| 1. |
- Jiang, X., et al.
(författare)
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Shared heritability and functional enrichment across six solid cancers
- 2019
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (r(g) = 0.57, p = 4.6 x 10(-8)), breast and ovarian cancer (r(g) = 0.24, p = 7 x 10(-5)), breast and lung cancer (r(g) = 0.18, p = 1.5 x 10(-6)) and breast and colorectal cancer (r(g) = 0.15, p = 1.1 x 10(-4)). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis.
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| 2. |
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| 4. |
- Ebersole, Charles R., et al.
(författare)
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Many Labs 5: Testing Pre-Data-Collection Peer Review as an Intervention to Increase Replicability
- 2020
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Ingår i: Advances in Methods and Practices in Psychological Science. - : Sage. - 2515-2467 .- 2515-2459. ; 3:3, s. 309-331
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Tidskriftsartikel (refereegranskat)abstract
- Replication studies in psychological science sometimes fail to reproduce prior findings. If these studies use methods that are unfaithful to the original study or ineffective in eliciting the phenomenon of interest, then a failure to replicate may be a failure of the protocol rather than a challenge to the original finding. Formal pre-data-collection peer review by experts may address shortcomings and increase replicability rates. We selected 10 replication studies from the Reproducibility Project: Psychology (RP:P; Open Science Collaboration, 2015) for which the original authors had expressed concerns about the replication designs before data collection; only one of these studies had yielded a statistically significant effect (p < .05). Commenters suggested that lack of adherence to expert review and low-powered tests were the reasons that most of these RP:P studies failed to replicate the original effects. We revised the replication protocols and received formal peer review prior to conducting new replication studies. We administered the RP:P and revised protocols in multiple laboratories (median number of laboratories per original study = 6.5, range = 3-9; median total sample = 1,279.5, range = 276-3,512) for high-powered tests of each original finding with both protocols. Overall, following the preregistered analysis plan, we found that the revised protocols produced effect sizes similar to those of the RP:P protocols (Delta r = .002 or .014, depending on analytic approach). The median effect size for the revised protocols (r = .05) was similar to that of the RP:P protocols (r = .04) and the original RP:P replications (r = .11), and smaller than that of the original studies (r = .37). Analysis of the cumulative evidence across the original studies and the corresponding three replication attempts provided very precise estimates of the 10 tested effects and indicated that their effect sizes (median r = .07, range = .00-.15) were 78% smaller, on average, than the original effect sizes (median r = .37, range = .19-.50).
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| 5. |
- ODonnell, Michael, et al.
(författare)
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Registered Replication Report: Dijksterhuis and van Knippenberg (1998)
- 2018
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Ingår i: Perspectives on Psychological Science. - : SAGE PUBLICATIONS LTD. - 1745-6916 .- 1745-6924. ; 13:2, s. 268-294
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Tidskriftsartikel (refereegranskat)abstract
- Dijksterhuis and van Knippenberg (1998) reported that participants primed with a category associated with intelligence (professor) subsequently performed 13% better on a trivia test than participants primed with a category associated with a lack of intelligence (soccer hooligans). In two unpublished replications of this study designed to verify the appropriate testing procedures, Dijksterhuis, van Knippenberg, and Holland observed a smaller difference between conditions (2%-3%) as well as a gender difference: Men showed the effect (9.3% and 7.6%), but women did not (0.3% and -0.3%). The procedure used in those replications served as the basis for this multilab Registered Replication Report. A total of 40 laboratories collected data for this project, and 23 of these laboratories met all inclusion criteria. Here we report the meta-analytic results for those 23 direct replications (total N = 4,493), which tested whether performance on a 30-item general-knowledge trivia task differed between these two priming conditions (results of supplementary analyses of the data from all 40 labs, N = 6,454, are also reported). We observed no overall difference in trivia performance between participants primed with the professor category and those primed with the hooligan category (0.14%) and no moderation by gender.
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| 6. |
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| 7. |
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| 8. |
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| 9. |
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| 10. |
- Huyghe, Jeroen R., et al.
(författare)
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Discovery of common and rare genetic risk variants for colorectal cancer
- 2019
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:1, s. 76-
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Tidskriftsartikel (refereegranskat)abstract
- To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.3% frequency variant signal at CHD1. In a combined meta-analysis of 125,478 individuals, we identified 40 new independent signals at P < 5 x 10(-8), bringing the number of known independent signals for CRC to similar to 100. New signals implicate lower-frequency variants, Kruppel-like factors, Hedgehog signaling, Hippo-YAP signaling, long noncoding RNAs and somatic drivers, and support a role for immune function. Heritability analyses suggest that CRC risk is highly polygenic, and larger, more comprehensive studies enabling rare variant analysis will improve understanding of biology underlying this risk and influence personalized screening strategies and drug development.
