| 1. |
- Abdoullaye, Doukary, et al.
(författare)
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Permanent genetic resources added to molecular ecology resources database 1 August 2009 - 30 September 2009
- 2010
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Ingår i: Molecular Ecology Resources. - : Wiley. - 1755-098X .- 1755-0998. ; 10:1, s. 232-236
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Tidskriftsartikel (refereegranskat)abstract
- This article documents the addition of 238 microsatellite marker loci and 72 pairs of Single Nucleotide Polymorphism (SNP) sequencing primers to the Molecular Ecology Resources Database. Loci were developed for the following species: Adelges tsugae, Artemisia tridentata, Astroides calycularis, Azorella selago, Botryllus schlosseri, Botrylloides violaceus, Cardiocrinum cordatum var. glehnii, Campylopterus curvipennis, Colocasia esculenta, Cynomys ludovicianus, Cynomys leucurus, Cynomys gunnisoni, Epinephelus coioides, Eunicella singularis, Gammarus pulex, Homoeosoma nebulella, Hyla squirella, Lateolabrax japonicus, Mastomys erythroleucus, Pararge aegeria, Pardosa sierra, Phoenicopterus ruber ruber and Silene latifolia. These loci were cross-tested on the following species: Adelges abietis, Adelges cooleyi, Adelges piceae, Pineus pini, Pineus strobi, Tubastrea micrantha, three other Tubastrea species, Botrylloides fuscus, Botrylloides simodensis, Campylopterus hemileucurus, Campylopterus rufus, Campylopterus largipennis, Campylopterus villaviscensio, Phaethornis longuemareus, Florisuga mellivora, Lampornis amethystinus, Amazilia cyanocephala, Archilochus colubris, Epinephelus lanceolatus, Epinephelus fuscoguttatus, Symbiodinium temperate-A clade, Gammarus fossarum, Gammarus roeselii, Dikerogammarus villosus and Limnomysis benedeni. This article also documents the addition of 72 sequencing primer pairs and 52 allele specific primers for Neophocaena phocaenoides.
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| 2. |
- Chen, Yong, et al.
(författare)
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A Vps21 endocytic module regulates autophagy
- 2014
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Ingår i: Molecular Biology of the Cell. - 1939-4586. ; 25:20, s. 3166-3177
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Tidskriftsartikel (refereegranskat)abstract
- In autophagy, the double-membrane autophagosome delivers cellular components for their degradation in the lysosome. The conserved Ypt/Rab GTPases regulate all cellular trafficking pathways, including autophagy. These GTPases function in modules that include guanine-nucleotide exchange factor (GEF) activators and downstream effectors. Rab7 and its yeast homologue, Ypt7, in the context of such a module, regulate the fusion of both late endosomes and autophagosomes with the lysosome. In yeast, the Rab5-related Vps21 is known for its role in early- to late-endosome transport. Here we show an additional role for Vps21 in autophagy. First, vps21Δ mutant cells are defective in selective and nonselective autophagy. Second, fluorescence and electron microscopy analyses show that vps21Δ mutant cells accumulate clusters of autophagosomal structures outside the vacuole. Third, cells with mutations in other members of the endocytic Vps21 module, including the GEF Vps9 and factors that function downstream of Vps21, Vac1, CORVET, Pep12, and Vps45, are also defective in autophagy and accumulate clusters of autophagosomes. Finally, Vps21 localizes to PAS. We propose that the endocytic Vps21 module also regulates autophagy. These findings support the idea that the two pathways leading to the lysosome—endocytosis and autophagy—converge through the Vps21 and Ypt7 GTPase modules.
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| 3. |
- Butler, Anne M., et al.
(författare)
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Novel Loci Associated With PR Interval in a Genome-Wide Association Study of 10 African American Cohorts
- 2012
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Ingår i: Circulation: Cardiovascular Genetics. - 1942-325X. ; 5:6, s. 639-646
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Tidskriftsartikel (refereegranskat)abstract
- Background-The PR interval, as measured by the resting, standard 12-lead ECG, reflects the duration of atrial/atrioventricular nodal depolarization. Substantial evidence exists for a genetic contribution to PR, including genome-wide association studies that have identified common genetic variants at 9 loci influencing PR in populations of European and Asian descent. However, few studies have examined loci associated with PR in African Americans. Methods and Results-We present results from the largest genome-wide association study to date of PR in 13 415 adults of African descent from 10 cohorts. We tested for association between PR (ms) and approximate to 2.8 million genotyped and imputed single-nucleotide polymorphisms. Imputation was performed using HapMap 2 YRI and CEU panels. Study-specific results, adjusted for global ancestry and clinical correlates of PR, were meta-analyzed using the inverse variance method. Variation in genome-wide test statistic distributions was noted within studies (lambda range: 0.9-1.1), although not after genomic control correction was applied to the overall meta-analysis (lambda: 1.008). In addition to generalizing previously reported associations with MEIS1, SCN5A, ARHGAP24, CAV1, and TBX5 to African American populations at the genome-wide significance level (P<5.0x10(-8)), we also identified a novel locus: ITGA9, located in a region previously implicated in SCN5A expression. The 3p21 region harboring SCN5A also contained 2 additional independent secondary signals influencing PR (P<5.0x10-8). Conclusions-This study demonstrates the ability to map novel loci in African Americans as well as the generalizability of loci associated with PR across populations of African, European, and Asian descent. (Circ Cardiovasc Genet. 2012;5:639-646.)
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| 4. |
- Ellinor, Patrick T., et al.
(författare)
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Meta-analysis identifies six new susceptibility loci for atrial fibrillation
- 2012
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 44:6, s. 88-670
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Tidskriftsartikel (refereegranskat)abstract
- Atrial fibrillation is a highly prevalent arrhythmia and a major risk factor for stroke, heart failure and death(1). We conducted a genome-wide association study (GWAS) in individuals of European ancestry, including 6,707 with and 52,426 without atrial fibrillation. Six new atrial fibrillation susceptibility loci were identified and replicated in an additional sample of individuals of European ancestry, including 5,381 subjects with and 10,030 subjects without atrial fibrillation (P < 5 x 10(-8)). Four of the loci identified in Europeans were further replicated in silico in a GWAS of Japanese individuals, including 843 individuals with and 3,350 individuals without atrial fibrillation. The identified loci implicate candidate genes that encode transcription factors related to cardiopulmonary development, cardiac-expressed ion channels and cell signaling molecules.
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| 5. |
- Estrada, Karol, et al.
(författare)
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Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture.
- 2012
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 44:5, s. 491-501
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Tidskriftsartikel (refereegranskat)abstract
- Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10(-8)). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10(-4), Bonferroni corrected), of which six reached P < 5 × 10(-8), including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.
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| 6. |
- Lange, Leslie A, et al.
(författare)
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Whole-Exome Sequencing Identifies Rare and Low-Frequency Coding Variants Associated with LDL Cholesterol.
