| 1. |
- Cardoso, F., et al.
(author)
-
Characterization of male breast cancer : Results of the EORTC 10085/TBCRC/BIG/NABCG International Male Breast Cancer Program
- 2018
-
In: Annals of Oncology. - : Elsevier BV. - 1569-8041 .- 0923-7534. ; 29:2, s. 405-417
-
Journal article (peer-reviewed)abstract
- Background: Male breast cancer (BC) is rare, managed by extrapolation from female BC. The International Male BC Program aims to better characterize and manage this disease. We report the results of part I, a retrospective joint analysis of cases diagnosed during a 20-year period. Methods: Patients with follow-up and tumor samples, treated between 1990 and 2010, in 93 centers/9 countries. Samples were centrally analyzed in three laboratories (the United Kingdom, the Netherlands and the United States). Results: Of 1822 patients enrolled, 1483 were analyzed; 63.5% were diagnosed between 2001 and 2010, 57 (5.1%) had metastatic disease (M1). Median age at diagnosis: 68.4 years. Of 1054 M0 cases, 56.2% were node-negative (N0) and 48.5% had T1 tumors; 4% had breast conserving surgery (BCS), 18% sentinel lymph-node biopsy; half received adjuvant radiotherapy; 29.8% (neo)adjuvant chemotherapy and 76.8% adjuvant endocrine therapy (ET), mostly tamoxifen (88.4%). Per central pathology, for M0 tumors: 84.8% ductal invasive carcinomas, 51.5% grade 2; 99.3% estrogen receptor (ER)-positive; 81.9% progesterone receptor (PR)-positive; 96.9% androgen receptor (AR)-positive [ER, PR or AR Allred score ≥ 3]; 61.1% Ki67 expression low (<14% positive cells); using immunohistochemistry (IHC) surrogates, 41.9% were Luminal-A-like, 48.6% Luminal-B-like/HER-2-negative, 8.7% HER-2-positive, 0.3% triple negative. Median follow-up: 8.2 years (0.0-23.8) for all, 7.2 years (0.0-23.2), for M0, 2.6 years (0.0-12.7) for M1 patients. A significant improvement over time was observed in age-corrected BC mortality. BC-specific-mortality was higher for men younger than 50 years. Better overall (OS) and recurrence-free survival (RFS) were observed for highly ER+(P=0.001), highly PR+(P=0.002), highly AR+ disease (P=0.019). There was no association between OS/RFS and HER-2 status, Ki67, IHC subtypes nor grade. Conclusions: Male BC is usually ER, PR and AR-positive, Luminal B-like/HER2-negative. Of note, 56% patients had T1 tumors but only 4% had BCS. ER was highly positive in > 90% of cases but only 77% received adjuvant ET. ER, PR and AR were associated with OS and RFS, whereas grade, Ki67 and IHC surrogates were not. Significant improvement in survival over time was observed.
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| 2. |
- Cooper, Alan, et al.
(author)
-
A global environmental crisis 42,000 years ago
- 2021
-
In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 371:6531, s. 811-818
-
Journal article (peer-reviewed)abstract
- Geological archives record multiple reversals of Earth’s magnetic poles, but the global impacts of these events, if any, remain unclear. Uncertain radiocarbon calibration has limited investigation of the potential effects of the last major magnetic inversion, known as the Laschamps Excursion [41 to 42 thousand years ago (ka)]. We use ancient New Zealand kauri trees (Agathis australis) to develop a detailed record of atmospheric radiocarbon levels across the Laschamps Excursion. We precisely characterize the geomagnetic reversal and perform global chemistry-climate modeling and detailed radiocarbon dating of paleoenvironmental records to investigate impacts. We find that geomagnetic field minima ~42 ka, in combination with Grand Solar Minima, caused substantial changes in atmospheric ozone concentration and circulation, driving synchronous global climate shifts that caused major environmental changes, extinction events, and transformations in the archaeological record.
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| 3. |
- Cooper, Alan, et al.
(author)
-
Response to comment on “A global environmental crisis 42,000 years ago”
- 2021
-
In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 374:6570
-
Journal article (peer-reviewed)abstract
- Our paper about the impacts of the Laschamps Geomagnetic Excursion 42,000 years ago has provoked considerable scientific and public interest, particularly in the so-called Adams Event associated with the initial transition of the magnetic poles. Although we welcome the opportunity to discuss our new ideas, Hawks’ assertions of misrepresentation are especially disappointing given his limited examination of the material.
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| 4. |
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| 5. |
- Melles, Martin, et al.
