| 1. |
- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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- Hollestelle, Antoinette, et al.
(författare)
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No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer
- 2016
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Ingår i: Gynecologic Oncology. - : Elsevier BV. - 0090-8258 .- 1095-6859. ; 141:2, s. 386-401
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Tidskriftsartikel (refereegranskat)abstract
- Objective Clinical genetic testing is commercially available for rs61764370, an inherited variant residing in a KRAS 3′ UTR microRNA binding site, based on suggested associations with increased ovarian and breast cancer risk as well as with survival time. However, prior studies, emphasizing particular subgroups, were relatively small. Therefore, we comprehensively evaluated ovarian and breast cancer risks as well as clinical outcome associated with rs61764370. Methods Centralized genotyping and analysis were performed for 140,012 women enrolled in the Ovarian Cancer Association Consortium (15,357 ovarian cancer patients; 30,816 controls), the Breast Cancer Association Consortium (33,530 breast cancer patients; 37,640 controls), and the Consortium of Modifiers of BRCA1 and BRCA2 (14,765 BRCA1 and 7904 BRCA2 mutation carriers). Results We found no association with risk of ovarian cancer (OR = 0.99, 95% CI 0.94-1.04, p = 0.74) or breast cancer (OR = 0.98, 95% CI 0.94-1.01, p = 0.19) and results were consistent among mutation carriers (BRCA1, ovarian cancer HR = 1.09, 95% CI 0.97-1.23, p = 0.14, breast cancer HR = 1.04, 95% CI 0.97-1.12, p = 0.27; BRCA2, ovarian cancer HR = 0.89, 95% CI 0.71-1.13, p = 0.34, breast cancer HR = 1.06, 95% CI 0.94-1.19, p = 0.35). Null results were also obtained for associations with overall survival following ovarian cancer (HR = 0.94, 95% CI 0.83-1.07, p = 0.38), breast cancer (HR = 0.96, 95% CI 0.87-1.06, p = 0.38), and all other previously-reported associations. Conclusions rs61764370 is not associated with risk of ovarian or breast cancer nor with clinical outcome for patients with these cancers. Therefore, genotyping this variant has no clinical utility related to the prediction or management of these cancers.
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| 27. |
- Jaffee, E. M., et al.
(författare)
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Future cancer research priorities in the USA: a Lancet Oncology Commission
- 2017
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Ingår i: Lancet Oncology. - 1470-2045. ; 18:11
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Forskningsöversikt (refereegranskat)abstract
- We are in the midst of a technological revolution that is providing new insights into human biology and cancer. In this era of big data, we are amassing large amounts of information that is transforming how we approach cancer treatment and prevention. Enactment of the Cancer Moonshot within the 21st Century Cures Act in the USA arrived at a propitious moment in the advancement of knowledge, providing nearly US$ 2 billion of funding for cancer research and precision medicine. In 2016, the Blue Ribbon Panel (BRP) set out a roadmap of recommendations designed to exploit new advances in cancer diagnosis, prevention, and treatment. Those recommendations provided a high-level view of how to accelerate the conversion of new scientific discoveries into effective treatments and prevention for cancer. The US National Cancer Institute is already implementing some of those recommendations. As experts in the priority areas identified by the BRP, we bolster those recommendations to implement this important scientific roadmap. In this Commission, we examine the BRP recommendations in greater detail and expand the discussion to include additional priority areas, including surgical oncology, radiation oncology, imaging, health systems and health disparities, regulation and financing, population science, and oncopolicy. We prioritise areas of research in the USA that we believe would accelerate efforts to benefit patients with cancer. Finally, we hope the recommendations in this report will facilitate new international collaborations to further enhance global efforts in cancer control.
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- Adamo, Angela, et al.