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| 11. |
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| 12. |
- Archambault, Alexi N., et al.
(författare)
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Cumulative Burden of Colorectal Cancer Associated Genetic Variants Is More Strongly Associated With Early-Onset vs Late-Onset Cancer
- 2020
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Ingår i: Gastroenterology. - : Elsevier BV. - 0016-5085 .- 1528-0012. ; 158:5, s. 1274-1286.e12
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: Early-onset colorectal cancer (CRC, in persons younger than 50 years old) is increasing in incidence; yet, in the absence of a family history of CRC, this population lacks harmonized recommendations for prevention. We aimed to determine whether a polygenic risk score (PRS) developed from 95 CRC-associated common genetic risk variants was associated with risk for early-onset CRC.METHODS: We studied risk for CRC associated with a weighted PRS in 12,197 participants younger than 50 years old vs 95,865 participants 50 years or older. PRS was calculated based on single nucleotide polymorphisms associated with CRC in a large-scale genome-wide association study as of January 2019. Participants were pooled from 3 large consortia that provided clinical and genotyping data: the Colon Cancer Family Registry, the Colorectal Transdisciplinary Study, and the Genetics and Epidemiology of Colorectal Cancer Consortium and were all of genetically defined European descent. Findings were replicated in an independent cohort of 72,573 participants.RESULTS: Overall associations with CRC per standard deviation of PRS were significant for early-onset cancer, and were stronger compared with late-onset cancer (P for interaction = .01); when we compared the highest PRS quartile with the lowest, risk increased 3.7-fold for early-onset CRC (95% CI 3.28-4.24) vs 2.9-fold for late-onset CRC (95% CI 2.80-3.04). This association was strongest for participants without a first-degree family history of CRC (P for interaction = 5.61 x 10(-5)). When we compared the highest with the lowest quartiles in this group, risk increased 4.3-fold for early-onset CRC (95% CI 3.61-5.01) vs 2.9-fold for late-onset CRC (95% CI 2.70-3.00). Sensitivity analyses were consistent with these findings.CONCLUSIONS: In an analysis of associations with CRC per standard deviation of PRS, we found the cumulative burden of CRC-associated common genetic variants to associate with early-onset cancer, and to be more strongly associated with early-onset than late-onset cancer, particularly in the absence of CRC family history. Analyses of PRS, along with environmental and lifestyle risk factors, might identify younger individuals who would benefit from preventive measures.
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| 13. |
- Berndt, Sonja, I, et al.
(författare)
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Distinct germline genetic susceptibility profiles identified for common non-Hodgkin lymphoma subtypes
- 2022
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Ingår i: Leukemia. - : Springer Nature. - 0887-6924 .- 1476-5551. ; 36:12, s. 2835-2844
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Tidskriftsartikel (refereegranskat)abstract
- Lymphoma risk is elevated for relatives with common non-Hodgkin lymphoma (NHL) subtypes, suggesting shared genetic susceptibility across subtypes. To evaluate the extent of mutual heritability among NHL subtypes and discover novel loci shared among subtypes, we analyzed data from eight genome-wide association studies within the InterLymph Consortium, including 10,629 cases and 9505 controls. We utilized Association analysis based on SubSETs (ASSET) to discover loci for subsets of NHL subtypes and evaluated shared heritability across the genome using Genome-wide Complex Trait Analysis (GCTA) and polygenic risk scores. We discovered 17 genome-wide significant loci (P < 5 × 10−8) for subsets of NHL subtypes, including a novel locus at 10q23.33 (HHEX) (P = 3.27 × 10−9). Most subset associations were driven primarily by only one subtype. Genome-wide genetic correlations between pairs of subtypes varied broadly from 0.20 to 0.86, suggesting substantial heterogeneity in the extent of shared heritability among subtypes. Polygenic risk score analyses of established loci for different lymphoid malignancies identified strong associations with some NHL subtypes (P < 5 × 10−8), but weak or null associations with others. Although our analyses suggest partially shared heritability and biological pathways, they reveal substantial heterogeneity among NHL subtypes with each having its own distinct germline genetic architecture.
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| 14. |
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| 15. |
- Chen, Zhishan, et al.
