| 101. |
- Kottyan, Leah C., et al.
(författare)
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The IRF5-TNPO3 association with systemic lupus erythematosus has two components that other autoimmune disorders variably share.
- 2015
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 24:2, s. 582-596
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Tidskriftsartikel (refereegranskat)abstract
- Exploiting genotyping, DNA sequencing, imputation and trans-ancestral mapping, we used Bayesian and frequentist approaches to model the IRF5-TNPO3 locus association, now implicated in two immunotherapies and seven autoimmune diseases. Specifically, in systemic lupus erythematosus (SLE), we resolved separate associations in the IRF5 promoter (all ancestries) and with an extended European haplotype. We captured 3230 IRF5-TNPO3 high-quality, common variants across 5 ethnicities in 8395 SLE cases and 7367 controls. The genetic effect from the IRF5 promoter can be explained by any one of four variants in 5.7 kb (P-valuemeta = 6 × 10(-49); OR = 1.38-1.97). The second genetic effect spanned an 85.5-kb, 24-variant haplotype that included the genes IRF5 and TNPO3 (P-valuesEU = 10(-27)-10(-32), OR = 1.7-1.81). Many variants at the IRF5 locus with previously assigned biological function are not members of either final credible set of potential causal variants identified herein. In addition to the known biologically functional variants, we demonstrated that the risk allele of rs4728142, a variant in the promoter among the lowest frequentist probability and highest Bayesian posterior probability, was correlated with IRF5 expression and differentially binds the transcription factor ZBTB3. Our analytical strategy provides a novel framework for future studies aimed at dissecting etiological genetic effects. Finally, both SLE elements of the statistical model appear to operate in Sjögrens syndrome and systemic sclerosis whereas only the IRF5-TNPO3 gene-spanning haplotype is associated with primary biliary cirrhosis, demonstrating the nuance of similarity and difference in autoimmune disease risk mechanisms at IRF5-TNPO3.
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| 102. |
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| 103. |
- Leonard, JA, et al.
(författare)
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From wild wolf to domestic dog
- 2006
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Ingår i: The dog and its genome. - : Cold Spring Harbor Laboratory Press, New York.
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 104. |
- Lessard, Christopher J., et al.
(författare)
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Identification of a Systemic Lupus Erythematosus Susceptibility Locus at 11p13 between PDHX and CD44 in a Multiethnic Study
- 2011
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 88:1, s. 83-91
-
Tidskriftsartikel (refereegranskat)abstract
- Systemic lupus erythematosus (SLE) is considered to be the prototypic autoimmune disease, with a complex genetic architecture influenced by environmental factors. We sought to replicate a putative association at 11p13 not yet exceeding genome-wide significance (p < 5 x 10(-8)) identified in a genome-wide association study (GWAS). Our GWA scan identified two intergenic SNPs located between PDHX and CD44 showing suggestive evidence of association with SLE in cases of European descent (rs2732552, p = 0.004, odds ratio [OR] = 0.78; rs387619, p = 0.003, OR = 0.78). The replication cohort consisted of >15,000 subjects, including 3562 SLE cases and 3491 controls of European ancestry, 1527 cases and 1811 controls of African American (AA) descent, and 1265 cases and 1260 controls of Asian origin. We observed robust association at both rs2732552 (p = 9.03 x 10(-8), OR = 0.83) and rs387619 (p = 7.7 x 10(-7), OR = 0.83) in the European samples with p(meta) = 1.82 x 10(-9) for rs2732552. The AA and Asian SLE cases also demonstrated association at rs2732552 (p = 5 x 10(-3), OR = 0.81 and p = 4.3 x 10(-4), OR = 0.80, respectively). A meta-analysis of rs2732552 for all racial and ethnic groups studied produced p(meta) = 2.36 x 10(-13). This locus contains multiple regulatory sites that could potentially affect expression and functions of CD44, a cell-surface glycoprotein influencing immunologic, inflammatory, and oncologic phenotypes, or PDHX, a subunit of the pyruvate dehydrogenase complex.
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| 105. |
- Lessard, Christopher J., et al.
(författare)
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Identification of IRF8, TMEM39A, and IKZF3-ZPBP2 as Susceptibility Loci for Systemic Lupus Erythematosus in a Large-Scale Multiracial Replication Study
- 2012
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 90:4, s. 648-660
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Tidskriftsartikel (refereegranskat)abstract
- Systemic lupus erythematosus (SLE) is a chronic heterogeneous autoimmune disorder characterized by the loss of tolerance to self-antigens and dysregulated interferon responses. The etiology of SLE is complex, involving both heritable and environmental factors. Candidate-gene studies and genome-wide association (GWA) scans have been successful in identifying new loci that contribute to disease susceptibility; however, much of the heritable risk has yet to be identified. In this study, we sought to replicate 1,580 variants showing suggestive association with SLE in a previously published GWA scan of European Americans; we tested a multiethnic population consisting of 7,998 SLE cases and 7,492 controls of European, African American, Asian, Hispanic, Gullah, and Amerindian ancestry to find association with the disease. Several genes relevant to immunological pathways showed association with SLE. Three loci exceeded the genome-wide significance threshold: interferon regulatory factor 8 (IRF8; rs11644034; p(meta-Euro) = 2.08 x 10(-10)), transmembrane protein 39A (TMEM39A; rs1132200; p(meta-all) 8.62 x 10(-9)), and 17q21 (rs1453560; p(meta-all) = 3.48 x 10(-10)) between IKAROS family of zinc finger 3 (AIOLOS; IKZF3) and zona pellucida binding protein 2 (ZPBP2). Fine mapping, resequencing, imputation, and haplotype analysis of IRF8 indicated that three independent effects tagged by rs8046526, rs450443, and rs4843869, respectively, were required for risk in individuals of European ancestry. Eleven additional replicated effects (5 x 10(-8) < p(meta-Euro) < 9.99 x 10(-5)) were observed with CFHR1, CADM2, LOC730109/IL12A, LPP, LOC63920, SLU7, ADAMTSL1, C10orf64, OR8D4 FAM19A2, and STXBP6. The results of this study increase the number of confirmed SLE risk loci and identify others warranting further investigation.
