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1.
  • Ade, Peter, et al. (författare)
  • The Simons Observatory : science goals and forecasts
  • 2019
  • Ingår i: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; :2
  • Tidskriftsartikel (refereegranskat)abstract
    • The Simons Observatory (SO) is a new cosmic microwave background experiment being built on Cerro Toco in Chile, due to begin observations in the early 2020s. We describe the scientific goals of the experiment, motivate the design, and forecast its performance. SO will measure the temperature and polarization anisotropy of the cosmic microwave background in six frequency bands centered at: 27, 39, 93, 145, 225 and 280 GHz. The initial con figuration of SO will have three small-aperture 0.5-m telescopes and one large-aperture 6-m telescope, with a total of 60,000 cryogenic bolometers. Our key science goals are to characterize the primordial perturbations, measure the number of relativistic species and the mass of neutrinos, test for deviations from a cosmological constant, improve our understanding of galaxy evolution, and constrain the duration of reionization. The small aperture telescopes will target the largest angular scales observable from Chile, mapping approximate to 10% of the sky to a white noise level of 2 mu K-arcmin in combined 93 and 145 GHz bands, to measure the primordial tensor-to-scalar ratio, r, at a target level of sigma(r) = 0.003. The large aperture telescope will map approximate to 40% of the sky at arcminute angular resolution to an expected white noise level of 6 mu K-arcmin in combined 93 and 145 GHz bands, overlapping with the majority of the Large Synoptic Survey Telescope sky region and partially with the Dark Energy Spectroscopic Instrument. With up to an order of magnitude lower polarization noise than maps from the Planck satellite, the high-resolution sky maps will constrain cosmological parameters derived from the damping tail, gravitational lensing of the microwave background, the primordial bispectrum, and the thermal and kinematic Sunyaev-Zel'dovich effects, and will aid in delensing the large-angle polarization signal to measure the tensor-to-scalar ratio. The survey will also provide a legacy catalog of 16,000 galaxy clusters and more than 20,000 extragalactic sources.
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3.
  • Ademuyiwa, Adesoji O., et al. (författare)
  • Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
  • 2016
  • Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
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4.
  • Lakens, Daniel, et al. (författare)
  • Justify your alpha
  • 2018
  • Ingår i: Nature Human Behaviour. - : Nature Publishing Group. - 2397-3374. ; 2:3, s. 168-171
  • Tidskriftsartikel (refereegranskat)abstract
    • In response to recommendations to redefine statistical significance to P ≤ 0.005, we propose that researchers should transparently report and justify all choices they make when designing a study, including the alpha level.
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5.
  • Abolfathi, Bela, et al. (författare)
  • The Fourteenth Data Release of the Sloan Digital Sky Survey : First Spectroscopic Data from the Extended Baryon Oscillation Spectroscopic Survey and from the Second Phase of the Apache Point Observatory Galactic Evolution Experiment
  • 2018
  • Ingår i: Astrophysical Journal Supplement Series. - : IOP Publishing Ltd. - 0067-0049 .- 1538-4365. ; 235:2
  • Tidskriftsartikel (refereegranskat)abstract
    • The fourth generation of the Sloan Digital Sky Survey (SDSS-IV) has been in operation since 2014 July. This paper describes the second data release from this phase, and the 14th from SDSS overall (making this Data Release Fourteen or DR14). This release makes the data taken by SDSS-IV in its first two years of operation (2014-2016 July) public. Like all previous SDSS releases, DR14 is cumulative, including the most recent reductions and calibrations of all data taken by SDSS since the first phase began operations in 2000. New in DR14 is the first public release of data from the extended Baryon Oscillation Spectroscopic Survey; the first data from the second phase of the Apache Point Observatory (APO) Galactic Evolution Experiment (APOGEE-2), including stellar parameter estimates from an innovative data-driven machine-learning algorithm known as "The Cannon"; and almost twice as many data cubes from the Mapping Nearby Galaxies at APO (MaNGA) survey as were in the previous release (N = 2812 in total). This paper describes the location and format of the publicly available data from the SDSS-IV surveys. We provide references to the important technical papers describing how these data have been taken (both targeting and observation details) and processed for scientific use. The SDSS web site (www.sdss.org) has been updated for this release and provides links to data downloads, as well as tutorials and examples of data use. SDSS-IV is planning to continue to collect astronomical data until 2020 and will be followed by SDSS-V.
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6.
