| 1. |
- Beal, Jacob, et al.
(författare)
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Robust estimation of bacterial cell count from optical density
- 2020
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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| 2. |
- Campbell, PJ, et al.
(författare)
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Pan-cancer analysis of whole genomes
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Tidskriftsartikel (refereegranskat)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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| 3. |
- Weinstein, John N., et al.
(författare)
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The cancer genome atlas pan-cancer analysis project
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:10, s. 1113-1120
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Forskningsöversikt (refereegranskat)abstract
- The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile. © 2013 Nature America, Inc. All rights reserved.
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| 4. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 5. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 6. |
- Birney, Ewan, et al.
(författare)
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Prepublication data sharing
- 2009
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 461:7261, s. 168-170
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Tidskriftsartikel (refereegranskat)abstract
- Rapid release of prepublication data has served the field of genomics well. Attendees at a workshop in Toronto recommend extending the practice to other biological data sets.
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| 7. |
- Clark, Andrew G., et al.
(författare)
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Evolution of genes and genomes on the Drosophila phylogeny
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 450:7167, s. 203-218
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Tidskriftsartikel (refereegranskat)abstract
- Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.
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| 8. |
- Franchi, Francesco, et al.
(författare)
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Impact of Diabetes Mellitus and Chronic Kidney Disease on Cardiovascular Outcomes and Platelet P2Y12 Receptor Antagonist Effects in Patients With Acute Coronary Syndromes : Insights From the PLATO Trial
- 2019
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Ingår i: Journal of the American Heart Association. - 2047-9980. ; 8:6
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Tidskriftsartikel (refereegranskat)abstract
- Background-There are limited data on how the combination of diabetes mellitus (DM) and chronic kidney disease (CKD) affects cardiovascular outcomes as well as response to different P2Y(12) receptor antagonists, which represented the aim of the present investigation. Methods and Results-In this post hoc analysis of the PLATO (Platelet Inhibition and Patient Outcomes) trial, which randomized acute coronary syndrome patients to ticagrelor versus clopidogrel, patients (n=15 108) with available DM and CKD status were classified into 4 groups: DM+/CKD+ (n=1058), DM+/CKD- (n=2748), DM-/CKD+ (n=2160), and DM-/CKD- (n=9142). The primary efficacy end point was a composite of cardiovascular death, myocardial infarction, or stroke at 12 months. The primary safety end point was PLATO major bleeding. DM+/CKD+ patients had a higher incidence of the primary end point compared with DM-/CKD- patients (23.3% versus 7.1%; adjusted hazard ratio 2.22; 95% CI 1.88-2.63; P<0.001). Patients with DM+/CKD- and DM-/CKD+ had an intermediate risk profile. The same trend was shown for the individual components of the primary end point and for major bleeding. Compared with clopidogrel, ticagrelor reduced the incidence of the primary end point consistently across subgroups (P-interaction=0.264), but with an increased absolute risk reduction in DM+/CKD+. The effects on major bleeding were also consistent across subgroups (P-interaction=0.288). Conclusions-In acute coronary syndrome patients, a gradient of risk was observed according to the presence or absence of DM and CKD, with patients having both risk factors at the highest risk. Although the ischemic benefit of ticagrelor over clopidogrel was consistent in all subgroups, the absolute risk reduction was greatest in patients with both DM and CKD.
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| 9. |
- Kanoni, Stavroula, et al.
(författare)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
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Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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| 10. |
- Salvo, Gloria, et al.
(författare)
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Open vs minimally invasive radical trachelectomy in early-stage cervical cancer : International Radical Trachelectomy Assessment Study
- 2022
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Ingår i: American Journal of Obstetrics and Gynecology. - : Elsevier BV. - 0002-9378 .- 1097-6868. ; 226:1, s. 1-97
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Tidskriftsartikel (refereegranskat)abstract
- Background: Minimally invasive radical trachelectomy has emerged as an alternative to open radical hysterectomy for patients with early-stage cervical cancer desiring future fertility. Recent data suggest worse oncologic outcomes after minimally invasive radical hysterectomy than after open radical hysterectomy in stage I cervical cancer. Objective: We aimed to compare 4.5-year disease-free survival after open vs minimally invasive radical trachelectomy. Study Design: This was a collaborative, international retrospective study (International Radical Trachelectomy Assessment Study) of patients treated during 2005–2017 at 18 centers in 12 countries. Eligible patients had squamous carcinoma, adenocarcinoma, or adenosquamous carcinoma; had a preoperative tumor size of ≤2 cm; and underwent open or minimally invasive (robotic or laparoscopic) radical trachelectomy with nodal assessment (pelvic lymphadenectomy and/or sentinel lymph node biopsy). The exclusion criteria included neoadjuvant chemotherapy or preoperative pelvic radiotherapy, previous lymphadenectomy or pelvic retroperitoneal surgery, pregnancy, stage IA1 disease with lymphovascular space invasion, aborted trachelectomy (conversion to radical hysterectomy), or vaginal approach. Surgical approach, indication, and adjuvant therapy regimen were at the discretion of the treating institution. A total of 715 patients were entered into the study database. However, 69 patients were excluded, leaving 646 in the analysis. Endpoints were the 4.5-year disease-free survival rate (primary), 4.5-year overall survival rate (secondary), and recurrence rate (secondary). Kaplan-Meier methods were used to estimate disease-free survival and overall survival. A post hoc weighted analysis was performed, comparing the recurrence rates between surgical approaches, with open surgery being considered as standard and minimally invasive surgery as experimental. Results: Of 646 patients, 358 underwent open surgery, and 288 underwent minimally invasive surgery. The median (range) patient age was 32 (20–42) years for open surgery vs 31 (18–45) years for minimally invasive surgery (P=.11). Median (range) pathologic tumor size was 15 (0–31) mm for open surgery and 12 (0.8–40) mm for minimally invasive surgery (P=.33). The rates of pelvic nodal involvement were 5.3% (19 of 358 patients) for open surgery and 4.9% (14 of 288 patients) for minimally invasive surgery (P=.81). Median (range) follow-up time was 5.5 (0.20–16.70) years for open surgery and 3.1 years (0.02–11.10) years for minimally invasive surgery (P<.001). At 4.5 years, 17 of 358 patients (4.7%) with open surgery and 18 of 288 patients (6.2%) with minimally invasive surgery had recurrence (P=.40). The 4.5-year disease-free survival rates were 94.3% (95% confidence interval, 91.6–97.0) for open surgery and 91.5% (95% confidence interval, 87.6–95.6) for minimally invasive surgery (log-rank P=.37). Post hoc propensity score analysis of recurrence risk showed no difference between surgical approaches (P=.42). At 4.5 years, there were 6 disease-related deaths (open surgery, 3; minimally invasive surgery, 3) (log-rank P=.49). The 4.5-year overall survival rates were 99.2% (95% confidence interval, 97.6–99.7) for open surgery and 99.0% (95% confidence interval, 79.0–99.8) for minimally invasive surgery. Conclusion: The 4.5-year disease-free survival rates did not differ between open radical trachelectomy and minimally invasive radical trachelectomy. However, recurrence rates in each group were low. Ongoing prospective studies of conservative management of early-stage cervical cancer may help guide future management.