- 2014
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297. ; 94:2, s. 233-245
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Tidskriftsartikel (refereegranskat)abstract
- Elevated low-density lipoprotein cholesterol (LDL-C) is a treatable, heritable risk factor for cardiovascular disease. Genome-wide association studies (GWASs) have identified 157 variants associated with lipid levels but are not well suited to assess the impact of rare and low-frequency variants. To determine whether rare or low-frequency coding variants are associated with LDL-C, we exome sequenced 2,005 individuals, including 554 individuals selected for extreme LDL-C (>98(th) or <2(nd) percentile). Follow-up analyses included sequencing of 1,302 additional individuals and genotype-based analysis of 52,221 individuals. We observed significant evidence of association between LDL-C and the burden of rare or low-frequency variants in PNPLA5, encoding a phospholipase-domain-containing protein, and both known and previously unidentified variants in PCSK9, LDLR and APOB, three known lipid-related genes. The effect sizes for the burden of rare variants for each associated gene were substantially higher than those observed for individual SNPs identified from GWASs. We replicated the PNPLA5 signal in an independent large-scale sequencing study of 2,084 individuals. In conclusion, this large whole-exome-sequencing study for LDL-C identified a gene not known to be implicated in LDL-C and provides unique insight into the design and analysis of similar experiments.
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| 7. |
- Li, Jian-Fang, et al.
(författare)
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Soy isoflavone delays the progression of thioacetamide-induced liver fibrosis in rats
- 2011
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 46:3, s. 341-349
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Tidskriftsartikel (refereegranskat)abstract
- Objective. Our aim was to investigate the effect of soy isoflavone (SI) on liver fibrosis in a thioacetamide (TAA)-induced rat model. Materials and methods. Twenty-eight rats were assigned to four groups: sham group, fibrosis group, low-dose treatment group (LDg) and high-dose treatment group (HDg). SI (90 or 270 mg/kg) was administered daily during the model development by TAA. Standard liver tests, platelet derived growth factor-BB (PDGF-BB) and tissue inhibitor of metalloproteinase-1 (TIMP-1) were measured. The expression of collagen, alpha alpha-smooth muscle actin (alpha alpha-SMA) and transforming growth factor-beta beta 1 (TGF-beta beta 1) in liver tissue was determined. Electron microscopy was used to perform ultrastructural analysis of the livers. Results. Hepatic fibrosis was induced by 8 weeks of TAA administration. However, following the administration of SI, collagen staining significantly declined as compared with the fibrosis group (p < 0.01). Less collagen fibers around the hepatic stellate cells (HSCs) were observed in HDg as compared to the fibrosis group and LDg. There was no significant difference in standard liver tests between the fibrosis group and the two treatment groups. The levels of PDGF-BB and TIMP-1 in the two SI-treated groups were significantly lower than in the fibrosis group (p < 0.01). The expression of alpha alpha-SMA and TGF-beta beta 1 in HDg was less than that in the fibrosis group and LDg (p < 0.01). Conclusion. Administration of a high dose of SI resulted in an obvious inhibitory effect on liver fibrosis induced by TAA in rats. One hypothesis is that the effect may be related to the inhibition of HSC activation and proliferation.
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| 8. |
- Li, Lanfen, et al.
(författare)
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Structural genomics studies of human caries pathogen Streptococcus mutans
- 2014
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Ingår i: Journal of Structural and Functional Genomics. - : Springer Science and Business Media LLC. - 1345-711X .- 1570-0267. ; 15:3, s. 9-91
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Tidskriftsartikel (refereegranskat)abstract
- Gram-positive bacterium Streptococcus mutans is the primary causative agent of human dental caries. To better understand this pathogen at the atomic structure level and to establish potential drug and vaccine targets, we have carried out structural genomics research since 2005. To achieve the goal, we have developed various in-house automation systems including novel high-throughput crystallization equipment and methods, based on which a large-scale, high-efficiency and low-cost platform has been establish in our laboratory. From a total of 1,963 annotated open reading frames, 1,391 non-membrane targets were selected prioritized by protein sequence similarities to unknown structures, and clustered by restriction sites to allow for cost-effective high-throughput conventional cloning. Selected proteins were over-expressed in different strains of Escherichia coli. Clones expressed soluble proteins were selected, expanded, and expressed proteins were purified and subjected to crystallization trials. Finally, protein crystals were subjected to X-ray analysis and structures were determined by crystallographic methods. Using the previously established procedures, we have so far obtained more than 200 kinds of protein crystals and 100 kinds of crystal structures involved in different biological pathways. In this paper we demonstrate and review a possibility of performing structural genomics studies at moderate laboratory scale. Furthermore, the techniques and methods developed in our study can be widely applied to conventional structural biology research practice.
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| 9. |
- Thompson, Paul M., et al.
(författare)
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The ENIGMA Consortium : large-scale collaborative analyses of neuroimaging and genetic data
- 2014
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Ingår i: BRAIN IMAGING BEHAV. - : Springer Science and Business Media LLC. - 1931-7557 .- 1931-7565. ; 8:2, s. 153-182
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Tidskriftsartikel (refereegranskat)abstract
- The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA's first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain. We review the current progress of the ENIGMA Consortium, along with challenges and unexpected discoveries made on the way.
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| 10. |
- Wang, Xiaofeng, et al.
(författare)
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Evidence for type ia supernova diversity from ultraviolet observations with the hubble space telescope
- 2012
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 749:2, s. 126-
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Tidskriftsartikel (refereegranskat)abstract
- We present ultraviolet (UV) spectroscopy and photometry of four Type Ia supernovae (SNe 2004dt, 2004ef, 2005M, and 2005cf) obtained with the UV prism of the Advanced Camera for Surveys on the Hubble Space Telescope. This data set provides unique spectral time series down to 2000 angstrom. Significant diversity is seen in the near-maximum-light spectra (similar to 2000-3500 angstrom) for this small sample. The corresponding photometric data, together with archival data from Swift Ultraviolet/Optical Telescope observations, provide further evidence of increased dispersion in the UV emission with respect to the optical. The peak luminositiesmeasured in the uvw1/F250W filter are found to correlate with the B-band light-curve shape parameter Delta m(15)(B), but with much larger scatter relative to the correlation in the broadband B band (e.g., similar to 0.4 mag versus similar to 0.2 mag for those with 0.8 mag < Delta m(15)(B) < 1.7 mag). SN 2004dt is found as an outlier of this correlation (at > 3 sigma), being brighter than normal SNe Ia such as SN 2005cf by similar to 0.9 mag and similar to 2.0 mag in the uvw1/F250W and uvm2/F220W filters, respectively. We show that different progenitor metallicity or line-expansion velocities alone cannot explain such a large discrepancy. Viewing-angle effects, such as due to an asymmetric explosion, may have a significant influence on the flux emitted in the UV region. Detailed modeling is needed to disentangle and quantify the above effects.