  • Flannick, Jason, et al. (författare)
  • Data Descriptor : Sequence data and association statistics from 12,940 type 2 diabetes cases and controls
  • 2017
  • Ingår i: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 4
  • Tidskriftsartikel (refereegranskat)abstract
    • To investigate the genetic basis of type 2 diabetes (T2D) to high resolution, the GoT2D and T2D-GENES consortia catalogued variation from whole-genome sequencing of 2,657 European individuals and exome sequencing of 12,940 individuals of multiple ancestries. Over 27M SNPs, indels, and structural variants were identified, including 99% of low-frequency (minor allele frequency [MAF] 0.1-5%) non-coding variants in the whole-genome sequenced individuals and 99.7% of low-frequency coding variants in the whole-exome sequenced individuals. Each variant was tested for association with T2D in the sequenced individuals, and, to increase power, most were tested in larger numbers of individuals (> 80% of low-frequency coding variants in similar to ~82 K Europeans via the exome chip, and similar to ~90% of low-frequency non-coding variants in similar to ~44 K Europeans via genotype imputation). The variants, genotypes, and association statistics from these analyses provide the largest reference to date of human genetic information relevant to T2D, for use in activities such as T2D-focused genotype imputation, functional characterization of variants or genes, and other novel analyses to detect associations between sequence variation and T2D.
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7.
  • Fuchsberger, Christian, et al. (författare)
  • The genetic architecture of type 2 diabetes
  • 2016
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 536:7614, s. 41-47
  • Tidskriftsartikel (refereegranskat)abstract
    • The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of the heritability of this disease. Here, to test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole-genome sequencing in 2,657 European individuals with and without diabetes, and exome sequencing in 12,940 individuals from five ancestry groups. To increase statistical power, we expanded the sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support the idea that lower-frequency variants have a major role in predisposition to type 2 diabetes.
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8.
  • 2019
  • Tidskriftsartikel (refereegranskat)
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9.
  • Berger, Ashton C, et al. (författare)
  • A Comprehensive Pan-Cancer Molecular Study of Gynecologic and Breast Cancers.
  • 2018
  • Ingår i: Cancer Cell. - : Elsevier BV. - 1535-6108 .- 1878-3686. ; 33:4, s. 690-705.e9
  • Tidskriftsartikel (refereegranskat)abstract
    • We analyzed molecular data on 2,579 tumors from The Cancer Genome Atlas (TCGA) of four gynecological types plus breast. Our aims were to identify shared and unique molecular features, clinically significant subtypes, and potential therapeutic targets. We found 61 somatic copy-number alterations (SCNAs) and 46 significantly mutated genes (SMGs). Eleven SCNAs and 11 SMGs had not been identified in previous TCGA studies of the individual tumor types. We found functionally significant estrogen receptor-regulated long non-coding RNAs (lncRNAs) and gene/lncRNA interaction networks. Pathway analysis identified subtypes with high leukocyte infiltration, raising potential implications for immunotherapy. Using 16 key molecular features, we identified five prognostic subtypes and developed a decision tree that classified patients into the subtypes based on just six features that are assessable in clinical laboratories.
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10.
  • Beyerlein, Kenneth, et al. (författare)
  • Ultrafast non-thermal heating of water initiated by an X-ray laser
  • 2018
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 115:22, s. 5652-5657
  • Tidskriftsartikel (refereegranskat)abstract
    • X-ray Free-Electron Lasers have opened the door to a new era in structural biology, enabling imaging of biomolecules and dynamics that were impossible to access with conventional methods. A vast majority of imaging experiments, including Serial Femtosecond Crystallography, use a liquid jet to deliver the sample into the interaction region. We have observed structural changes in the carrying water during X-ray exposure, showing how it transforms from the liquid phase to a plasma. This ultrafast phase transition observed in water provides evidence that any biological structure exposed to these X-ray pulses is destroyed during the X-ray exposure.The bright ultrafast pulses of X-ray Free-Electron Lasers allow investigation into the structure of matter under extreme conditions. We have used single pulses to ionize and probe water as it undergoes a phase transition from liquid to plasma. We report changes in the structure of liquid water on a femtosecond time scale when irradiated by single 6.86 keV X-ray pulses of more than 106 J/cm2. These observations are supported by simulations based on molecular dynamics and plasma dynamics of a water system that is rapidly ionized and driven out of equilibrium. This exotic ionic and disordered state with the density of a liquid is suggested to be structurally different from a neutral thermally disordered state.
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11.