(author)
-
2.8 million years of arctic climate change from Lake El'gygytgyn, NE Russia
- 2012
-
In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 337:6092, s. 315-320
-
Journal article (peer-reviewed)abstract
- The reliability of Arctic climate predictions is currently hampered by insufficient knowledge of natural climate variability in the past. A sediment core from Lake El'gygytgyn in northeastern (NE) Russia provides a continuous, high-resolution record from the Arctic, spanning the past 2.8 million years. This core reveals numerous "super interglacials" during the Quaternary; for marine benthic isotope stages (MIS) 11c and 31, maximum summer temperatures and annual precipitation values are similar to 4 degrees to 5 degrees C and similar to 300 millimeters higher than those of MIS 1 and 5e. Climate simulations show that these extreme warm conditions are difficult to explain with greenhouse gas and astronomical forcing alone, implying the importance of amplifying feedbacks and far field influences. The timing of Arctic warming relative to West Antarctic Ice Sheet retreats implies strong interhemispheric climate connectivity.
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| 6. |
- Navarro, Montserrat Perez, et al.
(author)
-
Ammonia binding to the oxygen-evolving complex of photosystem II identifies the solvent-exchangeable oxygen bridge (µ-oxo) of the manganese tetramer
- 2013
-
In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 110:39, s. 15561-15566
-
Journal article (peer-reviewed)abstract
- The assignment of the two substrate water sites of the tetramanganese penta-oxygen calcium (Mn4O5Ca) cluster of photosystem II is essential for the elucidation of the mechanism of biological O-O bond formation and the subsequent design of bio-inspired water-splitting catalysts. We recently demonstrated using pulsed EPR spectroscopy that one of the five oxygen bridges (mu-oxo) exchanges unusually rapidly with bulk water and is thus a likely candidate for one of the substrates. Ammonia, a water analog, was previously shown to bind to the Mn4O5Ca cluster, potentially displacing a water/substrate ligand [Britt RD, et al. (1989) J Am Chem Soc 111(10):3522-3532]. Here we show by a combination of EPR and time-resolved membrane inlet mass spectrometry that the binding of ammonia perturbs the exchangeable mu-oxo bridge without drastically altering the binding/exchange kinetics of the two substrates. In combination with broken-symmetry density functional theory, our results show that (i) the exchangable mu-oxo bridge is O5 {using the labeling of the current crystal structure [Umena Y, et al. (2011) Nature 473(7345):55-60]}; (ii) ammonia displaces a water ligand to the outer manganese (Mn-A4-W1); and (iii) as W1 is trans to O5, ammonia binding elongates the Mn-A4-O5 bond, leading to the perturbation of the mu-oxo bridge resonance and to a small change in the water exchange rates. These experimental results support O-O bond formation between O5 and possibly an oxyl radical as proposed by Siegbahn and exclude W1 as the second substrate water.
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| 7. |
- Nowaczyk, N. R., et al.
(author)
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Chronology of Lake El'gygytgyn sediments - a combined magnetostratigraphic, palaeoclimatic and orbital tuning study based on multi-parameter analyses
- 2013
-
In: Climate of the Past. - : Copernicus GmbH. - 1814-9324 .- 1814-9332. ; 9:6, s. 2413-2432
-
Journal article (peer-reviewed)abstract
- A 318-metre-long sedimentary profile drilled by the International Continental Scientific Drilling Program (ICDP) at Site 5011-1 in Lake El'gygytgyn, Far East Russian Arctic, has been analysed for its sedimentologic response to global climate modes by chronostratigraphic methods. The 12 km wide lake is sited off-centre in an 18 km large crater that was created by the impact of a meteorite 3.58 Ma ago. Since then sediments have been continuously deposited. For establishing their chronology, major reversals of the earth's magnetic field provided initial tie points for the age model, confirming that the impact occurred in the earliest geomagnetic Gauss chron. Various stratigraphic parameters, reflecting redox conditions at the lake floor and climatic conditions in the catchment were tuned synchronously to Northern Hemisphere insolation variations and the marine oxygen isotope stack, respectively. Thus, a robust age model comprising more than 600 tie points could be defined. It could be shown that deposition of sediments in Lake El'gygytgyn occurred in concert with global climatic cycles. The upper similar to 160m of sediments represent the past 3.3 Ma, equivalent to sedimentation rates of 4 to 5 cm ka(-1), whereas the lower 160m represent just the first 0.3 Ma after the impact, equivalent to sedimentation rates in the order of 45 cm ka(-1). This study also provides orbitally tuned ages for a total of 8 tephras deposited in Lake El'gygytgyn.
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| 8. |
- Nowaczyk, Sławomir, 1978-, et al.