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| 11. |
- Zhang, Xin, et al.
(författare)
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A Longitudinal Study of Sick Building Syndrome (SBS) among Pupils in Relation to SO2, NO2, O-3 and PM10 in Schools in China
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:11, s. e112933-
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Tidskriftsartikel (refereegranskat)abstract
- There are fewer longitudinal studies from China on symptoms as described for the sick building syndrome (SBS). Here, we performed a two-year prospective study and investigated associations between environmental parameters such as room temperature, relative air humidity (RH), carbon dioxide (CO2), nitrogen dioxide (NO2), sulphur dioxide (SO2), ozone (O-3), particulate matter (PM10), and health outcomes including prevalence, incidence and remission of SBS symptoms in junior high schools in Taiyuan, China. Totally 2134 pupils participated at baseline, and 1325 stayed in the same classrooms during the study period (2010-2012). The prevalence of mucosal symptoms, general symptoms and symptoms improved when away from school (school-related symptoms) was 22.7%, 20.4% and 39.2%, respectively, at baseline, and the prevalence increased during follow-up (P<0.001). At baseline, both indoor and outdoor SO2 were found positively associated with prevalence of school-related symptoms. Indoor O-3 was shown to be positively associated with prevalence of skin symptoms. At follow-up, indoor PM10 was found to be positively associated with new onset of skin, mucosal and general symptoms. CO2 and RH were positively associated with new onset of mucosal, general and school-related symptoms. Outdoor SO2 was positively associated with new onset of skin symptoms, while outdoor NO2 was positively associated with new onset of skin, general and mucosal symptoms. Outdoor PM10 was found to be positively associated with new onset of skin, general and mucosal symptoms as well as school-related symptoms. In conclusion, symptoms as described for SBS were commonly found in school children in Taiyuan City, China, and increased during the two-year follow-up period. Environmental pollution, including PM10, SO2 and NO2, could increase the prevalence and incidence of SBS and decrease the remission rate. Moreover, parental asthma and allergy (heredity) and pollen or pet allergy (atopy) can be risk factors for SBS.
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| 12. |
- Zhang, Yinping, et al.
(författare)
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Ten cities cross-sectional questionnaire survey of children asthma and other allergies in China
- 2013
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Ingår i: Chinese Science Bulletin. - : Springer Science and Business Media LLC. - 1001-6538 .- 1861-9541. ; 58:34, s. 4182-4189
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Tidskriftsartikel (refereegranskat)abstract
- Asthma, rhinitis and eczema (allergic or non-allergic) have increased throughout the world during the last decades, especially among children. Changes in the indoor environment are suspected to be important causes. China has experienced a dramatic change in indoor environmental exposures during the past two decades. However, such changes and their associations with children's asthma and other health aspects have not been thoroughly studied. China, Children, Homes, Health (CCHH), Phase I, was a cross-sectional questionnaire survey of 48219 children 1-8 years old in 10 Chinese cities during 2010-2012. The questionnaire includes the International Study of Asthma and Allergies in Childhood (ISAAC) core health questions and additional questions regarding housing, life habits and outdoor environment. In health analyses, children aged 3-6 years old were included. The prevalences of doctor diagnosed asthma varied from 1.7% to 9.8% (mean 6.8%), a large increase from 0.91% in 1999 and 1.50% in 2000. The prevalence of wheeze, rhinitis and atopic eczema (last 12 months) varied from 13.9% to 23.7%, 24.0% to 50.8% and 4.8% to 15.8%, respectively. Taiyuan had the lowest prevalences of all illnesses and Shanghai the highest, except for wheezewhere the highest value was for Urumqi. We found (1) no obvious association between disease prevalences and ambient PM10 concentrations and (2) higher prevalences of disease in humid climates with hot summers and cold winters, but with no centrally heated buildings. Associations between the diseases and economic status as indexed by Gross Domestic Product (GDP) requires further study.
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| 13. |
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| 14. |
- Berndt, Sonja I., et al.
(författare)
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Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:5, s. 501-U69
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Tidskriftsartikel (refereegranskat)abstract
- Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.
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| 15. |
- Bettegowda, Chetan, et al.
(författare)
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Detection of circulating tumor DNA in early- and late-stage human malignancies
- 2014
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Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6234 .- 1946-6242. ; 6:224, s. 224ra24-
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Tidskriftsartikel (refereegranskat)abstract
- The development of noninvasive methods to detect and monitor tumors continues to be a major challenge in oncology. We used digital polymerase chain reaction-based technologies to evaluate the ability of circulating tumor DNA (ctDNA) to detect tumors in 640 patients with various cancer types. We found that ctDNA was detectable in >75% of patients with advanced pancreatic, ovarian, colorectal, bladder, gastroesophageal, breast, melanoma, hepatocellular, and head and neck cancers, but in less than 50% of primary brain, renal, prostate, or thyroid cancers. In patients with localized tumors, ctDNA was detected in 73, 57, 48, and 50% of patients with colorectal cancer, gastroesophageal cancer, pancreatic cancer, and breast adenocarcinoma, respectively. ctDNA was often present in patients without detectable circulating tumor cells, suggesting that these two biomarkers are distinct entities. In a separate panel of 206 patients with metastatic colorectal cancers, we showed that the sensitivity of ctDNA for detection of clinically relevant KRAS gene mutations was 87.2% and its specificity was 99.2%. Finally, we assessed whether ctDNA could provide clues into the mechanisms underlying resistance to epidermal growth factor receptor blockade in 24 patients who objectively responded to therapy but subsequently relapsed. Twenty-three (96%) of these patients developed one or more mutations in genes involved in the mitogen-activated protein kinase pathway. Together, these data suggest that ctDNA is a broadly applicable, sensitive, and specific biomarker that can be used for a variety of clinical and research purposes in patients with multiple different types of cancer.
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| 16. |
- Boeger, Carsten A., et al.
(författare)
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CUBN Is a Gene Locus for Albuminuria
- 2011
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Ingår i: Journal of the American Society of Nephrology. - 1046-6673 .- 1533-3450. ; 22:3, s. 555-570
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Tidskriftsartikel (refereegranskat)abstract
- Identification of genetic risk factors for albuminuria may alter strategies for early prevention of CKD progression, particularly among patients with diabetes. Little is known about the influence of common genetic variants on albuminuria in both general and diabetic populations. We performed a meta-analysis of data from 63,153 individuals of European ancestry with genotype information from genome-wide association studies (CKDGen Consortium) and from a large candidate gene study (CARe Consortium) to identify susceptibility loci for the quantitative trait urinary albumin-to-creatinine ratio (UACR) and the clinical diagnosis microalbuminuria. We identified an association between a missense variant (I2984V) in the CUBN gene, which encodes cubilin, and both UACR (P = 1.1 x 10(-11)) and microalbuminuria (P = 0.001). We observed similar associations among 6981 African Americans in the CARe Consortium. The associations between this variant and both UACR and microalbuminuria were significant in individuals of European ancestry regardless of diabetes status. Finally, this variant associated with a 41% increased risk for the development of persistent microalbuminuria during 20 years of follow-up among 1304 participants with type 1 diabetes in the prospective DCCT/EDIC Study. In summary, we identified a missense CUBN variant that associates with levels of albuminuria in both the general population and in individuals with diabetes.