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| 106. |
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| 107. |
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| 108. |
- Malapelle, Umberto, et al.
(författare)
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Predictive molecular pathology in the time of coronavirus disease (COVID-19) in Europe
- 2021
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Ingår i: Journal of Clinical Pathology. - : BMJ. - 0021-9746 .- 1472-4146. ; 74:6, s. 391-395
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Tidskriftsartikel (refereegranskat)abstract
- Aims Lung cancer predictive biomarker testing is essential to select advanced-stage patients for targeted treatments and should be carried out without delays even during health emergencies, such as the coronavirus (COVID-19) outbreak. Methods Fifteen molecular laboratories from seven different European countries compared 4 weeks of national lockdown to a corresponding period in 2019, in terms of tissue and/or plasma-based molecular test workload, analytical platforms adopted, number of cases undergoing programmed death-ligand1 (PD-L1) expression assessment and DNA-based molecular tests turnaround time. Results In most laboratories (80.0%), tissue-based molecular test workload was reduced. In 40.0% of laboratories (6/15), the decrease was >25%, and in one, reduction was as high as 80.0%. In this instance, a concomitant increase in liquid biopsy was reported (60.0%). Remarkably, in 33.3% of the laboratories, real-time PCR (RT-PCR)-based methodologies increased, whereas highly multiplexing assays approaches decreased. Most laboratories (88.9%) did not report significant variations in PD-L1 volume testing. Conclusions The workload of molecular testing for patients with advanced-stage lung cancer during the lockdown showed little variations. Local strategies to overcome health emergency-related issues included the preference for RT-PCR tissue-based testing methodologies and, occasionally, for liquid biopsy.
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| 109. |
- Malapelle, Umberto, et al.
(författare)
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Reference standards for gene fusion molecular assays on cytological samples : an international validation study
- 2023
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Ingår i: Journal of Clinical Pathology. - : BMJ. - 0021-9746 .- 1472-4146. ; 76:1, s. 47-52
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Tidskriftsartikel (refereegranskat)abstract
- Aims Gene fusions assays are key for personalised treatments of advanced human cancers. Their implementation on cytological material requires a preliminary validation that may make use of cell line slides mimicking cytological samples. In this international multi-institutional study, gene fusion reference standards were developed and validated. Methods Cell lines harbouring EML4(13)–ALK(20) and SLC34A2(4)–ROS1(32) gene fusions were adopted to prepare reference standards. Eight laboratories (five adopting amplicon-based and three hybridisation-based platforms) received, at different dilution points two sets of slides (slide A 50.0%, slide B 25.0%, slide C 12.5% and slide D wild type) stained by Papanicolaou (Pap) and May Grunwald Giemsa (MGG). Analysis was carried out on a total of 64 slides. Results Four (50.0%) out of eight laboratories reported results on all slides and dilution points. While 12 (37.5%) out of 32 MGG slides were inadequate, 27 (84.4%) out of 32 Pap slides produced libraries adequate for variant calling. The laboratories using hybridisation-based platforms showed the highest rate of inadequate results (13/24 slides, 54.2%). Conversely, only 10.0% (4/40 slides) of inadequate results were reported by laboratories adopting amplicon-based platforms. Conclusions Reference standards in cytological format yield better results when Pap staining and processed by amplicon-based assays. Further investigation is required to optimise these standards for MGG stained cells and for hybridisation-based approaches.
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| 110. |
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| 111. |
- Maldonado, JE, et al.
(författare)
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Tripartite genetic subdivisions in the ornate shrew (Sorex ornatus)
- 2001
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Ingår i: MOLECULAR ECOLOGY. - : BLACKWELL SCIENCE LTD. - 0962-1083. ; 10:1, s. 127-147
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Tidskriftsartikel (refereegranskat)abstract
- We examined cytochrome b sequence variation in 251 ornate shrews (Sorex ornatus) from 20 localities distributed throughout their geographical range. Additionally, vagrant (S. vagrans) and montane (S. monticolus) shrews from four localities were used as ou
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| 112. |
- Mallor, Fermin, et al.
(författare)
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Modal decomposition of flow fields and convective heat transfer maps : An application to wall-proximity square ribs
- 2019
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Ingår i: Experimental Thermal and Fluid Science. - : Elsevier. - 0894-1777 .- 1879-2286. ; , s. 517-527
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Tidskriftsartikel (refereegranskat)abstract
- In this work the modal decomposition of convective heat transfer distributions in turbulent flows is explored. The organization and thermal footprint of the turbulent flow features generated downstream of wall-proximity two-dimensional square ribs immersed in a turbulent boundary layer are investigated experimentally. This study employs modal decomposition to investigate whether this analysis can allow identifying which characteristics of the flow topology are responsible for the Nusselt-number augmentation, aiming to uncover the underlying physics of heat-transfer enhancement. Heat transfer and flow velocity measurements are performed at a Reynolds number (based on the free-stream velocity and rib side-length) equal to 4600. Square ribs are tested for two different gap spacings from the wall (0.25 and 0.5 ribs side-length) and in wall-attached configuration. A low-thermal-inertia heat transfer sensor coupled with high-repetition-rate Infrared (IR) thermography is designed to study the unsteady variation of the convective heat-transfer coefficient downstream of the obstacles. Flow-field measurements are performed with non-time-resolved Particle Image Velocimetry (PIV). A modal analysis with Proper Orthogonal Decomposition (POD) is applied to both convective heat-transfer maps and velocity-fields. The comparison of the Nusselt-number spatial modes of the clean turbulent boundary layer configuration and of the configurations with the ribs shows a variation of the spatial pattern associated with oscillations with strong spanwise coherence, opposed to the thin elongated streaks which dominate the convective heat transfer in the clean turbulent boundary layer. In configurations where the convective heat transfer is enhanced by coherent structures located close to the wall, similar eigenspectra are observed for both flow field and convective heat transfer modes. The results of the modal analysis support a picture of a direct relation between the coherence of near-wall flow features and heat-transfer augmentation, providing a statistical evidence for the fact that near-wall coherent eddies are extremely efficient in enhancing heat transfer.
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| 113. |
- Martensson, Nils, et al.
