| 1. |
- Aad, G., et al.
(författare)
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- 2010
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swepub:Mat__t
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| 2. |
- Aad, G., et al.
(författare)
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- 2010
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swepub:Mat__t
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| 3. |
- Aad, G., et al.
(författare)
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- 2010
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swepub:Mat__t
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| 4. |
- Aad, G., et al.
(författare)
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- 2010
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swepub:Mat__t
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| 5. |
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| 6. |
- Aad, G., et al.
(författare)
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- 2011
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swepub:Mat__t
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| 7. |
- Glasbey, JC, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 8. |
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| 9. |
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| 10. |
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| 11. |
- Abt, I, et al.
(författare)
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Inclusive V-0 production cross sections from 920 GeV fixed target proton-nucleus collisions
- 2003
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Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 29:2, s. 181-190
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Tidskriftsartikel (refereegranskat)abstract
- Inclusive differential cross sections dsigma(pA)/dx(F) and dsigma(pA)/dp(t)(2) for the production of K-S(0), Lambda, and (&ULambda;) over bar particles are measured at HERA in proton-induced reactions on C, Al, Ti, and W targets. The incident beam energy is 920 GeV, corresponding to roots = 41.6 GeV in the proton-nucleon system. The ratios of differential cross sections dsigma(pA)(K-S(0))/dsigma(pA)(Lambda) and dsigma(pA)((&ULambda;) over bar)/dsigma(pA) (Lambda) are measured to be 6.2 +/- 0.5 and 0.66 +/- 0.07, respectively, for x(F) approximate to -0.06. No significant dependence upon the target material is observed. Within errors, the slopes of the transverse momentum distributions da,Ald t also show no significant dependence upon the target material. The dependence of the extrapolated total cross sections sigma(pA) on the atomic mass A of the target material is discussed, and the deduced cross sections per nucleon sigma(pN) are compared with results obtained at other energies.
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| 12. |
- Abt, I, et al.
(författare)
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Measurement of the b(b)over-bar production cross section in 920 GeV fixed-target proton-nucleus collisions
- 2003
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Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 26:3, s. 345-355
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Tidskriftsartikel (refereegranskat)abstract
- Using the HERA-B detector, the b (b) over bar production cross section has been measured in 920 GeV proton collisions on carbon and titanium targets. The b (b) over bar production was tagged via inclusive bottom quark decays into J/psi by exploiting the longitudinal separation of J/psi --> l(+)l(-) decay vertices from the primary proton-nucleus interaction. Both e(+)e(-) and mu(+)mu(-) channels have been reconstructed and the combined analysis yields the cross section sigma(b (b) over bar) = 32(-12)(+14)(stat) (+6)(-7)(sys) nb/nucleon.
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| 13. |
- Kjellsson, Ludvig, et al.
(författare)
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Resonant Inelastic X-Ray Scattering Reveals Hidden Local Transitions of the Aqueous OH Radical
- 2020
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Ingår i: Physical Review Letters. - : AMER PHYSICAL SOC. - 0031-9007 .- 1079-7114. ; 124:23
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Tidskriftsartikel (refereegranskat)abstract
- Resonant inelastic x-ray scattering (RIXS) provides remarkable opportunities to interrogate ultra-fast dynamics in liquids. Here we use RIXS to study the fundamentally and practically important hydroxyl radical in liquid water, OH(aq). Impulsive ionization of pure liquid water produced a short-lived population of OH(aq), which was probed using femtosecond x-rays from an x-ray free-electron laser. We find that RIXS reveals localized electronic transitions that are masked in the ultraviolet absorption spectrum by strong charge-transfer transitions-thus providing a means to investigate the evolving electronic structure and reactivity of the hydroxyl radical in aqueous and heterogeneous environments. First-principles calculations provide interpretation of the main spectral features.
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| 14. |
- Loh, Z-H, et al.
(författare)
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Observation of the fastest chemical processes in the radiolysis of water
- 2020
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Ingår i: Science. - : AMER ASSOC ADVANCEMENT SCIENCE. - 0036-8075 .- 1095-9203. ; 367:6474, s. 179-182
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Tidskriftsartikel (refereegranskat)abstract
- Elementary processes associated with ionization of liquid water provide a framework for understanding radiation-matter interactions in chemistry and biology. Although numerous studies have been conducted on the dynamics of the hydrated electron, its partner arising from ionization of liquid water, H2O+, remains elusive. We used tunable femtosecond soft x-ray pulses from an x-ray free electron laser to reveal the dynamics of the valence hole created by strong-field ionization and to track the primary proton transfer reaction giving rise to the formation of OH. The isolated resonance associated with the valence hole (H2O+/OH) enabled straightforward detection. Molecular dynamics simulations revealed that the x-ray spectra are sensitive to structural dynamics at the ionization site. We found signatures of hydrated-electron dynamics in the x-ray spectrum.
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| 15. |
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| 16. |
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| 17. |
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| 18. |
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| 19. |
- Cronin, Thomas M., et al.
