| 1. |
|
|
| 2. |
|
|
| 3. |
- Zaborowski, AM, et al.
(författare)
-
Microsatellite instability in young patients with rectal cancer: molecular findings and treatment response
- 2022
-
Ingår i: The British journal of surgery. - : Oxford University Press (OUP). - 1365-2168 .- 0007-1323. ; 109:3, s. 251-255
-
Tidskriftsartikel (refereegranskat)abstract
- In this study of 400 patients with early-onset rectal cancer, 12.5 per cent demonstrated microsatellite instability (MSI). MSI was associated with a reduced likelihood of nodal positivity, an increased rate of pathological complete response, and improved disease-specific survival.
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
- Dareng, EO, et al.
(författare)
-
Polygenic risk modeling for prediction of epithelial ovarian cancer risk
- 2022
-
Ingår i: European journal of human genetics : EJHG. - : Springer Science and Business Media LLC. - 1476-5438 .- 1018-4813. ; 30:3, s. 349-362
-
Tidskriftsartikel (refereegranskat)abstract
- Polygenic risk scores (PRS) for epithelial ovarian cancer (EOC) have the potential to improve risk stratification. Joint estimation of Single Nucleotide Polymorphism (SNP) effects in models could improve predictive performance over standard approaches of PRS construction. Here, we implemented computationally efficient, penalized, logistic regression models (lasso, elastic net, stepwise) to individual level genotype data and a Bayesian framework with continuous shrinkage, “select and shrink for summary statistics” (S4), to summary level data for epithelial non-mucinous ovarian cancer risk prediction. We developed the models in a dataset consisting of 23,564 non-mucinous EOC cases and 40,138 controls participating in the Ovarian Cancer Association Consortium (OCAC) and validated the best models in three populations of different ancestries: prospective data from 198,101 women of European ancestries; 7,669 women of East Asian ancestries; 1,072 women of African ancestries, and in 18,915 BRCA1 and 12,337 BRCA2 pathogenic variant carriers of European ancestries. In the external validation data, the model with the strongest association for non-mucinous EOC risk derived from the OCAC model development data was the S4 model (27,240 SNPs) with odds ratios (OR) of 1.38 (95% CI: 1.28–1.48, AUC: 0.588) per unit standard deviation, in women of European ancestries; 1.14 (95% CI: 1.08–1.19, AUC: 0.538) in women of East Asian ancestries; 1.38 (95% CI: 1.21–1.58, AUC: 0.593) in women of African ancestries; hazard ratios of 1.36 (95% CI: 1.29–1.43, AUC: 0.592) in BRCA1 pathogenic variant carriers and 1.49 (95% CI: 1.35–1.64, AUC: 0.624) in BRCA2 pathogenic variant carriers. Incorporation of the S4 PRS in risk prediction models for ovarian cancer may have clinical utility in ovarian cancer prevention programs.
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
|
|
| 11. |
- Coignard, J, et al.
(författare)
-
A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers
- 2021
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 1078-
-
Tidskriftsartikel (refereegranskat)abstract
- Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10−8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers.
|
|
| 12. |
- Klonoff, D. C., et al.
(författare)
-
A Glycemia Risk Index (GRI) of Hypoglycemia and Hyperglycemia for Continuous Glucose Monitoring Validated by Clinician Ratings
- 2022
-
Ingår i: Journal of Diabetes Science and Technology. - : SAGE Publications. - 1932-2968.
-
Tidskriftsartikel (refereegranskat)abstract
- Background: A composite metric for the quality of glycemia from continuous glucose monitor (CGM) tracings could be useful for assisting with basic clinical interpretation of CGM data. Methods: We assembled a data set of 14-day CGM tracings from 225 insulin-treated adults with diabetes. Using a balanced incomplete block design, 330 clinicians who were highly experienced with CGM analysis and interpretation ranked the CGM tracings from best to worst quality of glycemia. We used principal component analysis and multiple regressions to develop a model to predict the clinician ranking based on seven standard metrics in an Ambulatory Glucose Profile: very low–glucose and low-glucose hypoglycemia; very high–glucose and high-glucose hyperglycemia; time in range; mean glucose; and coefficient of variation. Results: The analysis showed that clinician rankings depend on two components, one related to hypoglycemia that gives more weight to very low-glucose than to low-glucose and the other related to hyperglycemia that likewise gives greater weight to very high-glucose than to high-glucose. These two components should be calculated and displayed separately, but they can also be combined into a single Glycemia Risk Index (GRI) that corresponds closely to the clinician rankings of the overall quality of glycemia (r = 0.95). The GRI can be displayed graphically on a GRI Grid with the hypoglycemia component on the horizontal axis and the hyperglycemia component on the vertical axis. Diagonal lines divide the graph into five zones (quintiles) corresponding to the best (0th to 20th percentile) to worst (81st to 100th percentile) overall quality of glycemia. The GRI Grid enables users to track sequential changes within an individual over time and compare groups of individuals. Conclusion: The GRI is a single-number summary of the quality of glycemia. Its hypoglycemia and hyperglycemia components provide actionable scores and a graphical display (the GRI Grid) that can be used by clinicians and researchers to determine the glycemic effects of prescribed and investigational treatments.