(författare)
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Fine-mapping analysis including over 254 000 East Asian and European descendants identifies 136 putative colorectal cancer susceptibility genes
- 2024
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have identified more than 200 common genetic variants independently associated with colorectal cancer (CRC) risk, but the causal variants and target genes are mostly unknown. We sought to fine-map all known CRC risk loci using GWAS data from 100,204 cases and 154,587 controls of East Asian and European ancestry. Our stepwise conditional analyses revealed 238 independent association signals of CRC risk, each with a set of credible causal variants (CCVs), of which 28 signals had a single CCV. Our cis-eQTL/mQTL and colocalization analyses using colorectal tissue-specific transcriptome and methylome data separately from 1299 and 321 individuals, along with functional genomic investigation, uncovered 136 putative CRC susceptibility genes, including 56 genes not previously reported. Analyses of single-cell RNA-seq data from colorectal tissues revealed 17 putative CRC susceptibility genes with distinct expression patterns in specific cell types. Analyses of whole exome sequencing data provided additional support for several target genes identified in this study as CRC susceptibility genes. Enrichment analyses of the 136 genes uncover pathways not previously linked to CRC risk. Our study substantially expanded association signals for CRC and provided additional insight into the biological mechanisms underlying CRC development.
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| 16. |
- Cozen, W., et al.
(författare)
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A meta-analysis of Hodgkin lymphoma reveals 19p13.3 TCF3 as a novel susceptibility locus
- 2014
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 5, s. 3856-
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Tidskriftsartikel (refereegranskat)abstract
- Recent genome-wide association studies (GWAS) of Hodgkin lymphoma (HL) have identified associations with genetic variation at both HLA and non-HLA loci; however, much of heritable HL susceptibility remains unexplained. Here we perform a meta-analysis of three HL GWAS totaling 1,816 cases and 7,877 controls followed by replication in an independent set of 1,281 cases and 3,218 controls to find novel risk loci. We identify a novel variant at 19p13.3 associated with HL (rs1860661; odds ratio (OR) = 0.81, 95% confidence interval (95% CI) = 0.76-0.86, P-combined 3.5 x 10(-10)), located in intron 2 of TCF3 (also known as E2A), a regulator of B-and T-cell lineage commitment known to be involved in HL pathogenesis. This meta-analysis also notes associations between previously published loci at 2p16, 5q31, 6p31, 8q24 and 10p14 and HL subtypes. We conclude that our data suggest a link between the 19p13.3 locus, including TCF3, and HL risk.
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| 17. |
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| 18. |
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| 19. |
- Newcomer, J. W., et al.
(författare)
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A 24-week, multicenter, open-label, randomized study to compare changes in glucose metabolism in patients with schizophrenia receiving treatment with olanzapine, quetiapine, or risperidone
- 2009
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Ingår i: J Clin Psychiatry. - 1555-2101 .- 1555-2101 .- 0160-6689. ; 70:4, s. 487-99
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: This randomized, 24-week, flexible-dose study compared changes in glucose metabolism in patients with DSM-IV schizophrenia receiving initial exposure to olanzapine, quetiapine, or risperidone. METHOD: The hypothesized primary endpoint was change (baseline to week 24) in area under the curve (AUC) 0- to 2-hour plasma glucose values during an oral glucose tolerance test (OGTT); primary analysis: olanzapine versus quetiapine. Secondary endpoints included mean change in AUC 0- to 2-hour plasma insulin values, insulin sensitivity index, and fasting lipids. The first patient enrolled on April 29, 2004, and the last patient completed the study on October 24, 2005. RESULTS: Mean weight change (kg) over 24 weeks was +3.7 (quetiapine), +4.6 (olanzapine), and +3.6 (risperidone). Based on data from 395 patients (quetiapine, N = 115 [mean dose = 607.0 mg/day], olanzapine, N = 146 [mean dose = 15.2 mg/day], and risperidone, N = 134 [mean dose = 5.2 mg/day]), mean change in AUC 0- to 2-hour glucose value (mg/dL x h) at week 24 was significantly lower for quetiapine versus olanzapine (t = 1.98, df = 377, p = .048). Increases in AUC 0- to 2-hour glucose values were statistically significant with olanzapine (+21.9 mg/dL x h, 95% CI = 11.5 to 32.4 mg/dL x h) and risperidone (+18.8 mg/dL x h, 95% CI = 8.1 to 29.4 mg/dL x h), but not quetiapine (+9.1 mg/dL x h, 95% CI = -2.3 to 20.5 mg/dL x h). AUC 0- to 2-hour insulin values increased statistically significantly with olanzapine (+24.5%, 95% CI = 11.5% to 39.0%), but not with quetiapine or risperidone. Reductions in insulin sensitivity index were statistically significant with olanzapine (-19.1%, 95% CI = -27.9% to -9.3%) and risperidone (-15.8%, 95% CI = -25.1% to -5.4%), but not quetiapine. Total cholesterol and low-density lipoprotein levels increased statistically significantly with olanzapine (+21.1 mg/dL, 95% CI = 13.0 to 29.2 mg/dL, and +20.5 mg/dL, 95% CI = 13.8 to 27.1 mg/dL, respectively) and quetiapine (+13.1 mg/dL, 95% CI = 4.3 to 21.9 mg/dL, and +13.3 mg/dL, 95% CI = 6.1 to 20.5 mg/dL, respectively), but not risperidone. Statistically significant increases in triglycerides (+30.9 mg/dL, 95% CI = 10.9 to 51.0 mg/dL), total cholesterol/high-density lipoprotein (HDL) ratio (0.5, 95% CI = 0.2 to 0.8), and triglyceride/HDL ratio (0.3, 95% CI = 0.0 to 0.6) were observed with olanzapine only. CONCLUSION: The results indicate a significant difference in the change in glucose tolerance during 6 months' treatment with olanzapine versus quetiapine, with significant reductions on olanzapine and risperidone, but not quetiapine; these differential changes were largely explained by changes in insulin sensitivity. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00214578.