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| 11. |
- Torne, Pablo, et al.
(författare)
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A Search for Pulsars around Sgr A* in the First Event Horizon Telescope Data Set
- 2023
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Ingår i: Astrophysical Journal. - 1538-4357 .- 0004-637X. ; 959:1
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Tidskriftsartikel (refereegranskat)abstract
- In 2017 the Event Horizon Telescope (EHT) observed the supermassive black hole at the center of the Milky Way, Sagittarius A* (Sgr A*), at a frequency of 228.1 GHz (lambda = 1.3 mm). The fundamental physics tests that even a single pulsar orbiting Sgr A* would enable motivate searching for pulsars in EHT data sets. The high observing frequency means that pulsars-which typically exhibit steep emission spectra-are expected to be very faint. However, it also negates pulse scattering, an effect that could hinder pulsar detections in the Galactic center. Additionally, magnetars or a secondary inverse Compton emission could be stronger at millimeter wavelengths than at lower frequencies. We present a search for pulsars close to Sgr A* using the data from the three most sensitive stations in the EHT 2017 campaign: the Atacama Large Millimeter/submillimeter Array, the Large Millimeter Telescope, and the IRAM 30 m Telescope. We apply three detection methods based on Fourier-domain analysis, the fast folding algorithm, and single-pulse searches targeting both pulsars and burst-like transient emission. We use the simultaneity of the observations to confirm potential candidates. No new pulsars or significant bursts were found. Being the first pulsar search ever carried out at such high radio frequencies, we detail our analysis methods and give a detailed estimation of the sensitivity of the search. We conclude that the EHT 2017 observations are only sensitive to a small fraction (less than or similar to 2.2%) of the pulsars that may exist close to Sgr A*, motivating further searches for fainter pulsars in the region.
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| 12. |
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| 13. |
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| 14. |
- Azevedo, Flavio, et al.
(författare)
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Social and moral psychology of COVID-19 across 69 countries
- 2023
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Ingår i: Scientific Data. - : NATURE PORTFOLIO. - 2052-4463. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- The COVID-19 pandemic has affected all domains of human life, including the economic and social fabric of societies. One of the central strategies for managing public health throughout the pandemic has been through persuasive messaging and collective behaviour change. To help scholars better understand the social and moral psychology behind public health behaviour, we present a dataset comprising of 51,404 individuals from 69 countries. This dataset was collected for the International Collaboration on Social & Moral Psychology of COVID-19 project (ICSMP COVID-19). This social science survey invited participants around the world to complete a series of moral and psychological measures and public health attitudes about COVID-19 during an early phase of the COVID-19 pandemic (between April and June 2020). The survey included seven broad categories of questions: COVID-19 beliefs and compliance behaviours; identity and social attitudes; ideology; health and well-being; moral beliefs and motivation; personality traits; and demographic variables. We report both raw and cleaned data, along with all survey materials, data visualisations, and psychometric evaluations of key variables.
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| 15. |
- Crosby, Jacy, et al.
(författare)
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Loss-of-Function Mutations in APOC3, Triglycerides, and Coronary Disease
- 2014
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 371:1, s. 22-31
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Tidskriftsartikel (refereegranskat)abstract
- Background Plasma triglyceride levels are heritable and are correlated with the risk of coronary heart disease. Sequencing of the protein-coding regions of the human genome (the exome) has the potential to identify rare mutations that have a large effect on phenotype. Methods We sequenced the protein-coding regions of 18,666 genes in each of 3734 participants of European or African ancestry in the Exome Sequencing Project. We conducted tests to determine whether rare mutations in coding sequence, individually or in aggregate within a gene, were associated with plasma triglyceride levels. For mutations associated with triglyceride levels, we subsequently evaluated their association with the risk of coronary heart disease in 110,970 persons. Results An aggregate of rare mutations in the gene encoding apolipoprotein C3 (APOC3) was associated with lower plasma triglyceride levels. Among the four mutations that drove this result, three were loss-of-function mutations: a nonsense mutation (R19X) and two splice-site mutations (IVS2+1G -> A and IVS3+1G -> T). The fourth was a missense mutation (A43T). Approximately 1 in 150 persons in the study was a heterozygous carrier of at least one of these four mutations. Triglyceride levels in the carriers were 39% lower than levels in noncarriers (P<1x10(-20)), and circulating levels of APOC3 in carriers were 46% lower than levels in noncarriers (P = 8x10(-10)). The risk of coronary heart disease among 498 carriers of any rare APOC3 mutation was 40% lower than the risk among 110,472 noncarriers (odds ratio, 0.60; 95% confidence interval, 0.47 to 0.75; P = 4x10(-6)). Conclusions Rare mutations that disrupt APOC3 function were associated with lower levels of plasma triglycerides and APOC3. Carriers of these mutations were found to have a reduced risk of coronary heart disease. (Funded by the National Heart, Lung, and Blood Institute and others.)
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| 16. |
- Dunn, Gabriel, et al.
(författare)
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Selective Insulation of Carbon nanotubes
- 2017
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Ingår i: Physica status solidi. B, Basic research. - : Wiley-VCH Verlagsgesellschaft. - 0370-1972 .- 1521-3951. ; 254:11
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Tidskriftsartikel (refereegranskat)abstract
- We demonstrate a method for the selective encapsulation of carbonnanotubes in thin parylene films using iron as a sacrificial lift-off layer. Theiron serves as an inhibitor of parylene deposition and prevents the parylenemolecules from linking, thus facilitating selective area coating after lift-off.
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| 17. |
- Engel, Katja, et al.
