| 1. |
- Weierstall, Uwe, et al.
(författare)
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Lipidic cubic phase injector facilitates membrane protein serial femtosecond crystallography
- 2014
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 5, s. 3309-
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Tidskriftsartikel (refereegranskat)abstract
- Lipidic cubic phase (LCP) crystallization has proven successful for high-resolution structure determination of challenging membrane proteins. Here we present a technique for extruding gel-like LCP with embedded membrane protein microcrystals, providing a continuously renewed source of material for serial femtosecond crystallography. Data collected from sub-10-mu m-sized crystals produced with less than 0.5 mg of purified protein yield structural insights regarding cyclopamine binding to the Smoothened receptor.
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| 2. |
- Liu, Jintao, et al.
(författare)
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Grid parameterization of a conceptual distributed hydrological model through integration of a sub-grid topographic index : necessity and practicability
- 2012
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Ingår i: Hydrological Sciences Journal. - : Informa UK Limited. - 0262-6667 .- 2150-3435. ; 57:2, s. 282-297
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Tidskriftsartikel (refereegranskat)abstract
- Grid-based distributed models have become popular for describing spatial hydrological processes. However, the influence of non-homogeneity within a grid on streamflow simulation was not adequately addressed in the literature. In this study, we investigated how the statistical characteristics of soil moisture storage within a grid impacts on streamflow simulations. The spatial variation of the topographic index, TI, within a grid was used to determine parameter B of the statistical curve of soil moisture storage in the Xinanjiang model. For comparison of influences of the non-homogeneity within a grid on streamflow simulation, two parameterization schemes of soil moisture storage capacity were developed: a grid-parameterization scheme for a distributed model and a catchment-averaged scheme for a semi-distributed model. The practicability and usefulness of the grid-parameterization method were evaluated through model comparisons. The two models were applied in Jiangwan experimental catchment Zhejiang Province, China. Streamflow discharge data at the catchment outlet from 1971 to 1986 at different temporal resolutions, e. g. 15 min and daily time step, were used for model calibration and validation. Statistical results for different grid scales demonstrated that the mean and variation of TI and B decline significantly as the grid scale increases. The simulated streamflow discharges of the two models were similar and the semi-distributed model outperformed the distributed model slightly when the streamflow at the outlet of the catchment was used as the only basis for comparison. In addition, a relatively larger bias in the predicted discharges between these two models was observed along with an abrupt increase of soil moisture saturation ratio. A further analysis of the simulated soil moisture content distribution revealed that the distributed model can provide a reasonable representation of the variable source area concept, which was justified to some extent by the field experiment data.
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| 3. |
- Liu, Wei, et al.
(författare)
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Serial Femtosecond Crystallography of G Protein-Coupled Receptors
- 2013
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 342:6165, s. 1521-1524
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Tidskriftsartikel (refereegranskat)abstract
- X-ray crystallography of G protein-coupled receptors and other membrane proteins is hampered by difficulties associated with growing sufficiently large crystals that withstand radiation damage and yield high-resolution data at synchrotron sources. We used an x-ray free-electron laser (XFEL) with individual 50-femtosecond-duration x-ray pulses to minimize radiation damage and obtained a high-resolution room-temperature structure of a human serotonin receptor using sub-10-micrometer microcrystals grown in a membrane mimetic matrix known as lipidic cubic phase. Compared with the structure solved by using traditional microcrystallography from cryo-cooled crystals of about two orders of magnitude larger volume, the room-temperature XFEL structure displays a distinct distribution of thermal motions and conformations of residues that likely more accurately represent the receptor structure and dynamics in a cellular environment.
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| 4. |
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| 5. |
- Toh, Soo Ting, et al.
(författare)
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Deep sequencing of the hepatitis B virus in hepatocellular carcinoma patients reveals enriched integration events, structural alterations and sequence variations
- 2013
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Ingår i: Carcinogenesis. - : Oxford University Press (OUP). - 0143-3334 .- 1460-2180. ; 34:4, s. 787-798
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Tidskriftsartikel (refereegranskat)abstract
- Chronic hepatitis B virus (HBV) infection is epidemiologically associated with hepatocellular carcinoma (HCC), but its role in HCC remains poorly understood due to technological limitations. In this study, we systematically characterize HBV in HCC patients. HBV sequences were enriched from 48 HCC patients using an oligo-bead-based strategy, pooled together and sequenced using the FLX-Genome-Sequencer. In the tumors, preferential integration of HBV into promoters of genes (P < 0.001) and significant enrichment of integration into chromosome 10 (P < 0.01) were observed. Integration into chromosome 10 was significantly associated with poorly differentiated tumors (P < 0.05). Notably, in the tumors, recurrent integration into the promoter of the human telomerase reverse transcriptase (TERT) gene was found to correlate with increased TERT expression. The preferred region within the HBV genome involved in integration and viral structural alteration is at the 3'-end of hepatitis B virus X protein (HBx), where viral replication/transcription initiates. Upon integration, the 3'-end of the HBx is often deleted. HBxhuman chimeric transcripts, the most common type of chimeric transcripts, can be expressed as chimeric proteins. Sequence variation resulting in non-conservative amino acid substitutions are commonly observed in HBV genome. This study highlights HBV as highly mutable in HCC patients with preferential regions within the host and virus genome for HBV integration/structural alterations.