(författare)
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Interglacial Paleoclimate in the Arctic
- 2019
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Ingår i: Paleoceanography and Paleoclimatology. - 2572-4517 .- 2572-4525. ; 34:12, s. 1959-1979
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Tidskriftsartikel (refereegranskat)abstract
- Marine Isotope Stage 11 from similar to 424 to 374 ka experienced peak interglacial warmth and highest global sea level similar to 410-400 ka. MIS 11 has received extensive study on the causes of its long duration and warmer than Holocene climate, which is anomalous in the last half million years. However, a major geographic gap in MIS 11 proxy records exists in the Arctic Ocean where fragmentary evidence exists for a seasonally sea ice-free summers and high sea-surface temperatures (SST; similar to 8-10 degrees C near the Mendeleev Ridge). We investigated MIS 11 in the western and central Arctic Ocean using 12 piston cores and several shorter cores using proxies for surface productivity (microfossil density), bottom water temperature (magnesium/calcium ratios), the proportion of Arctic Ocean Deep Water versus Arctic Intermediate Water (key ostracode species), sea ice (epipelagic sea ice dwelling ostracode abundance), and SST (planktic foraminifers). We produced a new benthic foraminiferal delta O-18 curve, which signifies changes in global ice volume, Arctic Ocean bottom temperature, and perhaps local oceanographic changes. Results indicate that peak warmth occurred in the Amerasian Basin during the middle of MIS 11 roughly from 410 to 400 ka. SST were as high as 8-10 degrees C for peak interglacial warmth, and sea ice was absent in summers. Evidence also exists for abrupt suborbital events punctuating the MIS 12-MIS 11-MIS 10 interval. These fluctuations in productivity, bottom water temperature, and deep and intermediate water masses (Arctic Ocean Deep Water and Arctic Intermediate Water) may represent Heinrich-like events possibly involving extensive ice shelves extending off Laurentide and Fennoscandian Ice Sheets bordering the Arctic.
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| 20. |
- Farmer, Jesse R., et al.
(författare)
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A 600 kyr reconstruction of deep Arctic seawater δ18O from benthic foraminiferal δ18O and ostracode Mg / Ca paleothermometry
- 2023
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Ingår i: Climate of the Past. - : Copernicus GmbH. - 1814-9324 .- 1814-9332. ; 19:3, s. 555-578
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Tidskriftsartikel (refereegranskat)abstract
- The oxygen isotopic composition of benthic foraminiferal tests (δ18Ob) is one of the pre-eminent tools for correlating marine sediments and interpreting past terrestrial ice volume and deep-ocean temperatures. Despite the prevalence of δ18Ob applications to marine sediment cores over the Quaternary, its use is limited in the Arctic Ocean because of low benthic foraminiferal abundances, challenges with constructing independent sediment core age models, and an apparent muted amplitude of Arctic δ18Ob variability compared to open-ocean records. Here we evaluate the controls on Arctic δ18Ob by using ostracode paleothermometry to generate a composite record of the δ18O of seawater (δ18Osw) from 12 sediment cores in the intermediate to deep Arctic Ocean (700–2700 m) that covers the last 600 kyr based on biostratigraphy and orbitally tuned age models. Results show that Arctic δ18Ob was generally higher than open-ocean δ18Ob during interglacials but was generally equivalent to global reference records during glacial periods. The reduced glacial–interglacial Arctic δ18Ob range resulted in part from the opposing effect of temperature, with intermediate to deep Arctic warming during glacials counteracting the whole-ocean δ18Osw increase from expanded terrestrial ice sheets. After removing the temperature effect from δ18Ob, we find that the intermediate to deep Arctic experienced large (≥1 ‰) variations in local δ18Osw, with generally higher local δ18Osw during interglacials and lower δ18Osw during glacials. Both the magnitude and timing of low local δ18Osw intervals are inconsistent with the recent proposal of freshwater intervals in the Arctic Ocean during past glaciations. Instead, we suggest that lower local δ18Osw in the intermediate to deep Arctic Ocean during glaciations reflected weaker upper-ocean stratification and more efficient transport of low-δ18Osw Arctic surface waters to depth by mixing and/or brine rejection.
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| 21. |
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| 22. |
- Hellmuth, Marc, 1980-, et al.
(författare)
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Clustering systems of phylogenetic networks
- 2023
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Ingår i: Theory in biosciences. - 1431-7613 .- 1611-7530. ; :142, s. 301-358
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Tidskriftsartikel (refereegranskat)abstract
- Rooted acyclic graphs appear naturally when the phylogenetic relationship of a set X of taxa involves not only speciations but also recombination, horizontal transfer, or hybridization that cannot be captured by trees. A variety of classes of such networks have been discussed in the literature, including phylogenetic, level-1, tree-child, tree-based, galled tree, regular, or normal networks as models of different types of evolutionary processes. Clusters arise in models of phylogeny as the sets C(v) of descendant taxa of a vertex v. The clustering system CN comprising the clusters of a network N conveys key information on N itself. In the special case of rooted phylogenetic trees, T is uniquely determined by its clustering system CT. Although this is no longer true for networks in general, it is of interest to relate properties of N and CN. Here, we systematically investigate the relationships of several well-studied classes of networks and their clustering systems. The main results are correspondences of classes of networks and clustering systems of the following form: If N is a network of type X, then CN satisfies Y, and conversely if C is a clustering system satisfying Y, then there is network N of type X such that C⊆CN.This, in turn, allows us to investigate the mutual dependencies between the distinct types of networks in much detail.
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| 23. |
- Hellmuth, Marc, et al.