  • Bowden, John A., et al. (författare)
  • Harmonizing lipidomics : NIST interlaboratory comparison exercise for lipidomics using SRM 1950-Metabolites in Frozen Human Plasma
  • 2017
  • Ingår i: Journal of Lipid Research. - 0022-2275 .- 1539-7262. ; 58:12, s. 2275-2288
  • Tidskriftsartikel (refereegranskat)abstract
    • As the lipidomics field continues to advance, self-evaluation within the community is critical. Here, we performed an interlaboratory comparison exercise for lipidomics using Standard Reference Material (SRM) 1950-Metabolites in Frozen Human Plasma, a commercially available reference material. The interlaboratory study comprised 31 diverse laboratories, with each laboratory using a different lipidomics workflow. A total of 1,527 unique lipids were measured across all laboratories and consensus location estimates and associated uncertainties were determined for 339 of these lipids measured at the sum composition level by five or more participating laboratories. These evaluated lipids detected in SRM 1950 serve as community-wide benchmarks for intra-and interlaboratory quality control and method validation. These analyses were performed using nonstandardized laboratory-independent workflows. The consensus locations were also compared with a previous examination of SRM 1950 by the LIPID MAPS consortium.jlr While the central theme of the interlaboratory study was to provide values to help harmonize lipids, lipid mediators, and precursor measurements across the community, it was also initiated to stimulate a discussion regarding areas in need of improvement.
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12.
  • Braasch, Ingo, et al. (författare)
  • The spotted gar genome illuminates vertebrate evolution and facilitates human-teleost comparisons
  • 2016
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 48:4, s. 427-437
  • Tidskriftsartikel (refereegranskat)abstract
    • To connect human biology to fish biomedical models, we sequenced the genome of spotted gar (Lepisosteus oculatus), whose lineage diverged from teleosts before teleost genome duplication (TGD). The slowly evolving gar genome has conserved in content and size many entire chromosomes from bony vertebrate ancestors. Gar bridges teleosts to tetrapods by illuminating the evolution of immunity, mineralization and development (mediated, for example, by Hox, ParaHox and microRNA genes). Numerous conserved noncoding elements (CNEs; often cis regulatory) undetectable in direct human-teleost comparisons become apparent using gar: functional studies uncovered conserved roles for such cryptic CNEs, facilitating annotation of sequences identified in human genome-wide association studies. Transcriptomic analyses showed that the sums of expression domains and expression levels for duplicated teleost genes often approximate the patterns and levels of expression for gar genes, consistent with subfunctionalization. The gar genome provides a resource for understanding evolution after genome duplication, the origin of vertebrate genomes and the function of human regulatory sequences.
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13.
  • Broadbent, David P., et al. (författare)
  • The impact of contextual priors and anxiety on performance effectiveness and processing efficiency in anticipation
  • 2019
  • Ingår i: Cognition & Emotion. - Abingdon : Routledge. - 0269-9931 .- 1464-0600. ; 33:3, s. 589-596
  • Tidskriftsartikel (refereegranskat)abstract
    • It is proposed that experts are able to integrate prior contextual knowledge with emergent visual information to make complex predictive judgments about the world around them, often under heightened levels of uncertainty and extreme time constraints. However, limited knowledge exists about the impact of anxiety on the use of such contextual priors when forming our decisions. We provide a novel insight into the combined impact of contextual priors and anxiety on anticipation in soccer. Altogether, 12 expert soccer players were required to predict the actions of an oncoming opponent while viewing life-sized video simulations of 2-versus-2 defensive scenarios. Performance effectiveness and processing efficiency were measured under four conditions: no contextual priors (CP) about the action tendencies of the opponent and low anxiety (LA); no CP and high anxiety (HA); CP and LA; CP and HA. The provision of contextual priors did not affect processing efficiency, but it improved performance effectiveness on congruent trials. Anxiety negatively affected processing efficiency, but this did not affect the use of contextual priors or influence performance effectiveness. It appears that anxiety and prior contextual information impact attentional resources independent of each other. Findings are discussed with reference to current models of anticipation and anxiety. © 2018, © 2018 Informa UK Limited, trading as Taylor & Francis Group.
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14.