|
|
| 13. |
|
|
| 14. |
|
|
| 15. |
|
|
| 16. |
|
|
| 17. |
- Mueller, Stefanie H., et al.
(författare)
-
Aggregation tests identify new gene associations with breast cancer in populations with diverse ancestry
- 2023
-
Ingår i: Genome Medicine. - : BioMed Central (BMC). - 1756-994X. ; 15
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Low-frequency variants play an important role in breast cancer (BC) susceptibility. Gene-based methods can increase power by combining multiple variants in the same gene and help identify target genes.Methods: We evaluated the potential of gene-based aggregation in the Breast Cancer Association Consortium cohorts including 83,471 cases and 59,199 controls. Low-frequency variants were aggregated for individual genes' coding and regulatory regions. Association results in European ancestry samples were compared to single-marker association results in the same cohort. Gene-based associations were also combined in meta-analysis across individuals with European, Asian, African, and Latin American and Hispanic ancestry.Results: In European ancestry samples, 14 genes were significantly associated (q < 0.05) with BC. Of those, two genes, FMNL3 (P = 6.11 x 10(-6)) and AC058822.1 (P = 1.47 x 10(-4)), represent new associations. High FMNL3 expression has previously been linked to poor prognosis in several other cancers. Meta-analysis of samples with diverse ancestry discovered further associations including established candidate genes ESR1 and CBLB. Furthermore, literature review and database query found further support for a biologically plausible link with cancer for genes CBLB, FMNL3, FGFR2, LSP1, MAP3K1, and SRGAP2C.Conclusions: Using extended gene-based aggregation tests including coding and regulatory variation, we report identification of plausible target genes for previously identified single-marker associations with BC as well as the discovery of novel genes implicated in BC development. Including multi ancestral cohorts in this study enabled the identification of otherwise missed disease associations as ESR1 (P = 1.31 x 10(-5)), demonstrating the importance of diversifying study cohorts.
|
|
| 18. |
- Dixon-Suen, Suzanne C, et al.
(författare)
-
Physical activity, sedentary time and breast cancer risk : a Mendelian randomisation study
- 2022
-
Ingår i: British Journal of Sports Medicine. - : BMJ Publishing Group Ltd. - 0306-3674 .- 1473-0480. ; 56:20, s. 1157-1170
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Physical inactivity and sedentary behaviour are associated with higher breast cancer risk in observational studies, but ascribing causality is difficult. Mendelian randomisation (MR) assesses causality by simulating randomised trial groups using genotype. We assessed whether lifelong physical activity or sedentary time, assessed using genotype, may be causally associated with breast cancer risk overall, pre/post-menopause, and by case-groups defined by tumour characteristics.METHODS: We performed two-sample inverse-variance-weighted MR using individual-level Breast Cancer Association Consortium case-control data from 130 957 European-ancestry women (69 838 invasive cases), and published UK Biobank data (n=91 105-377 234). Genetic instruments were single nucleotide polymorphisms (SNPs) associated in UK Biobank with wrist-worn accelerometer-measured overall physical activity (nsnps=5) or sedentary time (nsnps=6), or accelerometer-measured (nsnps=1) or self-reported (nsnps=5) vigorous physical activity.RESULTS: Greater genetically-predicted overall activity was associated with lower breast cancer overall risk (OR=0.59; 95% confidence interval (CI) 0.42 to 0.83 per-standard deviation (SD;~8 milligravities acceleration)) and for most case-groups. Genetically-predicted vigorous activity was associated with lower risk of pre/perimenopausal breast cancer (OR=0.62; 95% CI 0.45 to 0.87,≥3 vs. 0 self-reported days/week), with consistent estimates for most case-groups. Greater genetically-predicted sedentary time was associated with higher hormone-receptor-negative tumour risk (OR=1.77; 95% CI 1.07 to 2.92 per-SD (~7% time spent sedentary)), with elevated estimates for most case-groups. Results were robust to sensitivity analyses examining pleiotropy (including weighted-median-MR, MR-Egger).CONCLUSION: Our study provides strong evidence that greater overall physical activity, greater vigorous activity, and lower sedentary time are likely to reduce breast cancer risk. More widespread adoption of active lifestyles may reduce the burden from the most common cancer in women.