(författare)
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Meeting Report : 1st International Functional Metagenomics Workshop May 7-8, 2012, St. Jacobs, Ontario, Canada
- 2013
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Ingår i: Standards in Genomic Sciences. - : Springer Science and Business Media LLC. - 1944-3277. ; 8:1, s. 106-111
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- This report summarizes the events of the 1st International Functional Metagenomics Workshop. The workshop was held on May 7 and 8, 2012, in St. Jacobs, Ontario, Canada and was focused on building an international functional metagenomics community, exploring strategic research areas, and identifying opportunities for future collaboration and funding. The workshop was initiated by researchers at the University of Waterloo with support from the Ontario Genomics Institute (OGI), Natural Sciences and Engineering Research Council of Canada (NSERC) and the University of Waterloo.
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| 18. |
- Gu, Gucci Jijuan, et al.
(författare)
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Role of Individual MARK Isoforms in Phosphorylation of Tau at Ser262 in Alzheimer's Disease
- 2013
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Ingår i: Neuromolecular medicine. - : Springer. - 1535-1084 .- 1559-1174. ; 15:3, s. 458-469
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Tidskriftsartikel (refereegranskat)abstract
- The microtubule-affinity regulating kinase (MARK) family consists of four highly conserved members that have been implicated in phosphorylation of tau protein, causing formation of neurofibrillary tangles in Alzheimer’s disease (AD). Understanding of roles by individual MARK isoform in phosphorylating tau has been limited due to lack of antibodies selective for each MARK isoform. In this study, we first applied the proximity ligation assay on cells to select antibodies specific for each MARK isoform. In cells, a CagA peptide specifically and significantly inhibited tau phosphorylation at Ser262 mediated by MARK4 but not other MARK isoforms. We then used these antibodies to study expression levels of MARK isoforms and interactions between tau and individual MARK isoforms in postmortem human brains. We found a strong and significant elevation of MARK4 expression and MARK4–tau interactions in AD brains, correlating with the Braak stages of the disease. These results suggest the MARK4–tau interactions are of functional importance in the progression of AD and the results also identify MARK4 as a promising target for AD therapy.
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| 19. |
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| 20. |
- Jones, Benedict C, et al.
(författare)
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To which world regions does the valence-dominance model of social perception apply?
- 2021
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Ingår i: Nature Human Behaviour. - : Springer Science and Business Media LLC. - 2397-3374. ; 5:1, s. 159-169
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Tidskriftsartikel (refereegranskat)abstract
- Over the past 10 years, Oosterhof and Todorov's valence-dominance model has emerged as the most prominent account of how people evaluate faces on social dimensions. In this model, two dimensions (valence and dominance) underpin social judgements of faces. Because this model has primarily been developed and tested in Western regions, it is unclear whether these findings apply to other regions. We addressed this question by replicating Oosterhof and Todorov's methodology across 11 world regions, 41 countries and 11,570 participants. When we used Oosterhof and Todorov's original analysis strategy, the valence-dominance model generalized across regions. When we used an alternative methodology to allow for correlated dimensions, we observed much less generalization. Collectively, these results suggest that, while the valence-dominance model generalizes very well across regions when dimensions are forced to be orthogonal, regional differences are revealed when we use different extraction methods and correlate and rotate the dimension reduction solution. PROTOCOL REGISTRATION: The stage 1 protocol for this Registered Report was accepted in principle on 5 November 2018. The protocol, as accepted by the journal, can be found at https://doi.org/10.6084/m9.figshare.7611443.v1 .
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| 21. |
- Kilpelainen, TO, et al.
(författare)
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Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity
- 2019
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Ingår i: Nature communications. - London : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 376-
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Tidskriftsartikel (refereegranskat)abstract
- Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci and attenuate the LDL cholesterol-increasing effect of the CNTNAP2 locus. The CLASP1, LHX1, and SNTA1 regions harbor genes linked to muscle function and lipid metabolism. Our results elucidate the role of physical activity interactions in the genetic contribution to blood lipid levels.
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| 22. |
- Kunadian, Vijay, et al.
(författare)
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Angiographic Outcomes in the PLATO Trial (Platelet Inhibition and Patient Outcomes)
- 2013
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Ingår i: JACC-CARDIOVASCULAR INTERVENTIONS. - : Elsevier BV. - 1936-8798. ; 6:7, s. 671-683
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Tidskriftsartikel (refereegranskat)abstract
- Objectives The PLATO (Platelet Inhibition and Patient Outcomes) angiographic substudy sought to compare the efficacy of ticagrelor versus clopidogrel with respect to angiographic outcomes before and after PCI in the setting of acute coronary syndrome. Background Greater platelet inhibition has been associated with improved angiographic outcomes before and after percutaneous coronary intervention (PCI). Therefore, it was hypothesized that treatment with ticagrelor, which achieves more rapid, higher, and more consistent platelet inhibition, would be associated with improved angiographic outcomes when compared with those of clopidogrel treatment. Methods The angiographic cohort consists of 2,616 patients drawn from the 18,624-patient PLATO trial. Clopidogrel naive or pre-treated patients were randomized to 180 mg of ticagrelor or 300 mg of clopidogrel (75 mg for clopidogrel pre-treated patients). PCI patients were administered, as per treatment group: 1) an additional 90 mg of ticagrelor if >24 h following the initial loading dose; or 2) an optional further 300 mg of clopidogrel or placebo (total 600 mg) prior to PCI. The substudy primary endpoint was the incidence of post-PCI TIMI (Thrombolysis In Myocardial Infarction) myocardial perfusion grade 3 (TMPG 3) among patients who received a study drug prior to PCI. Results In total, 21.3% of patients were pretreated with clopidogrel prior to randomization. There was a short time interval between randomization and PCI (median: 0.68 [interquartile range (IQR): 0.30 to 2.21] h) among all patients. Post-PCI TMPG 3 was similar between the ticagrelor and clopidogrel groups (47.1% vs. 46.9%; p = 0.96). Likewise, the following pre-PCI outcomes were similar in the ticagrelor and clopidogrel groups, respectively: TMPG 3 (30.5% vs. 31.2%), TIMI flow grade 3 (37.1% vs. 39.3%), corrected TIMI frame count (median: 100 vs. 71 frames), TIMI thrombus grade 0 (24.1% vs. 27.6%), minimum lumen diameter (median: 0.3 [IQR: 0.0 to 0.6] vs. 0.3 [IQR: 0.0 to 0.6] mm) and percentage of diameter stenosis (median: 89 [IQR: 78 to 100] vs. 89 [IQR: 77 to 100]). Conclusions Neither coronary flow nor myocardial perfusion, evaluated on coronary angiograms performed before or following PCI procedures within a few hours after the start of oral antiplatelet treatment in the setting of acute coronary syndromes, demonstrated a difference with ticagrelor versus clopidogrel. (A Comparison of Ticagrelor [AZD6140] and Clopidogrel in Patients With Acute Coronary Syndrome [PLATO]; NCT00391872)
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| 23. |
- Lou, Xiutao, et al.