(författare)
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On the relation between X-ray Photoelectron Spectroscopy and XAFS
- 2013
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Ingår i: 15th International Conference On X-Ray Absorption Fine Structure (XAFS15). - : IOP Publishing.
-
Konferensbidrag (refereegranskat)abstract
- XAFS and X-ray Photoelectron Spectroscopy (XPS) are element specific techniques used in a great variety of research fields. The near edge regime of XAFS provides information on the unoccupied electronic states of a system. For the detailed interpretation of the XAFS results, input from XPS is crucial. The combination of the two techniques is also the basis for the so called core-hole clock technique. One of the important aspects of photoelectron spectroscopy is its chemical sensitivity and that one can obtain detailed information about the composition of a sample. We have for a series of carbon based model molecules carefully investigated the relationship between core level photoelectron intensities and stoichiometry. We find strong EXAFS-like modulations of the core ionization cross sections as function of photon energy and that the intensities at high photon energies converge towards values that do not correspond to the stoichiometric ratios. The photoelectron intensities are dependent on the local molecular structure around the ionized atoms. These effects are well described by molecular calculations using multiple scattering theory and by considering the effects due to monopole shake-up and shake-off as well as to intramolecular inelastic scattering processes.
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| 114. |
- Mila-Aloma, M., et al.
(författare)
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Amyloid beta, tau, synaptic, neurodegeneration, and glial biomarkers in the preclinical stage of the Alzheimer's continuum
- 2020
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Ingår i: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 16:10, s. 1358-1371
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The biological pathways involved in the preclinical stage of the Alzheimer's continuum are not well understood. Methods: We used NeuroToolKit and Elecsys (R) immunoassays to measure cerebrospinal fluid (CSF) amyloid-beta (A beta)42, A beta 40, phosphorylated tau (p-tau), total tau (t-tau), neurofilament light (NfL), neurogranin, sTREM2, YKL40, GFAP, IL6, S100, and alpha-synuclein in cognitively unimpaired participants of the ALFA+ study, many within the Alzheimer's continuum. Results: CSF t-tau, p-tau, and neurogranin increase throughout aging only in A beta-positive individuals, whereas NfL and glial biomarkers increase with aging regardless of A beta status. We modelled biomarker changes as a function of CSF A beta 42/40, p-tau and p-tau/A beta 42 as proxies of disease progression. The first change observed in the Alzheimer's continuum was a decrease in the CSF A4 beta 42/40 ratio. This is followed by a steep increase in CSF p-tau; t-tau; neurogranin; and, to a lesser extent, in NfL and glial biomarkers. Discussion: Multiple biological pathways are altered and could be targeted very early in the Alzheimer's continuum.
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| 115. |
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| 116. |
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| 117. |
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| 118. |
- Murari, A., et al.
(författare)
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Implementation and exploitation of JET enhancements at different fuel mixtures in preparation for DT operation and next step devices
- 2019
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Ingår i: Fusion engineering and design. - : ELSEVIER SCIENCE SA. - 0920-3796 .- 1873-7196. ; 146, s. 741-744
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Tidskriftsartikel (refereegranskat)abstract
- In the framework of the ITER Physics Department of the EUROfusion Consortium, JET mission is focused on preparing for the next step devices by developing high performance scenarios and testing reactor relevant techniques and technologies. In terms of scenario development, a complete scan in isotopic composition has already started and, according to the present schedule, should include full T operation and culminate in a 50/50 DT campaign by 2020. In DD, significant increases in input power and various adjustments in fueling have allowed reaching the IPBp8(y,2) scaling up to 3 MA. A complete set of diagnostic upgrades is being implemented to support operation and to guarantee adequate scientific exploitation of the experiments. With regard to the technology, the main enhancements and specific tests are focused on maximizing the returns from the unprecedented 14 MeV neutron field and the tritium fuel cycle.
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| 119. |
- Oakman, C, et al.
(författare)
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Overall survival benefit for sequential doxorubicin-docetaxel compared with concurrent doxorubicin and docetaxel in node-positive breast cancer-8-year results of the Breast International Group 02-98 phase III trial
- 2013
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Ingår i: Annals of Oncology. - : Oxford University Press (OUP): Policy A1. - 0923-7534 .- 1569-8041. ; 24:5, s. 1203-1211
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Tidskriftsartikel (refereegranskat)abstract
- Background: In women with node-positive breast cancer, the Breast International Group (BIG) 02-98 tested the incorporation of docetaxel (Taxotere) into doxorubicin (Adriamycin)-based chemotherapy, and compared sequential and concurrent docetaxel. At 5 years, there was a trend for improved disease-free survival (DFS) with docetaxel. We present results at 8-year median follow-up and exploratory analyses within biologically defined subtypes. less thanbrgreater than less thanbrgreater thanMethods: Patients were randomly assigned to one of four treatments: (i) sequential control: doxorubicin (A) (75 mg/m(2)) x 4 -andgt; classical cyclophosphamide, methotrexate, 5-fluorouracil (CMF); (ii) concurrent control: doxorubicin, cyclophosphamide (AC)(60/600 mg/m(2)) x 4 -andgt; CMF; (iii) sequential docetaxel: A (75 mg/m(2)) x3 -andgt; docetaxel (T) (100 mg/m(2)) x3. CMF and (iv) concurrent docetaxel: AT(50/75 mg/m(2)) x 4 -andgt; CMF. The primary comparison evaluated docetaxel efficacy regardless of the schedule. Exploratory analyses were undertaken within biologically defined subtypes. less thanbrgreater than less thanbrgreater thanResults: Two thousand eight hundred and eighty-seven patients were enrolled. After 93.4 months of median follow-up, there were 916 DFS events. For the primary comparison, there was no significant improvement in DFS from docetaxel [hazard ratio (HR) = 0.91, 95% confidence interval (CI) = 0.80-1.05, P = 0.187]. In secondary comparisons, sequential docetaxel significantly improved DFS compared with sequential control (HR = 0.81, 95% CI = 0.67-0.99, P = 0.036), and significantly improved DFS (HR = 0.84, 95% CI = 0.72-0.99, P = 0.035) and overall survival (OS) (HR = 0.79, 95% CI = 0.65-0.98, P = 0.028) compared with concurrent doxorubicin-docetaxel. Luminal-A disease had the best prognosis. HRs favored addition of sequential docetaxel in all subtypes, except luminal-A; but this observation was not statistically supported because of limited numbers. less thanbrgreater than less thanbrgreater thanConclusion: With further follow-up, the sequential docetaxel schedule resulted in significantly better OS than concurrent doxorubicin-docetaxel, and continued to show better DFS than sequential doxorubicin-based control.