|
|
| 19. |
-
The Seventeenth Data Release of the Sloan Digital Sky Surveys : Complete Release of MaNGA, MaStar, and APOGEE-2 Data
- 2022
-
Ingår i: Astrophysical Journal Supplement Series. - : Institute of Physics (IOP). - 0067-0049 .- 1538-4365. ; 259:2
-
Tidskriftsartikel (refereegranskat)abstract
- This paper documents the seventeenth data release (DR17) from the Sloan Digital Sky Surveys; the fifth and final release from the fourth phase (SDSS-IV). DR17 contains the complete release of the Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey, which reached its goal of surveying over 10,000 nearby galaxies. The complete release of the MaNGA Stellar Library accompanies this data, providing observations of almost 30,000 stars through the MaNGA instrument during bright time. DR17 also contains the complete release of the Apache Point Observatory Galactic Evolution Experiment 2 survey that publicly releases infrared spectra of over 650,000 stars. The main sample from the Extended Baryon Oscillation Spectroscopic Survey (eBOSS), as well as the subsurvey Time Domain Spectroscopic Survey data were fully released in DR16. New single-fiber optical spectroscopy released in DR17 is from the SPectroscipic IDentification of ERosita Survey subsurvey and the eBOSS-RM program. Along with the primary data sets, DR17 includes 25 new or updated value-added catalogs. This paper concludes the release of SDSS-IV survey data. SDSS continues into its fifth phase with observations already underway for the Milky Way Mapper, Local Volume Mapper, and Black Hole Mapper surveys.
|
|
| 20. |
- Ahearn, Thomas U., et al.
(författare)
-
Common variants in breast cancer risk loci predispose to distinct tumor subtypes
- 2022
-
Ingår i: Breast Cancer Research. - : Springer Nature. - 1465-5411 .- 1465-542X. ; 24:1
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundGenome-wide association studies (GWAS) have identified multiple common breast cancer susceptibility variants. Many of these variants have differential associations by estrogen receptor (ER) status, but how these variants relate with other tumor features and intrinsic molecular subtypes is unclear.MethodsAmong 106,571 invasive breast cancer cases and 95,762 controls of European ancestry with data on 173 breast cancer variants identified in previous GWAS, we used novel two-stage polytomous logistic regression models to evaluate variants in relation to multiple tumor features (ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and grade) adjusting for each other, and to intrinsic-like subtypes.ResultsEighty-five of 173 variants were associated with at least one tumor feature (false discovery rate < 5%), most commonly ER and grade, followed by PR and HER2. Models for intrinsic-like subtypes found nearly all of these variants (83 of 85) associated at p < 0.05 with risk for at least one luminal-like subtype, and approximately half (41 of 85) of the variants were associated with risk of at least one non-luminal subtype, including 32 variants associated with triple-negative (TN) disease. Ten variants were associated with risk of all subtypes in different magnitude. Five variants were associated with risk of luminal A-like and TN subtypes in opposite directions.ConclusionThis report demonstrates a high level of complexity in the etiology heterogeneity of breast cancer susceptibility variants and can inform investigations of subtype-specific risk prediction.
|
|
| 21. |
|
|
| 22. |
- Kapoor, Pooja Middha, et al.
(författare)
-
Combined associations of a polygenic risk score and classical risk factors with breast cancer risk
- 2021
-
Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 113:3, s. 329-337
-
Tidskriftsartikel (refereegranskat)abstract
- We evaluated the joint associations between a new 313-variant PRS (PRS313) and questionnaire-based breast cancer risk factors for women of European ancestry, using 72 284 cases and 80 354 controls from the Breast Cancer Association Consortium. Interactions were evaluated using standard logistic regression and a newly developed case-only method for breast cancer risk overall and by estrogen receptor status. After accounting for multiple testing, we did not find evidence that per-standard deviation PRS313 odds ratio differed across strata defined by individual risk factors. Goodness-of-fit tests did not reject the assumption of a multiplicative model between PRS313 and each risk factor. Variation in projected absolute lifetime risk of breast cancer associated with classical risk factors was greater for women with higher genetic risk (PRS313 and family history) and, on average, 17.5% higher in the highest vs lowest deciles of genetic risk. These findings have implications for risk prevention for women at increased risk of breast cancer.
|
|
| 23. |
- Zanti, Maria, et al.