(författare)
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Detection of elemental mercury by multimode diode laser correlation spectroscopy
- 2012
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Ingår i: Optics Express. - 1094-4087. ; 20:5, s. 4927-4938
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Tidskriftsartikel (refereegranskat)abstract
- We demonstrate a method for elemental mercury detection based on correlation spectroscopy employing UV laser radiation generated by sum-frequency mixing of two visible multimode diode lasers. Resonance matching of the multimode UV laser is achieved in a wide wavelength range and with good tolerance for various operating conditions. Large mode-hops provide an off-resonance baseline, eliminating interferences from other gas species with broadband absorption. A sensitivity of 1 mu g/m(3) is obtained for a 1-m path length and 30-s integration time. The performance of the system shows promise for mercury monitoring in industrial applications.
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| 24. |
- Lou, X. T., et al.
(författare)
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Simultaneous detection of multiple-gas species by correlation spectroscopy using a multimode diode laser
- 2010
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Ingår i: Optics Letters. - 0146-9592 .- 1539-4794. ; 35:11, s. 1749-1751
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Tidskriftsartikel (refereegranskat)abstract
- Simultaneous detection of multiple-gas species has for the first time (to our knowledge) been demonstrated by using a multimode diode-laser-based correlation spectroscopy (MDL-COSPEC) scheme. Concentration measurements of a mixture of CO2 and CO gas were performed by probing overlapping line spectra around 1.57 using an MDL. Species identification and corresponding quantitive analysis were implemented by correlating the recorded absorption signals of the sample gas mixtures with those of the reference gases of particular interest, attaining accuracies of 2% and 1%, respectively. MDL-COSPEC is a generic technique with potential application for simultaneous detection of multiple gases having resolvable narrow lines.
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| 25. |
- Lou, Xiutao, et al.
(författare)
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Temperature-Corrected Oxygen Detection Based on Multi-Mode Diode Laser Correlation Spectroscopy
- 2013
-
Ingår i: Journal of Spectroscopy. - : Hindawi Limited. - 2314-4920 .- 2314-4939. ; 2013, s. 1-8
-
Tidskriftsartikel (refereegranskat)abstract
- Temperature-corrected oxygen measurements were performed by using multi-mode diode laser correlation spectroscopy at temperatures ranging between 300 and 473 K. The experiments simulate in situ monitoring of oxygen in coal-combustion exhaust gases at the tail of the flue. A linear relationship with a correlation coefficient of -0.999 was found between the evaluated concentration and the gas temperature. Temperature effects were either auto-corrected by keeping the reference gas at the same conditions as the sample gas, or rectified by using a predetermined effective temperature-correction coefficient calibrated for a range of absorption wavelengths. Relative standard deviations of the temperature-correction coefficient calibrated for a range of absorption wavelengths. Relative standard deviations of the temperature-corrected oxygen concentrations obtained by different schemes and at various temperatures were estimated, yielding a measurement precision of 0.6%.
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| 26. |
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| 27. |
- Manning, Alisa, et al.
(författare)
-
A Low-Frequency Inactivating AKT2 Variant Enriched in the Finnish Population Is Associated With Fasting Insulin Levels and Type 2 Diabetes Risk
- 2017
-
Ingår i: Diabetes. - : AMER DIABETES ASSOC. - 0012-1797 .- 1939-327X. ; 66:7, s. 2019-2032
-
Tidskriftsartikel (refereegranskat)abstract
- To identify novel coding association signals and facilitate characterization of mechanisms influencing glycemic traits and type 2 diabetes risk, we analyzed 109,215 variants derived from exome array genotyping together with an additional 390,225 variants from exome sequence in up to 39,339 normoglycemic individuals from five ancestry groups. We identified a novel association between the coding variant (p.Pro50Thr) in AKT2 and fasting plasma insulin (FI), a gene in which rare fully penetrant mutations are causal for monogenic glycemic disorders. The low-frequency allele is associated with a 12% increase in FI levels. This variant is present at 1.1% frequency in Finns but virtually absent in individuals from other ancestries. Carriers of the FI-increasing allele had increased 2-h insulin values, decreased insulin sensitivity, and increased risk of type 2 diabetes (odds ratio 1.05). In cellular studies, the AKT2-Thr50 protein exhibited a partial loss of function. We extend the allelic spectrum for coding variants in AKT2 associated with disorders of glucose homeostasis and demonstrate bidirectional effects of variants within the pleckstrin homology domain of AKT2.
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| 28. |
- Marouli, Eirini, et al.
(författare)
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Rare and low-frequency coding variants alter human adult height
- 2017
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 542:7640, s. 186-190
-
Tidskriftsartikel (refereegranskat)abstract
- Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.
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| 29. |
- Menkveld, Albert J., et al.
(författare)
-
Nonstandard Errors
- 2024
-
Ingår i: JOURNAL OF FINANCE. - : Wiley-Blackwell. - 0022-1082 .- 1540-6261. ; 79:3, s. 2339-2390
-
Tidskriftsartikel (refereegranskat)abstract
- In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty-nonstandard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for more reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants.
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| 30. |
- Pironi, Loris, et al.