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| 17. |
- Caudle, Kelly E, et al.
(författare)
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Incorporation of Pharmacogenomics into Routine Clinical Practice : the Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline Development Process
- 2014
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Ingår i: Current drug metabolism. - : Bentham Science Publishers Ltd.. - 1389-2002 .- 1875-5453. ; 15:2, s. 209-217
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Tidskriftsartikel (refereegranskat)abstract
- The Clinical Pharmacogenetics Implementation Consortium (CPIC) publishes genotype-based drug guidelines to help clinicians understand how available genetic test results could be used to optimize drug therapy. CPIC has focused initially on well-known examples of pharmacogenomic associations that have been implemented in selected clinical settings, publishing nine to date. Each CPIC guideline adheres to a standardized format and includes a standard system for grading levels of evidence linking genotypes to phenotypes and assigning a level of strength to each prescribing recommendation. CPIC guidelines contain the necessary information to help clinicians translate patient-specific diplotypes for each gene into clinical phenotypes or drug dosing groups. This paper reviews the development process of the CPIC guidelines and compares this process to the Institute of Medicine's Standards for Developing Trustworthy Clinical Practice Guidelines.
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| 18. |
- Daranciang, Dan, et al.
(författare)
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Ultrafast Photovoltaic Response in Ferroelectric Nanolayers
- 2012
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Ingår i: Physical Review Letters. - 1079-7114. ; 108:8
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Tidskriftsartikel (refereegranskat)abstract
- We show that light drives large-amplitude structural changes in thin films of the prototypical ferroelectric PbTiO3 via direct coupling to its intrinsic photovoltaic response. Using time-resolved x-ray scattering to visualize atomic displacements on femtosecond time scales, photoinduced changes in the unit-cell tetragonality are observed. These are driven by the motion of photogenerated free charges within the ferroelectric and can be simply explained by a model including both shift and screening currents, associated with the displacement of electrons first antiparallel to and then parallel to the ferroelectric polarization direction.
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| 19. |
- Escott-Price, Valentina, et al.
(författare)
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Gene-Wide Analysis Detects Two New Susceptibility Genes for Alzheimer's Disease
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:6, s. e94661-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls. Principal Findings: In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4x10(-6)) and 14 (IGHV1-67 p = 7.9x10(-8)) which indexed novel susceptibility loci. Significance: The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.
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| 20. |
- Frank, Matthias, et al.
(författare)
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Femtosecond X-ray diffraction from two-dimensional protein crystals
- 2014
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Ingår i: IUCrJ. - 2052-2525. ; 1:2, s. 95-100
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Tidskriftsartikel (refereegranskat)abstract
- X-ray diffraction patterns from two-dimensional (2-D) protein crystals obtained using femtosecond X-ray pulses from an X-ray free-electron laser (XFEL) are presented. To date, it has not been possible to acquire transmission X-ray diffraction patterns from individual 2-D protein crystals due to radiation damage. However, the intense and ultrafast pulses generated by an XFEL permit a new method of collecting diffraction data before the sample is destroyed. Utilizing a diffract-before-destroy approach at the Linac Coherent Light Source, Bragg diffraction was acquired to better than 8.5 Å resolution for two different 2-D protein crystal samples each less than 10 nm thick and maintained at room temperature. These proof-of-principle results show promise for structural analysis of both soluble and membrane proteins arranged as 2-D crystals without requiring cryogenic conditions or the formation of three-dimensional crystals.
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| 21. |
- Furberg, Helena, et al.
(författare)
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Genome-wide meta-analyses identify multiple loci associated with smoking behavior
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 42:5, s. 134-441
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Tidskriftsartikel (refereegranskat)abstract
- Consistent but indirect evidence has implicated genetic factors in smoking behavior1,2. We report meta-analyses of several smoking phenotypes within cohorts of the Tobacco and Genetics Consortium (n = 74,053). We also partnered with the European Network of Genetic and Genomic Epidemiology (ENGAGE) and Oxford-GlaxoSmithKline (Ox-GSK) consortia to follow up the 15 most significant regions (n > 140,000). We identified three loci associated with number of cigarettes smoked per day. The strongest association was a synonymous 15q25 SNP in the nicotinic receptor gene CHRNA3 (rs1051730[A], b = 1.03, standard error (s.e.) = 0.053, beta = 2.8 x 10(-73)). Two 10q25 SNPs (rs1329650[G], b = 0.367, s. e. = 0.059, beta = 5.7 x 10(-10); and rs1028936[A], b = 0.446, s. e. = 0.074, beta = 1.3 x 10(-9)) and one 9q13 SNP in EGLN2 (rs3733829[G], b = 0.333, s. e. = 0.058, P = 1.0 x 10(-8)) also exceeded genome-wide significance for cigarettes per day. For smoking initiation, eight SNPs exceeded genome-wide significance, with the strongest association at a nonsynonymous SNP in BDNF on chromosome 11 (rs6265[C], odds ratio (OR) = 1.06, 95% confidence interval (Cl) 1.04-1.08, P = 1.8 x 10(-8)). One SNP located near DBH on chromosome 9 (rs3025343[G], OR = 1.12, 95% Cl 1.08-1.18, P = 3.6 x 10(-8)) was significantly associated with smoking cessation.
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| 22. |
- Gustafsson, Dan J, et al.
(författare)
-
Adenovirus 11p downregulates CD46 early in infection
- 2010
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Ingår i: Virology. - : Elsevier BV. - 0042-6822 .- 1096-0341. ; 405:2, s. 474-482
-
Tidskriftsartikel (refereegranskat)abstract
- Adenovirus 11 prototype (Ad11p), belonging to species B, uses CD46 as an attachment receptor. CD46, a complement regulatory molecule, is expressed on all human nucleated cells. We show here that Ad11p virions downregulate CD46 on the surface of K562 cells as early as 5min p.i. Specific binding to CD46 by the Ad11p fiber knob was required to mediate downregulation. The complement regulatory factors CD55 and CD59 were also reduced to a significant extent as a consequence of Ad11p binding to K562 cells. In contrast, binding of Ad7p did not result in downregulation of CD46 early in infection. Thus, the presumed interaction between Ad7p and CD46 did not have the same consequences as the Ad11p-CD46 interaction, the latter virus (Ad11p) being a promising gene therapy vector candidate. These findings may lead to a better understanding of the pathogenesis of species B adenovirus infections.
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| 23. |
- Hsu, Li-Han, 1981, et al.