(författare)
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Combining Orthology and Xenology Data in a Common Phylogenetic Tree
- 2021
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Ingår i: Advances in Bioinformatics and Computational Biology. - Cham : Springer. - 9783030918132 - 9783030918149 ; , s. 53-64
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Konferensbidrag (refereegranskat)abstract
- In mathematical phylogenetics, types of events in a gene tree T are formalized by vertex labels t(v) and set-valued edge labels λ(e). The orthology and paralogy relations between genes are a special case of a map δ on the pairs of leaves of T defined by δ(x,y)=q if the last common ancestor lca(x,y) of x and y is labeled by an event type q, e.g., speciation or duplication. Similarly, a map εε with m∈ε(x,y) if m∈λ(e) for at least one edge e along the path from lca(x,y) to y generalizes xenology, i.e., horizontal gene transfer. We show that a pair of maps (δ,ε) derives from a tree (T,t,λ) in this manner if and only if there exists a common refinement of the (unique) least-resolved vertex labeled tree (Tδ,tδ) that explains δ and the (unique) least-resolved edge labeled tree (Tε,λε) that explains ε (provided both trees exist). This result remains true if certain combinations of labels at incident vertices and edges are forbidden.
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| 24. |
- Hellmuth, Marc, et al.
(författare)
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Compatibility of partitions with trees, hierarchies, and split systems
- 2022
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Ingår i: Discrete Applied Mathematics. - : Elsevier BV. - 0166-218X .- 1872-6771. ; 314, s. 265-283
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Tidskriftsartikel (refereegranskat)abstract
- The question whether a partition P and a hierarchy H or a tree-like split system S are compatible naturally arises in a wide range of classification problems. In the setting of phylogenetic trees, one asks whether the sets of P coincide with leaf sets of connected components obtained by deleting some edges from the tree T that represents H or S, respectively. More generally, we ask whether a refinement T∗ of T exists such that T∗ and P are compatible in this sense. The latter is closely related to the question as to whether there exists a tree at all that is compatible with P. We report several characterizations for (refinements of) hierarchies and split systems that are compatible with (systems of) partitions. In addition, we provide a linear-time algorithm to check whether refinements of trees and a given partition are compatible. The latter problem becomes NP-complete but fixed-parameter tractable if a system of partitions is considered instead of a single partition. In this context, we also explore the close relationship of the concept of compatibility and so-called Fitch maps.
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| 25. |
- Jadersten, M., et al.
(författare)
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Targeting SAMHD1 with hydroxyurea in first-line cytarabine-based therapy of newly diagnosed acute myeloid leukaemia: Results from the HEAT-AML trial
- 2022
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 292:6, s. 925-940
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Tidskriftsartikel (refereegranskat)abstract
- Background Treatment of newly diagnosed acute myeloid leukaemia (AML) is based on combination chemotherapy with cytarabine (ara-C) and anthracyclines. Five-year overall survival is below 30%, which has partly been attributed to cytarabine resistance. Preclinical data suggest that the addition of hydroxyurea potentiates cytarabine efficacy by increasing ara-C triphosphate (ara-CTP) levels through targeted inhibition of SAMHD1. Objectives In this phase 1 trial, we evaluated the feasibility, safety and efficacy of the addition of hydroxyurea to standard chemotherapy with cytarabine/daunorubicin in newly diagnosed AML patients. Methods Nine patients were enrolled and received at least two courses of ara-C (1 g/m(2)/2 h b.i.d. d1-5, i.e., a total of 10 g/m(2) per course), hydroxyurea (1-2 g d1-5) and daunorubicin (60 mg/m(2) d1-3). The primary endpoint was safety; secondary endpoints were complete remission rate and measurable residual disease (MRD). Additionally, pharmacokinetic studies of ara-CTP and ex vivo drug sensitivity assays were performed. Results The most common grade 3-4 toxicity was febrile neutropenia (100%). No unexpected toxicities were observed. Pharmacokinetic analyses showed a significant increase in median ara-CTP levels (1.5-fold; p = 0.04) in patients receiving doses of 1 g hydroxyurea. Ex vivo, diagnostic leukaemic bone marrow blasts from study patients were significantly sensitised to ara-C by a median factor of 2.1 (p = 0.0047). All nine patients (100%) achieved complete remission, and all eight (100%) with validated MRD measurements (flow cytometry or real-time quantitative polymerase chain reaction [RT-qPCR]) had an MRD level <0.1% after two cycles of chemotherapy. Treatment was well-tolerated, and median time to neutrophil recovery >1.0 x 10(9)/L and to platelet recovery >50 x 10(9)/L after the start of cycle 1 was 19 days and 22 days, respectively. Six of nine patients underwent allogeneic haematopoietic stem-cell transplantation (allo-HSCT). With a median follow-up of 18.0 (range 14.9-20.5) months, one patient with adverse risk not fit for HSCT experienced a relapse after 11.9 months but is now in second complete remission. Conclusion Targeted inhibition of SAMHD1 by the addition of hydroxyurea to conventional AML therapy is safe and appears efficacious within the limitations of the small phase 1 patient cohort. These results need to be corroborated in a larger study.
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| 26. |
- Korchmaros, Annachiara, et al.
(författare)
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Quasi-best match graphs
- 2023
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Ingår i: Discrete Applied Mathematics. - : Elsevier BV. - 0166-218X .- 1872-6771. ; 331, s. 104-125
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Tidskriftsartikel (refereegranskat)abstract
- Quasi-best match graphs (qBMGs) are a hereditary class of directed, properly vertex -colored graphs. They arise naturally in mathematical phylogenetics as a generalization of best match graphs, which formalize the notion of evolutionary closest relatedness of genes (vertices) in multiple species (vertex colors). They are explained by rooted trees whose leaves correspond to vertices. In contrast to BMGs, qBMGs represent only best matches at a restricted phylogenetic distance. We provide characterizations of qBMGs that give rise to polynomial-time recognition algorithms and identify the BMGs as the qBMGs that are color-sink-free. Furthermore, two-colored qBMGs are characterized as directed graphs satisfying three simple local conditions, two of which have appeared previously, namely bi-transitivity in the sense of Das et al. (2021) and a hierarchy-like structure of out-neighborhoods, i.e., N(x) n N(y) E {N(x), N(y), 0} for any two vertices x and y. Further results characterize qBMGs that can be explained by binary phylogenetic trees.