  • Daurer, Benedikt J., et al. (författare)
  • Experimental strategies for imaging bioparticles with femtosecond hard X-ray pulses
  • 2017
  • Ingår i: IUCrJ. - : INT UNION CRYSTALLOGRAPHY. - 2052-2525. ; 4, s. 251-262
  • Tidskriftsartikel (refereegranskat)abstract
    • This study explores the capabilities of the Coherent X-ray Imaging Instrument at the Linac Coherent Light Source to image small biological samples. The weak signal from small samples puts a significant demand on the experiment. Aerosolized Omono River virus particles of similar to 40 nm in diameter were injected into the submicrometre X-ray focus at a reduced pressure. Diffraction patterns were recorded on two area detectors. The statistical nature of the measurements from many individual particles provided information about the intensity profile of the X-ray beam, phase variations in the wavefront and the size distribution of the injected particles. The results point to a wider than expected size distribution (from similar to 35 to similar to 300 nm in diameter). This is likely to be owing to nonvolatile contaminants from larger droplets during aerosolization and droplet evaporation. The results suggest that the concentration of nonvolatile contaminants and the ratio between the volumes of the initial droplet and the sample particles is critical in such studies. The maximum beam intensity in the focus was found to be 1.9 * 10(12) photons per mu m(2) per pulse. The full-width of the focus at half-maximum was estimated to be 500 nm (assuming 20% beamline transmission), and this width is larger than expected. Under these conditions, the diffraction signal from a sample-sized particle remained above the average background to a resolution of 4.25 nm. The results suggest that reducing the size of the initial droplets during aerosolization is necessary to bring small particles into the scope of detailed structural studies with X-ray lasers.
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15.
  • Garcaa-Fernandez, Angel F., et al. (författare)
  • Gaussian implementation of the multi-Bernoulli mixture filter
  • 2019
  • Ingår i: FUSION 2019 - 22nd International Conference on Information Fusion.
  • Konferensbidrag (refereegranskat)abstract
    • This paper presents the Gaussian implementation of the multi-Bernoulli mixture (MBM) filter. The MBM filter provides the filtering (multi-target) density for the standard dynamic and radar measurement models when the birth model is multi-Bernoulli or multi-Bernoulli mixture. Under linear/Gaussian models, the single target densities of the MBM mixture admit Gaussian closed-form expressions. Murty's algorithm is used to select the global hypotheses with highest weights. The MBM filter is compared with other algorithms in the literature via numerical simulations.
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16.
  • Garcia, Angel, 1984, et al. (författare)
  • Poisson Multi-Bernoulli Mixture Filter: Direct Derivation and Implementation
  • 2018
  • Ingår i: IEEE Transactions on Aerospace and Electronic Systems. - 1557-9603 .- 0018-9251. ; 54:4, s. 1883-1901
  • Tidskriftsartikel (refereegranskat)abstract
    • We provide a derivation of the Poisson multi-Bernoulli mixture (PMBM) filter for multitarget tracking with the standard point target measurements without using probability generating functionals or functional derivatives. We also establish the connection with the δ-generalized labeled multi-Bernoulli (δ -GLMB) filter, showing that a δ-GLMB density represents a multi-Bernoulli mixture with labeled targets so it can be seen as a special case of PMBM. In addition, we propose an implementation for linear/Gaussian dynamic and measurement models and how to efficiently obtain typical estimators in the literature from the PMBM. The PMBM filter is shown to outperform other filters in the literature in a challenging scenario.
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17.
  • Granström, Karl, 1981, et al. (författare)
  • Poisson Multi-Bernoulli Mixture Trackers: Continuity Through Random Finite Sets of Trajectories
  • 2018
  • Ingår i: 2018 21st International Conference on Information Fusion, FUSION 2018. ; , s. 973-981
  • Konferensbidrag (refereegranskat)abstract
    • The Poisson multi-Bernoulli mixture (PMBM) is an unlabelled multi-target distribution for which the prediction and update are closed. It has a Poisson birth process, and new Bernoulli components are generated on each new measurement as a part of the Bayesian measurement update. The PMBM filter is similar to the multiple hypothesis tracker (MHT), but seemingly does not provide explicit continuity between time steps. This paper considers a recently developed formulation of the multi-target tracking problem as a random finite set (RFS) of trajectories, and derives two trajectory RFS filters, called PMBM trackers. The PMBM trackers efficiently estimate the set of trajectories, and share hypothesis structure with the PMBM filter. By showing that the prediction and update in the PMBM filter can be viewed as an efficient method for calculating the time marginals of the RFS of trajectories, continuity in the same sense as MHT is established for the PMBM filter.
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18.
  • Hudson, Lawrence N, et al. (författare)
  • The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project
  • 2017
  • Ingår i: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 7:1, s. 145-188
  • Tidskriftsartikel (refereegranskat)abstract
    • The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.
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19.