(author)
-
An Architecture for Resource Bounded Agents
- 2007
-
In: Proceedings of the International Multiconference on Computer Science and Information Technology. - Katowice : PTI Press. - 1896-7094. ; 2, s. 59-69
-
Conference paper (peer-reviewed)abstract
- We study agents situated in partially observable environments, who do not have sufficient resources to create conformant (complete) plans. Instead, they create plans which are conditional and partial, execute or simulate them, and learn from experience to evaluate their quality. Our agents employ an incomplete symbolic deduction system based on Active Logic and Situation Calculus for reasoning about actions and their consequences. An Inductive Logic Programming algorithm generalises observations and deduced knowledge so that the agents can choose the best plan for execution. We describe an architecture which allows ideas and solutions from several subfields of Artificial Intelligence to be joined together in a controlled and manageable way. In our opinion, no situated agent can achieve true rationality without using at least logical reasoning and learning. In practice, it is clear that pure logic is not able to cope with all the requirements put on reasoning, thus more domain- specific solutions, like planners, are also necessary. Finally, any realistic agent needs a reactive module to meet demands of dynamic environments. Our architecture is designed in such a way that those three elements interact in order to complement each other’s weaknesses and reinforce each other’s strengths.
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| 9. |
- Rapatskiy, Leonid, et al.
(author)
-
Detection of the Water-Binding Sites of the Oxygen-Evolving Complex of Photosystem II Using W-Band 17O Electron–Electron Double Resonance-Detected NMR Spectroscopy
- 2012
-
In: Journal of the American Chemical Society. - Washington : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 134:40, s. 16619-16634
-
Journal article (peer-reviewed)abstract
- Water binding to the Mn4O5Ca cluster of the oxygen-evolving complex (OEC) of Photosystem II (PSII) poised in the S2 state was studied via H217O- and 2H2O-labeling and high-field electron paramagnetic resonance (EPR) spectroscopy. Hyperfine couplings of coordinating 17O (I = 5/2) nuclei were detected using W-band (94 GHz) electron–electron double resonance (ELDOR) detected NMR and Davies/Mims electron–nuclear double resonance (ENDOR) techniques. Universal 15N (I = 1/2) labeling was employed to clearly discriminate the 17O hyperfine couplings that overlap with 14N (I = 1) signals from the D1-His332 ligand of the OEC (Stich Biochemistry 2011, 50 (34), 7390−7404). Three classes of 17O nuclei were identified: (i) one μ-oxo bridge; (ii) a terminal Mn–OH/OH2 ligand; and (iii) Mn/Ca–H2O ligand(s). These assignments are based on 17O model complex data, on comparison to the recent 1.9 Å resolution PSII crystal structure (Umena Nature 2011, 473, 55−60), on NH3 perturbation of the 17O signal envelope and density functional theory calculations. The relative orientation of the putative 17O μ-oxo bridge hyperfine tensor to the 14N(15N) hyperfine tensor of the D1-His332 ligand suggests that the exchangeable μ-oxo bridge links the outer Mn to the Mn3O3Ca open-cuboidal unit (O4 and O5 in the Umena et al. structure). Comparison to literature data favors the Ca-linked O5 oxygen over the alternative assignment to O4. All 17O signals were seen even after very short (≤15 s) incubations in H217O suggesting that all exchange sites identified could represent bound substrate in the S1 state including the μ-oxo bridge. 1H/2H (I = 1/2, 1) ENDOR data performed at Q- (34 GHz) and W-bands complement the above findings. The relatively small 1H/2H couplings observed require that all the μ-oxo bridges of the Mn4O5Ca cluster are deprotonated in the S2 state. Together, these results further limit the possible substrate water-binding sites and modes within the OEC. This information restricts the number of possible reaction pathways for O–O bond formation, supporting an oxo/oxyl coupling mechanism in S4.
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| 10. |
- Scherer, SW, et al.
(author)
-
Human chromosome 7: DNA sequence and biology
- 2003
-
In: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 300:5620, s. 767-772
-
Journal article (peer-reviewed)abstract
- DNA sequence and annotation of the entire human chromosome 7, encompassing nearly 158 million nucleotides of DNA and 1917 gene structures, are presented. To generate a higher order description, additional structural features such as imprinted genes, fragile sites, and segmental duplications were integrated at the level of the DNA sequence with medical genetic data, including 440 chromosome rearrangement breakpoints associated with disease. This approach enabled the discovery of candidate genes for developmental diseases including autism.
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| 11. |
- Schuller, Jan M., et al.