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| 120. |
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| 121. |
- Padial, José M., et al.
(författare)
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Deciphering the products of evolution at the species level: the need for an integrative taxonomy
- 2009
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Ingår i: Zoologica Scripta. - : Wiley. - 0300-3256 .- 1463-6409. ; 38:4, s. 431-447
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Tidskriftsartikel (refereegranskat)abstract
- Progress in molecular techniques together with the incorporation of phylogenetic analyses of DNA into taxonomy have caused an increase in the number of species' discoveries in groups with morphological characters that are difficult to study or in those containing polytypic species. But some emerged criticisms plead for a taxonomic conservatism grounded either on the requirement of providing evidences of morphological distinctiveness or reproductive barriers to erect new species names. In a case study of taxonomic research on Neotropical frogs, we combine several lines of evidence (morphological characters, prezygotic reproductive isolation and phylogenetic analyses of mitochondrial DNA) to test the status of 15 nominal species and to assess the degree of agreement of the different lines of evidence. Our study reveals that morphology alone is not sufficient to uncover all species, as there is no other single line of evidence independently. Full congruence between lines of evidence is restricted to only four out of the 15 species. Five species show congruence of two lines of evidence, whereas the remaining six are supported by only one. The use of divergence in morphological characters seems to be the most conservative approach to delineate species boundaries because it does not allow the identification of some sibling reciprocally monophyletic species differing in their advertisement calls. The separate analysis of differences in advertisement calls (evidence of reproductive isolation) or of phylogenetic data alone also shows limitations, because they do not support some morphological species. Our study shows that only an integrative approach combining all sources of evidence provides the necessary feedback to evaluate the taxonomic status of existing species and to detect putative new ones. Furthermore, the application of integrative taxonomy enables the identification of hypotheses about the existence of species that will probably be rejected or changed, and those that can be expected to persist.
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| 122. |
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| 123. |
- Pearman, Peter B., et al.
(författare)
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Monitoring of species' genetic diversity in Europe varies greatly and overlooks potential climate change impacts
- 2024
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Ingår i: Nature Ecology & Evolution. - : Springer Nature. - 2397-334X. ; 8:2, s. 267-281
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Tidskriftsartikel (refereegranskat)abstract
- Genetic monitoring of populations currently attracts interest in the context of the Convention on Biological Diversity but needs long-term planning and investments. However, genetic diversity has been largely neglected in biodiversity monitoring, and when addressed, it is treated separately, detached from other conservation issues, such as habitat alteration due to climate change. We report an accounting of efforts to monitor population genetic diversity in Europe (genetic monitoring effort, GME), the evaluation of which can help guide future capacity building and collaboration towards areas most in need of expanded monitoring. Overlaying GME with areas where the ranges of selected species of conservation interest approach current and future climate niche limits helps identify whether GME coincides with anticipated climate change effects on biodiversity. Our analysis suggests that country area, financial resources and conservation policy influence GME, high values of which only partially match species' joint patterns of limits to suitable climatic conditions. Populations at trailing climatic niche margins probably hold genetic diversity that is important for adaptation to changing climate. Our results illuminate the need in Europe for expanded investment in genetic monitoring across climate gradients occupied by focal species, a need arguably greatest in southeastern European countries. This need could be met in part by expanding the European Union's Birds and Habitats Directives to fully address the conservation and monitoring of genetic diversity. Comparing data on genetic monitoring efforts across Europe with the distributions of areas at species' climatic niche margins, the authors show that monitoring efforts should be expanded to populations at trailing niche margins to include genetic variation that may prove important for adaptation to ongoing climate warming.
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| 124. |
- Pérez-Granados, Cristian, et al.
(författare)
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European scenarios for future biological invasions
- 2024
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Ingår i: People and Nature. - 2575-8314. ; 6:1, s. 245-259
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Tidskriftsartikel (refereegranskat)abstract
- Invasive alien species are one of the major threats to global biodiversity, ecosystem integrity, nature's contributions to people and human health. While scenarios about potential future developments have been available for other global change drivers for quite some time, we largely lack an understanding of how biological invasions might unfold in the future across spatial scales.Based on previous work on global invasion scenarios, we developed a workflow to downscale global scenarios to a regional and policy-relevant context. We applied this workflow at the European scale to create four European scenarios of biological invasions until 2050 that consider different environmental, socio-economic and socio-cultural trajectories, namely the European Alien Species Narratives (Eur-ASNs).We compared the Eur-ASNs with their previously published global counterparts (Global-ASNs), assessing changes in 26 scenario variables. This assessment showed a high consistency between global and European scenarios in the logic and assumptions of the scenario variables. However, several discrepancies in scenario variable trends were detected that could be attributed to scale differences. This suggests that the workflow is able to capture scale-dependent differences across scenarios.We also compared the Global- and Eur-ASNs with the widely used Global and European Shared Socioeconomic Pathways (SSPs), a set of scenarios developed in the context of climate change to capture different future socio-economic trends. Our comparison showed considerable divergences in the scenario space occupied by the different scenarios, with overall larger differences between the ASNs and SSPs than across scales (global vs. European) within the scenario initiatives.Given the differences between the ASNs and SSPs, it seems that the SSPs do not adequately capture the scenario space relevant to understanding the complex future of biological invasions. This underlines the importance of developing independent but complementary scenarios focussed on biological invasions. The downscaling workflow we implemented and presented here provides a tool to develop such scenarios across different regions and contexts. This is a major step towards an improved understanding of all major drivers of global change, including biological invasions.
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| 125. |
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| 126. |
- Polikarpov, M., et al.