(författare)
-
Flip-chip assembled 7 GHz ultra-low phase-noise InGaP HBT oscillator
- 2010
-
Ingår i: 2010 International Conference on Compound Semiconductor Manufacturing Technology; Portland, OR; United States; 17 May 2010 through 20 May 2010. - 9781893580152
-
Konferensbidrag (refereegranskat)abstract
- This paper reports on a flip-chip assembled 7 GHz ultra-low phase-noise GaAs InGaP heterojunction bipolar transistor (HBT) monolithic microwave integrated circuit (MMIC) oscillator. The cross-coupled oscillator was flip-chip bonded to an in-house fabricated Al2O3 carrier with patterns optimized for low-loss transitions. After flip-chip, the phase noise of the crosscoupled InGaP HBT oscillator was improved due to an increased Q-factor of the resonant tank. An ultra-low phase-noise of -112 dBc/Hz @ 100 kHz offset and -128 dBc/Hz @ 1 MHz offset with a high output power of 7 dBm at 7 GHz was achieved. To our best knowledge, this is the lowest phase noise reported for a flip-chip assembled oscillator.
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| 24. |
- Hsu, Li-Han, 1981, et al.
(författare)
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Flip-Chip-Based Multichip Module for Low Phase-Noise V -Band Frequency Generation
- 2010
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Ingår i: IEEE Transactions on Microwave Theory and Techniques. - 0018-9480 .- 1557-9670. ; 58:9, s. 2408-2419
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- This paper reports on a flip-chip (FC)-based multichip module (MCM) for low phase-noise (PN) V -band frequency generation. A high-performance x8 GaAs metamorphic high-electron mobility transistor monolithic microwave integrated circuit (MMIC) multiplier and a low PN 7-GHz GaAs InGaP heterojunction bipolar transistor (HBT) MMIC oscillator were used in the module. The microstrip MMICs were FC bonded to an Al2O3 carrier with patterns optimized for low-loss transitions. The FC-based module was experimentally characterized to have a PN of -88 dBe/Hz @ 100-kHz offset and -112 dBc/Hz @ 1-MHz offset with an output power of 11 dBm. For comparison, the MMICs were also FC bonded as individual chips and the performance was compared with the bare dies without FC bonding. It was verified that the FC bonding has no detrimental effect on the MMIC performance. The tests revealed that the FC module provided improved performance. To our best knowledge, this is the first FC-based module for millimeter-wave frequency generation. The module also presents one of the best PN reported for millimeter-wave frequency sources.
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| 25. |
- Juan, Wang, et al.
(författare)
-
Sick building syndrome among parents of preschool children in relation to home environment in Chongqing, China
- 2013
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Ingår i: Chinese Science Bulletin. - : Springer Science and Business Media LLC. - 1001-6538 .- 1861-9541. ; 58:34, s. 4267-4276
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Tidskriftsartikel (refereegranskat)abstract
- The prevalence and risk factors of sick building syndrome (SBS) symptoms in domestic environments were studied by a questionnaire survey on the home environment. Parents of 5299 3-6 years old children from randomly selected kindergartens in Chongqing, China returned completed questionnaires between December 2010 and April 2011. The prevalence of parents' SBS symptoms (often (every week) compared with never) were: 11.4% for general symptoms, 7.1% for mucosal symptoms and 4.4% for skin symptoms. Multiple logistic regressions were applied controlling for gender and asthma/allergic rhinitis/eczema. Living near a main road or highway was a strong risk factor for general symptoms (adjusted odds ratio, aOR=2.16, P<0.001), skin symptoms (aOR=2.69, P<0.001), and mucosal symptoms (aOR=1.63, P<0.01). Redecoration was a risk factor for general symptoms (aOR=2.00, P<0.001), skin symptoms (aOR=1.66, P<0.01), and mucosal symptoms (aOR=1.66, P<0.05). New furniture was a risk factor for general symptoms (aOR=2.16, P<0.001) and skin symptoms (aOR=1.67, P<0.01). Dampness related problems (mould spot, damp stain, water damage and condensation) were all risk factors for SBS symptoms, as was the presence of cockroaches, rats, and mosquitoes/flies and use of incense. Protective factors include cleaning the child's bedroom every day and frequently exposing bedding to sunshine. In conclusion, adults' SBS symptoms were related to factors of the home environment.
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| 26. |
- Kharaziha, Pedram, et al.
(författare)
-
Sorafenib Has Potent Antitumor Activity against Multiple Myeloma In Vitro, Ex Vivo, and In Vivo in the 5T33MM Mouse Model
- 2012
-
Ingår i: Cancer Research. - 0008-5472 .- 1538-7445. ; 72:20, s. 5348-5362
-
Tidskriftsartikel (refereegranskat)abstract
- Multiple myeloma (MM) is a B-cell malignancy characterized by the expansion of clonal plasma blasts/plasma cells within the bone marrow that relies on multiple signaling cascades, including tyrosine kinase activated pathways, to proliferate and evade cell death. Despite emerging new treatment strategies, multiple myeloma remains at present incurable. Thus, novel approaches targeting several signaling cascades by using the multi-tyrosine kinase inhibitor (TKI), sorafenib, seem a promising treatment approach for multiple myeloma. Here, we show that sorafenib induces cell death in multiple myeloma cell lines and in CD138(+)-enriched primary multiple myeloma patient samples in a caspase-dependent and -independent manner. Furthermore, sorafenib has a strong antitumoral and -angiogenic activity in the 5T33MM mouse model leading to increased overall survival. Multiple myeloma cells undergo autophagy in response to sorafenib, and inhibition of this cytoprotective pathway potentiated the efficacy of this TKI. Mcl-1, a survival factor in multiple myeloma, is downregulated at the protein level by sorafenib allowing for the execution of cell death, as ectopic overexpression of this protein protects multiple myeloma cells. Concomitant targeting of Mcl-1 by sorafenib and of Bcl-2/Bcl-xL by the antagonist ABT737 improves the efficacy of sorafenib in multiple myeloma cell lines and CD138(+)-enriched primary cells in the presence of bone marrow stromal cells. Altogether, our data support the use of sorafenib as a novel therapeutic modality against human multiple myeloma, and its efficacy may be potentiated in combination with ABT737.
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| 27. |
- Killela, Patrick J., et al.