(författare)
-
A Likelihood Ratio Approach for Utilizing Case-Control Data in the Clinical Classification of Rare Sequence Variants : Application to BRCA1 and BRCA2
- 2023
-
Ingår i: Human Mutation. - : John Wiley & Sons. - 1059-7794 .- 1098-1004. ; 2023
-
Tidskriftsartikel (refereegranskat)abstract
- A large number of variants identified through clinical genetic testing in disease susceptibility genes are of uncertain significance (VUS). Following the recommendations of the American College of Medical Genetics and Genomics (ACMG) and Association for Molecular Pathology (AMP), the frequency in case-control datasets (PS4 criterion) can inform their interpretation. We present a novel case-control likelihood ratio-based method that incorporates gene-specific age-related penetrance. We demonstrate the utility of this method in the analysis of simulated and real datasets. In the analysis of simulated data, the likelihood ratio method was more powerful compared to other methods. Likelihood ratios were calculated for a case-control dataset of BRCA1 and BRCA2 variants from the Breast Cancer Association Consortium (BCAC) and compared with logistic regression results. A larger number of variants reached evidence in favor of pathogenicity, and a substantial number of variants had evidence against pathogenicity-findings that would not have been reached using other case-control analysis methods. Our novel method provides greater power to classify rare variants compared with classical case-control methods. As an initiative from the ENIGMA Analytical Working Group, we provide user-friendly scripts and preformatted Excel calculators for implementation of the method for rare variants in BRCA1, BRCA2, and other high-risk genes with known penetrance.
|
|
| 24. |
- Middha, Pooja K., et al.
(författare)
-
A genome-wide gene-environment interaction study of breast cancer risk for women of European ancestry
- 2023
-
Ingår i: Breast Cancer Research. - : BioMed Central (BMC). - 1465-5411 .- 1465-542X. ; 25:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background Genome-wide studies of gene-environment interactions (GxE) may identify variants associated with disease risk in conjunction with lifestyle/environmental exposures. We conducted a genome-wide GxE analysis of similar to 7.6 million common variants and seven lifestyle/environmental risk factors for breast cancer risk overall and for estrogen receptor positive (ER +) breast cancer. Methods Analyses were conducted using 72,285 breast cancer cases and 80,354 controls of European ancestry from the Breast Cancer Association Consortium. Gene-environment interactions were evaluated using standard unconditional logistic regression models and likelihood ratio tests for breast cancer risk overall and for ER + breast cancer. Bayesian False Discovery Probability was employed to assess the noteworthiness of each SNP-risk factor pairs. Results Assuming a 1 x 10(-5) prior probability of a true association for each SNP-risk factor pairs and a Bayesian False Discovery Probability < 15%, we identified two independent SNP-risk factor pairs: rs80018847(9p13)-LINGO2 and adult height in association with overall breast cancer risk (ORint = 0.94, 95% CI 0.92-0.96), and rs4770552(13q12)-SPATA13 and age at menarche for ER + breast cancer risk (ORint = 0.91, 95% CI 0.88-0.94). Conclusions Overall, the contribution of GxE interactions to the heritability of breast cancer is very small. At the population level, multiplicative GxE interactions do not make an important contribution to risk prediction in breast cancer.
|
|
| 25. |
- Divaris, K., et al.
(författare)
-
Phenotype Harmonization in the GLIDE2 Oral Health Genomics Consortium
- 2022
-
Ingår i: Journal of Dental Research. - : Sage Publications. - 0022-0345 .- 1544-0591. ; 101:11, s. 1408-1416
-
Tidskriftsartikel (refereegranskat)abstract
- Genetic risk factors play important roles in the etiology of oral, dental, and craniofacial diseases. Identifying the relevant risk loci and understanding their molecular biology could highlight new prevention and management avenues. Our current understanding of oral health genomics suggests that dental caries and periodontitis are polygenic diseases, and very large sample sizes and informative phenotypic measures are required to discover signals and adequately map associations across the human genome. In this article, we introduce the second wave of the Gene-Lifestyle Interactions and Dental Endpoints consortium (GLIDE2) and discuss relevant data analytics challenges, opportunities, and applications. In this phase, the consortium comprises a diverse, multiethnic sample of over 700,000 participants from 21 studies contributing clinical data on dental caries experience and periodontitis. We outline the methodological challenges of combining data from heterogeneous populations, as well as the data reduction problem in resolving detailed clinical examination records into tractable phenotypes, and describe a strategy that addresses this. Specifically, we propose a 3-tiered phenotyping approach aimed at leveraging both the large sample size in the consortium and the detailed clinical information available in some studies, wherein binary, severity-encompassing, and “precision,” data-driven clinical traits are employed. As an illustration of the use of data-driven traits across multiple cohorts, we present an application of dental caries experience data harmonization in 8 participating studies (N = 55,143) using previously developed permanent dentition tooth surface–level dental caries pattern traits. We demonstrate that these clinical patterns are transferable across multiple cohorts, have similar relative contributions within each study, and thus are prime targets for genetic interrogation in the expanded and diverse multiethnic sample of GLIDE2. We anticipate that results from GLIDE2 will decisively advance the knowledge base of mechanisms at play in oral, dental, and craniofacial health and disease and further catalyze international collaboration and data and resource sharing in genomics research.
|
|
| 26. |
- Von Holle, Ann, et al.
