect, co-segregation, family cancer history profile, co-occurrence with a pathogenic variant in the same gene, breast tumor pathology, and case-control information. Research and clinical data for multifactorial likelihood analysis were collated for 1395 BRCA1/2 predominantly intronic and missense variants, enabling classification based on posterior probability of pathogenicity for 734 variants: 447 variants were classified as (likely) benign, and 94 as (likely) pathogenic; 248 classifications were new or considerably altered relative to ClinVar submissions. Classifications were compared to information not yet included in the likelihood model, and evidence strengths aligned to those recommended for ACMG/AMP classification codes. Altered mRNA splicing or function relative to known non-pathogenic variant controls were moderately to strongly predictive of variant pathogenicity. Variant absence in population datasets provided supporting evidence for variant pathogenicity. These findings have direct relevance for BRCA1 and BRCA2 variant evaluation, and justify the need for gene-specific calibration of evidence types used for variant classification. This article is protected by copyright. All rights reserved.
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| 8. |
- Yang, Shilei, et al.
(författare)
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Impact of grassland degradation on the distribution and bioavailability of soil silicon: Implications for the Si cycle in grasslands
- 2019
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Ingår i: Science of the Total Environment. - : Elsevier. - 0048-9697 .- 1879-1026. ; 657, s. 811-818
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Tidskriftsartikel (refereegranskat)abstract
- Grassland ecosystems play an important role in the global terrestrial silicon (Si) cycle, and Si is a beneficial elementand structural constituent for the growth of grasses. In previous decades, grasslands have been degradedto different degrees because of the drying climate and intense human disturbance. However, the impact of grasslanddegradation on the distribution and bioavailability of soil Si is largely unknown. Here, we investigated vegetationand soil conditions of 30 sites to characterize different degrees of degradation for grasslands in the agropastoralecotone of northern China. We then explored the impact of grassland degradation on the distributionand bioavailability of soil Si, including total Si and four forms of noncrystalline Si in three horizons (0–10,10–20 and 20–40 cm) of different soil profiles. The concentrations of noncrystalline Si in soil profiles significantlydecreased with increasing degrees of degradation, being 7.35 ± 0.88 mg g−1, 5.36 ± 0.39 mg g−1, 3.81 ±0.37 mg g−1 and 3.60±0.26 mg g−1 in non-degraded, lightly degraded, moderately degraded and seriously degradedgrasslands, respectively. Moreover, the storage of noncrystalline Si decreased from higher than 40 t ha−1to lower than 23 t ha−1. The corresponding bioavailability of soil Si also generally decreased with grassland degradation.These processes may not only affect the Si pools and fluxes in soils but also influence the Si uptake in plants. We suggest that grassland degradation can significantly affect the global grassland Si cycle. Grasslandmanagement methods such as fertilizing and avoiding overgrazing can potentially double the content and storageof noncrystalline Si in soils, thereby enhancing the soil Si bioavailability by N17%.
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