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| 27. |
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| 28. |
- Nuding, Sabine, et al.
(författare)
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Gastric Antimicrobial Peptides Fail to Eradicate Helicobacter pylori Infection Due to Selective Induction and Resistance
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 8:9
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Tidskriftsartikel (refereegranskat)abstract
- Background: Although antimicrobial peptides protect mucus and mucosa from bacteria, Helicobacter pylori is able to colonize the gastric mucus. To clarify in which extend Helicobacter escapes the antimicrobial defense, we systematically assessed susceptibility and expression levels of different antimicrobial host factors in gastric mucosa with and without H. pylori infection.Materials and Methods: We investigated the expression levels of HBD1 (gene name DEFB1), HBD2 (DEFB4A), HBD3 (DEFB103A), HBD4 (DEFB104A), LL37 (CAMP) and elafin (PI3) by real time PCR in gastric biopsy samples in a total of 20 controls versus 12 patients colonized with H. pylori. Immunostaining was performed for HBD2 and HBD3. We assessed antimicrobial susceptibility by flow cytometry, growth on blood agar, radial diffusion assay and electron microscopy.Results: H. pylori infection was associated with increased gastric levels of the inducible defensin HBD2 and of the antiprotease elafin, whereas the expression levels of the constitutive defensin HBD1, inducible HBD3 and LL37 remained unchanged. HBD4 was not expressed in significant levels in gastric mucosa. H. pylori strains were resistant to the defensins HBD1 as well as to elafin, and strain specific minimally susceptible to HBD2, whereas HBD3 and LL37 killed all H. pylori strains effectively. We demonstrated the binding of HBD2 and LL37 on the surface of H. pylori cells. Comparing the antibacterial activity of extracts from H. pylori negative and positive biopsies, we found only a minimal killing against H. pylori that was not increased by the induction of HBD2 in H. pylori positive samples.Conclusion: These data support the hypothesis that gastric H. pylori evades the host defense shield to allow colonization.
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| 29. |
- Puglisi, A., et al.
(författare)
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KURVS: the outer rotation curve shapes and dark matter fractions of z ∼1.5 star-forming galaxies
- 2023
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Ingår i: Monthly Notices of the Royal Astronomical Society. - 0035-8711 .- 1365-2966. ; 524:2, s. 2814-2835
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Tidskriftsartikel (refereegranskat)abstract
- We present first results from the KMOS Ultra-deep Rotation Velocity Survey (KURVS), aimed at studying the outer rotation curves shape and dark matter content of 22 star-forming galaxies at z ∼1.5. These galaxies represent 'typical' star-forming discs at z ∼1.5, being located within the star-forming main sequence and stellar mass-size relation with stellar masses 9.5 ≤ log(M*/M⊙) ≤ 11.5. We use the spatially resolved H α emission to extract individual rotation curves out to 4 times the effective radius, on average, or ∼10-15 kpc. Most rotation curves are flat or rising between three and six disc scale radii. Only three objects with dispersion-dominated dynamics (vrot/σ0 ∼0.2) have declining outer rotation curves at more than 5σ significance. After accounting for seeing and pressure support, the nine rotation-dominated discs with vrot/σ0 ≥ 1.5 have average dark matter fractions of at the effective radius, similar to local discs. Together with previous observations of star-forming galaxies at cosmic noon, our measurements suggest a trend of declining dark matter fraction with increasing stellar mass and stellar mass surface density at the effective radius. Measurements of simulated EAGLE galaxies are in quantitative agreement with observations up to log, and overpredict the dark matter fraction of galaxies with higher mass surface densities by a factor of ∼3. We conclude that the dynamics of typical rotationally-supported discs at z ∼1.5 is dominated by dark matter from effective radius scales, in broad agreement with cosmological models. The tension with observations at high stellar mass surface density suggests that the prescriptions for baryonic processes occurring in the most massive galaxies (such as bulge growth and quenching) need to be reassessed.
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| 30. |
- Rassidakis, GZ, et al.
(författare)
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Low-level expression of SAMHD1 in acute myeloid leukemia (AML) blasts correlates with improved outcome upon consolidation chemotherapy with high-dose cytarabine-based regimens
- 2018
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Ingår i: Blood cancer journal. - : Springer Science and Business Media LLC. - 2044-5385. ; 8:11, s. 98-
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Tidskriftsartikel (refereegranskat)abstract
- Sterile alpha motif and histidine/aspartic acid domain containing protein 1 (SAMHD1) limits the efficacy of cytarabine (ara-C) used in AML by hydrolyzing its active metabolite ara-CTP and thus represents a promising therapeutic target. SAMHD1 has also been implicated in DNA damage repair that may impact DNA damage-inducing therapies such as anthracyclines, during induction therapy. To determine whether SAMHD1 limits ara-C efficacy during induction or consolidation therapy, SAMHD1 protein levels were assessed in two patient cohorts of de novo AML from The University of Texas MD Anderson Cancer Center (USA) and the National University Hospital (Singapore), respectively, using immunohistochemistry and tissue microarrays. SAMHD1 was expressed at a variable level by AML blasts but not in a broad range of normal hematopoietic cells in reactive bone marrows. A sizeable patient subset with low SAMHD1 expression (<25% of positive blasts) was identified, which was significantly associated with longer event-free (EFS) and overall (OS) survival in patients receiving high-dose cytarabine (HDAC) during consolidation. Therefore, evaluation of SAMHD1 expression level in AML blasts at diagnosis, may stratify patient groups for future clinical trials combining HDAC with novel SAMHD1 inhibitors as consolidation therapy.