(författare)
-
BMI and breast cancer risk around age at menopause
- 2024
-
Ingår i: Cancer Epidemiology. - : Elsevier. - 1877-7821 .- 1877-783X. ; 89
-
Tidskriftsartikel (refereegranskat)abstract
- Background: A high body mass index (BMI, kg/m2) is associated with decreased risk of breast cancer before menopause, but increased risk after menopause. Exactly when this reversal occurs in relation to menopause is unclear. Locating that change point could provide insight into the role of adiposity in breast cancer etiology.Methods: We examined the association between BMI and breast cancer risk in the Premenopausal Breast Cancer Collaborative Group, from age 45 up to breast cancer diagnosis, loss to follow-up, death, or age 55, whichever came first. Analyses included 609,880 women in 16 prospective studies, including 9956 who developed breast cancer before age 55. We fitted three BMI hazard ratio (HR) models over age-time: constant, linear, or nonlinear (via splines), applying piecewise exponential additive mixed models, with age as the primary time scale. We divided person-time into four strata: premenopause; postmenopause due to natural menopause; postmenopause because of interventional loss of ovarian function (bilateral oophorectomy (BO) or chemotherapy); postmenopause due to hysterectomy without BO. Sensitivity analyses included stratifying by BMI in young adulthood, or excluding women using menopausal hormone therapy.Results: The constant BMI HR model provided the best fit for all four menopausal status groups. Under this model, the estimated association between a five-unit increment in BMI and breast cancer risk was HR=0.87 (95% CI: 0.85, 0.89) before menopause, HR=1.00 (95% CI: 0.96, 1.04) after natural menopause, HR=0.99 (95% CI: 0.93, 1.05) after interventional loss of ovarian function, and HR=0.88 (95% CI: 0.76, 1.02) after hysterectomy without BO.Conclusion: The BMI breast cancer HRs remained less than or near one during the 45–55 year age range indicating that the transition to a positive association between BMI and risk occurs after age 55.
|
|
| 27. |
- Weinberg, David H., et al.
(författare)
-
Chemical Cartography with APOGEE : Mapping Disk Populations with a 2-process Model and Residual Abundances
- 2022
-
Ingår i: Astrophysical Journal Supplement Series. - : IOP Publishing Ltd. - 0067-0049 .- 1538-4365. ; 260:2, s. 1-46
-
Tidskriftsartikel (refereegranskat)abstract
- We apply a novel statistical analysis to measurements of 16 elemental abundances in 34,410 Milky Way disk stars from the final data release (DR17) of APOGEE-2. Building on recent work, we fit median abundance ratio trends [X/Mg] versus [Mg/H] with a 2-process model, which decomposes abundance patterns into a "prompt" component tracing core-collapse supernovae and a "delayed" component tracing Type Ia supernovae. For each sample star, we fit the amplitudes of these two components, then compute the residuals Delta[X/H] from this two-parameter fit. The rms residuals range from similar to 0.01-0.03 dex for the most precisely measured APOGEE abundances to similar to 0.1 dex for Na, V, and Ce. The correlations of residuals reveal a complex underlying structure, including a correlated element group comprised of Ca, Na, Al, K, Cr, and Ce and a separate group comprised of Ni, V, Mn, and Co. Selecting stars poorly fit by the 2-process model reveals a rich variety of physical outliers and sometimes subtle measurement errors. Residual abundances allow for the comparison of populations controlled for differences in metallicity and [alpha/Fe]. Relative to the main disk (R = 3-13 kpc), we find nearly identical abundance patterns in the outer disk (R = 15-17 kpc), 0.05-0.2 dex depressions of multiple elements in LMC and Gaia Sausage/Enceladus stars, and wild deviations (0.4-1 dex) of multiple elements in omega Cen. The residual abundance analysis opens new opportunities for discovering chemically distinctive stars and stellar populations, for empirically constraining nucleosynthetic yields, and for testing chemical evolution models that include stochasticity in the production and redistribution of elements.
|
|
| 28. |
|
|
| 29. |
- Yang, J, et al.