  • Jung, Christian, et al. (författare)
  • A comparison of very old patients admitted to intensive care unit after acute versus elective surgery or intervention
  • 2019
  • Ingår i: Journal of critical care. - : W B SAUNDERS CO-ELSEVIER INC. - 0883-9441 .- 1557-8615. ; 52, s. 141-148
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: We aimed to evaluate differences in outcome between patients admitted to intensive care unit (ICU) after elective versus acute surgery in a multinational cohort of very old patients (80 years; VIP). Predictors of mortality, with special emphasis on frailty, were assessed.Methods: In total, 5063 VIPs were induded in this analysis, 922 were admitted after elective surgery or intervention, 4141 acutely, with 402 after acute surgery. Differences were calculated using Mann-Whitney-U test and Wilcoxon test. Univariate and multivariable logistic regression were used to assess associations with mortality.Results: Compared patients admitted after acute surgery, patients admitted after elective surgery suffered less often from frailty as defined as CFS (28% vs 46%; p < 0.001), evidenced lower SOFA scores (4 +/- 5 vs 7 +/- 7; p < 0.001). Presence of frailty (CFS >4) was associated with significantly increased mortality both in elective surgery patients (7% vs 12%; p = 0.01), in acute surgery (7% vs 12%; p = 0.02).Conclusions: VIPs admitted to ICU after elective surgery evidenced favorable outcome over patients after acute surgery even after correction for relevant confounders. Frailty might be used to guide clinicians in risk stratification in both patients admitted after elective and acute surgery. 
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20.
  • Mesmar, Fahmi, et al. (författare)
  • Clinical candidate and genistein analogue AXP107-11 has chemoenhancing functions in pancreatic adenocarcinoma through G protein-coupled estrogen receptor signaling
  • 2019
  • Ingår i: Cancer Medicine. - : Wiley. - 2045-7634. ; 8:18, s. 7705-7719
  • Tidskriftsartikel (refereegranskat)abstract
    • Despite advances in cancer therapeutics, pancreatic cancer remains difficult to treat and often develops resistance to chemotherapies. We have evaluated a bioavailable genistein analogue, AXP107-11 which has completed phase Ib clinical trial, as an approach to sensitize tumor cells to chemotherapy. Using organotypic cultures of 14 patient-derived xenografts (PDX) of pancreatic ductal adenocarcinoma, we found that addition of AXP107-11 indeed sensitized 57% of cases to gemcitabine treatment. Results were validated using PDX models in vivo. Further, RNA-Seq from responsive and unresponsive tumors proposed a 41-gene treatment-predictive signature. Functional and molecular assays were performed in cell lines and demonstrated that the effect was synergistic. Transcriptome analysis indicated activation of G-protein-coupled estrogen receptor (GPER1) as the main underlying mechanism of action, which was corroborated using GPER1-selective agonists and antagonists. GPER1 expression in pancreatic tumors was indicative of survival, and our study proposes that activation of GPER1 may constitute a new avenue for pancreatic cancer therapeutics.
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21.
  • Nass, Karol, et al. (författare)
  • Indications of radiation damage in ferredoxin microcrystals using high-intensity X-FEL beams
  • 2015
  • Ingår i: Journal of Synchrotron Radiation. - 0909-0495 .- 1600-5775. ; 22:2, s. 225-238
  • Tidskriftsartikel (refereegranskat)abstract
    • Proteins that contain metal cofactors are expected to be highly radiation sensitive since the degree of X-ray absorption correlates with the presence of high-atomic-number elements and X-ray energy. To explore the effects of local damage in serial femtosecond crystallography (SFX), Clostridium ferredoxin was used as a model system. The protein contains two [4Fe–4S] clusters that serve as sensitive probes for radiation-induced electronic and structural changes. High-dose room-temperature SFX datasets were collected at the Linac Coherent Light Source of ferredoxin microcrystals. Difference electron density maps calculated from high-dose SFX and synchrotron data show peaks at the iron positions of the clusters, indicative of decrease of atomic scattering factors due to ionization. The electron density of the two [4Fe–4S] clusters differs in the FEL data, but not in the synchrotron data. Since the clusters differ in their detailed architecture, this observation is suggestive of an influence of the molecular bonding and geometry on the atomic displacement dynamics following initial photoionization. The experiments are complemented by plasma code calculations.
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22.