(författare)
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Towards virtual histology with X-ray grating interferometry
- 2023
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Ingår i: Scientific Reports. - 2045-2322. ; 13, s. 1-11
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Tidskriftsartikel (refereegranskat)abstract
- Breast cancer is the most common type of cancer worldwide. Diagnosing breast cancer relies on clinical examination, imaging and biopsy. A core-needle biopsy enables a morphological and biochemical characterization of the cancer and is considered the gold standard for breast cancer diagnosis. A histopathological examination uses high-resolution microscopes with outstanding contrast in the 2D plane, but the spatial resolution in the third, Z-direction, is reduced. In the present paper, we propose two high-resolution table-top systems for phase-contrast X-ray tomography of soft-tissue samples. The first system implements a classical Talbot–Lau interferometer and allows to perform ex-vivo imaging of human breast samples with a voxel size of 5.57 μm. The second system with a comparable voxel size relies on a Sigray MAAST X-ray source with structured anode. For the first time, we demonstrate the applicability of the latter to perform X-ray imaging of human breast specimens with ductal carcinoma in-situ. We assessed image quality of both setups and compared it to histology. We showed that both setups made it possible to target internal features of breast specimens with better resolution and contrast than previously achieved, demonstrating that grating-based phase-contrast X-ray CT could be a complementary tool for clinical histopathology.
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| 127. |
- Potts, Simon G., et al.
(författare)
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Developing European conservation and mitigation tools for pollination services: approaches of the STEP (Status and Trends of European Pollinators) project
- 2011
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Ingår i: Journal of Apicultural Research. - 0021-8839 .- 2078-6913. ; 50:2, s. 152-164
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Forskningsöversikt (refereegranskat)abstract
- Pollinating insects form a key component of European biodiversity, and provide a vital ecosystem service to crops and wild plants. There is growing evidence of declines in both wild and domesticated pollinators, and parallel declines in plants relying upon them. The STEP project (Status and Trends of European Pollinators, 2010-2015, www.step-project.net) is documenting critical elements in the nature and extent of these declines, examining key functional traits associated with pollination deficits, and developing a Red List for some European pollinator groups. Together these activities are laying the groundwork for future pollinator monitoring programmes. STEP is also assessing the relative importance of potential drivers of pollinator declines, including climate change, habitat loss and fragmentation, agrochemicals, pathogens, alien species, light pollution, and their interactions. We are measuring the ecological and economic impacts of declining pollinator services and floral resources, including effects on wild plant populations, crop production and human nutrition. STEP is reviewing existing and potential mitigation options, and providing novel tests of their effectiveness across Europe. Our work is building upon existing and newly developed datasets and models, complemented by spatially-replicated campaigns of field research to fill gaps in current knowledge. Findings are being integrated into a policy-relevant framework to create evidence-based decision support tools. STEP is establishing communication links to a wide range of stakeholders across Europe and beyond, including policy makers, beekeepers, farmers, academics and the general public. Taken together, the STEP research programme aims to improve our understanding of the nature, causes, consequences and potential mitigation of declines in pollination services at local, national, continental and global scales.
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| 128. |
- Prieto, C, et al.
(författare)
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Structural order and chemical disorder in the mechanically alloyed Fe-Co-Cu nano-crystalline system
- 2001
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Ingår i: Recent Res. Devel. Non-Crystalline Solids. - : Transworld Research Network, Kerala, India. ; 1, s. 151-169
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Tidskriftsartikel (refereegranskat)abstract
- In this paper we present a structural study of the formation of a metastable Fe-Co-Cu alloy that can be prepared by mechanical alloying. Several steps in the alloy formation are described by using three different techniques: X-ray absorption spectroscopy,
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| 129. |
- Ramirez, O., et al.
(författare)
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Genetic assessment of the Iberian wolf Canis lupus signatus captive breeding program
- 2006
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Ingår i: Conservation Genetics. - : Springer Science and Business Media LLC. - 1566-0621 .- 1572-9737. ; 7:6, s. 861-878
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Tidskriftsartikel (refereegranskat)abstract
- The main goal of ex situ conservation programs is to improve the chances of long term survival of natural populations by founding and managing captive colonies that can serve as a source of individuals for future reintroductions or to reinforce existing populations. The degree in which a captive breeding program has captured the genetic diversity existing in the source wild population has seldom been evaluated. In this study we evaluate the genetic diversity in wild and captive populations of the Iberian wolf, Canis lupus signatus, in order to assess how much genetic diversity is being preserved in the ongoing ex situ conservation program for this subspecies. A sample of domestic dogs was also included in the analysis for comparison. Seventy-four wolves and 135 dogs were genotyped at 13 unlinked microsatellite loci. The results show that genetic diversity in Iberian wolves is comparable in magnitude to that of other wild populations of gray wolf. Both the wild and the captive Iberian wolf populations have a similarly high genetic diversity indicating that no substantial loss of diversity has occurred in the captive-breeding program. The effective number of founders of the program was estimated as similar to 16, suggesting that all founders in the studbook pedigree were genetically independent. Our results emphasize also the genetic divergence between wolves and domestic dogs and indicate that our set of 13 microsatellite loci provide a powerful diagnostic test to distinguish wolves, dogs and their hybrids.
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| 130. |
- Roura-Pascual, Nuria, et al.
(författare)
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A scenario-guided strategy for the future management of biological invasions
- 2024
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Ingår i: Frontiers in Ecology and the Environment. - 1540-9295 .- 1540-9309.
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Forskningsöversikt (refereegranskat)abstract
- Future dynamics of biological invasions are highly uncertain because they depend on multiple social-ecological drivers. We used a scenario-based approach to explore potential management options for invasive species in Europe. During two workshops involving a multidisciplinary team of experts, we developed a management strategy arranged into 19 goals relating to policy, research, public awareness, and biosecurity. We conceived solutions for achieving these goals under different plausible future scenarios, and identified four interrelated recommendations around which any long-term strategy for managing invasive species can be structured: (1) a European biosecurity regime, (2) a dedicated communication strategy, (3) data standardization and management tools, and (4) a monitoring and assessment system. Finally, we assessed the feasibility of the management strategy and found substantial differences among scenarios. Collectively, our results indicate that it is time for a new strategy for managing biological invasions in Europe, one that is based on a more integrative approach across socioeconomic sectors and countries.