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| 31. |
- Schaller, David, et al.
(författare)
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A simpler linear-time algorithm for the common refinement of rooted phylogenetic trees on a common leaf set
- 2021
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Ingår i: Algorithms for Molecular Biology. - : Springer Science and Business Media LLC. - 1748-7188. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- Background: The supertree problem, i.e., the task of finding a common refinement of a set of rooted trees is an important topic in mathematical phylogenetics. The special case of a common leaf set L is known to be solvable in linear time. Existing approaches refine one input tree using information of the others and then test whether the results are isomorphic.Results: An O(k|L|) algorithm, LinCR, for constructing the common refinement T of k input trees with a common leaf set L is proposed that explicitly computes the parent function of T in a bottom-up approach.Conclusion: LinCR is simpler to implement than other asymptotically optimal algorithms for the problem and outperforms the alternatives in empirical comparisons.
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| 32. |
- Schaller, David, et al.
(författare)
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Arc-Completion of 2-Colored Best Match Graphs to Binary-Explainable Best Match Graphs
- 2021
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Ingår i: Algorithms. - : MDPI AG. - 1999-4893. ; 14:4
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Best match graphs (BMGs) are vertex-colored digraphs that naturally arise in mathematical phylogenetics to formalize the notion of evolutionary closest genes w.r.t. an a priori unknown phylogenetic tree. BMGs are explained by unique least resolved trees. We prove that the property of a rooted, leaf-colored tree to be least resolved for some BMG is preserved by the contraction of inner edges. For the special case of two-colored BMGs, this leads to a characterization of the least resolved trees (LRTs) of binary-explainable trees and a simple, polynomial-time algorithm for the minimum cardinality completion of the arc set of a BMG to reach a BMG that can be explained by a binary tree.
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| 33. |
- Schaller, David, et al.
(författare)
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Best Match Graphs with Binary Trees
- 2021
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Ingår i: Algorithms for Computational Biology. - Cham : Springer. - 9783030744311 - 9783030744328 ; , s. 82-93
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Konferensbidrag (refereegranskat)abstract
- Best match graphs (BMG) are a key intermediate in graph-based orthology detection and contain a large amount of information on the gene tree. We provide a near-cubic algorithm to determine whether a BMG can be explained by a fully resolved gene tree and, if so, to construct such a tree. Moreover, we show that all such binary trees are refinements of the unique binary-resolvable tree (BRT), which in general is a substantial refinement of the also unique least resolved tree of a BMG.
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| 34. |
- Schaller, David, et al.
(författare)
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Best Match Graphs With Binary Trees
- 2023
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Ingår i: IEEE/ACM Transactions on Computational Biology & Bioinformatics. - 1545-5963 .- 1557-9964. ; 20:3, s. 1679-1690
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Tidskriftsartikel (refereegranskat)abstract
- Best match graphs (BMG) are a key intermediate in graph-based orthology detection and contain a large amount of information on the gene tree. We provide a near-cubic algorithm to determine whether a BMG is binary-explainable, i.e., whether it can be explained by a fully resolved gene tree and, if so, to construct such a tree. Moreover, we show that all such binary trees are refinements of the unique binary-refinable tree (BRT), which in general is a substantial refinement of the also unique least resolved tree of a BMG. Finally, we show that the problem of editing an arbitrary vertex-colored graph to a binary-explainable BMG is NP-complete and provide an integer linear program formulation for this task.
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| 35. |
- Schaller, David, et al.
(författare)
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Complete Characterization of Incorrect Orthology Assignments in Best Match Graphs
- 2021
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Ingår i: Journal of Mathematical Biology. - : Springer Science and Business Media LLC. - 0303-6812 .- 1432-1416. ; 82:20
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Tidskriftsartikel (refereegranskat)abstract
- Genome-scale orthology assignments are usually based on reciprocal best matches. In the absence of horizontal gene transfer (HGT), every pair of orthologs forms a reciprocal best match. Incorrect orthology assignments therefore are always false positives in the reciprocal best match graph. We consider duplication/loss scenarios and characterize unambiguous false-positive (u-fp) orthology assignments, that is, edges in the best match graphs (BMGs) that cannot correspond to orthologs for any gene tree that explains the BMG. Moreover, we provide a polynomial-time algorithm to identify all u-fp orthology assignments in a BMG. Simulations show that at least 75% of all incorrect orthology assignments can be detected in this manner. All results rely only on the structure of the BMGs and not on any a priori knowledge about underlying gene or species trees.
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| 36. |
- Schaller, David, et al.