  • Popp, David, et al. (författare)
  • Flow-aligned, single-shot fiber diffraction using a femtosecond X-ray free-electron laser
  • 2017
  • Ingår i: CYTOSKELETON. - : WILEY. - 1949-3584 .- 1949-3592. ; 74:12, s. 472-481
  • Tidskriftsartikel (refereegranskat)abstract
    • A major goal for X-ray free-electron laser (XFEL) based science is to elucidate structures of biological molecules without the need for crystals. Filament systems may provide some of the first single macromolecular structures elucidated by XFEL radiation, since they contain one-dimensional translational symmetry and thereby occupy the diffraction intensity region between the extremes of crystals and single molecules. Here, we demonstrate flow alignment of as few as 100 filaments (Escherichia coli pili, F-actin, and amyloid fibrils), which when intersected by femtosecond X-ray pulses result in diffraction patterns similar to those obtained from classical fiber diffraction studies. We also determine that F-actin can be flow-aligned to a disorientation of approximately 5 degrees. Using this XFEL-based technique, we determine that gelsolin amyloids are comprised of stacked -strands running perpendicular to the filament axis, and that a range of order from fibrillar to crystalline is discernable for individual -synuclein amyloids.
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23.
  • Stephens, Lucas, et al. (författare)
  • Archaeological assessment reveals Earth’s early transformation through land use
  • 2019
  • Ingår i: Science. - : American Association for the Advancement of Science. - 0036-8075 .- 1095-9203. ; 365:6456, s. 897-902
  • Tidskriftsartikel (refereegranskat)abstract
    • Humans began to leave lasting impacts on Earth’s surface starting 10,000 to 8000 years ago. Through a synthetic collaboration with archaeologists around the globe, Stephens et al. compiled a comprehensive picture of the trajectory of human land use worldwide during the Holocene (see the Perspective by Roberts). Hunter-gatherers, farmers, and pastoralists transformed the face of Earth earlier and to a greater extent than has been widely appreciated, a transformation that was essentially global by 3000 years before the present.Science, this issue p. 897; see also p. 865Environmentally transformative human use of land accelerated with the emergence of agriculture, but the extent, trajectory, and implications of these early changes are not well understood. An empirical global assessment of land use from 10,000 years before the present (yr B.P.) to 1850 CE reveals a planet largely transformed by hunter-gatherers, farmers, and pastoralists by 3000 years ago, considerably earlier than the dates in the land-use reconstructions commonly used by Earth scientists. Synthesis of knowledge contributed by more than 250 archaeologists highlighted gaps in archaeological expertise and data quality, which peaked for 2000 yr B.P. and in traditionally studied and wealthier regions. Archaeological reconstruction of global land-use history illuminates the deep roots of Earth’s transformation and challenges the emerging Anthropocene paradigm that large-scale anthropogenic global environmental change is mostly a recent phenomenon.
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24.
  • Tonomura, Noriko, et al. (författare)
  • Genome-wide Association Study Identifies Shared Risk Loci Common to Two Malignancies in Golden Retrievers
  • 2015
  • Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 11:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Dogs, with their breed-determined limited genetic background, are great models of human disease including cancer. Canine B-cell lymphoma and hemangiosarcoma are both malignancies of the hematologic system that are clinically and histologically similar to human B-cell non-Hodgkin lymphoma and angiosarcoma, respectively. Golden retrievers in the US show significantly elevated lifetime risk for both B-cell lymphoma (6%) and hemangiosarcoma (20%). We conducted genome-wide association studies for hemangiosarcoma and B-cell lymphoma, identifying two shared predisposing loci. The two associated loci are located on chromosome 5, and together contribute similar to 20% of the risk of developing these cancers. Genome-wide p-values for the top SNP of each locus are 4.6x10(-7) and 2.7x10(-6), respectively. Whole genome resequencing of nine cases and controls followed by genotyping and detailed analysis identified three shared and one B-cell lymphoma specific risk haplotypes within the two loci, but no coding changes were associated with the risk haplotypes. Gene expression analysis of B-cell lymphoma tumors revealed that carrying the risk haplotypes at the first locus is associated with down-regulation of several nearby genes including the proximal gene TRPC6, a transient receptor Ca2+-channel involved in T-cell activation, among other functions. The shared risk haplotype in the second locus overlaps the vesicle transport and release gene STX8. Carrying the shared risk haplotype is associated with gene expression changes of 100 genes enriched for pathways involved in immune cell activation. Thus, the predisposing germ-line mutations in B-cell lymphoma and hemangio-sarcoma appear to be regulatory, and affect pathways involved in T-cell mediated immune response in the tumor. This suggests that the interaction between the immune system and malignant cells plays a common role in the tumorigenesis of these relatively different cancers.
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25.