(författare)
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Legacy ExtraGalactic UV Survey with The Hubble Space Telescope : Stellar Cluster Catalogs and First Insights Into Cluster Formation and Evolution in NGC 628
- 2017
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Ingår i: Astrophysical Journal. - : IOP PUBLISHING LTD. - 0004-637X .- 1538-4357. ; 841:2
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Tidskriftsartikel (refereegranskat)abstract
- We report the large effort that is producing comprehensive high-level young star cluster (YSC) catalogs for a significant fraction of galaxies observed with the Legacy ExtraGalactic UV Survey (LEGUS) Hubble treasury program. We present the methodology developed to extract cluster positions, verify their genuine nature, produce multiband photometry (from NUV to NIR), and derive their physical properties via spectral energy distribution fitting analyses. We use the nearby spiral galaxy NGC 628 as a test case for demonstrating the impact that LEGUS will have on our understanding of the formation and evolution of YSCs and compact stellar associations within their host galaxy. Our analysis of the cluster luminosity function from the UV to the NIR finds a steepening at the bright end and at all wavelengths suggesting a dearth of luminous clusters. The cluster mass function of NGC 628 is consistent with a power-law distribution of slopes similar to-2 and a truncation of a few times 10(5) M-circle dot. After their formation, YSCs and compact associations follow different evolutionary paths. YSCs survive for a longer time frame, confirming their being potentially bound systems. Associations disappear on timescales comparable to hierarchically organized star-forming regions, suggesting that they are expanding systems. We find massindependent cluster disruption in the inner region of NGC 628, while in the outer part of the galaxy there is little or no disruption. We observe faster disruption rates for low mass (<= 10(4) M-circle dot) clusters, suggesting that a massdependent component is necessary to fully describe the YSC disruption process in NGC 628.
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| 33. |
- Cook, D. O., et al.
(författare)
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Star cluster catalogues for the LEGUS dwarf galaxies
- 2019
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 484:4, s. 4897-4919
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Tidskriftsartikel (refereegranskat)abstract
- We present the star cluster catalogues for 17 dwarf and irregular galaxies in the HST Treasury Program 'Legacy ExtraGalactic UV Survey' (LEGUS). Cluster identification and photometry in this sub-sample are similar to that of the entire LEGUS sample, but special methods were developed to provide robust catalogues with accurate fluxes due to low cluster statistics. The colours and ages are largely consistent for two widely used aperture corrections, but a significant fraction of the clusters are more compact than the average training cluster. However, the ensemble luminosity, mass, and age distributions are consistent suggesting that the systematics between the two methods are less than the random errors. When compared with the clusters from previous dwarf galaxy samples, we find that the LEGUS catalogues are more complete and provide more accurate total fluxes. Combining all clusters into a composite dwarf galaxy, we find that the luminosity and mass functions can be described by a power law with the canonical index of -2 independent of age and global SFR binning. The age distribution declines as a power law, with an index of approximate to -0.80 +/- 0.15, independent of cluster mass and global SFR binning. This decline of clusters is dominated by cluster disruption since the combined star formation histories and integrated-light SFRs are both approximately constant over the last few hundred Myr. Finally, we find little evidence for an upper-mass cut-off (< 2 sigma) in the composite cluster mass function, and can rule out a truncation mass below approximate to 10(4.5)M(circle dot) but cannot rule out the existence of a truncation at higher masses.
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| 35. |
- Enciso-Mora, Victor, et al.
(författare)
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A genome-wide association study of Hodgkin's lymphoma identifies new susceptibility loci at 2p16.1 (REL), 8q24.21 and 10p14 (GATA3)
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:12, s. 1126-1130
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Tidskriftsartikel (refereegranskat)abstract
- To identify susceptibility loci for classical Hodgkin's lymphoma (cHL), we conducted a genome-wide association study of 589 individuals with cHL (cases) and 5,199 controls with validation in four independent samples totaling 2,057 cases and 3,416 controls. We identified three new susceptibility loci at 2p16.1 (rs1432295, REL, odds ratio (OR) = 1.22, combined P = 1.91 × 10−8), 8q24.21 (rs2019960, PVT1, OR = 1.33, combined P = 1.26 × 10−13) and 10p14 (rs501764, GATA3, OR = 1.25, combined P = 7.05 × 10−8). Furthermore, we confirmed the role of the major histocompatibility complex in disease etiology by revealing a strong human leukocyte antigen (HLA) association (rs6903608, OR = 1.70, combined P = 2.84 × 10−50). These data provide new insight into the pathogenesis of cHL.