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| 20. |
- Schmit, Stephanie L, et al.
(författare)
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Novel Common Genetic Susceptibility Loci for Colorectal Cancer.
- 2019
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 111:2, s. 146-157
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Tidskriftsartikel (refereegranskat)abstract
- Background: Previous genome-wide association studies (GWAS) have identified 42 loci (P < 5 × 10-8) associated with risk of colorectal cancer (CRC). Expanded consortium efforts facilitating the discovery of additional susceptibility loci may capture unexplained familial risk.Methods: We conducted a GWAS in European descent CRC cases and control subjects using a discovery-replication design, followed by examination of novel findings in a multiethnic sample (cumulative n = 163 315). In the discovery stage (36 948 case subjects/30 864 control subjects), we identified genetic variants with a minor allele frequency of 1% or greater associated with risk of CRC using logistic regression followed by a fixed-effects inverse variance weighted meta-analysis. All novel independent variants reaching genome-wide statistical significance (two-sided P < 5 × 10-8) were tested for replication in separate European ancestry samples (12 952 case subjects/48 383 control subjects). Next, we examined the generalizability of discovered variants in East Asians, African Americans, and Hispanics (12 085 case subjects/22 083 control subjects). Finally, we examined the contributions of novel risk variants to familial relative risk and examined the prediction capabilities of a polygenic risk score. All statistical tests were two-sided.Results: The discovery GWAS identified 11 variants associated with CRC at P < 5 × 10-8, of which nine (at 4q22.2/5p15.33/5p13.1/6p21.31/6p12.1/10q11.23/12q24.21/16q24.1/20q13.13) independently replicated at a P value of less than .05. Multiethnic follow-up supported the generalizability of discovery findings. These results demonstrated a 14.7% increase in familial relative risk explained by common risk alleles from 10.3% (95% confidence interval [CI] = 7.9% to 13.7%; known variants) to 11.9% (95% CI = 9.2% to 15.5%; known and novel variants). A polygenic risk score identified 4.3% of the population at an odds ratio for developing CRC of at least 2.0.Conclusions: This study provides insight into the architecture of common genetic variation contributing to CRC etiology and improves risk prediction for individualized screening.
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| 27. |
- Pfeiffer, Thomas, et al.
(författare)
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Predicting the replicability of social and behavioural science claims in a crisis: The COVID-19 Preprint Replication Project
- 2023
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Replications are important for assessing the reliability of published findings. However, they are costly, and it is infeasible to replicate everything. Accurate, fast, lower-cost alternatives such as eliciting predictions could accelerate assessment for rapid policy implementation in a crisis. We elicited judgments from participants on 100 claims from preprints about an emerging area of research (COVID-19 pandemic) using an interactive structured elicitation protocol, and we conducted 29 new high-powered replications. After interacting with their peers, participant groups with lower task expertise (‘beginners’) updated their estimates and confidence in their judgements significantly more than groups with greater task expertise (‘experienced’). For experienced individuals, the average accuracy was 0.57 (95% CI: [0.53, 0.61]) after interaction, and they correctly classified 61% of claims; beginners’ average accuracy was 0.58 (95% CI: [0.54, 0.62]), correctly classifying 69% of claims. The difference in accuracy between groups was not statistically significant, and their judgments on the full set of claims were correlated (r=.48). These results suggest that both beginners and more experienced participants using a structured process have some ability to make better-than-chance predictions about the reliability of ‘fast science’ under conditions of high uncertainty. However, given the importance of such assessments for making evidence-based critical decisions in a crisis, more research is required to understand who the right experts in forecasting replicability are and how their judgements ought to be elicited.
