| 1. |
- Cardoso, F., et al.
(författare)
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Characterization of male breast cancer : Results of the EORTC 10085/TBCRC/BIG/NABCG International Male Breast Cancer Program
- 2018
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Ingår i: Annals of Oncology. - : Elsevier BV. - 1569-8041 .- 0923-7534. ; 29:2, s. 405-417
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Tidskriftsartikel (refereegranskat)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.
(författare)
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A global environmental crisis 42,000 years ago
- 2021
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 371:6531, s. 811-818
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Tidskriftsartikel (refereegranskat)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.
(författare)
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Response to comment on “A global environmental crisis 42,000 years ago”
- 2021
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 374:6570
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Tidskriftsartikel (refereegranskat)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.
(författare)
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2.8 million years of arctic climate change from Lake El'gygytgyn, NE Russia
- 2012
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 337:6092, s. 315-320
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Tidskriftsartikel (refereegranskat)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.
(författare)
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Ammonia binding to the oxygen-evolving complex of photosystem II identifies the solvent-exchangeable oxygen bridge (µ-oxo) of the manganese tetramer
- 2013
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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. ; 110:39, s. 15561-15566
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Tidskriftsartikel (refereegranskat)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.
(författare)
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Chronology of Lake El'gygytgyn sediments - a combined magnetostratigraphic, palaeoclimatic and orbital tuning study based on multi-parameter analyses
- 2013
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Ingår i: Climate of the Past. - : Copernicus GmbH. - 1814-9324 .- 1814-9332. ; 9:6, s. 2413-2432
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Tidskriftsartikel (refereegranskat)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.
(författare)
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An Architecture for Resource Bounded Agents
- 2007
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Ingår i: Proceedings of the International Multiconference on Computer Science and Information Technology. - Katowice : PTI Press. - 1896-7094. ; 2, s. 59-69
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Konferensbidrag (refereegranskat)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.
(författare)
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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
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Ingår i: Journal of the American Chemical Society. - Washington : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 134:40, s. 16619-16634
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Tidskriftsartikel (refereegranskat)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.
(författare)
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Human chromosome 7: DNA sequence and biology
- 2003
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Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 300:5620, s. 767-772
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Tidskriftsartikel (refereegranskat)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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