(författare)
-
Characteristics of adult patients with chronic intestinal failure due to short bowel syndrome: An international multicenter survey
- 2021
-
Ingår i: Clinical Nutrition ESPEN. - : Elsevier BV. - 2405-4577. ; 45, s. 433-441
-
Tidskriftsartikel (refereegranskat)abstract
- Background and aims: The case-mix of patients with intestinal failure due to short bowel syndrome (SBS-IF) can differ among centres and may also be affected by the timeframe of data collection. Therefore, the ESPEN international multicenter cross-sectional survey was analyzed to compare the characteristics of SBS-IF cohorts collected within the same timeframe in different countries. Methods: The study included 1880 adult SBS-IF patients collected in 2015 by 65 centres from 22 countries. The demographic, nutritional, SBS type (end jejunostomy, SBS-J; jejuno-colic anastomosis, SBS-JC; jejunoileal anastomosis with an intact colon and ileocecal valve, SBS-JIC), underlying disease and intravenous supplementation (IVS) characteristics were analyzed. IVS was classified as fluid and electrolyte alone (FE) or parenteral nutrition admixture (PN). The mean daily IVS volume, calculated on a weekly basis, was categorized as <1, 1–2, 2–3 and >3 L/day. Results: In the entire group: 60.7% were females and SBS-J comprised 60% of cases, while mesenteric ischaemia (MI) and Crohn’ disease (CD) were the main underlying diseases. IVS dependency was longer than 3 years in around 50% of cases; IVS was infused ≥5 days/week in 75% and FE in 10% of cases. Within the SBS-IF cohort: CD was twice and thrice more frequent in SBS-J than SBS-JC and SBS-JIC, respectively, while MI was more frequent in SBS-JC and SBS-JIC. Within countries: SBS-J represented 75% or more of patients in UK and Denmark and 50-60% in the other countries, except Poland where SBS-JC prevailed. CD was the main underlying disease in UK, USA, Denmark and The Netherlands, while MI prevailed in France, Italy and Poland. Conclusions: SBS-IF type is primarily determined by the underlying disease, with significant variation between countries. These novel data will be useful for planning and managing both clinical activity and research studies on SBS.
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| 31. |
- Rothman, Nathaniel, et al.
(författare)
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A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci
- 2010
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 978-984
-
Tidskriftsartikel (refereegranskat)abstract
- We conducted a multi-stage, genome-wide association study of bladder cancer with a primary scan of 591,637 SNPs in 3,532 affected individuals (cases) and 5,120 controls of European descent from five studies followed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified three new regions associated with bladder cancer on chromosomes 22q13.1, 19q12 and 2q37.1: rs1014971, (P = 8 × 10⁻¹²) maps to a non-genic region of chromosome 22q13.1, rs8102137 (P = 2 × 10⁻¹¹) on 19q12 maps to CCNE1 and rs11892031 (P = 1 × 10⁻⁷) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide associations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate associations for the GSTM1 deletion (P = 4 × 10⁻¹¹) and a tag SNP for NAT2 acetylation status (P = 4 × 10⁻¹¹), and found interactions with smoking in both regions. Our findings on common variants associated with bladder cancer risk should provide new insights into the mechanisms of carcinogenesis.
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| 32. |
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| 33. |
- Santangelo, James S., et al.
(författare)
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Global urban environmental change drives adaptation in white clover
- 2022
-
Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 375
-
Tidskriftsartikel (refereegranskat)abstract
- Urbanization transforms environments in ways that alter biological evolution. We examined whether urban environmental change drives parallel evolution by sampling 110,019 white clover plants from 6169 populations in 160 cities globally. Plants were assayed for a Mendelian antiherbivore defense that also affects tolerance to abiotic stressors. Urban-rural gradients were associated with the evolution of clines in defense in 47% of cities throughout the world. Variation in the strength of clines was explained by environmental changes in drought stress and vegetation cover that varied among cities. Sequencing 2074 genomes from 26 cities revealed that the evolution of urban-rural dines was best explained by adaptive evolution, but the degree of parallel adaptation varied among cities. Our results demonstrate that urbanization leads to adaptation at a global scale.
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| 34. |
- Turcot, Valerie, et al.
(författare)
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Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity
- 2018
-
Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:1, s. 26-41
-
Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are similar to 10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed similar to 7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.
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| 35. |
- Van Bavel, Jay J., et al.
(författare)
-
National identity predicts public health support during a global pandemic
- 2022
-
Ingår i: Nature Communications. - : Nature Portfolio. - 2041-1723. ; 13:1
-
Tidskriftsartikel (refereegranskat)abstract
- Understanding collective behaviour is an important aspect of managing the pandemic response. Here the authors show in a large global study that participants that reported identifying more strongly with their nation reported greater engagement in public health behaviours and support for public health policies in the context of the pandemic. Changing collective behaviour and supporting non-pharmaceutical interventions is an important component in mitigating virus transmission during a pandemic. In a large international collaboration (Study 1, N = 49,968 across 67 countries), we investigated self-reported factors associated with public health behaviours (e.g., spatial distancing and stricter hygiene) and endorsed public policy interventions (e.g., closing bars and restaurants) during the early stage of the COVID-19 pandemic (April-May 2020). Respondents who reported identifying more strongly with their nation consistently reported greater engagement in public health behaviours and support for public health policies. Results were similar for representative and non-representative national samples. Study 2 (N = 42 countries) conceptually replicated the central finding using aggregate indices of national identity (obtained using the World Values Survey) and a measure of actual behaviour change during the pandemic (obtained from Google mobility reports). Higher levels of national identification prior to the pandemic predicted lower mobility during the early stage of the pandemic (r = -0.40). We discuss the potential implications of links between national identity, leadership, and public health for managing COVID-19 and future pandemics.
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| 36. |
- Wen, Bo, et al.
(författare)
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Comparison for the effects of different components of temperature variability on mortality : A multi-country time-series study
- 2024
-
Ingår i: Environment International. - : Elsevier. - 0160-4120 .- 1873-6750. ; 187
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Temperature variability (TV) is associated with increased mortality risk. However, it is still unknown whether intra-day or inter-day TV has different effects. Objectives: We aimed to assess the association of intra-day TV and inter-day TV with all-cause, cardiovascular, and respiratory mortality.Methods: We collected data on total, cardiovascular, and respiratory mortality and meteorology from 758 locations in 47 countries or regions from 1972 to 2020. We defined inter-day TV as the standard deviation (SD) of daily mean temperatures across the lag interval, and intra-day TV as the average SD of minimum and maximum temperatures on each day. In the first stage, inter-day and intra-day TVs were modelled simultaneously in the quasi-Poisson time-series model for each location. In the second stage, a multi-level analysis was used to pool the location-specific estimates.Results: Overall, the mortality risk due to each interquartile range [IQR] increase was higher for intra-day TV than for inter-day TV. The risk increased by 0.59% (95% confidence interval [CI]: 0.53, 0.65) for all-cause mortality, 0.64% (95% CI: 0.56, 0.73) for cardiovascular mortality, and 0.65% (95% CI: 0.49, 0.80) for respiratory mortality per IQR increase in intra-day TV0–7 (0.9 °C). An IQR increase in inter-day TV0–7 (1.6 °C) was associated with 0.22% (95% CI: 0.18, 0.26) increase in all-cause mortality, 0.44% (95% CI: 0.37, 0.50) increase in cardiovascular mortality, and 0.31% (95% CI: 0.21, 0.41) increase in respiratory mortality. The proportion of all-cause deaths attributable to intra-day TV0–7 and inter-day TV0–7 was 1.45% and 0.35%, respectively. The mortality risks varied by lag interval, climate area, season, and climate type.Conclusions: Our results indicated that intra-day TV may explain the main part of the mortality risk related to TV and suggested that comprehensive evaluations should be proposed in more countries to help protect human health.