(författare)
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Complexity of modification problems for best match graphs
- 2021
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Ingår i: Theoretical Computer Science. - : Elsevier BV. - 0304-3975 .- 1879-2294. ; 865, s. 63-84
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Tidskriftsartikel (refereegranskat)abstract
- Best match graphs (BMGs) are vertex-colored directed graphs that were introduced to model the relationships of genes (vertices) from different species (colors) given an underlying evolutionary tree that is assumed to be unknown. In real-life applications, BMGs are estimated from sequence similarity data. Measurement noise and approximation errors usually result in empirically determined graphs that in general violate characteristic properties of BMGs. The arc modification problems for BMGs aim at correcting such violations and thus provide a means to improve the initial estimates of best match data. We show here that the arc deletion, arc completion and arc editing problems for BMGs are NP-complete and that they can be formulated and solved as integer linear programs. To this end, we provide a novel characterization of BMGs in terms of triples (binary trees on three leaves) and a characterization of BMGs with two colors in terms of forbidden subgraphs.
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| 37. |
- Schaller, David, et al.
(författare)
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Corrigendum to “Best match graphs”
- 2021
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Ingår i: Journal of Mathematical Biology. - : Springer Science and Business Media LLC. - 0303-6812 .- 1432-1416. ; 82:6
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Two errors in the article Best Match Graphs (Geiß et al. in JMB 78: 2015–2057, 2019) are corrected. One concerns the tacit assumption that digraphs are sink-free, which has to be added as an additional precondition in Lemma 9, Lemma 11, Theorem 4. Correspondingly, Algorithm 2 requires that its input is sink-free. The second correction concerns an additional necessary condition in Theorem 9 required to characterize best match graphs. The amended results simplify the construction of least resolved trees for n-cBMGs, i.e., Algorithm 1. All other results remain unchanged and are correct as stated.
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| 38. |
- Schaller, David, et al.
(författare)
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Heuristic algorithms for best match graph editing
- 2021
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Ingår i: Algorithms for Molecular Biology. - : Springer Science and Business Media LLC. - 1748-7188. ; 16:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Best match graphs (BMGs) are a class of colored digraphs that naturally appear in mathematical phylogenetics as a representation of the pairwise most closely related genes among multiple species. An arc connects a gene x with a gene y from another species (vertex color) Y whenever it is one of the phylogenetically closest relatives of x. BMGs can be approximated with the help of similarity measures between gene sequences, albeit not without errors. Empirical estimates thus will usually violate the theoretical properties of BMGs. The corresponding graph editing problem can be used to guide error correction for best match data. Since the arc set modification problems for BMGs are NP-complete, efficient heuristics are needed if BMGs are to be used for the practical analysis of biological sequence data.Results: Since BMGs have a characterization in terms of consistency of a certain set of rooted triples (binary trees on three vertices) defined on the set of genes, we consider heuristics that operate on triple sets. As an alternative, we show that there is a close connection to a set partitioning problem that leads to a class of top-down recursive algorithms that are similar to Aho’s supertree algorithm and give rise to BMG editing algorithms that are consistent in the sense that they leave BMGs invariant. Extensive benchmarking shows that community detection algorithms for the partitioning steps perform best for BMG editing.Conclusion: Noisy BMG data can be corrected with sufficient accuracy and efficiency to make BMGs an attractive alternative to classical phylogenetic methods.
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| 39. |
- Schaller, David, et al.
(författare)
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Indirect identification of horizontal gene transfer
- 2021
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Ingår i: Journal of Mathematical Biology. - : Springer Science and Business Media LLC. - 0303-6812 .- 1432-1416. ; 83:1
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Tidskriftsartikel (refereegranskat)abstract
- Several implicit methods to infer horizontal gene transfer (HGT) focus on pairs of genes that have diverged only after the divergence of the two species in which the genes reside. This situation defines the edge set of a graph, the later-divergence-time (LDT) graph, whose vertices correspond to genes colored by their species. We investigate these graphs in the setting of relaxed scenarios, i.e., evolutionary scenarios that encompass all commonly used variants of duplication-transfer-loss scenarios in the literature. We characterize LDT graphs as a subclass of properly vertex-colored cographs, and provide a polynomial-time recognition algorithm as well as an algorithm to construct a relaxed scenario that explains a given LDT. An edge in an LDT graph implies that the two corresponding genes are separated by at least one HGT event. The converse is not true, however. We show that the complete xenology relation is described by an rs-Fitch graph, i.e., a complete multipartite graph satisfying constraints on the vertex coloring. This class of vertex-colored graphs is also recognizable in polynomial time. We finally address the question “how much information about all HGT events is contained in LDT graphs” with the help of simulations of evolutionary scenarios with a wide range of duplication, loss, and HGT events. In particular, we show that a simple greedy graph editing scheme can be used to efficiently detect HGT events that are implicitly contained in LDT graphs.
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| 40. |
- Schaller, David, et al.
(författare)
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Least resolved trees for two-colored best match graphs
- 2021
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Ingår i: Journal of Graph Algorithms and Applications. - : Journal of Graph Algorithms and Applications. - 1526-1719. ; 25:1, s. 397-416
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Tidskriftsartikel (refereegranskat)abstract
- In phylogenetic combinatorics, 2-colored best match graphs (2-BMGs) form a subclass of sink-free bi-transitive digraphs that describe the most closely related genes between a pair of species in an evolutionary scenario. They are explained by a unique least resolved tree (LRT). In this paper, the concept of support vertices is introduced and used to derive an O(|V|+|E|log2|V|)-time algorithm that recognizes a 2-BMG and constructs its LRT. The approach can be extended to allow the recognition of binary-explainable 2-BMGs with the same complexity. An empirical comparison emphasizes the efficiency of the new algorithm.