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| 6. |
- Wang, Zhaoming, et al.
(författare)
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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
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:24, s. 6616-6633
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Tidskriftsartikel (refereegranskat)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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| 7. |
- Ye, Xuchun, et al.
(författare)
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Distinguishing the relative impacts of climate change and human activities on variation of streamflow in the Poyang Lake catchment, China
- 2013
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Ingår i: Journal of Hydrology. - : Elsevier BV. - 0022-1694 .- 1879-2707. ; 494, s. 83-95
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Tidskriftsartikel (refereegranskat)abstract
- Under the background of global climate change and local anthropogenic stresses, many regions of the world have suffered from frequent droughts and floods in recent decades. Assessing the relative effect of climate change and human activities is essential not only for understanding the mechanism of hydrological response in the catchment, but also for local water resources management as well as floods and droughts protection. The Poyang Lake catchment in the middle reaches of the Yangtze River has experienced significant changes in hydro-climatic variables and human activities during the past decades and therefore provides an excellent site for studying the hydrological impact of climate change and human activities. In this study, the characteristics of hydro-climatic changes of the Poyang Lake catchment were analyzed based on the observed data for the period 1960-2007. The relative effect of climate change and human activities was first empirically distinguished by a coupled water and energy budgets analysis, and then the result was further confirmed by a quantitative assessment. A major finding of this study is that the relative effects of climate change and human activities varied among sub-catchments as well as the whole catchment under different decades. For the whole Poyang Lake catchment, the variations of mean annual streamflow in 1970-2007 were primarily affected by climate change with reference to 1960s, while human activities played a complementary role. However, due to the intensified water utilization, the decrease of streamflow in the Fuhe River sub-catchment in 2000s was primarily affected by human activities, rather than climate change. For the catchment average water balance, quantitative assessment revealed that climate change resulted in an increased annual runoff of 75.3-261.7 mm in 1970s-2000s for the Poyang Lake catchment, accounting for 105.0-212.1% of runoff changes relative to 1960s. However, human activities should be responsible for the decreased annual runoff of 5.4-56.3 mm in the other decades, accounting for -5.0% to -112.1% of runoff changes. It is noted that the effects of human activities including soil conservation, water conservancy projects and changes in land cover might accumulate or counteract each other simultaneously, and attempts were not made in this paper to further distinguish them.
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| 8. |
- Ye, Xuchun, et al.
(författare)
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Variation of reference evapotranspiration and its contributing climatic factors in the Poyang Lake catchment, China
- 2014
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Ingår i: Hydrological Processes. - : Wiley. - 0885-6087 .- 1099-1085. ; 28:25, s. 6151-6162
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Tidskriftsartikel (refereegranskat)abstract
- By using linear regression (parametric), Mann–Kendall (nonparametric) and attribution analysis methods, this study systematically analysed the changing properties of reference evapotranspiration (ETr) calculated using the Penman–Monteith method over the Poyang Lake catchment during 1960–2008 and investigated the contribution of major climatic variables to ETr changes and their temporal evolution. Generally, a significant decreasing trend of annual ETr is found in the catchment. The decrease of annual ETr in the Poyang Lake basin is mostly affected by the decline of summer ETr. Over the study period, climatic variables, i.e. sunshine duration (SD), relative humidity (RH), wind speed (WS) and vapour pressure all showed decreasing trends, whereas mean daily temperature (DT) increased significantly. Multivariate regression analysis indicated that SD is the most sensitive climatic variable to the variability of ETr on annual basis, followed by RH, WS and DT, whereas the effect of vapour pressure is obscure. Although recent warming trend and decrease of relative humidity over the catchment could have increased ETr, the combined effect of shortened SD and reduced WS negated the effect and caused significant decrease of ETr. Our investigation reveals that the relative contributions of climatic variables to ETr are temporally unstable and vary considerably with large fluctuation. In consideration of the changes of climatic variables over time, further analysis indicated that changes of mean annual ETr in 1970–2008 were primarily affected by SD followed by WS, RH and DT with reference to 1960s. However, WS became the predominant factor during the period 2000–2008 compared with reference period 1960s, and followed by SD.
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