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| 37. |
- Wesolowska, Paulina, et al.
(författare)
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Testing the methodology for a dosimetric end-to-end audit of IMRT/VMAT: results of IAEA multicentre and national studies
- 2019
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Ingår i: Acta Oncologica. - : TAYLOR & FRANCIS LTD. - 0284-186X .- 1651-226X. ; 58:12, s. 1731-1739
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: Within an International Atomic Energy Agency (IAEA) co-ordinated research project (CRP), a remote end-to-end dosimetric quality audit for intensity modulated radiation therapy (IMRT)/ volumetric arc therapy (VMAT) was developed to verify the radiotherapy chain including imaging, treatment planning and dose delivery. The methodology as well as the results obtained in a multicentre pilot study and national trial runs conducted in close cooperation with dosimetry audit networks (DANs) of IAEA Member States are presented. Material and methods: A solid polystyrene phantom containing a dosimetry insert with an irregular solid water planning target volume (PTV) and organ at risk (OAR) was designed for this audit. The insert can be preloaded with radiochromic film and four thermoluminescent dosimeters (TLDs). For the audit, radiotherapy centres were asked to scan the phantom, contour the structures, create an IMRT/VMAT treatment plan and irradiate the phantom. The dose prescription was to deliver 4 Gy to the PTV in two fractions and to limit the OAR dose to a maximum of 2.8 Gy. The TLD measured doses and film measured dose distributions were compared with the TPS calculations. Results: Sixteen hospitals from 13 countries and 64 hospitals from 6 countries participated in the multicenter pilot study and in the national runs, respectively. The TLD results for the PTV were all within +/- 5% acceptance limit for the multicentre pilot study, whereas for national runs, 17 participants failed to meet this criterion. All measured doses in the OAR were below the treatment planning constraint. The film analysis identified seven plans in national runs below the 90% passing rate gamma criteria. Conclusion: The results proved that the methodology of the IMRT/VMAT dosimetric end-to-end audit was feasible for its intended purpose, i.e., the phantom design and materials were suitable; the phantom was easy to use and it was robust enough for shipment. Most importantly the audit methodology was capable of identifying suboptimal IMRT/VMAT delivery.
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| 38. |
- Wu, Hua, et al.
(författare)
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Bandgap Tuning of Silver Bismuth Iodide via Controllable Bromide Substitution for Improved Photovoltaic Performance
- 2019
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Ingår i: ACS Applied Energy Materials. - : American Chemical Society (ACS). - 2574-0962. ; 2:8, s. 5356-5362
-
Tidskriftsartikel (refereegranskat)abstract
- In this work, silver-bismuth-halide thin films, exhibiting low toxicity and good stability, were explored systemically by gradually substituting iodide, I, with bromide, Br, in the AgBi2I7 system. It was found that the optical bandgap can be tuned by varying the I/Br ratio. Moreover, the film quality was improved when introducing a small amount of Br. The solar cell was demonstrated to be more stable at ambient conditions and most efficient when incorporating 10% Br, as a result of decreased recombination originating from the increased grain size. Thus, replacing a small amount of I with Br was beneficial for photovoltaic performance.
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| 39. |
- Wu, Hemmings, et al.
(författare)
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Deep brain stimulation for refractory obsessive-compulsive disorder (OCD) : emerging or established therapy?
- 2021
-
Ingår i: Molecular Psychiatry. - : Springer Nature. - 1359-4184 .- 1476-5578. ; 26, s. 60-65
-
Tidskriftsartikel (refereegranskat)abstract
- A consensus has yet to emerge whether deep brain stimulation (DBS) for treatment-refractory obsessive-compulsive disorder (OCD) can be considered an established therapy. In 2014, the World Society for Stereotactic and Functional Neurosurgery (WSSFN) published consensus guidelines stating that a therapy becomes established when "at least two blinded randomized controlled clinical trials from two different groups of researchers are published, both reporting an acceptable risk-benefit ratio, at least comparable with other existing therapies. The clinical trials should be on the same brain area for the same psychiatric indication." The authors have now compiled the available evidence to make a clear statement on whether DBS for OCD is established therapy. Two blinded randomized controlled trials have been published, one with level I evidence (Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score improved 37% during stimulation on), the other with level II evidence (25% improvement). A clinical cohort study (N = 70) showed 40% Y-BOCS score improvement during DBS, and a prospective international multi-center study 42% improvement (N = 30). The WSSFN states that electrical stimulation for otherwise treatment refractory OCD using a multipolar electrode implanted in the ventral anterior capsule region (including bed nucleus of stria terminalis and nucleus accumbens) remains investigational. It represents an emerging, but not yet established therapy. A multidisciplinary team involving psychiatrists and neurosurgeons is a prerequisite for such therapy, and the future of surgical treatment of psychiatric patients remains in the realm of the psychiatrist.
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| 40. |
- Wu, Haizhou, 1987, et al.