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| 28. |
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| 29. |
- Sharapov, S.E., et al.
(författare)
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Energetic particle instabilities in fusion plasmas
- 2013
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 53:10, s. 104022-
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Tidskriftsartikel (refereegranskat)abstract
- Remarkable progress has been made in diagnosing energetic particle instabilities on present-day machines and in establishing a theoretical framework for describing them. This overview describes the much improved diagnostics of Alfvén instabilities and modelling tools developed world-wide, and discusses progress in interpreting the observed phenomena. A multi-machine comparison is presented giving information on the performance of both diagnostics and modelling tools for different plasma conditions outlining expectations for ITER based on our present knowledge.
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| 30. |
- Woitowich, N. C., et al.
(författare)
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Structural basis for light control of cell development revealed by crystal structures of a myxobacterial phytochrome
- 2018
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Ingår i: Iucrj. - : International Union of Crystallography (IUCr). - 2052-2525. ; 5:Part 5, s. 619-634
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Tidskriftsartikel (refereegranskat)abstract
- Phytochromes are red-light photoreceptors that were first characterized in plants, with homologs in photosynthetic and non-photosynthetic bacteria known as bacteriophytochromes (BphPs). Upon absorption of light, BphPs interconvert between two states denoted Pr and Pfr with distinct absorption spectra in the red and far-red. They have recently been engineered as enzymatic photoswitches for fluorescent-marker applications in non-invasive tissue imaging of mammals. This article presents cryo- and room-temperature crystal structures of the unusual phytochrome from the non-photosynthetic myxobacterium Stigmatella aurantiaca (SaBphP1) and reveals its role in the fruitingbody formation of this photomorphogenic bacterium. SaBphP1 lacks a conserved histidine (His) in the chromophore-binding domain that stabilizes the Pr state in the classical BphPs. Instead it contains a threonine (Thr), a feature that is restricted to several myxobacterial phytochromes and is not evolutionarily understood. SaBphP1 structures of the chromophore binding domain (CBD) and the complete photosensory core module (PCM) in wild-type and Thr-to-His mutant forms reveal details of the molecular mechanism of the Pr/Pfr transition associated with the physiological response of this myxobacterium to red light. Specifically, key structural differences in the CBD and PCM between the wild-type and the Thr-to-His mutant involve essential chromophore contacts with proximal amino acids, and point to how the photosignal is transduced through the rest of the protein, impacting the essential enzymatic activity in the photomorphogenic response of this myxobacterium.
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| 31. |
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| 32. |
- Berg, Staffan, et al.
(författare)
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Considerations in the developability of peptides for oral administration when formulated together with transient permeation enhancers
- 2022
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Ingår i: International Journal of Pharmaceutics. - : Elsevier. - 0378-5173 .- 1873-3476. ; 628
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Tidskriftsartikel (refereegranskat)abstract
- This paper reviews many of the properties of a peptide that need to be considered prior to development as an oral dosage form when co-formulated with a permeation enhancer to improve oral bioavailability, including the importance and implications of peptide half-life on variability in pharmacokinetic profiles. Clinical consider-ations in terms of food and drug-drug interactions are also discussed. The paper further gives a brief overview how permeation enhancers overcome barriers that limit oral absorption of peptides and thereby improve their oral bioavailability, albeit bioavailabilities are still low single digit and variability is high.
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| 33. |
- Bertl, Kristina, et al.
(författare)
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Bacterial colonization of a power-driven water flosser during regular use : A proof-of-principle study
- 2021
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Ingår i: Clinical and Experimental Dental Research. - : John Wiley & Sons. - 2057-4347. ; 7:5, s. 656-663
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The present proof-of-principle study assessed whether daily use of a power-driven water flosser (Sonicare AirFloss; SAF) leads to bacterial colonization in the nozzle and/or the device, resulting in contaminated water-jet.MATERIAL AND METHODS: In five participants, saliva samples at baseline and water-jet samples of devices used daily with bottled water for 3 weeks (test) were collected. Additionally, water-jet samples from devices used daily with bottled water extra-orally for 3 weeks (positive control) and from brand new devices (negative control), as well as samples from newly opened and 1- and 3-week opened water bottles were collected. Colony forming units (CFU) were recorded after 48 h culturing and 20 oral pathogens were assessed by polymerase chain reaction-based analysis.RESULTS: Distinct inter-individual differences regarding the number of detected bacteria were observed; water-jet samples of test devices included both aerobic and anaerobic bacterial species, with some similarities to the saliva sample of the user. Water-jet samples from positive control devices showed limited number of aerobic and anaerobic bacterial species, while the samples from negative control devices did not show any bacterial species. Very few aerobic bacteria were detected only in the 3-week-old bottled water samples, while samples of newly and 1-week opened water bottles did not show any bacterial growth.CONCLUSIONS: The present proof-of-principle study showed that daily use of a power-driven water flosser for 3 weeks resulted in bacterial colonization in the nozzle and/or device with both aerobic and anaerobic, not only oral, species, that are transmitted via the water-jet.