(author)
-
Redox-coupled proton pumping drives carbon concentration in the photosynthetic complex I
- 2020
-
In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
-
Journal article (peer-reviewed)abstract
- Photosynthetic organisms capture light energy to drive their energy metabolism, and employ the chemical reducing power to convert carbon dioxide (CO2) into organic molecules. Photorespiration, however, significantly reduces the photosynthetic yields. To survive under low CO2 concentrations, cyanobacteria evolved unique carbon-concentration mechanisms that enhance the efficiency of photosynthetic CO2 fixation, for which the molecular principles have remained unknown. We show here how modular adaptations enabled the cyanobacterial photosynthetic complex I to concentrate CO2 using a redox-driven proton-pumping machinery. Our cryo-electron microscopy structure at 3.2 angstrom resolution shows a catalytic carbonic anhydrase module that harbours a Zn2+ active site, with connectivity to proton-pumping subunits that are activated by electron transfer from photosystem I. Our findings illustrate molecular principles in the photosynthetic complex I machinery that enabled cyanobacteria to survive in drastically changing CO2 conditions. Cyanobacteria evolved carbon-concentration mechanisms to enhance the efficiency of photosynthetic CO2 fixation, but the molecular principles have remained unknown. Here authors use cryo-EM to reveal how modular adaptations enabled the photosynthetic complex I from the cyanobacterium Thermosynechococcus elongatus to concentrate CO2.
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| 12. |
- Tarasov, P. E., et al.
(author)
-
A pollen-based biome reconstruction over the last 3.562 million years in the Far East Russian Arctic - new insights into climate-vegetation relationships at the regional scale
- 2013
-
In: Climate of the Past. - : Copernicus GmbH. - 1814-9332. ; 9:6, s. 2759-2775
-
Journal article (peer-reviewed)abstract
- The recent and fossil pollen data obtained under the frame of the multi-disciplinary international El'gygytgyn Drilling Project represent a unique archive, which allows the testing of a range of pollen-based reconstruction approaches and the deciphering of changes in the regional vegetation and climate. In the current study we provide details of the biome reconstruction method applied to the late Pliocene and Quaternary pollen records from Lake El'gygytgyn. All terrestrial pollen taxa identified in the spectra from Lake El'gygytgyn were assigned to major vegetation types (biomes), which today occur near the lake and in the broader region of eastern and northern Asia and, thus, could be potentially present in this region during the past. When applied to the pollen spectra from the middle Pleistocene to present, the method suggests (1) a predominance of tundra during the Holocene, (2) a short interval during the marine isotope stage (MIS) 5.5 interglacial distinguished by cold deciduous forest, and (3) long phases of taiga dominance during MIS 31 and, particularly, MIS 11.3. These two latter interglacials seem to be some of the longest and warmest intervals in the study region within the past million years. During the late Pliocene-early Pleistocene interval (i.e., similar to 3.562-2.200 Ma), there is good correspondence between the millennial-scale vegetation changes documented in the Lake El'gygytgyn record and the alternation of cold and warm marine isotope stages, which reflect changes in the global ice volume and sea level. The biome reconstruction demonstrates changes in the regional vegetation from generally warmer/wetter environments of the earlier (i. e., Pliocene) interval towards colder/drier environments of the Pleistocene. The reconstruction indicates that the taxon-rich cool mixed and cool conifer forest biomes are mostly characteristic of the time prior to MIS G16, whereas the tundra biome becomes a prominent feature starting from MIS G6. These results consistently indicate that the study region supported significant tree populations during most of the interval prior to similar to 2.730 Ma. The cold-and drought-tolerant steppe biome first appears in the reconstruction similar to 3.298 Ma during the tundra-dominated MIS M2, whereas the tundra biome initially occurs between similar to 3.379 and similar to 3.378 Ma within MIS MG4. Prior to similar to 2.800 Ma, several other cold stages during this generally warm Pliocene interval were characterized by the tundra biome.
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| 13. |
- van Kuilenburg, André B P, et al.