(författare)
-
Guidelines and definitions for research on epithelial-mesenchymal transition
- 2020
-
Ingår i: Nature reviews. Molecular cell biology. - : Springer Science and Business Media LLC. - 1471-0080 .- 1471-0072. ; 21:6, s. 341-352
-
Tidskriftsartikel (refereegranskat)abstract
- Epithelial–mesenchymal transition (EMT) encompasses dynamic changes in cellular organization from epithelial to mesenchymal phenotypes, which leads to functional changes in cell migration and invasion. EMT occurs in a diverse range of physiological and pathological conditions and is driven by a conserved set of inducing signals, transcriptional regulators and downstream effectors. With over 5,700 publications indexed by Web of Science in 2019 alone, research on EMT is expanding rapidly. This growing interest warrants the need for a consensus among researchers when referring to and undertaking research on EMT. This Consensus Statement, mediated by ‘the EMT International Association’ (TEMTIA), is the outcome of a 2-year-long discussion among EMT researchers and aims to both clarify the nomenclature and provide definitions and guidelines for EMT research in future publications. We trust that these guidelines will help to reduce misunderstanding and misinterpretation of research data generated in various experimental models and to promote cross-disciplinary collaboration to identify and address key open questions in this research field. While recognizing the importance of maintaining diversity in experimental approaches and conceptual frameworks, we emphasize that lasting contributions of EMT research to increasing our understanding of developmental processes and combatting cancer and other diseases depend on the adoption of a unified terminology to describe EMT.
|
|
| 30. |
- Enright, Michael J., et al.
(författare)
-
Role of Atomic Structure on Exciton Dynamics and Photoluminescence in NIR Emissive InAs/InP/ZnSe Quantum Dots
- 2022
-
Ingår i: The Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 126:17, s. 7576-7587
-
Tidskriftsartikel (refereegranskat)abstract
- The development of bright, near-infrared-emissive quantum dots (QDs) is a necessary requirement for the realization of important new classes of technology. Specifically, there exist significant needs for brighter, heavy metal-free, near-infrared (NIR) QDs for applications with high radiative efficiency that span diverse applications, including down-conversion emitters for high-performance luminescent solar concentrators. We use a combination of theoretical and experimental approaches to synthesize bright, NIR luminescent InAs/InP/ZnSe QDs and elucidate fundamental material attributes that remain obstacles for development of near-unity NIR QD luminophores. First, using Monte Carlo ray tracing, we identify the atomic and electronic structural attributes of InAs core/shell, NIR emitters, whose luminescence properties can be tailored by synthetic design to match most beneficially those of high-performance, single-band-gap photovoltaic devices based on important semiconductor materials, such Si or GaAs. Second, we synthesize InAs/InP/ZnSe QDs based on the optical attributes found to maximize LSC performance and develop methods to improve the emissive qualities of NIR emitters with large, tunable Stokes ratios, narrow emission linewidths, and high luminescence quantum yields (here reaching 60 +/- 2%). Third, we employ atomistic electronic structure calculations to explore charge carrier behavior at the nanoscale affected by interfacial atomic structures and find that significant exciton occupation of the InP shell occurs in most cases despite the InAs/InP type I bulk band alignment. Furthermore, the density of the valence band maximum state extends anisotropically through the (111) crystal planes to the terminal InP surfaces/interfaces, indicating that surface defects, such as unpassivated phosphorus dangling bonds, located on the (111) facets play an outsized role in disrupting the valence band maximum and quenching photoluminescence.
|
|
| 31. |
- Griffith, Emily, et al.
(författare)
-
The Similarity of Abundance Ratio Trends and Nucleosynthetic Patterns in the Milky Way Disk and Bulge
- 2021
-
Ingår i: Astrophysical Journal. - : Institute of Physics Publishing (IOPP). - 0004-637X .- 1538-4357. ; 909:1
-
Tidskriftsartikel (refereegranskat)abstract
- We compare abundance ratio trends in a sample of similar to 11,000 Milky Way bulge stars (R-GC < 3 kpc) from the Apache Point Observatory Galactic Evolution Experiment (APOGEE) to those of APOGEE stars in the Galactic disk (5 kpc < R-GC < 11 kpc). We divide each sample into low-Ia (high-[Mg/Fe]) and high-Ia (low-[Mg/Fe]) populations, and in each population, we examine the median trends of [X/Mg] versus [Mg/H] for elements X = Fe, O, Na, Al, Si, P, S, K, Ca, V, Cr, Mn, Co, Ni, Cu, and Ce. To remove small systematic trends of APOGEE abundances with stellar log(g), we resample the disk stars to match the log(g) distributions of the bulge data. After doing so, we find nearly identical median trends for low-Ia disk and bulge stars for all elements. High-Ia trends are similar for most elements, with noticeable (0.05-0.1 dex) differences for Mn, Na, and Co. The close agreement of abundance trends (with typical differences less than or similar to 0.03 dex) implies that similar nucleosynthetic processes enriched bulge and disk stars despite the different star formation histories and physical conditions of these regions. For example, we infer that differences in the high-mass slope of the stellar initial mass function between disk and bulge must have been less than or similar to 0.30. This agreement, and the generally small scatter about the median sequences, means that one can predict all of a bulge star's APOGEE abundances with good accuracy knowing only its measured [Mg/Fe] and [Mg/H] and the observed trends of disk stars.