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| 34. |
- Borin, L., et al.
(författare)
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Språkbanken 2018 : Research resources for text, speech, & society
- 2018
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Ingår i: CEUR Workshop Proceedings. - : CEUR-WS. ; , s. 504-506
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Konferensbidrag (refereegranskat)abstract
- We introduce an expanded version of the Swedish research resource Språkbanken (the Swedish Language Bank). In 2018, Språkbanken, which has supported national and international research for over four decades, adds two branches, one focusing on speech and one on societal aspects of language, to its existing organization, which targets text.
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| 35. |
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| 36. |
- Båth, Petra, 1988, et al.
(författare)
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Lipidic cubic phase serial femtosecond crystallography structure of a photosynthetic reaction centre
- 2022
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Ingår i: Acta Crystallographica Section D-Structural Biology. - : International Union of Crystallography (IUCr). - 2059-7983. ; 78, s. 698-708
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Tidskriftsartikel (refereegranskat)abstract
- Serial crystallography is a rapidly growing method that can yield structural insights from microcrystals that were previously considered to be too small to be useful in conventional X-ray crystallography. Here, conditions for growing microcrystals of the photosynthetic reaction centre of Blastochloris viridis within a lipidic cubic phase (LCP) crystallization matrix that employ a seeding protocol utilizing detergent-grown crystals with a different crystal packing are described. LCP microcrystals diffracted to 2.25 angstrom resolution when exposed to XFEL radiation, which is an improvement of 0.15 angstrom over previous microcrystal forms. Ubiquinone was incorporated into the LCP crystallization media and the resulting electron density within the mobile Q(B) pocket is comparable to that of other cofactors within the structure. As such, LCP microcrystallization conditions will facilitate time-resolved diffraction studies of electron-transfer reactions to the mobile quinone, potentially allowing the observation of structural changes associated with the two electron-transfer reactions leading to complete reduction of the ubiquinone ligand.
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| 37. |
- Chriett, S., et al.
(författare)
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SCRT1 is a novel beta cell transcription factor with insulin regulatory properties
- 2021
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Ingår i: Molecular and Cellular Endocrinology. - : Elsevier BV. - 0303-7207 .- 1872-8057. ; 521
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Tidskriftsartikel (refereegranskat)abstract
- Here we show that scratch family transcriptional repressor 1 (SCRT1), a zinc finger transcriptional regulator, is a novel regulator of beta cell function. SCRT1 was found to be expressed in beta cells in rodent and human islets. In human islets, expression of SCRT1 correlated with insulin secretion capacity and the expression of the insulin (INS) gene. Furthermore, SCRT1 mRNA expression was lower in beta cells from T2D patients. siRNA-mediated Scrt1 silencing in INS-1832/13 cells, mouse- and human islets resulted in impaired glucose-stimulated insulin secretion and decreased expression of the insulin gene. This is most likely due to binding of SCRT1 to E-boxes of the Ins1 gene as shown with ChIP. Scrt1 silencing also reduced the expression of several key beta cell transcription factors. Moreover, Scrt1 mRNA expression was reduced by glucose and SCRT1 protein was found to translocate between the nucleus and the cytosol in a glucose-dependent fashion in INS-1832/13 cells as well as in a rodent model of T2D. SCRT1 was also regulated by a GSK3β-dependent SCRT1-serine phosphorylation. Taken together, SCRT1 is a novel beta cell transcription factor that regulates insulin secretion and is affected in T2D.
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| 38. |
- Clark, Leigh, et al.
(författare)
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Mapping Theoretical and Methodological Perspectives for Understanding Speech Interface Interactions
- 2019
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Ingår i: CHI EA '19 EXTENDED ABSTRACTS. - New York, NY, USA : ASSOC COMPUTING MACHINERY.