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| 36. |
- Fry, Ellen L., et al.
(författare)
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Vegetation type, not the legacy of warming, modifies the response of microbial functional genes and greenhouse gas fluxes to drought in Oro-Arctic and alpine regions
- 2023
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Ingår i: FEMS microbiology ecology. - 1574-6941. ; 99:12
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Tidskriftsartikel (refereegranskat)abstract
- Climate warming and summer droughts alter soil microbial activity, affecting greenhouse gas (GHG) emissions in Arctic and alpine regions. However, the long-term effects of warming, and implications for future microbial resilience, are poorly understood. Using one alpine and three Arctic soils subjected to in situ long-term experimental warming, we simulated drought in laboratory incubations to test how microbial functional-gene abundance affects fluxes in three GHGs: carbon dioxide, methane, and nitrous oxide. We found that responses of functional gene abundances to drought and warming are strongly associated with vegetation type and soil carbon. Our sites ranged from a wet, forb dominated, soil carbon-rich systems to a drier, soil carbon-poor alpine site. Resilience of functional gene abundances, and in turn methane and carbon dioxide fluxes, was lower in the wetter, carbon-rich systems. However, we did not detect an effect of drought or warming on nitrous oxide fluxes. All gene-GHG relationships were modified by vegetation type, with stronger effects being observed in wetter, forb-rich soils. These results suggest that impacts of warming and drought on GHG emissions are linked to a complex set of microbial gene abundances and may be habitat-specific.
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| 37. |
- 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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| 38. |
- Kahre, L., et al.
(författare)
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Extinction Maps and Dust-to-gas Ratios in Nearby Galaxies with LEGUS
- 2018
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 855:2
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Tidskriftsartikel (refereegranskat)abstract
- We present a study of the dust-to-gas ratios in five nearby galaxies: NGC 628 (M74), NGC 6503, NGC 7793, UGC 5139 (Holmberg I), and UGC 4305 (Holmberg II). Using Hubble Space Telescope broadband WFC3/UVIS UV and optical images from the Treasury program Legacy ExtraGalactic UV Survey (LEGUS) combined with archival HST/Advanced Camera for Surveys data, we correct thousands of individual stars for extinction across these five galaxies using an isochrone-matching (reddening-free Q) method. We generate extinction maps for each galaxy from the individual stellar extinctions using both adaptive and fixed resolution techniques and correlate these maps with neutral H I and CO gas maps from the literature, including the H I Nearby Galaxy Survey and the HERA CO-Line Extragalactic Survey. We calculate dust-to-gas ratios and investigate variations in the dust-to-gas ratio with galaxy metallicity. We find a power-law relationship between dust-to-gas ratio and metallicity, consistent with other studies of dust-to-gas ratio compared to metallicity. We find a change in the relation when H-2 is not included. This implies that underestimation of N-H2 in low-metallicity dwarfs from a too-low CO-to-H-2 conversion factor X-CO could have produced too low a slope in the derived relationship between dust-to-gas ratio and metallicity. We also compare our extinctions to those derived from fitting the spectral energy distribution (SED) using the Bayesian Extinction and Stellar Tool for NGC 7793 and find systematically lower extinctions from SED fitting as compared to isochrone matching.
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| 39. |
- Lee, Jason W. L., et al.