(författare)
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Protein-binding approaches for improving bioaccessibility and bioavailability of anthocyanins
- 2023
-
Ingår i: Comprehensive Reviews in Food Science and Food Safety. - : Wiley. - 1541-4337. ; 22:1, s. 333-354
-
Forskningsöversikt (refereegranskat)abstract
- Color is an important characteristic of food. Over the last 15 years, more attention has been paid to natural colorants because of the rising demand for clean-label food products. Anthocyanins, which are a group of phytochemicals responsible for the purple, blue or red hues of many plants, offer a market advantage. In addition, anthocyanin-rich foods are associated with protection against cardiovascular disease, thrombosis, diabetes, cancer, microbial-based disorders, neurological disorders, and vision ailments. However, the real health value of anthocyanins, whether as a natural colorant or a functional ingredient, is dependent on the ultimate bioaccessibility and bioavailability in the human body. Many animal and human clinical studies revealed that, after intake of anthocyanin-rich foods or anthocyanin extracts, only trace amounts (< 1% of ingested content) of anthocyanins or their predicted metabolites were detected in plasma after a standard blood draw, which was indicative of low bioavailability of anthocyanins. Protein binding to anthocyanins is a strategy that has recently been reported to enhance the ultimate bioactivity, bioaccessibility, and bioavailability of anthocyanins as compared to anthocyanins delivered without a protein carrier. Therefore, in this review, we address anthocyanin properties in food processing and digestion, anthocyanin-protein complexes used in food matrices, and changes in the bioaccessibility and bioavailability of anthocyanins when bound into anthocyanin-protein complexes in foods. Finally, we summarize the challenges and prospects of this delivery system for anthocyanin pigments.
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| 41. |
- Wu, Ping-Hsun, 1982-, et al.
(författare)
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The relationship of indoxyl sulfate and p-cresyl sulfate with target cardiovascular proteins in hemodialysis patients
- 2021
-
Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 11
-
Tidskriftsartikel (refereegranskat)abstract
- Protein-bound uremic toxins (Indoxyl sulfate [IS] and p-cresyl sulfate [PCS]) are both associated with cardiovascular (CV) and all-cause mortality in subjects with chronic kidney disease (CKD). Possible mechanisms have not been elucidated. In hemodialysis patients, we investigated the relationship between the free form of IS and PCS and 181 CV-related proteins. First, IS or PCS concentrations were checked, and high levels were associated with an increased risk of acute coronary syndrome (ACS) in 333 stable HD patients. CV proteins were further quantified by a proximity extension assay. We examined associations between the free form protein-bound uremic toxins and the quantified proteins with correction for multiple testing in the discovery process. In the second step, the independent association was evaluated by multivariable-adjusted models. We rank the CV proteins related to protein-bound uremic toxins by bootstrapped confidence intervals and ascending p-value. Six proteins (signaling lymphocytic activation molecule family member 5, complement component C1q receptor, C-C motif chemokine 15 [CCL15], bleomycin hydrolase, perlecan, and cluster of differentiation 166 antigen) were negatively associated with IS. Fibroblast growth factor 23 [FGF23] was the only CV protein positively associated with IS. Three proteins (complement component C1q receptor, CCL15, and interleukin-1 receptor-like 2) were negatively associated with PCS. Similar findings were obtained after adjusting for classical CV risk factors. However, only higher levels of FGF23 was related to increased risk of ACS. In conclusion, IS and PCS were associated with several CV-related proteins involved in endothelial barrier function, complement system, cell adhesion, phosphate homeostasis, and inflammation. Multiplex proteomics seems to be a promising way to discover novel pathophysiology of the uremic toxin.
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| 42. |
- Wu, Yao, et al.
(författare)
-
Fluctuating temperature modifies heat-mortality association around the globe
- 2022
-
Ingår i: The Innovation. - : Cell Press. - 2666-6758. ; 3:2
-
Tidskriftsartikel (refereegranskat)abstract
- Studies have investigated the effects of heat and temperature variability (TV) on mortality. However, few assessed whether TV modifies the heat-mortality association. Data on daily temperature and mortality in the warm season were collected from 717 locations across 36 countries. TV was calculated as the standard deviation of the average of the same and previous days’ minimum and maximum temperatures. We used location-specific quasi-Poisson regression models with an interaction term between the cross-basis term for mean temperature and quartiles of TV to obtain heat-mortality associations under each quartile of TV, and then pooled estimates at the country, regional, and global levels. Results show the increased risk in heat-related mortality with increments in TV, accounting for 0.70% (95% confidence interval [CI]: −0.33 to 1.69), 1.34% (95% CI: −0.14 to 2.73), 1.99% (95% CI: 0.29–3.57), and 2.73% (95% CI: 0.76–4.50) of total deaths for Q1–Q4 (first quartile–fourth quartile) of TV. The modification effects of TV varied geographically. Central Europe had the highest attributable fractions (AFs), corresponding to 7.68% (95% CI: 5.25–9.89) of total deaths for Q4 of TV, while the lowest AFs were observed in North America, with the values for Q4 of 1.74% (95% CI: −0.09 to 3.39). TV had a significant modification effect on the heat-mortality association, causing a higher heat-related mortality burden with increments of TV. Implementing targeted strategies against heat exposure and fluctuant temperatures simultaneously would benefit public health.
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| 43. |
- Wu, Yao, et al.
(författare)
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Global, regional, and national burden of mortality associated with short-term temperature variability from 2000–19 : a three-stage modelling study
- 2022
-
Ingår i: The Lancet Planetary Health. - : Elsevier. - 2542-5196. ; 6:5, s. e410-e421
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Increased mortality risk is associated with short-term temperature variability. However, to our knowledge, there has been no comprehensive assessment of the temperature variability-related mortality burden worldwide. In this study, using data from the MCC Collaborative Research Network, we first explored the association between temperature variability and mortality across 43 countries or regions. Then, to provide a more comprehensive picture of the global burden of mortality associated with temperature variability, global gridded temperature data with a resolution of 0·5° × 0·5° were used to assess the temperature variability-related mortality burden at the global, regional, and national levels. Furthermore, temporal trends in temperature variability-related mortality burden were also explored from 2000–19.Methods: In this modelling study, we applied a three-stage meta-analytical approach to assess the global temperature variability-related mortality burden at a spatial resolution of 0·5° × 0·5° from 2000–19. Temperature variability was calculated as the SD of the average of the same and previous days’ minimum and maximum temperatures. We first obtained location-specific temperature variability related-mortality associations based on a daily time series of 750 locations from the Multi-country Multi-city Collaborative Research Network. We subsequently constructed a multivariable meta-regression model with five predictors to estimate grid-specific temperature variability related-mortality associations across the globe. Finally, percentage excess in mortality and excess mortality rate were calculated to quantify the temperature variability-related mortality burden and to further explore its temporal trend over two decades.Findings: An increasing trend in temperature variability was identified at the global level from 2000 to 2019. Globally, 1 753 392 deaths (95% CI 1 159 901–2 357 718) were associated with temperature variability per year, accounting for 3·4% (2·2–4·6) of all deaths. Most of Asia, Australia, and New Zealand were observed to have a higher percentage excess in mortality than the global mean. Globally, the percentage excess in mortality increased by about 4·6% (3·7–5·3) per decade. The largest increase occurred in Australia and New Zealand (7·3%, 95% CI 4·3–10·4), followed by Europe (4·4%, 2·2–5·6) and Africa (3·3, 1·9–4·6).Interpretation: Globally, a substantial mortality burden was associated with temperature variability, showing geographical heterogeneity and a slightly increasing temporal trend. Our findings could assist in raising public awareness and improving the understanding of the health impacts of temperature variability. Funding: Australian Research Council, Australian National Health & Medical Research Council.