(author)
-
Novel disease-causing mutations in the dihydropyrimidine dehydrogenase gene interpreted by analysis of the three-dimensional protein structure
- 2002
-
In: Biochemical Journal. - : Portland Press Ltd.. - 0264-6021 .- 1470-8728. ; 364:Pt 1, s. 157-163
-
Journal article (peer-reviewed)abstract
- Dihydropyrimidine dehydrogenase (DPD) deficiency is an autosomal recessive disease characterized by thymine-uraciluria in homozygous deficient patients. Cancer patients with a partial deficiency of DPD are at risk of developing severe life-threatening toxicities after the administration of 5-fluorouracil. Thus, identification of novel disease-causing mutations is of the utmost importance to allow screening of patients at risk. In eight patients presenting with a complete DPD deficiency, a considerable variation in the clinical presentation was noted. Whereas motor retardation was observed in all patients, no patients presented with convulsive disorders. In this group of patients, nine novel mutations were identified including one deletion of two nucleotides [1039-1042delTG] and eight missense mutations. Analysis of the crystal structure of pig DPD suggested that five out of eight amino acid exchanges present in these patients with a complete DPD deficiency, Pro86Leu, Ser201Arg, Ser492Leu, Asp949Val and His978Arg, interfered directly or indirectly with cofactor binding or electron transport. Furthermore, the mutations Ile560Ser and Tyr211Cys most likely affected the structural integrity of the DPD protein. Only the effect of the Ile370Val and a previously identified Cys29Arg mutation could not be readily explained by analysis of the three-dimensional structure of the DPD enzyme, suggesting that at least the latter might be a common polymorphism. Our data demonstrate for the first time the possible consequences of missense mutations in the DPD gene on the function and stability of the DPD enzyme.
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| 14. |
- Abuella, Mohamed, 1980-, et al.
(author)
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Data-Driven Explainable Artificial Intelligence for Energy Efficiency in Short-Sea Shipping
- 2023
-
In: Machine Learning and Knowledge Discovery in Databases. - Cham : Springer. - 9783031434297 - 9783031434303 ; , s. 226-241
-
Conference paper (peer-reviewed)abstract
- The maritime industry is under pressure to increase energy efficiency for climate change mitigation. Navigational data, combining vessel operational and environmental measurements from onboard instruments and external sources, are critical for achieving this goal. Short-sea shipping presents a unique challenge due to the significant influence of surrounding landscape characteristics. With high-resolution onboard data increasingly accessible through IoT devices, appropriate data representations and AI/ML analytical tools are needed for effective decision support. The aim of this study is to investigate the fuel consumption estimation model’s role in developing an energy efficiency decision support tool. ML models that lacking explainability may neglect important factors and essential constraints, such as the need to meet arrival time requirements. Onboard weather measurements are compared to external forecasts, and our findings demonstrate the necessity of eXplainable Artificial Intelligence (XAI) techniques for effective decision support. Real-world data from a short-sea passenger vessel in southern Sweden, consisting of 1754 voyages over 15 months (More of data description and code sources of this study can be found in the GitHub repository at https://github.com/MohamedAbuella/ST4EESSS), are used to support our conclusions. © 2023, The Author(s), under exclusive license to Springer Nature Switzerland AG.
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| 15. |
- Abuella, Mohamed, Postdoktor, 1980-, et al.
(author)
-
Spatial Clustering Approach for Vessel Path Identification
- 2024
-
In: IEEE Access. - Piscataway, NJ : IEEE. - 2169-3536. ; 12, s. 66248-66258
-
Journal article (peer-reviewed)abstract
- This paper addresses the challenge of identifying the paths for vessels with operating routes of repetitive paths, partially repetitive paths, and new paths. We propose a spatial clustering approach for labeling the vessel paths by using only position information. We develop a path clustering framework employing two methods: a distance-based path modeling and a likelihood estimation method. The former enhances the accuracy of path clustering through the integration of unsupervised machine learning techniques, while the latter focuses on likelihood-based path modeling and introduces segmentation for a more detailed analysis. The result findings highlight the superior performance and efficiency of the developed approach, as both methods for clustering vessel paths into five clusters achieve a perfect F1-score. The approach aims to offer valuable insights for route planning, ultimately contributing to improving safety and efficiency in maritime transportation. © 2013 IEEE.
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| 16. |
- Archibald, M., et al.
(author)
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Characterization of Break in Quantum Grid
- 2020
-
In: Acta Physica Polonica. A. - : Institute of Physics, Polish Academy of Sciences. - 0587-4246 .- 1898-794X. ; 138:3, s. 383-391
-
Journal article (peer-reviewed)
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| 17. |
- Archibald, M., et al.
(author)
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Finding the hole in a wall
- 2020
-
In: Journal of Mathematical Chemistry. - : Springer Science and Business Media LLC. - 0259-9791 .- 1572-8897. ; 58:10, s. 2313-2323
-
Journal article (peer-reviewed)
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| 18. |
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| 19. |
-
Artificial Intelligence in Medicine : Knowledge Representation and Transparent and Explainable Systems
- 2019
-
Editorial proceedings (peer-reviewed)abstract
- This book constitutes revised selected papers from the AIME 2019 workshops KR4HC/ProHealth 2019, the Workshop on Knowledge Representation for Health Care and Process-Oriented Information Systems in Health Care, and TEAAM 2019, the Workshop on Transparent, Explainable and Affective AI in Medical Systems.The volume contains 5 full papers from KR4HC/ProHealth, which were selected out of 13 submissions. For TEAAM 8 papers out of 10 submissions were accepted for publication. © 2019 Springer Nature Switzerland AG. Part of Springer Nature.