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| 131. |
- Sanmiguel Vila, C., et al.
(författare)
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Experimental realisation of near-equilibrium adverse-pressure-gradient turbulent boundary layers
- 2020
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Ingår i: Experimental Thermal and Fluid Science. - : Elsevier Inc.. - 0894-1777 .- 1879-2286. ; 112
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Tidskriftsartikel (refereegranskat)abstract
- A new experimental database of adverse-pressure-gradient (APG) turbulent boundary layers (TBLs) obtained through hot-wire anemometry and oil-film interferometry covering a momentum–loss Reynolds number 450<Reθ<23450 and Clauser pressure-gradient-parameter range up to β≈2.4 is presented. Both increasing and approximately constant β distributions with the same upstream history are characterised. Turbulence statistics are compared among the different pressure-gradient distributions with additional numerical and experimental zero-pressure-gradient (ZPG) TBL data. Cases at approximately constant β, which can be considered as canonical representations of the boundary layer under a certain pressure-gradient magnitude, exhibit skin-friction and shape-factor curves consistent with the ones proposed by Vinuesa et al. (2017). These curves show a similar scaling behaviour as those proposed by Nagib et al. (2007) for ZPG TBLs. The pre-multiplied power-spectral density is employed to study the differences in the large-scale energy content throughout the boundary layer. Two different large-scale phenomena are identified, the first one related to the pressure gradient and the second one (also present in high-Re ZPG TBLs) due to the Reynolds number. Recently proposed scaling laws by Kitsios et al. (2016) and Maciel et al. (2018) are tested over a wider Reynolds-number range and for different β cases. The mean velocity and streamwise velocity fluctuation profiles are found to be dependent on the upstream development. The mean velocity profile is found to be self-similar only in the outer region, in agreement with classical theory. The mean and higher-order statistics of the new APG TBL database are made available under www.flow.kth.se.
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| 132. |
- Sanmiguel Vila, C., et al.
(författare)
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Identifying well-behaved turbulent boundary layers
- 2017
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Ingår i: Progress in Turbulence VII. - Cham : Springer Science+Business Media B.V.. - 9783319579337 ; , s. 67-72
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Konferensbidrag (refereegranskat)abstract
- This paper presents a study focused on the development of zero-pressure-gradient turbulent boundary layers (ZPG TBL) towards well-behaved conditions in the low Reynolds-number range. A new method to assess the length required for the ZPG TBL to exhibit well-behaved conditions is proposed. The proposed method is based on the diagnostic-plot concept (Alfredsson et al., Phys. Fluids, 23:041702, 2011), which only requires mean and turbulence intensity measurements in the outer region of the boundary layer. In contrast to the existing methods which rely on empirical skin-friction curves, shape-factor or wake-parameter, the quantities required by this method are generally much easier to measure. To test the method, the evolution of six different tripping configurations, including weak, late and strong overtripping, are studied in a wind-tunnel experiment to assess the convergence of ZPG TBLs towards well-behaved conditions in the momentum-thickness based Reynolds-number range 500 < Reθ < 4000.
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| 133. |
- Sanmiguel Vila, C., et al.
(författare)
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Large-scale energy in turbulent boundary layers : Reynolds-number and pressure-gradient effects
- 2019
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Ingår i: Springer Proceedings in Physics. - Cham : Springer Nature. ; , s. 69-74
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Konferensbidrag (refereegranskat)abstract
- Adverse-pressure-gradient (APG) turbulent boundary layers (TBLs) are studied using hot-wire measurements which cover a Clauser pressure-gradient-parameter range up to β ≈ 2.4. Constant and non-constant β distributions with the same upstream history are studied. The pre-multiplied power-spectral density is employed to study the differences in the large-scale energy content throughout the boundary layer. Two different large-scale phenomena are identified, the first one due to the pressure gradient and the second one due to the Reynolds number; the latter is also present in high-Re ZPG TBLs. A decomposition of the streamwise velocity fluctuations using a temporal filter shows that the small-scale velocity fluctuations do not scale in APG TBL flows since the effect of the large-scale features extends up to the near-wall region.
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| 134. |
- Sanmiguel Vila, C., et al.
(författare)
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On the identification of well-behaved turbulent boundary layers
- 2017
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Ingår i: Journal of Fluid Mechanics. - : Cambridge University Press. - 0022-1120 .- 1469-7645. ; 822, s. 109-138
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Tidskriftsartikel (refereegranskat)abstract
- This paper introduces a new method based on the diagnostic plot (Alfredsson et al., Phys. Fluids, vol. 23, 2011, 041702) to assess the convergence towards a well-behaved zero-pressure-gradient (ZPG) turbulent boundary layer (TBL). The most popular and well-understood methods to assess the convergence towards a well-behaved state rely on empirical skin-friction curves (requiring accurate skin-friction measurements), shape-factor curves (requiring full velocity profile measurements with an accurate wall position determination) or wake-parameter curves (requiring both of the previous quantities). On the other hand, the proposed diagnostic-plot method only needs measurements of mean and fluctuating velocities in the outer region of the boundary layer at arbitrary wall-normal positions. To test the method, six tripping configurations, including optimal set-ups as well as both under- and overtripped cases, are used to quantify the convergence of ZPG TBLs towards well-behaved conditions in the Reynolds-number range covered by recent high-fidelity direct numerical simulation data up to a Reynolds number based on the momentum thickness and free-stream velocity of approximately 4000 (corresponding to 2.5 m from the leading edge) in a wind-tunnel experiment. Additionally, recent high-Reynolds-number data sets have been employed to validate the method. The results show that weak tripping configurations lead to deviations in the mean flow and the velocity fluctuations within the logarithmic region with respect to optimally tripped boundary layers. On the other hand, a strong trip leads to a more energized outer region, manifested in the emergence of an outer peak in the velocity-fluctuation profile and in a more prominent wake region. While established criteria based on skin-friction and shape-factor correlations yield generally equivalent results with the diagnostic-plot method in terms of convergence towards a well-behaved state, the proposed method has the advantage of being a practical surrogate that is a more efficient tool when designing the set-up for TBL experiments, since it diagnoses the state of the boundary layer without the need to perform extensive velocity profile measurements.