  • Unsalan, Ozan, et al. (författare)
  • The Sariçiçek howardite fall in Turkey : Source crater of HED meteorites on Vesta and impact risk of Vestoids
  • 2019
  • Ingår i: Meteoritics and Planetary Science. - Hoboken : John Wiley & Sons. - 1086-9379 .- 1945-5100. ; 54:5, s. 953-1008
  • Tidskriftsartikel (refereegranskat)abstract
    • The Sariçiçek howardite meteorite shower consisting of 343 documented stones occurred on September 2, 2015 in Turkey and is the first documented howardite fall. Cosmogenic isotopes show that Sariçiçek experienced a complex cosmic‐ray exposure history, exposed during ~12–14 Ma in a regolith near the surface of a parent asteroid, and that an ~1 m sized meteoroid was launched by an impact 22 ± 2 Ma ago to Earth (as did one‐third of all HED meteorites). SIMS dating of zircon and baddeleyite yielded 4550.4 ± 2.5 Ma and 4553 ± 8.8 Ma crystallization ages for the basaltic magma clasts. The apatite U‐Pb age of 4525 ± 17 Ma, K‐Ar age of ~3.9 Ga, and the U,Th‐He ages of 1.8 ± 0.7 and 2.6 ± 0.3 Ga are interpreted to represent thermal metamorphic and impact‐related resetting ages, respectively. Petrographic; geochemical; and O‐, Cr‐, and Ti‐isotopic studies confirm that Sariçiçek belongs to the normal clan of HED meteorites. Petrographic observations and analysis of organic material indicate a small portion of carbonaceous chondrite material in the Sariçiçek regolith and organic contamination of the meteorite after a few days on soil. Video observations of the fall show an atmospheric entry at 17.3 ± 0.8 km s−1 from NW; fragmentations at 37, 33, 31, and 27 km altitude; and provide a pre‐atmospheric orbit that is the first dynamical link between the normal HED meteorite clan and the inner Main Belt. Spectral data indicate the similarity of Sariçiçek with the Vesta asteroid family (V‐class) spectra, a group of asteroids stretching to delivery resonances, which includes (4) Vesta. Dynamical modeling of meteoroid delivery to Earth shows that the complete disruption of a ~1 km sized Vesta family asteroid or a ~10 km sized impact crater on Vesta is required to provide sufficient meteoroids ≤4 m in size to account for the influx of meteorites from this HED clan. The 16.7 km diameter Antionia impact crater on Vesta was formed on terrain of the same age as given by the 4He retention age of Sariçiçek. Lunar scaling for crater production to crater counts of its ejecta blanket show it was formed ~22 Ma ago.
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26.
  • Whitley, Rhys, et al. (författare)
  • A model inter-comparison study to examine limiting factors in modelling Australian tropical savannas
  • 2016
  • Ingår i: Biogeosciences. - : Copernicus GmbH. - 1726-4170 .- 1726-4189. ; 13:11, s. 3245-3265
  • Tidskriftsartikel (refereegranskat)abstract
    • The savanna ecosystem is one of the most dominant and complex terrestrial biomes, deriving from a distinct vegetative surface comprised of co-dominant tree and grass populations. While these two vegetation types co-exist functionally, demographically they are not static but are dynamically changing in response to environmental forces such as annual fire events and rainfall variability. Modelling savanna environments with the current generation of terrestrial biosphere models (TBMs) has presented many problems, particularly describing fire frequency and intensity, phenology, leaf biochemistry of C3 and C4 photosynthesis vegetation, and root-water uptake. In order to better understand why TBMs perform so poorly in savannas, we conducted a model inter-comparison of six TBMs and assessed their performance at simulating latent energy (LE) and gross primary productivity (GPP) for five savanna sites along a rainfall gradient in northern Australia. Performance in predicting LE and GPP was measured using an empirical benchmarking system, which ranks models by their ability to utilise meteorological driving information to predict the fluxes. On average, the TBMs performed as well as a multi-linear regression of the fluxes against solar radiation, temperature and vapour pressure deficit but were outperformed by a more complicated nonlinear response model that also included the leaf area index (LAI). This identified that the TBMs are not fully utilising their input information effectively in determining savanna LE and GPP and highlights that savanna dynamics cannot be calibrated into models and that there are problems in underlying model processes. We identified key weaknesses in a model's ability to simulate savanna fluxes and their seasonal variation, related to the representation of vegetation by the models and root-water uptake. We underline these weaknesses in terms of three critical areas for development. First, prescribed tree-rooting depths must be deep enough, enabling the extraction of deep soil-water stores to maintain photosynthesis and transpiration during the dry season. Second, models must treat grasses as a co-dominant interface for water and carbon exchange rather than a secondary one to trees. Third, models need a dynamic representation of LAI that encompasses the dynamic phenology of savanna vegetation and its response to rainfall interannual variability. We believe that this study is the first to assess how well TBMs simulate savanna ecosystems and that these results will be used to improve the representation of savannas ecosystems in future global climate model studies.