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Konferensbidrag (refereegranskat)abstract
- The use of speech as an interaction modality has grown considerably through the integration of Intelligent Personal Assistants (IPAs- e.g. Siri, Google Assistant) into smartphones and voice based devices (e.g. Amazon Echo). However, there remain significant gaps in using theoretical frameworks to understand user behaviours and choices and how they may applied to specific speech interface interactions. This part-day multidisciplinary workshop aims to critically map out and evaluate theoretical frameworks and methodological approaches across a number of disciplines and establish directions for new paradigms in understanding speech interface user behaviour. In doing so, we will bring together participants from HCI and other speech related domains to establish a cohesive, diverse and collaborative community of researchers from academia and industry with interest in exploring theoretical and methodological issues in the field.
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| 39. |
- Clark, Leigh, et al.
(författare)
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The State of Speech in HCI : Trends, Themes and Challenges
- 2019
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Ingår i: Interacting with computers. - : Oxford University Press. - 0953-5438 .- 1873-7951. ; 31:4, s. 349-371
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Tidskriftsartikel (refereegranskat)abstract
- Speech interfaces are growing in popularity. Through a review of 99 research papers this work maps the trends, themes, findings and methods of empirical research on speech interfaces in the field of human-computer interaction (HCI). We find that studies are usability/theory-focused or explore wider system experiences, evaluating Wizard of Oz, prototypes or developed systems. Measuring task and interaction was common, as was using self-report questionnaires to measure concepts like usability and user attitudes. A thematic analysis of the research found that speech HCI work focuses on nine key topics: system speech production, design insight, modality comparison, experiences with interactive voice response systems, assistive technology and accessibility, user speech production, using speech technology for development, peoples' experiences with intelligent personal assistants and how user memory affects speech interface interaction. From these insights we identify gaps and challenges in speech research, notably taking into account technological advancements, the need to develop theories of speech interface interaction, grow critical mass in this domain, increase design work and expand research from single to multiple user interaction contexts so as to reflect current use contexts. We also highlight the need to improve measure reliability, validity and consistency, in the wild deployment and reduce barriers to building fully functional speech interfaces for research.
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| 40. |
- Crabtree, Judy S, et al.
(författare)
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Of mice and MEN1 : Insulinomas in a conditional mouse knockout.
- 2003
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Ingår i: Molecular and Cellular Biology. - 0270-7306 .- 1098-5549. ; 23:17, s. 6075-6085
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Tidskriftsartikel (refereegranskat)abstract
- Patients with multiple endocrine neoplasia type 1 (MEN1) develop multiple endocrine tumors, primarily affecting the parathyroid, pituitary, and endocrine pancreas, due to the inactivation of the MEN1 gene. A conditional mouse model was developed to evaluate the loss of the mouse homolog, Men1, in the pancreatic beta cell. Men1 in these mice contains exons 3 to 8 flanked by loxP sites, such that, when the mice are crossed to transgenic mice expressing cre from the rat insulin promoter (RIP-cre), exons 3 to 8 are deleted in beta cells. By 60 weeks of age, >80% of mice homozygous for the floxed Men1 gene and expressing RIP-cre develop multiple pancreatic islet adenomas. The formation of adenomas results in elevated serum insulin levels and decreased blood glucose levels. The delay in tumor appearance, even with early loss of both copies of Men1, implies that additional somatic events are required for adenoma formation in beta cells. Comparative genomic hybridization of beta cell tumor DNA from these mice reveals duplication of chromosome 11, potentially revealing regions of interest with respect to tumorigenesis.
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| 41. |
- Dalmas, T., et al.
(författare)
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Introduction
- 2014
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Ingår i: Proceedings 2014 Workshop on Dialogue in Motion, DM 2014. - : Association for Computational Linguistics (ACL).
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Konferensbidrag (refereegranskat)
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| 42. |
- Edlund, Christoffer, et al.
(författare)
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LIVECell : a large-scale dataset for label-free live cell segmentation
- 2021
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Ingår i: Nature Methods. - : Nature Publishing Group. - 1548-7091 .- 1548-7105. ; 18:9, s. 1038-1045
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Light microscopy combined with well-established protocols of two-dimensional cell culture facilitates high-throughput quantitative imaging to study biological phenomena. Accurate segmentation of individual cells in images enables exploration of complex biological questions, but can require sophisticated imaging processing pipelines in cases of low contrast and high object density. Deep learning-based methods are considered state-of-the-art for image segmentation but typically require vast amounts of annotated data, for which there is no suitable resource available in the field of label-free cellular imaging. Here, we present LIVECell, a large, high-quality, manually annotated and expert-validated dataset of phase-contrast images, consisting of over 1.6 million cells from a diverse set of cell morphologies and culture densities. To further demonstrate its use, we train convolutional neural network-based models using LIVECell and evaluate model segmentation accuracy with a proposed a suite of benchmarks.