|
|
| 32. |
- Nguyen-Cong, K., et al.
(författare)
-
Billion atom molecular dynamics simulations of carbon at extreme conditions and experimental time and length scales
- 2021
-
Ingår i: SC '21: Proceedings of the International Conference for High Performance Computing, Networking, Storage and Analysis. - New York, NY, USA : Association for Computing Machinery (ACM).
-
Konferensbidrag (refereegranskat)abstract
- Billion atom molecular dynamics (MD) using quantum-Accurate machine-learning Spectral Neighbor Analysis Potential (SNAP) observed long-sought high pressure BC8 phase of carbon at extreme pressure (12 Mbar) and temperature (5,000 K). 24-hour, 4650 node production simulation on OLCF Summit demonstrated an unprecedented scaling and unmatched real-world performance of SNAP MD while sampling 1 nanosecond of physical time. Efficient implementation of SNAP force kernel in LAMMPS using the Kokkos CUDA backend on NVIDIA GPUs combined with excellent strong scaling (better than 97% parallel efficiency) enabled a peak computing rate of 50.0 PFLOPs (24.9% of theoretical peak) for a 20 billion atom MD simulation on the full Summit machine (27,900 GPUs). The peak MD performance of 6.21 Matom-steps/node-s is 22.9 times greater than a previous record for quantum-Accurate MD. Near perfect weak scaling of SNAP MD highlights its excellent potential to advance the frontier of quantum-Accurate MD to trillion atom simulations on upcoming exascale platforms.
|
|
| 33. |
- Sales-Silva, J. V., et al.
(författare)
-
Exploring the S-process History in the Galactic Disk : Cerium Abundances and Gradients in Open Clusters from the OCCAM/APOGEE Sample
- 2022
-
Ingår i: Astrophysical Journal. - : Institute of Physics (IOP). - 0004-637X .- 1538-4357. ; 926:2
-
Tidskriftsartikel (refereegranskat)abstract
- The APOGEE Open Cluster Chemical Abundances and Mapping survey is used to probe the chemical evolution of the s-process element cerium in the Galactic disk. Cerium abundances were derived from measurements of Ce ii lines in the APOGEE spectra using the Brussels Automatic Code for Characterizing High Accuracy Spectra in 218 stars belonging to 42 open clusters. Our results indicate that, in general, for ages < 4 Gyr, younger open clusters have higher [Ce/Fe] and [Ce/α-element] ratios than older clusters. In addition, metallicity segregates open clusters in the [Ce/X]–age plane (where X can be H, Fe, or the α-elements O, Mg, Si, or Ca). These metallicity-dependent relations result in [Ce/Fe] and [Ce/α] ratios with ages that are not universal clocks. Radial gradients of [Ce/H] and [Ce/Fe] ratios in open clusters, binned by age, were derived for the first time, with d[Ce/H]/dRGC being negative, while d[Ce/Fe]/dRGC is positive. [Ce/H] and [Ce/Fe] gradients are approximately constant over time, with the [Ce/Fe] gradient becoming slightly steeper, changing by ∼+0.009 dex kpc−1 Gyr−1. Both the [Ce/H] and [Ce/Fe] gradients are shifted to lower values of [Ce/H] and [Ce/Fe] for older open clusters. The chemical pattern of Ce in open clusters across the Galactic disk is discussed within the context of s-process yields from asymptotic giant branch (AGB) stars, gigayear time delays in Ce enrichment of the interstellar medium, and the strong dependence of Ce nucleosynthesis on the metallicity of its AGB stellar sources.
|
|
| 34. |
- Vlasceanu, Madalina, et al.