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| 135. |
- Sanmiguel Vila, C., et al.
(författare)
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Separating adverse-pressure-gradient and Reynolds-number effects in turbulent boundary layers
- 2020
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Ingår i: Physical Review Fluids. - : American Physical Society. - 2469-990X. ; 5:6
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Tidskriftsartikel (refereegranskat)abstract
- Zero pressure-gradient (ZPG) turbulent boundary layers (TBLs) at high Reynolds numbers (Re) and TBLs with adverse pressure gradients (APGs) share some similarities such as the emergence of an outer peak in the streamwise variance profile related to the enhancement of large-scale energy. Reynolds-number and pressure-gradient effects tend to cause such an energizing of the outer-layer structures, which makes it difficult to distinguish them, mainly because both effects are usually coupled. Using two experimental data sets of ZPG and APG TBLs in which Re and pressure gradient are analyzed independently, the present paper shows that the two effects have different imprints on the flow. In particular, the analysis shows that (1) the small-scale energy in APG TBLs is, contrary to canonical ZPG TBLs, not universal, but is dependent on the APG strength, (2) the APG enhances both the small- and large-scale energy in the outer region, and (3) the outer-peak location and the amplitude of the streamwise variance scale differently for increasing Re and APG magnitude. These findings may have ramifications on the development of turbulence models since the pressure gradient has a direct influence on the near-wall dynamics.
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| 136. |
- Sels, S., et al.
(författare)
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Doppler and sympathetic cooling for the investigation of short-lived radioactive ions
- 2022
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Ingår i: Physical Review Research. - 2643-1564. ; 4:3
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Tidskriftsartikel (refereegranskat)abstract
- At radioactive ion beam (RIB) facilities, ions of short-lived radionuclides are cooled and bunched in buffer-gas-filled Paul traps to improve the ion-beam quality for subsequent experiments. To deliver even colder ions, beneficial to RIB experiments' sensitivity or accuracy, we employ Doppler and sympathetic cooling in a Paul trap cooler-buncher. The improved emittance of Mg+, K+, and O2+ ion beams is demonstrated by a reduced time-of-flight spread of the extracted ion bunches with respect to room-temperature buffer-gas cooling. Cooling externally-produced hot ions with energies of at least 7 eV down to a few Kelvin is achieved in a timescale of O(100 ms) by combining a low-pressure helium background gas with laser cooling. This is sufficiently short to cool short-lived radioactive ions. As an example of this technique's use for RIB research, the mass-resolving power in a multireflection time-of-flight mass spectrometer is shown to increase by up to a factor of 4.6 with respect to buffer-gas cooling. Simulations show good agreement with the experimental results and guide further improvements and applications. These results open a path to a significant emittance improvement and, thus, unprecedented ion-beam qualities at RIB facilities, achievable with standard equipment readily available. The same method provides opportunities for future high-precision experiments with radioactive cold trapped ions.
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| 137. |
- Shafer, Aaron B. A., et al.
(författare)
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Genomics and the challenging translation into conservation practice
- 2015
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Ingår i: Trends in Ecology & Evolution. - : Elsevier. - 0169-5347 .- 1872-8383. ; 30:2, s. 78-87
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Tidskriftsartikel (refereegranskat)abstract
- The global loss of biodiversity continues at an alarming rate. Genomic approaches have been suggested as a promising tool for conservation practice as scaling up to genome-wide data can improve traditional conservation genetic inferences and provide qualitatively novel insights. However, the generation of genomic data and subsequent analyses and interpretations remain challenging and largely confined to academic research in ecology and evolution. This generates a gap between basic research and applicable solutions for conservation managers faced with multifaceted problems. Before the real-world conservation potential of genomic research can be realized, we suggest that current infrastructures need to be modified, methods must mature, analytical pipelines need to be developed, and successful case studies must be disseminated to practitioners.
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| 138. |
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| 139. |
- Shafer, Aaron B A, et al.
(författare)
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Reply to Garner et al
- 2016
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Ingår i: Trends in Ecology & Evolution. - : Elsevier BV. - 0169-5347 .- 1872-8383. ; 31:2, s. 83-84
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Tidskriftsartikel (refereegranskat)
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| 140. |
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| 141. |
- Stirpe, G. M., et al.
(författare)
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Monitoring of active galactic nuclei. V. The Seyfert 1 galaxy Markarian 279
- 1994
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Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 285:3, s. 857-867867
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Tidskriftsartikel (refereegranskat)abstract
- For pt. IV see ibid., vol.284, no.1, p.33-43 (1994). Reports on the Lovers of Active Galaxies' (LAG) monitoring of the Seyfert 1 galaxy Markarian 279 from January to June 1990. The source, which was in a very bright state, gradually weakened after the first month of monitoring: the Halpha and Hbeta flux decreased by 20% and 35% respectively, and the continuum under Halpha by 30%. The luminosity-weighted radius of the broad line region (BLR), as derived from the cross-correlation function, is of the order of 10 light days. This result is very uncertain because the features in the light curves are very shallow, but it is unlikely that the radius of the BLR is more than 1 light month. The profile variations of Halpha confirm that the prevailing motions are not radial. The data of the present campaign and those obtained in previous years, when the source was in a much weaker state, show that the red asymmetry of the Balmer lines correlates positively with the broad line flux. This new effect is briefly discussed
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| 142. |
- Strömberg, Ingrid, et al.
(författare)
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Blueberry- and spirulina-enriched diets enhance striatal dopamine recovery and induce a rapid, transient microglia activation after injury of the rat nigrostriatal dopamine system.