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| 43. |
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| 44. |
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| 45. |
- Edlund, Petra, et al.
(författare)
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The room temperature crystal structure of a bacterial phytochrome determined by serial femtosecond crystallography
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Phytochromes are a family of photoreceptors that control light responses of plants, fungi and bacteria. A sequence of structural changes, which is not yet fully understood, leads to activation of an output domain. Time-resolved serial femtosecond crystallography (SFX) can potentially shine light on these conformational changes. Here we report the room temperature crystal structure of the chromophore-binding domains of the Deinococcus radiodurans phytochrome at 2.1 angstrom resolution. The structure was obtained by serial femtosecond X-ray crystallography from microcrystals at an X-ray free electron laser. We find overall good agreement compared to a crystal structure at 1.35 angstrom resolution derived from conventional crystallography at cryogenic temperatures, which we also report here. The thioether linkage between chromophore and protein is subject to positional ambiguity at the synchrotron, but is fully resolved with SFX. The study paves the way for time-resolved structural investigations of the phytochrome photocycle with time-resolved SFX.
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| 46. |
- Edlund, R, et al.
(författare)
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Cone-Beam CT in diagnosis of scaphoid fractures
- 2016
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Ingår i: Skeletal radiology. - : Springer Science and Business Media LLC. - 1432-2161 .- 0364-2348. ; 45:2, s. 197-204
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Tidskriftsartikel (refereegranskat)
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| 47. |
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| 48. |
- Ekström, Axel G., et al.
(författare)
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Chimpanzee utterances refute purported missing links for novel vocalizations and syllabic speech
- 2024
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Nonhuman great apes have been claimed to be unable to learn human words due to a lack of the necessary neural circuitry. We recovered original footage of two enculturated chimpanzees uttering the word “mama” and subjected recordings to phonetic analysis. Our analyses demonstrate that chimpanzees are capable of syllabic production, achieving consonant-to-vowel phonetic contrasts via the simultaneous recruitment and coupling of voice, jaw and lips. In an online experiment, human listeners naive to the recordings’ origins reliably perceived chimpanzee utterances as syllabic utterances, primarily as “ma-ma”, among foil syllables. Our findings demonstrate that in the absence of direct data-driven examination, great ape vocal production capacities have been underestimated. Chimpanzees possess the neural building blocks necessary for speech.
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| 49. |
- Ekström, Axel G., et al.
(författare)
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Gibbon vowel-like quality is tied to superhuman articulator landmarks
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Understanding the production of vowel-like sounds by nonhuman primates requires bridging the gap between animal calls and human speech. In particular, it has been argued that call behaviors whose acoustic properties seemingly overlap with human vowels reflect disparate production mechanisms. However, there are no as of yet agreed-upon methods for the study of primate articulation. We explore the potential of video content analysis for illuminating the production of primate vowel‒like qualities and provide evidence bearing on primate articulation using an audiovisual corpus (N=29 videos) of gibbon (Hylobatidae) call behavior, sourced from online video sites. Videos were coded for apparent jaw height, lip rounding, visible tongue movements, and visible inflation of species’ throat sacs (for Symphalangus Syndactylus), and the audible vowel‒like or diphthong‒like quality of the call. Results illustrate that the vowel-like quality of gibbon calls is tightly connected to degrees of jaw height and lip rounding. For “diphthong‒like” vocalizations, articulator trajectories effectively constitute movements between the same two extremes: high jaw-rounded lips, and low jaw-flared oral cavity. Animals’ tongues were often visible but never observed moving to systematically affect the vowel-like quality of the call (though several instances of possible tongue retraction were noted). The study adds to available methods for the study of articulation by nonhuman primates.
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| 50. |
- Ekström, Axel G., et al.
(författare)
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No neural “missing link” for verbal control in chimpanzees
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Nonhuman great apes have been claimed to be unable to learn human words due to a lack of the necessary neural circuitry. We recovered original footage of two enculturated chimpanzees uttering the word “mama” and subjected recordings to phonetic analysis. Our analyses demonstrate that chimpanzees are capable of syllabic production, achieving consonant-to-vowel phonetic contrasts via the simultaneous recruitment and coupling of voice, jaw and lips. In an online experiment, human listeners naive to the recordings’ origins reliably perceived chimpanzee utterances as syllabic utterances, primarily as “ma-ma”, among foil syllables. Our findings demonstrate that in the absence of direct data-driven examination, great ape vocal production capacities have been underestimated. Chimpanzees possess the neural building blocks necessary for speech.
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