(författare)
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Cooling dynamics of energized naphthalene and azulene radical cations
- 2023
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Ingår i: Journal of Chemical Physics. - 0021-9606 .- 1089-7690. ; 158:17
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Tidskriftsartikel (refereegranskat)abstract
- Naphthalene and azulene are isomeric polycyclic aromatic hydrocarbons (PAHs) and are topical in the context of astrochemistry due to the recent discovery of substituted naphthalenes in the Taurus Molecular Cloud-1 (TMC-1). Here, the thermal- and photo-induced isomerization, dissociation, and radiative cooling dynamics of energized (vibrationally hot) naphthalene (Np+) and azulene (Az(+)) radical cations, occurring over the microsecond to seconds timescale, are investigated using a cryogenic electrostatic ion storage ring, affording molecular cloud in a box conditions. Measurement of the cooling dynamics and kinetic energy release distributions for neutrals formed through dissociation, until several seconds after hot ion formation, are consistent with the establishment of a rapid (sub-microsecond) Np+ reversible arrow Az(+) quasi-equilibrium. Consequently, dissociation by C2H2-elimination proceeds predominantly through common Az(+) decomposition pathways. Simulation of the isomerization, dissociation, recurrent fluorescence, and infrared cooling dynamics using a coupled master equation combined with high-level potential energy surface calculations [CCSD(T)/cc-pVTZ], reproduce the trends in the measurements. The data show that radiative cooling via recurrent fluorescence, predominately through the Np+ D-0 <- D-2 transition, efficiently quenches dissociation for vibrational energies up to approximate to 1 eV above dissociation thresholds. Our measurements support the suggestion that small cations, such as naphthalene, may be more abundant in space than previously thought. The strategy presented in this work could be extended to fingerprint the cooling dynamics of other PAH ions for which isomerization is predicted to precede dissociation.
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| 40. |
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| 41. |
- Rajan, N., et al.
(författare)
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Overexpression of MYB drives proliferation of CYLD-defective cylindroma cells
- 2016
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Ingår i: Journal of Pathology. - : Wiley. - 0022-3417. ; 239:2, s. 197-205
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Tidskriftsartikel (refereegranskat)abstract
- Cutaneous cylindroma is an adnexal tumour with apocrine differentiation. A predisposition to multiple cylindromas is seen in patients with Brooke-Spiegler syndrome, who carry germline mutations in the tumour suppressor gene CYLD. Previous studies of inherited cylindromas have highlighted the frequent presence of bi-allelic truncating CYLD mutations as a recurrent driver mutation. We have previously shown that sporadic cylindromas express either MYB-NFIB fusion transcripts or show evidence of MYB activation in the absence of such fusions. Here, we investigated inherited cylindromas from several families with germline CYLD mutations for the presence of MYB activation. Strikingly, none of the inherited CYLD-defective (n = 23) tumours expressed MYB-NFIB fusion transcripts. However, MYB expression was increased in the majority of tumours (69%) and global gene expression analysis revealed that well-established MYB target genes were up-regulated in CYLD-defective tumours. Moreover, knock-down of MYB expression caused a significant reduction in cylindroma cell proliferation, suggesting that MYB is also a key player and oncogenic driver in inherited cylindromas. Taken together, our findings suggest molecular heterogeneity in the pathogenesis of sporadic and inherited cutaneous cylindromas, with convergence on MYB activation. (C) 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
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| 42. |
- Sabbi, E., et al.