(författare)
-
TERT promoter mutations occur frequently in gliomas and a subset of tumors derived from cells with low rates of self-renewal
- 2013
-
Ingår i: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 110:15, s. 6021-6026
-
Tidskriftsartikel (refereegranskat)abstract
- Malignant cells, like all actively growing cells, must maintain their telomeres, but genetic mechanisms responsible for telomere maintenance in tumors have only recently been discovered. In particular, mutations of the telomere binding proteins alpha thalassemia/mental retardation syndrome X-linked (ATRX) or death-domain associated protein (DAXX) have been shown to underlie a telomere maintenance mechanism not involving telomerase (alternative lengthening of telomeres), and point mutations in the promoter of the telomerase reverse transcriptase (TERT) gene increase telomerase expression and have been shown to occur in melanomas and a small number of other tumors. To further define the tumor types in which this latter mechanism plays a role, we surveyed 1,230 tumors of 60 different types. We found that tumors could be divided into types with low (<15%) and high (>= 15%) frequencies of TERT promoter mutations. The nine TERT-high tumor types almost always originated in tissues with relatively low rates of self renewal, including melanomas, liposarcomas, hepatocellular carcinomas, urothelial carcinomas, squamous cell carcinomas of the tongue, medulloblastomas, and subtypes of gliomas (including 83% of primary glioblastoma, the most common brain tumor type). TERT and ATRX mutations were mutually exclusive, suggesting that these two genetic mechanisms confer equivalent selective growth advantages. In addition to their implications for understanding the relationship between telomeres and tumorigenesis, TERT mutations provide a biomarker that may be useful for the early detection of urinary tract and liver tumors and aid in the classification and prognostication of brain tumors.
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| 28. |
- Köttgen, Anna, et al.
(författare)
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New loci associated with kidney function and chronic kidney disease
- 2010
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:5, s. 376-384
-
Tidskriftsartikel (refereegranskat)abstract
- Chronic kidney disease (CKD) is a significant public health problem, and recent genetic studies have identified common CKD susceptibility variants. The CKDGen consortium performed a meta-analysis of genome-wide association data in 67,093 individuals of European ancestry from 20 predominantly population-based studies in order to identify new susceptibility loci for reduced renal function as estimated by serum creatinine (eGFRcrea), serum cystatin c (eGFRcys) and CKD (eGFRcrea < 60 ml/min/1.73 m2; n = 5,807 individuals with CKD (cases)). Follow-up of the 23 new genome-wide–significant loci (P < 5 × 10−8) in 22,982 replication samples identified 13 new loci affecting renal function and CKD (in or near LASS2, GCKR, ALMS1, TFDP2, DAB2, SLC34A1, VEGFA, PRKAG2, PIP5K1B, ATXN2, DACH1, UBE2Q2 and SLC7A9) and 7 loci suspected to affect creatinine production and secretion (CPS1, SLC22A2, TMEM60, WDR37, SLC6A13, WDR72 and BCAS3). These results further our understanding of the biologic mechanisms of kidney function by identifying loci that potentially influence nephrogenesis, podocyte function, angiogenesis, solute transport and metabolic functions of the kidney.
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| 29. |
- Li, Dan, 1990, et al.
(författare)
-
HOW CHANGES IN COGNITIVE AUTOMATION CAN AFFECT OPERATOR PERFORMANCE AND PRODUCTIVITY
- 2014
-
Ingår i: The sixth Swedish Production Symposium.
-
Konferensbidrag (refereegranskat)abstract
- To predict system performance, understanding what affects operator performance and productivity is important. This notion was tested in a LEGO experiment including 40 students. After introducing changes in assembly instructions and material façade operator performance and productivity was increased. The aggregated results gave an indication of how cognitive automation affects the operators’ initial assembly performance. Industrial studies are needed to ensure observed trends and to further study the impact of cognitive automation characteristics. The trends however point toward that cognitive support has an impact on the final assembly and it is therefore possible to achieve better operator performance if instructions and material façade are improved.
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| 30. |
- Li, H., et al.
(författare)
-
FADEC : Fast authentication for dynamic electric vehicle charging
- 2013
-
Ingår i: 2013 IEEE Conference on Communications and Network Security, CNS 2013. - : IEEE. - 9781479908950 ; , s. 369-370
-
Konferensbidrag (refereegranskat)abstract
- Dynamic wireless charging [1], [2] is a promising technology for charging electric vehicles (EV) while driving. The basic idea is to place charging coils under the charging pads on the road and attach charging coils to the EV's battery. When the EV is driving above the coil, the electromagnetic interaction between the coils under the road and the coils in the EV can charge the EV battery.
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| 31. |
- Li, Hongyang, et al.
(författare)
-
Portunes : Privacy-Preserving Fast Authentication for Dynamic Electric Vehicle Charging
- 2014
-
Konferensbidrag (refereegranskat)abstract
- Dynamic contactless charging is an emerging technology for charging electric vehicles (EV) on the move. For efficient charging and for proper billing, dynamic charging requires secure communication between the charging infrastructure and the EVs that supports very frequent real-time message exchange for EV authentication. In this paper we propose Portunes, an authentication protocol for charging pads to authenticate an EV's identity. Portunes uses pseudonyms to provide location privacy, allows EVs to roam between different charging sections and receive a single bill, and achieves fast authentication by relying on symmetric keys and on the spatio-temporal location of the EV. We have implemented Portunes on RaspberryPi Model B with 700 MHz CPU and 512 MB RAM. Portunes allows the EV to generate authentication information within 0.3 ms, and allows charging pads to verify the information within 0.5 ms. In comparison, ECDSA signature generation and verification take over 25 ms and over 40 ms respectively.
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| 32. |
- Li, Jie, et al.
(författare)
-
Performance analysis of local caching replacement policies for internet video streaming services
- 2014
-
Ingår i: SoftCOM 2014. - : IEEE Communications Society. - 9789532900521
-
Konferensbidrag (refereegranskat)abstract
- In this work, the performance of 5 representative caching replacement policies was investigated and compared for caching Internet video-on-demand (VoD) in local access networks. Two measured traces of end-user requests were used in the analyses for two typical VoD services: TV-on-demand and user generated content represented by YouTube. The studied policies range from simple least recently used (LRU) and least frequently used (LFU) algorithms to more advanced ones denoted as LFU-dynamic lifespan (LFU-DL), Adaptive replacement cache (ARC) and Greedy-dual size frequency (GDSF). Our results show that the ARC policy always outperforms the other policies due to its adaptive nature and its ability to track changes in the traffic patterns. On the other hand, the simple LRU policy can also achieve a caching performance which is comparable to that of the more advanced ARC policy especially for the TV-on-demand service when the potential caching gain is high. On the contrary, the simple LFU policy always shows the poorest performance.However, by applying a proper lifespan supplement under the LFU-DL policy, the caching performance can be effectively enhanced to the level achievable using ARC and LRU policies. Moreover, the GDSF policy does not outperform simple LRU or LFU-DL, especially for YouTube video clips when the potential caching gain is relatively low. The advantage of GDSF manifested in our analysis is, however, its outstanding cache space usage efficiency among the five studied caching algorithms.
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| 33. |
- Li, J., et al.