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| 20. |
- Bayani, Jane, et al.
(author)
-
Evaluation of multiple transcriptomic gene risk signatures in male breast cancer
- 2021
-
In: npj Breast Cancer. - : Springer Science and Business Media LLC. - 2374-4677. ; 7:1
-
Journal article (peer-reviewed)abstract
- Male breast cancer (BCa) is a rare disease accounting for less than 1% of all breast cancers and 1% of all cancers in males. The clinical management is largely extrapolated from female BCa. Several multigene assays are increasingly used to guide clinical treatment decisions in female BCa, however, there are limited data on the utility of these tests in male BCa. Here we present the gene expression results of 381 M0, ER+ve, HER2-ve male BCa patients enrolled in the Part 1 (retrospective analysis) of the International Male Breast Cancer Program. Using a custom NanoString™ panel comprised of the genes from the commercial risk tests Prosigna®, OncotypeDX®, and MammaPrint®, risk scores and intrinsic subtyping data were generated to recapitulate the commercial tests as described by us previously. We also examined the prognostic value of other risk scores such as the Genomic Grade Index (GGI), IHC4-mRNA and our prognostic 95-gene signature. In this sample set of male BCa, we demonstrated prognostic utility on univariate analysis. Across all signatures, patients whose samples were identified as low-risk experienced better outcomes than intermediate-risk, with those classed as high risk experiencing the poorest outcomes. As seen with female BCa, the concordance between tests was poor, with C-index values ranging from 40.3% to 78.2% and Kappa values ranging from 0.17 to 0.58. To our knowledge, this is the largest study of male breast cancers assayed to generate risk scores of the current commercial and academic risk tests demonstrating comparable clinical utility to female BCa.
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| 21. |
- Chrysina, Maria, et al.
(author)
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Five-coordinate Mn-IV intermediate in the activation of nature's water splitting cofactor
- 2019
-
In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 116:34, s. 16841-16846
-
Journal article (peer-reviewed)abstract
- Nature's water splitting cofactor passes through a series of catalytic intermediates (S-0-S-4) before O-O bond formation and O-2 release. In the second last transition (S-2 to S-3) cofactor oxidation is coupled to water molecule binding to Mn1. It is this activated, water-enriched all Mn-IV form of the cofactor that goes on to form the O-O bond, after the next light-induced oxidation to S-4. How cofactor activation proceeds remains an open question. Here, we report a so far not described intermediate (S-3') in which cofactor oxidation has occurred without water insertion. This intermediate can be trapped in a significant fraction of centers (> 50%) in (i) chemical-modified cofactors in which Ca2+ is exchanged with Sr2+; the Mn4O5Sr cofactor remains active, but the S-2-S-3 and S-3-S-0 transitions are slower than for the Mn4O5Ca cofactor; and (ii) upon addition of 3% vol/vol methanol; methanol is thought to act as a substrate water analog. The S-3' electron paramagnetic resonance (EPR) signal is significantly broader than the untreated S-3 signal (2.5 T vs. 1.5 T), indicating the cofactor still contains a 5-coordinate Mn ion, as seen in the preceding S-2 state. Magnetic double resonance data extend these findings revealing the electronic connectivity of the S-3' cofactor is similar to the high spin form of the preceding S-2 state, which contains a cuboidal Mn3O4Ca unit tethered to an external, 5-coordinate Mn ion (Mn-4). These results demonstrate that cofactor oxidation regulates water molecule insertion via binding to Mn-4. The interaction of ammonia with the cofactor is also discussed.
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| 22. |
- de Lichtenberg, Casper, et al.