(författare)
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The Resolved Stellar Populations in the LEGUS Galaxies
- 2018
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Ingår i: Astrophysical Journal Supplement Series. - : American Astronomical Society. - 0067-0049 .- 1538-4365. ; 235:1
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Tidskriftsartikel (refereegranskat)abstract
- The Legacy ExtraGalactic UV Survey (LEGUS) is a multiwavelength Cycle 21 Treasury program on the Hubble Space Telescope. It studied 50 nearby star-forming galaxies in 5 bands from the near-UV to the I-band, combining new Wide Field Camera 3 observations with archival Advanced Camera for Surveys data. LEGUS was designed to investigate how star formation occurs and develops on both small and large scales, and how it relates to the galactic environments. In this paper we present the photometric catalogs for all the apparently single stars identified in the 50 LEGUS galaxies. Photometric catalogs and mosaicked images for all filters are available for download. We present optical and near-UV color-magnitude diagrams for all the galaxies. For each galaxy we derived the distance from the tip of the red giant branch. We then used the NUV color-magnitude diagrams to identify stars more massive than 14 Me, and compared their number with the number of massive stars expected from the GALEX FUV luminosity. Our analysis shows that the fraction of massive stars forming in star clusters and stellar associations is about constant with the star formation rate. This lack of a relation suggests that the timescale for evaporation of unbound structures is comparable or longer than 10 Myr. At low star formation rates this translates to an excess of mass in clustered environments as compared to model predictions of cluster evolution, suggesting that a significant fraction of stars form in unbound systems.
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| 44. |
- Steward, C. G., et al.
(författare)
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Severe pulmonary hypertension: a frequent complication of stem cell transplantation for malignant infantile osteopetrosis
- 2004
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Ingår i: Br J Haematol. - 0007-1048. ; 124:1, s. 63-71
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Tidskriftsartikel (refereegranskat)abstract
- This report describes eight infants who developed acute severe pulmonary arterial hypertension (PAH) at days -2 to +89 after allogeneic stem cell transplantation (SCT) for malignant infantile osteopetrosis (MIOP). They were taken from a total of 28 children (frequency 29%) transplanted for this disease at three institutions between 1996 and 2002. Typical presentations were acute dyspnoea, hypoxia and brady/tachycardia usually in the absence of fever, crepitations or other evidence of infection. Six patients (75%) required assisted ventilation and five (62%) died. There was clinical or pathological evidence of veno-occlusive disease (VOD) in three children, but absence of VOD in the remaining five suggests that a separate disease process may be responsible for the PAH. Responses to nitric oxide (NO), defibrotide (DF), nicardipine and steroids in varying combinations were disappointing. Three children showed sustained improvement after administration of epoprostenol (EP, prostacyclin) in conjunction with NO and/or DF and remain well and free of PAH 25, 31 and 32 months post-transplant. PAH must therefore be excluded in any child who becomes acutely breathless after SCT for osteopetrosis.
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| 45. |
- Williams, John W., et al.
(författare)
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The neotoma paleoecology database, a multiproxy, international, community-curated data resource
- 2018
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Ingår i: Quaternary Research. - : Cambridge University Press. - 0033-5894 .- 1096-0287. ; 89:1, s. 156-177
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Tidskriftsartikel (refereegranskat)abstract
- The Neotoma Paleoecology Database is a community-curated data resource that supports interdisciplinary global change research by enabling broad-scale studies of taxon and community diversity, distributions, and dynamics during the large environmental changes of the past. By consolidating many kinds of data into a common repository, Neotoma lowers costs of paleodata management, makes paleoecological data openly available, and offers a high-quality, curated resource. Neotoma’s distributed scientific governance model is flexible and scalable, with many open pathways for participation by new members, data contributors, stewards, and research communities. The Neotoma data model supports, or can be extended to support, any kind of paleoecological or paleoenvironmental data from sedimentary archives. Data additions to Neotoma are growing and now include >3.8 million observations, >17,000 datasets, and >9200 sites. Dataset types currently include fossil pollen, vertebrates, diatoms, ostracodes, macroinvertebrates, plant macrofossils, insects, testate amoebae, geochronological data, and the recently added organic biomarkers, stable isotopes, and specimen-level data. Multiple avenues exist to obtain Neotoma data, including the Explorer map-based interface, an application programming interface, the neotoma R package, and digital object identifiers. As the volume and variety of scientific data grow, community-curated data resources such as Neotoma have become foundational infrastructure for big data science.
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