- 2005
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Ingår i: Experimental Neurology. - : Elsevier BV. - 0014-4886. ; 196:2, s. 298-307
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Tidskriftsartikel (refereegranskat)abstract
- Neuroinflammation plays a critical role in loss of dopamine neurons during brain injury and in neurodegenerative diseases. Diets enriched in foods with antioxidant and anti-inflammatory actions may modulate this neuroinflammation. The model of 6-hydroxydopamine (6-OHDA) injected into the dorsal striatum of normal rats, causes a progressive loss of dopamine neurons in the ventral mesencephalon. In this study, we have investigated the inflammatory response following 6-OHDA injected into the striatum of adult rats treated with diet enriched in blueberry or spirulina. One week after the dopamine lesion, a similar size of dopamine degeneration was found in the striatum and in the globus pallidus in all lesioned animals. At 1 week, a significant increase in OX-6- (MHC class II) positive microglia was found in animals fed with blueberry- and spirulina-enriched diets in both the striatum and the globus pallidus. These OX-6-positive cells were located within the area of tyrosine hydroxylase (TH) -negativity. At 1 month after the lesion, the number of OX-6-positive cells was reduced in diet-treated animals while a significant increase beyond that observed at 1 week was now present in lesioned control animals. Dopamine recovery as revealed by TH-immunohistochemistry was significantly enhanced at 4 weeks postlesion in the striatum while in the globus pallidus the density of TH-positive nerve fibers was not different from control-fed lesioned animals. In conclusion, enhanced striatal dopamine recovery appeared in animals treated with diet enriched in antioxidants and anti-inflammatory phytochemicals and coincided with an early, transient increase in OX-6-positive microglia.
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| 143. |
- Sublet, J. -Ch., et al.
(författare)
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Neutron-induced damage simulations : Beyond defect production cross-section, displacement per atom and iron-based metrics
- 2019
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Ingår i: The European Physical Journal Plus. - : Springer Berlin/Heidelberg. - 2190-5444. ; 134:7
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Forskningsöversikt (refereegranskat)abstract
- Nuclear interactions can be the source of atomic displacement and post-short-term cascade annealing defects in irradiated structural materials. Such quantities are derived from, or can be correlated to, nuclear kinematic simulations of primary atomic energy distributions spectra and the quantification of the numbers of secondary defects produced per primary as a function of the available recoils, residual and emitted, energies. Recoils kinematics of neutral, residual, charged and multi-particle emissions are now more rigorously treated based on modern, complete and enhanced nuclear data parsed in state of the art processing tools. Defect production metrics are the starting point in this complex problem of correlating and simulating the behaviour of materials under irradiation, as direct measurements are extremely improbable. The multi-scale dimensions (nuclear-atomic-molecular-material) of the simulation process is tackled from the Fermi gradation to provide the atomic- and meso-scale dimensions with better metrics relying upon a deeper understanding and modelling capabilities of the nuclear level. Detailed, segregated primary knock-on-atom metrics are now available as the starting point of further simulation processes of isolated and clustered defects in material lattices. This allows more materials, incident energy ranges and particles, and irradiations conditions to be explored, with sufficient data to adequately cover both standard applications and novel ones, such as advanced-fission, accelerators, nuclear medicine, space and fusion. This paper reviews the theory, describes the latest methodologies and metrics, and provides recommendations for standard and novel approaches.
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| 144. |
- Sundqvist, A-K, et al.
(författare)
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Unequal contribution of sexes in the origin of dog breeds.
- 2006
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Ingår i: Genetics. - 0016-6731. ; 172:2, s. 1121-8
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Tidskriftsartikel (refereegranskat)abstract
- Department of Evolutionary Biology, Uppsala University, Sweden. anna-karin.sundqvist@ebc.uu.seDogs (Canis familiaris) were domesticated from the gray wolf (Canis lupus) at least 14,000 years ago, and there is evidence of dogs with phenotypes similar to those in modern breeds 4000 years ago. However, recent genetic analyses have suggested that modern dog breeds have a much more recent origin, probably <200 years ago. To study the origin of contemporaneous breeds we combined the analysis of paternally inherited Y chromosome markers with maternally inherited mitochondrial DNA and biparentally inherited autosomal microsatellite markers in both domestic dogs and their wild ancestor, the gray wolf. Our results show a sex bias in the origin of breeds, with fewer males than females contributing genetically, which clearly differs from the breeding patterns in wild gray wolf populations where both sexes have similar contributions. Furthermore, a comparison of mitochondrial DNA and Y chromosome diversity in dog groups recognized by the World Canine Organization, as well as in groups defined by the breeds' genetic composition, shows that paternal lineages are more differentiated among groups than maternal lineages. This demonstrates a lower exchange of males than of females between breeds belonging to different groups, which illustrates how breed founders may have been chosen.
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| 145. |
- Söderström, Johan, et al.
(författare)
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Nonstoichiometric Intensities in Core Photoelectron Spectroscopy
- 2012
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Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 108:19, s. 193005-
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Tidskriftsartikel (refereegranskat)abstract
- X-ray photoemission spectroscopy is used in a great variety of research fields; one observable is the sample's stoichiometry. The stoichiometry can be deduced based on the expectation that the ionization cross sections for innershell orbitals are independent of the molecular composition. Here we used chlorine-substituted ethanes in the gas phase to investigate the apparent carbon stoichiometry. We observe a nonstoichiometric ratio for a wide range of photon energies, the ratio exhibits x-ray-absorption fine structure spectroscopy (EXAFS)-like oscillations and hundreds of eV above the C1s ionization approaches a value far from 1. These effects can be accounted for by considering the scattering of the outgoing photoelectron, which we model by multiple-scattering EXAFS calculations, and by considering the effects of losses due to monopole shakeup and shakeoff and to intramolecular inelastic scattering processes.
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| 146. |
- Travnikova, O., et al.
(författare)
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Energy dependent relative cross sections in carbon 1s photoionization
- 2020
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Ingår i: 31ST INTERNATIONAL CONFERENCE ON PHOTONIC, ELECTRONIC AND ATOMIC COLLISIONS (ICPEAC XXXI). - : IOP PUBLISHING LTD.
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Konferensbidrag (refereegranskat)abstract
- We demonstrate that the possibility of monitoring relative photoionization cross sections over a large photon energy range extending to hard x-rays allows studying and disentangling shake processes and intramolecular inelastic scattering effects. An "EXAFS"-type of oscillatory behaviour of the relative C is cross sections is observed in a wide photon energy range up to 1 keV due to multiple intramolecular elastic scattering of the photoelectron. These effects are also present in solids and constitute a significant part of all elastic and inelastic scattering effects occurring in solids.
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| 147. |
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| 148. |
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| 149. |
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| 150. |
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