(author)
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Assignment of the slowly exchanging substrate water of nature's water-splitting cofactor
- 2024
-
In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences (PNAS). - 0027-8424 .- 1091-6490. ; 121:11
-
Journal article (peer-reviewed)abstract
- Identifying the two substrate water sites of nature's water-splitting cofactor (Mn4CaO5 cluster) provides important information toward resolving the mechanism of O-O bond formation in Photosystem II (PSII). To this end, we have performed parallel substrate water exchange experiments in the S1 state of native Ca-PSII and biosynthetically substituted Sr-PSII employing Time-Resolved Membrane Inlet Mass Spectrometry (TR-MIMS) and a Time-Resolved 17O-Electron-electron Double resonance detected NMR (TR-17O-EDNMR) approach. TR-MIMS resolves the kinetics for incorporation of the oxygen-isotope label into the substrate sites after addition of H218O to the medium, while the magnetic resonance technique allows, in principle, the characterization of all exchangeable oxygen ligands of the Mn4CaO5 cofactor after mixing with H217O. This unique combination shows i) that the central oxygen bridge (O5) of Ca-PSII core complexes isolated from Thermosynechococcus vestitus has, within experimental conditions, the same rate of exchange as the slowly exchanging substrate water (WS) in the TR-MIMS experiments and ii) that the exchange rates of O5 and WS are both enhanced by Ca2+→Sr2+ substitution in a similar manner. In the context of previous TR-MIMS results, this shows that only O5 fulfills all criteria for being WS. This strongly restricts options for the mechanism of water oxidation.
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| 23. |
- Grasse, Nicole, et al.
(author)
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Role of Novel Dimeric Photosystem II (PSII)-Psb27 Protein Complex in PSII Repair
- 2011
-
In: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 286:34, s. 29548-29555
-
Journal article (peer-reviewed)abstract
- The multisubunit membrane protein complex Photosystem II (PSII) catalyzes one of the key reactions in photosynthesis: the light-driven oxidation of water. Here, we focus on the role of the Psb27 assembly factor, which is involved in biogenesis and repair after light-induced damage of the complex. Weshow that Psb27 is essential for the survival of cyanobacterial cells grown under stress conditions. The combination of cold stress (30 degrees C) and high light stress (1000 mu mol of photons x m(-2) x s(-1)) led to complete inhibition of growth in a Delta psb27 mutant strain of the thermophilic cyanobacterium Thermosynechococcus elongatus, whereas wild-type cells continued to grow. Moreover, Psb27-containing PSII complexes became the predominant PSII species in preparations from wild-type cells grown under cold stress. Two different PSII-Psb27 complexes were isolated and characterized in this study. The first complex represents the known monomeric PSII-Psb27 species, which is involved in the assembly of PSII. Additionally, a novel dimeric PSII-Psb27 complex could be allocated in the repair cycle, i.e. in processes after inactivation of PSII, by (15)N pulse-label experiments followed by mass spectrometry analysis. Comparison with the corresponding PSII species from Delta psb27 mutant cells showed that Psb27 prevented the release of manganese from the previously inactivated complex. These results indicate a more complex role of the Psb27 protein within the life cycle of PSII, especially under stress conditions.
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| 24. |
- Mamedov, Fikret, et al.
(author)
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Functional characterization of monomeric photosystem II core preparations from Thermosynechococcus elongatus with or without the Psb27 protein
- 2007
-
In: Biochemistry. - : American Chemical Society (ACS). - 0006-2960 .- 1520-4995. ; 46:18, s. 5542-5551
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Journal article (peer-reviewed)abstract
- Two monomeric fractions of photosystem II (PS II) core pacticles from the thermophilic cyanobacterium Thermosynechococcus elongatus have been investigated using flash-induced variable fluorescence kinetics and EPR spectroscopy. One fraction was highly active in oxygen evolution and contained the extrinsic protein subunits PsbO, PsbU, and PsbV. The other monomeric fraction lacked oxygen evolving activity as well as the three extrinsic subunits, but the luminally located, extrinsic Psb27 lipoprotein was present. In the monomeric fraction with bound Psb27, flash-induced variable fluorescence showed an absence of oxidizable Mn on the donor side of PS II and impaired forward electron transfer from the primary quinone acceptor, QA. These results were confirmed with EPR spectroscopy by the absence of the \"split S1\" interaction signal from YZ.bul. and the CaMn4 cluster and by the absence of the S2-state multiline signal. A different protein compn. on the donor side of PS II monomers with Psb27 was also supported by the lack of an EPR signal from cytochrome c550 (in the PsbV subunit). In addn., we did not observe any oxidn. of cytochrome b559 at low temp. in this fraction. The presence of Psb27 and the absence of the CaMn4 cluster did not affect the protein matrix around YD or the acceptor side quinones as can be judged from the appearance of the corresponding EPR signals. The diminished electron transport capabilities on both the donor and the acceptor side of PS II when Psb27 is present give further indications that this PS II complex is involved in the earlier steps of the PS II repair cycle.
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| 25. |
- Mashad Nemati, Hassan, 1982-, et al.