  •  
27.
  • Whitley, Rhys, et al. (författare)
  • Challenges and opportunities in land surface modelling of savanna ecosystems
  • 2017
  • Ingår i: Biogeosciences. - : Copernicus GmbH. - 1726-4170 .- 1726-4189. ; 14:20, s. 4711-4732
  • Tidskriftsartikel (refereegranskat)abstract
    • The savanna complex is a highly diverse global biome that occurs within the seasonally dry tropical to sub-tropical equatorial latitudes and are structurally and functionally distinct from grasslands and forests. Savannas are open-canopy environments that encompass a broad demographic continuum, often characterised by a changing dominance between C3-tree and C4-grass vegetation, where frequent environmental disturbances such as fire modulates the balance between ephemeral and perennial life forms. Climate change is projected to result in significant changes to the savanna floristic structure, with increases to woody biomass expected through CO2 fertilisation in mesic savannas and increased tree mortality expected through increased rainfall interannual variability in xeric savannas. The complex interaction between vegetation and climate that occurs in savannas has traditionally challenged terrestrial biosphere models (TBMs), which aim to simulate the interaction between the atmosphere and the land surface to predict responses of vegetation to changing in environmental forcing. In this review, we examine whether TBMs are able to adequately represent savanna fluxes and what implications potential deficiencies may have for climate change projection scenarios that rely on these models. We start by highlighting the defining characteristic traits and behaviours of savannas, how these differ across continents and how this information is (or is not) represented in the structural framework of many TBMs. We highlight three dynamic processes that we believe directly affect the water use and productivity of the savanna system: phenology, root-water access and fire dynamics. Following this, we discuss how these processes are represented in many current-generation TBMs and whether they are suitable for simulating savanna fluxes.Finally, we give an overview of how eddy-covariance observations in combination with other data sources can be used in model benchmarking and intercomparison frameworks to diagnose the performance of TBMs in this environment and formulate road maps for future development. Our investigation reveals that many TBMs systematically misrepresent phenology, the effects of fire and root-water access (if they are considered at all) and that these should be critical areas for future development. Furthermore, such processes must not be static (i.e. prescribed behaviour) but be capable of responding to the changing environmental conditions in order to emulate the dynamic behaviour of savannas. Without such developments, however, TBMs will have limited predictive capability in making the critical projections needed to understand how savannas will respond to future global change.
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28.
  • Xia, Yuxuan, 1993, et al. (författare)
  • Extended target Poisson multi-Bernoulli mixture trackers based on sets of trajectories
  • 2019
  • Ingår i: FUSION 2019 - 22nd International Conference on Information Fusion.
  • Konferensbidrag (refereegranskat)abstract
    • The Poisson multi-Bernoulli mixture (PMBM) is a multi-target distribution for which the prediction and update are closed. By applying the random finite set (RFS) framework to multi-target tracking with sets of trajectories as the variable of interest, the PMBM trackers can efficiently estimate the set of target trajectories. This paper derives two trajectory RFS filters for extended target tracking, called extended target PMBM trackers. Compared to the extended target PMBM filter based on sets on targets, explicit track continuity between time steps is provided in the extended target PMBM trackers.
  •  
29.
  • Xia, Yuxuan, 1993, et al. (författare)
  • Multiscan implementation of the trajectory poisson multi-Bernoulli mixture filter
  • 2019
  • Ingår i: Journal of Advances in Information Fusion. - 1557-6418. ; 14:2, s. 213-235
  • Tidskriftsartikel (refereegranskat)abstract
    • The Poisson multi-Bernoulli mixture (PMBM) and the multi-Bernoulli mixture (MBM) are two multitarget distributions for which closed-form filtering recursions exist. The PMBM has a Poisson birth process, whereas the MBM has a multi-Bernoulli birth process. This paper considers a recently developed formulation of the multitarget tracking problem using a random finite set of trajectories, through which the track continuity is explicitly established. A multiscan trajectory PMBM filter and a multiscan trajectory MBM filter, with the ability to correct past data association decisions to improve current decisions, are presented. In addition, a multiscan trajectory MBM01 filter, in which the existence probabilities of all Bernoulli components are either 0 or 1, is presented. This paper proposes an efficient implementation that performs track-oriented N-scan pruning to limit computational complexity, and uses dual decomposition to solve the involved multiframe assignment problem. The performance of the presented multitarget trackers, applied with an efficient fixed-lag smoothing method, is evaluated in a simulation study.
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