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| 44. |
- Xu, Feng, et al.
(författare)
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Broadband spectroscopic sensor for real-time monitoring of industrial SO2 emissions
- 2007
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Ingår i: Applied Optics. - 2155-3165. ; 46:13, s. 2503-2506
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Tidskriftsartikel (refereegranskat)abstract
- A spectroscopic system for continuous real-time monitoring of SO2, concentrations in industrial emissions was developed. The sensor is well suited for field applications due to simple and compact instrumental design, and robust data evaluation based on ultraviolet broadband absorption without the use of any calibration cell. The sensor has a detection limit of 1 ppm, and was employed both for gas-flow simulations with and without suspended particles, and for in situ measurement of SO2 concentrations in the flue gas emitted from an industrial coal-fired boiler. The price/performance ratio of the instrument is expected to be superior to other comparable real-time monitoring systems.
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| 45. |
- Xu, F., et al.
(författare)
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Temperature-corrected spectroscopic evaluation method for gas concentration monitoring
- 2007
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Ingår i: Applied Physics B. - : Springer Science and Business Media LLC. - 0946-2171 .- 1432-0649. ; 86:2, s. 361-364
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Tidskriftsartikel (refereegranskat)abstract
- Combustion exhaust monitoring was simulated by measurement on a sulfur dioxide flow at different temperatures using broadband absorption spectroscopy and electrochemical analysis. A linear relationship with varying rates of slope for different temperatures was found between the gas concentrations obtained using the two methods, attributed to the influence of gas volume increase and absorption line broadening. By utilizing the differential absorption at an on/off pair combined with an experimentally determined temperature correction coefficient, the sulfur dioxide concentration was evaluated with the spectroscopic method yielding a measurement precision of 4%.
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| 46. |
- Yang, Tianhao, et al.
(författare)
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Simultaneous Control of Soot Emissions and Pressure Rise Rate in Gasoline PPC Engine
- 2017
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Ingår i: Proceedings of the 2017 IEEE Conference on Control Technology and Applications (CCTA). - 9781509021826 ; , s. 572-577
-
Konferensbidrag (refereegranskat)abstract
- Partially Premixed Combustion (PPC) is an advanced combustion concept resulting in high efficiencies and low emission levels by the use of high levels of EGR and pilot injections. The main limitation of PPC to use in practice lies in the high pressure rise rate, which causes issues on engine noise and durability. In addition, soot emissions face with the overshoot problem during the transient operations. This paper proposes an approach to simultaneously control soot emissions and maximum pressure rise rate. The controller presented in this paper consists of measured cylinder pressure, a control-oriented soot model, a set of feedforward PI controllers for combustion phasing and engine load, and a set of gain-scheduled PI controllers for soot and pressure rise rate. The controller was implemented on a Scania D13 heavy-duty engine, and evaluated during a load transient operation. By manipulating the pilot injection strategy, soot emissions were able to meet the Euro 6 heavy-duty emission standard without an aftertreatment system, and pressure rise rate was limited to a relatively low level without too much compromising the engine efficiency.
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| 47. |
- Zhang, Y. G., et al.
(författare)
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An optical system for measuring nitric oxide using spectral separation techniques
- 2012
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Ingår i: Applied physics. B, Lasers and optics (Print). - : Springer Science and Business Media LLC. - 0946-2171 .- 1432-0649. ; 107:2, s. 435-440
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Tidskriftsartikel (refereegranskat)abstract
- An optical sensor based on differential absorption spectroscopy for real-time monitoring of industrial nitric oxide (NO) gas emission is described. The influence of gas absorption interference from sulfur dioxide (SO2) in the environment was considered and a spectral separation technique was developed in order to eliminate this interference effect. The absorption spectrum of SO2 around 226 nm was evaluated by the SO2 concentration obtained using the experimentally recorded absorption spectrum around 300 nm. The absorption spectrum of NO around 226 nm was obtained by subtracting the absorption of SO2 from the integral absorption spectrum of SO2 and NO. The concentration measurements were performed at atmospheric pressure. The technique was found to have a lower detection limit of 0.8 ppm for NO per meter path length (SNR=2) and be immune from the influence from SO2 on the NO measurement. The sensor based on this technique was successfully employed for in situ measurement of SO2 and NO concentrations in the flue gas emitted from an industrial coal-fired boiler.
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| 48. |
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| 49. |
- Zhu, Huimin, et al.
(författare)
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Tuning the Bandgap in Silver Bismuth Iodide Materials by Partly Substituting Bismuth with Antimony for Improved Solar Cell Performance
- 2020
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Ingår i: ACS Applied Energy Materials. - : American Chemical Society (ACS). - 2574-0962. ; 3:8, s. 7372-7382
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Tidskriftsartikel (refereegranskat)abstract
- Silver bismuth iodide (Ag–Bi–I) light absorbers are interesting candidates as lead-free and low-toxic metal-halide materials for solar cell applications. In this work, the partial exchange of bismuth, Bi, with antimony, Sb, is investigated in samples prepared from a solution targeting stoichiometry AgBi2I7. Samples with a gradually increased exchange of Bi by Sb are prepared and light absorption measurements show that the absorption edge is gradually blue-shifted with increasing the amount of Sb. This trend in the shift in combination with the X-ray diffraction and X-ray photoelectron spectroscopy measurements, suggest that new materials with a mixture of Sb and Bi are formed. The density functional theory based electronic structure calculations reproduce the trend observed in the experiments when including spin–orbit coupling, which indicates the importance of relativistic effects in these materials. X-ray photoelectron spectroscopy is used to characterize the materials, and confirms the exchange of Bi to Sb in the samples. When Sb is included in the material, the grain size changes between 50 and 200 nm and the solar cell performance also changes. An optimal power conversion efficiency with excellent reproducibility and stability is obtained for a solar cell with the ratio of Sb/Bi equal to 3.
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