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| 41. |
- Schaller, David, et al.
(författare)
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Orientation of Fitch Graphs and Reconciliation-Free Inference of Horizontal Gene Transfer in Gene Trees
- 2023
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Ingår i: SIAM Journal on Discrete Mathematics. - 0895-4801 .- 1095-7146. ; 37:3, s. 2172-2207
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Tidskriftsartikel (refereegranskat)abstract
- Horizontal gene transfer (HGT) events partition a gene tree T, and thus its leaf set X, into subsets of genes whose evolutionary history is described by speciation and duplication events alone. Two genes thus are xenologs if and only if they belong to two different sets of this partition P. Indirect phylogenetic methods can be used to infer the partition P of X from sequence similarity or evolutionary distances without any a priori knowledge about the underlying tree T. In this contribution, we assume that a partition P of the gene set X and a usually incompletely resolved estimate T of the original gene tree on X are known. We then ask to what extent T and P can be combined to determine the horizontal transfer edges in T and thus the orientation of the HGT events that separate the sets of P. If T and P are compatible, it can be decided for each pair of genes x and y whether there always exists or never exists a horizontal gene transfer in T along the path connecting y and the most recent common ancestor of x and y, and thus a directed edge (x, y) in the so-called Fitch graph of the gene family. We generalize this result to insufficiently resolved gene trees. We show that the classification of a gene pair (x, y) can be computed in constant time after linear-time preprocessing. Using simulated gene family histories, we observe empirically that the vast majority of horizontal transfer edges in the gene tree T can be recovered unambiguously from the knowledge of the partition P. All algorithms developed here are implemented and freely available within the Python package AsymmeTree hosted at https://github.com/david-schaller/AsymmeTree.
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| 42. |
- Schaller, David, et al.
(författare)
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Relative timing information and orthology in evolutionary scenarios
- 2023
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Ingår i: Algorithms for Molecular Biology. - 1748-7188. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Evolutionary scenarios describing the evolution of a family of genes within a collection of species comprise the mapping of the vertices of a gene tree T to vertices and edges of a species tree S. The relative timing of the last common ancestors of two extant genes (leaves of T) and the last common ancestors of the two species (leaves of S) in which they reside is indicative of horizontal gene transfers (HGT) and ancient duplications. Orthologous gene pairs, on the other hand, require that their last common ancestors coincides with a corresponding speciation event. The relative timing information of gene and species divergences is captured by three colored graphs that have the extant genes as vertices and the species in which the genes are found as vertex colors: the equal-divergence-time (EDT) graph, the later-divergence-time (LDT) graph and the prior-divergence-time (PDT) graph, which together form an edge partition of the complete graph.ResultsHere we give a complete characterization in terms of informative and forbidden triples that can be read off the three graphs and provide a polynomial time algorithm for constructing an evolutionary scenario that explains the graphs, provided such a scenario exists. While both LDT and PDT graphs are cographs, this is not true for the EDT graph in general. We show that every EDT graph is perfect. While the information about LDT and PDT graphs is necessary to recognize EDT graphs in polynomial-time for general scenarios, this extra information can be dropped in the HGT-free case. However, recognition of EDT graphs without knowledge of putative LDT and PDT graphs is NP-complete for general scenarios. In contrast, PDT graphs can be recognized in polynomial-time. We finally connect the EDT graph to the alternative definitions of orthology that have been proposed for scenarios with horizontal gene transfer. With one exception, the corresponding graphs are shown to be colored cographs.
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| 43. |
- Schröder, Björn, et al.
(författare)
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Paneth cell α-defensin 6 (HD-6) is an antimicrobial peptide
- 2015
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Ingår i: Mucosal Immunology. - : Nature Publishing Group. - 1933-0219 .- 1935-3456. ; 8:3, s. 661-671
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Tidskriftsartikel (refereegranskat)abstract
- Defensins protect human barriers from commensal and pathogenic microorganisms. Human α-defensin 6 (HD-6) is produced exclusively by small intestinal Paneth cells but, in contrast to other antimicrobial peptides (AMPs) for HD-6, no direct antibacterial killing activity has been detected so far. Herein, we systematically tested how environmental factors, like pH and reducing conditions, affect antimicrobial activity of different defensins against anaerobic bacteria of the human intestinal microbiota. Remarkably, by mimicking the intestinal milieu we detected for the first time antibacterial activity of HD-6. Activity was observed against anaerobic gut commensals but not against some pathogenic strains. Antibiotic activity was attributable to the reduced peptide and independent of free cysteines or a conserved histidine residue. Furthermore, the oxidoreductase thioredoxin, which is also expressed in Paneth cells, is able to reduce a truncated physiological variant of HD-6. Ultrastructural analyses revealed that reduced HD-6 causes disintegration of cytoplasmic structures and alterations in the bacterial cell envelope, while maintaining extracellular net-like structures. We conclude that HD-6 is an antimicrobial peptide. Our data suggest two distinct antimicrobial mechanisms by one peptide: HD-6 kills specific microbes depending on the local environmental conditions, whereas known microbial trapping by extracellular net structures is independent of the reducing milieu.
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| 44. |
- Schröder, Björn, et al.