(författare)
-
Addressing climate change with behavioral science: A global intervention tournament in 63 countries
- 2024
-
Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 10:6
-
Tidskriftsartikel (refereegranskat)abstract
- Effectively reducing climate change requires marked, global behavior change. However, it is unclear which strategies are most likely to motivate people to change their climate beliefs and behaviors. Here, we tested 11 expert-crowdsourced interventions on four climate mitigation outcomes: beliefs, policy support, information sharing intention, and an effortful tree-planting behavioral task. Across 59,440 participants from 63 countries, the interventions’ effectiveness was small, largely limited to nonclimate skeptics, and differed across outcomes: Beliefs were strengthened mostly by decreasing psychological distance (by 2.3%), policy support by writing a letter to a future-generation member (2.6%), information sharing by negative emotion induction (12.1%), and no intervention increased the more effortful behavior—several interventions even reduced tree planting. Last, the effects of each intervention differed depending on people’s initial climate beliefs. These findings suggest that the impact of behavioral climate interventions varies across audiences and target behaviors.
|
|
| 35. |
- Hanson, Britt, et al.
(författare)
-
Non-uniform dystrophin re-expression after CRISPR-mediated exon excision in the dystrophin/utrophin double-knockout mouse model of DMD
- 2022
-
Ingår i: Molecular Therapy Nucleic Acids. - : Elsevier. - 2162-2531. ; 30, s. 379-397
-
Tidskriftsartikel (refereegranskat)abstract
- Duchenne muscular dystrophy (DMD) is the most prevalent inherited myopathy affecting children, caused by genetic loss of the gene encoding the dystrophin protein. Here we have investigated the use of the Staphylococcus aureus CRISPR-Cas9 system and a double-cut strategy, delivered using a pair of adeno-associated virus serotype 9 (AAV9) vectors, for dystrophin restoration in the severely affected dystrophin/utrophin double-knockout (dKO) mouse. Single guide RNAs were designed to excise Dmd exon 23, with flanking intronic regions repaired by non-homologous end joining. Exon 23 deletion was confirmed at the DNA level by PCR and Sanger sequencing, and at the RNA level by RT-qPCR. Restoration of dystrophin protein expression was demonstrated by western blot and immunofluorescence staining in mice treated via either intraperitoneal or intravenous routes of delivery. Dystrophin restoration was most effective in the diaphragm, where a maximum of 5.7% of wild-type dystrophin expression was observed. CRISPR treatment was insufficient to extend lifespan in the dKO mouse, and dystrophin was expressed in a within-fiber patchy manner in skeletal muscle tissues. Further analysis revealed a plethora of non-productive DNA repair events, including AAV genome integration at the CRISPR cut sites. This study highlights potential challenges for the successful development of CRISPR therapies in the context of DMD.
|
|
| 36. |
- Liebi, Marianne, 1984, et al.
(författare)
-
3D nanoscale analysis of bone healing around degrading Mg implants evaluated by X-ray scattering tensor tomography
- 2021
-
Ingår i: Acta Biomaterialia. - : Elsevier BV. - 1878-7568 .- 1742-7061. ; 134, s. 804-817
-
Tidskriftsartikel (refereegranskat)abstract
- The nanostructural adaptation of bone is crucial for its biocompatibility with orthopedic implants. The bone nanostructure also determines its mechanical properties and performance. However, the bone's temporal and spatial nanoadaptation around degrading implants remains largely unknown. Here, we present insights into this important bone adaptation by applying scanning electron microscopy, elemental analysis, and small-angle X-ray scattering tensor tomography (SASTT). We extend the novel SASTT reconstruction method and provide a 3D scattering reciprocal space map per voxel of the sample's volume. From this reconstruction, parameters such as the thickness of the bone mineral particles are quantified, which provide additional information on nanostructural adaptation of bone during healing. We selected a rat femoral bone and a degrading ZX10 magnesium implant as model system, and investigated it over the course of 18 months, using a sham as control. We observe that the bone's nanostructural adaptation starts with an initially fast interfacial bone growth close to the implant, which spreads by a re-orientation of the nanostructure in the bone volume around the implant, and is consolidated in the later degradation stages. These observations reveal the complex bulk bone-implant interactions and enable future research on the related biomechanical bone responses. Statement of significance: Traumatic bone injuries are among the most frequent causes of surgical treatment, and often require the placement of an implant. The ideal implant supports and induces bone formation, while being mechanically and chemically adapted to the bone structure, ensuring a gradual load transfer. While magnesium implants fulfill these requirements, the nanostructural changes during bone healing and implant degradation remain not completely elucidated. Here, we unveil these processes in rat femoral bones with ZX10 magnesium implants and show different stages of bone healing in such a model system.
|
|
| 37. |
|
|
| 38. |
|
|