(författare)
-
Performance analysis of local caching replacement policies for internet video streaming services
- 2014
-
Ingår i: 2014 22nd International Conference on Software, Telecommunications and Computer Networks, SoftCOM 2014. - : IEEE conference proceedings. - 9789532900521 ; , s. 341-348
-
Konferensbidrag (refereegranskat)abstract
- In this work, the performance of 5 representative caching replacement policies was investigated and compared for caching Internet video-on-demand (VoD) in local access networks. Two measured traces of end-user requests were used in the analyses for two typical VoD services: TV-on-demand and user generated content represented by YouTube. The studied policies range from simple least recently used (LRU) and least frequently used (LFU) algorithms to more advanced ones denoted as LFU-dynamic lifespan (LFU-DL), Adaptive replacement cache (ARC) and Greedy-dual size frequency (GDSF). Our results show that the ARC policy always outperforms the other policies due to its adaptive nature and its ability to track changes in the traffic patterns. On the other hand, the simple LRU policy can also achieve a caching performance which is comparable to that of the more advanced ARC policy especially for the TV-on-demand service when the potential caching gain is high. On the contrary, the simple LFU policy always shows the poorest performance. However, by applying a proper lifespan supplement under the LFU-DL policy, the caching performance can be effectively enhanced to the level achievable using ARC and LRU policies. Moreover, the GDSF policy does not outperform simple LRU or LFU-DL, especially for YouTube video clips when the potential caching gain is relatively low. The advantage of GDSF manifested in our analysis is, however, its outstanding cache space usage efficiency among the five studied caching algorithms.
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| 34. |
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| 35. |
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| 36. |
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| 37. |
- Li, Qiang, et al.
(författare)
-
Direct numerical simulation of a turbulent boundary layer with passive scalar transport
- 2010
-
Ingår i: Direct and Large-Eddy Simulation 7. - Dordrecht : Springer Netherlands. ; , s. 321-327
-
Konferensbidrag (refereegranskat)abstract
- A fully-resolved direct numerical simulation (DNS) of a spatially developing turbulent boundary layer with passive scalars over a flat plate under zero pressure gradient (ZPG) has been carried out using a spectral method with about 40M grid points. The highest Reynolds number based on the momentum thickness and free-stream velocity is Re θ = 850 and the molecular Prandtl numbers for the scalars range from 0.2 to 2.0. The intermittent region near the boundary-layer edge was identified by investigating the high-order moments and PDF. In addition, it was found that the streamwise velocity is similar to the scalar distribution at Pr = 0. 71 with isoscalar wall boundary condition. Far away from the wall, the two quantities become less correlated.
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| 38. |
- Li, Qiang, et al.
(författare)
-
Simulations of heat transfer in a boundary layer subject to free-stream turbulence
- 2010
-
Ingår i: Journal of Turbulence. - : Informa UK Limited. - 1468-5248. ; 11:45, s. 1-33
-
Tidskriftsartikel (refereegranskat)abstract
- The present study investigates the effects of ambient free-stream turbulence (FST) on the momentum and heat transfer in a spatially developing, turbulent flat-plate boundary layer via large-eddy simulations using the ADM-RT model. Due to a local turbulence intensity Tu of 7% in the free stream, the skin-friction coefficient cf and Stanton number St are substantially elevated up to 25% and 32%, respectively, in the fully turbulent region (Reτ=300). This observation is in qualitative agreement with earlier experimental studies. Moreover, the Reynolds analogy factor is found to increase with the FST intensity Tu. The depression of both mean velocity and temperature profiles in the wake region due to FST is observed. In addition, the pre-multiplied spanwise spectra show that the outer peak residing in the logarithmic region in the case without FST is replaced by a new peak located near the boundary layer edge with a spanwise scale of about 3-4δ95. It is suggested that these large-scale events and their imprint throughout the boundary layer cause the elevation of both the skin friction and heat transfer on the solid surface.
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| 39. |
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| 40. |
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| 41. |
- Liu, Ching-Ti, et al.
(författare)
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Assessment of gene-by-sex interaction effect on bone mineral density
- 2012
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 1523-4681 .- 0884-0431. ; 27:10, s. 2051-2064
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Tidskriftsartikel (refereegranskat)abstract
- Sexual dimorphism in various bone phenotypes, including bone mineral density (BMD), is widely observed; however, the extent to which genes explain these sex differences is unclear. To identify variants with different effects by sex, we examined gene-by-sex autosomal interactions genome-wide, and performed expression quantitative trait loci (eQTL) analysis and bioinformatics network analysis. We conducted an autosomal genome-wide meta-analysis of gene-by-sex interaction on lumbar spine (LS) and femoral neck (FN) BMD in 25,353 individuals from 8 cohorts. In a second stage, we followed up the 12 top single-nucleotide polymorphisms (SNPs; p?
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| 42. |
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| 43. |
- O'Seaghdha, Conall M., et al.
(författare)
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Meta-Analysis of Genome-Wide Association Studies Identifies Six New Loci for Serum Calcium Concentrations
- 2013
-
Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 9:9, s. e1003796-
-
Tidskriftsartikel (refereegranskat)abstract
- Calcium is vital to the normal functioning of multiple organ systems and its serum concentration is tightly regulated. Apart from CASR, the genes associated with serum calcium are largely unknown. We conducted a genome-wide association meta-analysis of 39,400 individuals from 17 population-based cohorts and investigated the 14 most strongly associated loci in <= 21,679 additional individuals. Seven loci (six new regions) in association with serum calcium were identified and replicated. Rs1570669 near CYP24A1 (P = 9.1E-12), rs10491003 upstream of GATA3 (P = 4.8E-09) and rs7481584 in CARS (P = 1.2E-10) implicate regions involved in Mendelian calcemic disorders: Rs1550532 in DGKD (P = 8.2E-11), also associated with bone density, and rs7336933 near DGKH/KIAA0564 (P = 9.1E-10) are near genes that encode distinct isoforms of diacylglycerol kinase. Rs780094 is in GCKR. We characterized the expression of these genes in gut, kidney, and bone, and demonstrate modulation of gene expression in bone in response to dietary calcium in mice. Our results shed new light on the genetics of calcium homeostasis.
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| 44. |
- Perry, John R. B., et al.