(författare)
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Reduction of disulphide bonds unmasks potent antimicrobial activity of human β-defensin 1
- 2011
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Ingår i: Nature. - : Macmillan Publishers Ltd.. - 0028-0836 .- 1476-4687. ; 469:7330, s. 419-423
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Tidskriftsartikel (refereegranskat)abstract
- Human epithelia are permanently challenged by bacteria and fungi, including commensal and pathogenic microbiota. In the gut, the fraction of strict anaerobes increases from proximal to distal, reaching 99% of bacterial species in the colon. At colonic mucosa, oxygen partial pressure is below 25% of airborne oxygen content, moreover microbial metabolism causes reduction to a low redox potential of -200 mV to -300 mV in the colon. Defensins, characterized by three intramolecular disulphide-bridges, are key effector molecules of innate immunity that protect the host from infectious microbes and shape the composition of microbiota at mucosal surfaces. Human β-defensin 1 (hBD-1) is one of the most prominent peptides of its class but despite ubiquitous expression by all human epithelia, comparison with other defensins suggested only minor antibiotic killing activity. Whereas much is known about the activity of antimicrobial peptides in aerobic environments, data about reducing environments are limited. Herein we show that after reduction of disulphide-bridges hBD-1 becomes a potent antimicrobial peptide against the opportunistic pathogenic fungus Candida albicans and against anaerobic, Gram-positive commensals of Bifidobacterium and Lactobacillus species. Reduced hBD-1 differs structurally from oxidized hBD-1 and free cysteines in the carboxy terminus seem important for the bactericidal effect. In vitro, the thioredoxin (TRX) system is able to reduce hBD-1 and TRX co-localizes with reduced hBD-1 in human epithelia. Hence our study indicates that reduced hBD-1 shields the healthy epithelium against colonisation by commensal bacteria and opportunistic fungi. Accordingly, an intimate interplay between redox-regulation and innate immune defence seems crucial for an effective barrier protecting human epithelia.
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| 45. |
- Stienen, Martin N, et al.
(författare)
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Procedures performed during neurosurgery residency in Europe.
- 2020
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Ingår i: Acta Neurochirurgica. - : Springer Science and Business Media LLC. - 0001-6268 .- 0942-0940. ; 162:10, s. 2303-2311
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In a previous article ( https://doi.org/10.1007/s00701-019-03888-3 ), preliminary results of a survey, aiming to shed light on the number of surgical procedures performed and assisted during neurosurgery residency in Europe were reported. We here present the final results and extend the analyses.METHODS: Board-certified neurosurgeons of European Association of Neurosurgical Societies (EANS) member countries were asked to review their residency case logs and participate in a 31-question electronic survey (SurveyMonkey Inc., San Mateo, CA). The responses received between April 25, 2018, and April 25, 2020, were considered. We excluded responses that were incomplete, from non-EANS member countries, or from respondents that have not yet completed their residency.RESULTS: Of 430 responses, 168 were considered for analysis after checking in- and exclusion criteria. Survey responders had a mean age of 42.7 ± 8.8 years, and 88.8% were male. Responses mainly came from surgeons employed at university/teaching hospitals (85.1%) in Germany (22.0%), France (12.5%), the United Kingdom (UK; 8.3%), Switzerland (7.7%), and Greece (7.1%). Most responders graduated in the years between 2011 and 2019 (57.7%). Thirty-eight responders (22.6%) graduated before and 130 responders (77.4%) after the European WTD 2003/88/EC came into effect. The mean number of surgical procedures performed independently, supervised or assisted throughout residency was 540 (95% CI 424-657), 482 (95% CI 398-568), and 579 (95% CI 441-717), respectively. Detailed numbers for cranial, spinal, adult, and pediatric subgroups are presented in the article. There was an annual decrease of about 33 cases in total caseload between 1976 and 2019 (coeff. - 33, 95% CI - 62 to - 4, p = 0.025). Variables associated with lesser total caseload during residency were training abroad (1210 vs. 1747, p = 0.083) and female sex by trend (947 vs. 1671, p = 0.111), whereas case numbers were comparable across the EANS countries (p = 0.443).CONCLUSION: The final results of this survey largely confirm the previously reported numbers. They provide an opportunity for current trainees to compare their own case logs with. Again, we confirm a significant decline in surgical exposure during training between 1976 and 2019. In addition, the current analysis reveals that female sex and training abroad may be variables associated with lesser case numbers during residency.
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| 46. |
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| 47. |
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| 48. |
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| 49. |
- Wendler, Judith, et al.
(författare)
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Proteolytic Degradation of reduced Human Beta Defensin 1 generates a Novel Antibiotic Octapeptide
- 2019
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Microbial resistance against clinical used antibiotics is on the rise. Accordingly, there is a high demand for new innovative antimicrobial strategies. The host-defense peptide human beta-defensin 1 (hBD-1) is produced continuously by epithelial cells and exhibits compelling antimicrobial activity after reduction of its disulphide bridges. Here we report that proteolysis of reduced hBD-1 by gastrointestinal proteases as well as human duodenal secretions produces an eight-amino acid carboxy-terminal fragment. The generated octapeptide retains antibiotic activity, yet with distinct characteristics differing from the full-length peptide. We modified the octapeptide by stabilizing its termini and by using non-natural D-amino acids. The native and modified peptide variants showed antibiotic activity against pathogenic as well as antibiotic-resistant microorganisms, including E. coli, P. aeruginosa and C. albicans. Moreover, in an in vitro C. albicans infection model the tested peptides demonstrated effective amelioration of C. albicans infection without showing cytotoxity on human cells. In summary, protease degradation of hBD-1 provides a yet unknown mechanism to broaden antimicrobial host defense, which could be used to develop defensin-derived therapeutic applications.
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