(author)
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Stream Data Cleaning for Dynamic Line Rating Application
- 2018
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In: Energies. - Basel : MDPI. - 1996-1073. ; 11:8
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Journal article (peer-reviewed)abstract
- The maximum current that an overhead transmission line can continuously carry depends on external weather conditions, most commonly obtained from real-time streaming weather sensors. The accuracy of the sensor data is very important in order to avoid problems such as overheating. Furthermore, faulty sensor readings may cause operators to limit or even stop the energy production from renewable sources in radial networks. This paper presents a method for detecting and replacing sequences of consecutive faulty data originating from streaming weather sensors. The method is based on a combination of (a) a set of constraints obtained from derivatives in consecutive data, and (b) association rules that are automatically generated from historical data. In smart grids, a large amount of historical data from different weather stations are available but rarely used. In this work, we show that mining and analyzing this historical data provides valuable information that can be used for detecting and replacing faulty sensor readings. We compare the result of the proposed method against the exponentially weighted moving average and vector autoregression models. Experiments on data sets with real and synthetic errors demonstrate the good performance of the proposed method for monitoring weather sensors.
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| 26. |
- Wennrich, Volker, et al.
(author)
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Impact processes, permafrost dynamics, and climate and environmental variability in the terrestrial Arctic as inferred from the unique 3.6 Myr record of Lake El'gygytgyn, Far East Russia - A review
- 2016
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In: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 147, s. 221-244
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Journal article (peer-reviewed)abstract
- Lake El'gygytgyn in Far East Russia is a 3.6 Myr old impact crater lake. Located in an area that has never been affected by Cenozoic glaciations nor desiccation, the unique sediment record of the lake represents the longest continuous sediment archive of the terrestrial Arctic. The surrounding crater is the only impact structure on Earth developed in mostly acid volcanic rocks. Recent studies on the impactite, permafrost, and sediment sequences recovered within the framework of the ICDP "El'gygytgyn Drilling Project" and multiple pre-site surveys yielded new insight into the bedrock origin and cratering processes as well as permafrost dynamics and the climate and environmental history of the terrestrial Arctic back to the mid-Pliocene. Results from the impact rock section recovered during the deep drilling clearly confirm the impact genesis of the El'gygytgyn crater, but indicate an only very reduced fallback impactite sequence without larger coherent melt bodies. Isotope and element data of impact melt samples indicate a F-type asteroid of mixed composition or an ordinary chondrite as the likely impactor. The impact event caused a long-lasting hydrothermal activity in the crater that is assumed to have persisted for c. 300 kyr. Geochemical and microbial analyses of the permafrost core indicate a subaquatic formation of the lower part during lake-level highstand, but a subaerial genesis of the upper part after a lake-level drop after the Allerod. The isotope signal and ion compositions of ground ice is overprinted by several thaw freeze cycles due to variations in the talik underneath the lake. Modeling results suggest a modern permafrost thickness in the crater of c. 340 m, and further confirm a pervasive character of the talik below Lake El'gygytgyn. The lake sediment sequences shed new leight into the Pliocene and Pleistocene climate and environmental evolution of the Arctic. During the mid-Pliocene, significantly warmer and wetter climatic conditions in western Beringia than today enabled dense boreal forests to grow around Lake Ergygytgyn and, in combination with a higher nutrient flux into the lake, promoted primary production. The exceptional warmth during the mid-Pliocene is in accordance with other marine and terrestrial records from the Arctic and indicates a period of enhanced "Arctic amplification". The favourable conditions during the mid-Pliocene were repeatedly interrupted by climate deteriorations, e.g., during Marine Isotope Stage (MIS) M2, when pollen data and sediment proxies indicate a major cooling and the onset of local permafrost around the lake. A gradual vegetation change after c. 3.0 Ma points to the onset of a long-term cooling trend during the Late Pliocene that culminated in major temperature drops, first during MIS G6, and later during MIS 104. These cold events coincide with the onset of an intensified Northern Hemisphere (NH) glaciation and the largest extent of the Cordilleran Ice Sheet, respectively. After the Pliocene/Pleistocene transition, local vegetation and primary production in Lake El'gygtygyn experienced a major change from relatively uniform conditions to a high-amplitude glacial-to-interglacial cyclicity that fluctuated on a dominant 41 kyr obliquity band, but changed to a 100 kyr eccentricity dominance during the Middle Pleistocene transition (MPT) at c. 1.2-0.6 Ma. Periods of exceptional warming in the Pleistocene record of Lake El'gygytgyn with dense boreal forests around and peaks of primary production in the lake are assigned to so-called "super-interglacial" periods. The occurrence of these super-interglacials well corresponds to collapses of the West Antarctic Ice Sheet (WAIS) recorded in ice-free periods in the ANDRILL core, which suggests strong intrahemispheric teleconnections presumably driven by changes in the thermocline ocean circulation.
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