(författare)
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Stratifying Type 2 Diabetes Cases by BMI Identifies Genetic Risk Variants in LAMA1 and Enrichment for Risk Variants in Lean Compared to Obese Cases
- 2012
-
Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 8:5
-
Tidskriftsartikel (refereegranskat)abstract
- Common diseases such as type 2 diabetes are phenotypically heterogeneous. Obesity is a major risk factor for type 2 diabetes, but patients vary appreciably in body mass index. We hypothesized that the genetic predisposition to the disease may be different in lean (BMI<25 Kg/m(2)) compared to obese cases (BMI >= 30 Kg/m(2)). We performed two case-control genome-wide studies using two accepted cut-offs for defining individuals as overweight or obese. We used 2,112 lean type 2 diabetes cases (BMI<25 kg/m(2)) or 4,123 obese cases (BMI >= 30 kg/m(2)), and 54,412 un-stratified controls. Replication was performed in 2,881 lean cases or 8,702 obese cases, and 18,957 un-stratified controls. To assess the effects of known signals, we tested the individual and combined effects of SNPs representing 36 type 2 diabetes loci. After combining data from discovery and replication datasets, we identified two signals not previously reported in Europeans. A variant (rs8090011) in the LAMA1 gene was associated with type 2 diabetes in lean cases (P = 8.4610 29, OR = 1.13 [95% CI 1.09-1.18]), and this association was stronger than that in obese cases (P = 0.04, OR = 1.03 [95% CI 1.00-1.06]). A variant in HMG20A-previously identified in South Asians but not Europeans-was associated with type 2 diabetes in obese cases (P = 1.3 x 10(-8), OR= 1.11 [95% CI 1.07-1.15]), although this association was not significantly stronger than that in lean cases (P = 0.02, OR = 1.09 [95% CI 1.02-1.17]). For 36 known type 2 diabetes loci, 29 had a larger odds ratio in the lean compared to obese (binomial P = 0.0002). In the lean analysis, we observed a weighted per-risk allele OR = 1.13 [95% CI 1.10-1.17], P = 3.2 x 10(-14). This was larger than the same model fitted in the obese analysis where the OR = 1.06 [95% CI 1.05-1.08], P = 2.2 x 10(-16). This study provides evidence that stratification of type 2 diabetes cases by BMI may help identify additional risk variants and that lean cases may have a stronger genetic predisposition to type 2 diabetes.
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| 45. |
- Qian, Jun, et al.
(författare)
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Fluorescence-surface enhanced Raman scattering co-functionalized gold nanorods as near-infrared probes for purely optical in vivo imaging
- 2011
-
Ingår i: Biomaterials. - : Elsevier BV. - 0142-9612 .- 1878-5905. ; 32:6, s. 1601-1610
-
Tidskriftsartikel (refereegranskat)abstract
- Gold nanorods (GNRs) have been widely used for bio-imaging. However, GNRs assisted optical in vivo deep tissue imaging is severely restricted due to signal attenuation, low contrast, complex process or low real-timing. To overcome these problems, we functionalized GNRs with both near-infrared (NIR) fluorescence and surface enhanced Raman scattering (SERS) and utilized these co-functionalized GNRs for purely optical in vivo imaging of live mice. Our proposed technology has the combined advantages of high real-timing, high imaging contrast and deep detection ability. The distribution and excretion of intravenously injected GNRs in deep tissues of live mice were observed in vivo for the first time through purely optical imaging. We also demonstrated successfully in vivo biomedical applications of the co-functionalized GNRs to sentinel lymph node (SLN) mapping and tumor targeting of mice. The present technology has great future potentials for disease diagnosis and clinical therapies.
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| 46. |
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| 47. |
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| 48. |
- Schlatter, Philipp, et al.
(författare)
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On the near-wall vortical structures at moderate Reynolds numbers
- 2014
-
Ingår i: European journal of mechanics. B, Fluids. - : Elsevier BV. - 0997-7546 .- 1873-7390. ; 48, s. 75-93
-
Tidskriftsartikel (refereegranskat)abstract
- A recent database from direct numerical simulation (DNS) of a turbulent boundary layer up to Re-theta = 4300 (Schlatter and Orlu, 2010) is analysed to extract the dominant flow structures in the near-wall region. In particular, the question of whether hairpin vortices are significant features of near-wall turbulence is addressed. A number of different methods based on the lambda(2) criterion (Jeong and Hussain, 1995) is used to extract turbulent coherent structures: three-dimensional flow visualisation with quantitative estimates of hairpin population, conditional averaging and planar hairpin vortex signatures (HVS). First, visualisations show that during the initial phase of laminar turbulent transition induced via tripping, hairpin vortices evolving from transitional A vortices are numerous and can be considered as the dominant structure of the immediate post-transition stage of the boundary layer. This is in agreement with previous experiments and low-Reynolds-number simulations such as Wu & Moin (2009). When the Reynolds number is increased, the fraction of hairpin vortices decreases to less than 2% for Re-theta > 4000. Second, conditional ensemble averages (Jeong et al., 1997) find hairpins close to the wall at low Reynolds number, while at a sufficient distance downstream from transition, the flow close to the wall is dominated by single quasi-streamwise vortices; even quantitatively, no major differences between boundary layer and channel can be detected. Moreover, three-dimensional visualisations of the neighbourhood of regions of strong swirling motion in planar cuts through the layer (the HVS) do not reveal hairpin vortices, thereby impairing statistical evidences based on HVS. The present results thus clearly confirm that transitional hairpin vortices do not persist in fully developed turbulent boundary layers, and that their dominant appearance as instantaneous flow structures in the outer boundary-layer region is very unlikely .
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| 49. |
- Schlatter, Philipp, et al.
(författare)
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On the vortical structures of a turbulent boundary layer at high Reynolds number
- 2011
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- A recent data base from direct numerical simulation of a turbulent boundary layer up to Reθ = 4300 [Schlatter & Örlü, J. Fluid Mech. 659, 2010] has been analysed in an effort to educe the dominant flow structures populating the near-wall region. In particular, the question of whether hairpin vortices are indeed observable as a dominant building block of near-wall turbulence is addressed. It is shown that during the initial phase, dominanted by the specific laminar-turbulent transition induced via the tripping mechanism, hairpin vortices are very numerous, and can certainly be considered as the dominant structure. This is in agreement with previous experiments and low Reynolds number simulations such as Wu & Moin [J. Fluid Mech. 630, 2009]. At sufficient distance from transition, the flow is dominated by a staggered array of quasi-streamwise vortices which is the same situation as in previous channel flows. It turns out that even quantitatively, no major differences between boundary layers and channels can be detected; structures are about 200 viscous units in length, and inclined by about 9 degrees [Jeong et al., J. Fluid Mech. 332, 1997]. The present results clearly show that the regeneration process of turbulence does not involve the generation of (symmetric) hairpin vortices, and that their dominant appearance as instantaneous flow structures in the outer boundary-layer region is at least very unlikely.
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| 50. |
- Schlatter, Philipp, et al.
(författare)
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Progress in simulations of turbulent boundary layers
- 2011
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Ingår i: Proc. 7th International Symposium on Turbulence and Shear Flow Phenomena.
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Konferensbidrag (refereegranskat)abstract
- Recent efforts in the simulation of turbulent boundary layers using direct and large-eddy simulations are described. The focus is naturally on a series of simulations performed at KTH Stockholm. These results have been used to examine various aspects of the boundary layer; starting from estimates of the extent of the transitional region, the detailed comparison to wind-tunnel experiments, the effect of ambient freestream turbulence on the boundary layer and to quantifications of the spectral composition of the turbulent signal. Furthermore, selected aspects of boundary layers with coupled scalar (e.g. heat) transport are summarised, including profiles of the turbulent Prandtl number.
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