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- Ullah, I., et al.
(författare)
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Evolutionary history of metastatic breast cancer reveals minimal seeding from axillary lymph nodes
- 2018
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Ingår i: Journal of Clinical Investigation. - : American Society for Clinical Investigation. - 0021-9738 .- 1558-8238. ; 128:4, s. 1355-1370
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Tidskriftsartikel (refereegranskat)abstract
- Metastatic breast cancers are still incurable. Characterizing the evolutionary landscape of these cancers, including the role of metastatic axillary lymph nodes (ALNs) in seeding distant organ metastasis, can provide a rational basis for effective treatments. Here, we have described the genomic analyses of the primary tumors and metastatic lesions from 99 samples obtained from 20 patients with breast cancer. Our evolutionary analyses revealed diverse spreading and seeding patterns that govern tumor progression. Although linear evolution to successive metastatic sites was common, parallel evolution from the primary tumor to multiple distant sites was also evident. Metastatic spreading was frequently coupled with polyclonal seeding, in which multiple metastatic subclones originated from the primary tumor and/or other distant metastases. Synchronous ALN metastasis, a well-established prognosticator of breast cancer, was not involved in seeding the distant metastasis, suggesting a hematogenous route for cancer dissemination. Clonal evolution coincided frequently with emerging driver alterations and evolving mutational processes, notably an increase in apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like-associated (APOBEC-associated) mutagenesis. Our data provide genomic evidence for a role of ALN metastasis in seeding distant organ metastasis and elucidate the evolving mutational landscape during cancer progression.
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| 3. |
- Carlström, Johan, et al.
(författare)
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Knotted non-Hermitian metals
- 2019
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Ingår i: Physical Review B. - 2469-9950 .- 2469-9969. ; 99:16
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Tidskriftsartikel (refereegranskat)abstract
- We report on the occurrence of knotted metallic band structures as stable topological phases in non-Hermitian (NH) systems. These knotted NH metals are characterized by open Fermi surfaces, known in mathematics as Seifert surfaces, that are bounded by knotted lines of exceptional points. Quite remarkably, and in contrast to the situation in Hermitian systems, no fine tuning or symmetries are required in order to stabilize these exotic phases of matter. By explicit construction, we derive microscopic tight-binding models hosting knotted NH metals with strictly short-ranged hopping, and investigate the stability of their topological properties against perturbations. Building up on recently developed experimental techniques for the realization of NH band structures, we discuss how the proposed models may be experimentally implemented in photonic systems.
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| 4. |
- Lannergård, Jonas, et al.
(författare)
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Sequence variability is correlated with weak immunogenicity in Streptococcus pyogenes M protein.
- 2015
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Ingår i: MicrobiologyOpen. - : Wiley. - 2045-8827. ; 4:5, s. 774-789
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Tidskriftsartikel (refereegranskat)abstract
- The M protein of Streptococcus pyogenes, a major bacterial virulence factor, has an amino-terminal hypervariable region (HVR) that is a target for type-specific protective antibodies. Intriguingly, the HVR elicits a weak antibody response, indicating that it escapes host immunity by two mechanisms, sequence variability and weak immunogenicity. However, the properties influencing the immunogenicity of regions in an M protein remain poorly understood. Here, we studied the antibody response to different regions of the classical M1 and M5 proteins, in which not only the HVR but also the adjacent fibrinogen-binding B repeat region exhibits extensive sequence divergence. Analysis of antisera from S. pyogenes-infected patients, infected mice, and immunized mice showed that both the HVR and the B repeat region elicited weak antibody responses, while the conserved carboxy-terminal part was immunodominant. Thus, we identified a correlation between sequence variability and weak immunogenicity for M protein regions. A potential explanation for the weak immunogenicity was provided by the demonstration that protease digestion selectively eliminated the HVR-B part from whole M protein-expressing bacteria. These data support a coherent model, in which the entire variable HVR-B part evades antibody attack, not only by sequence variability but also by weak immunogenicity resulting from protease attack.
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| 8. |
- Stålhammar, Marcus, et al.
(författare)
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Hyperbolic nodal band structures and knot invariants
- 2019
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Ingår i: SciPost Physics. - 2542-4653. ; 7:2
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Tidskriftsartikel (refereegranskat)abstract
- We extend the list of known band structure topologies to include a large family of hyperbolic nodal links and knots, occurring both in conventional Hermitian systems where their stability relies on discrete symmetries, and in the dissipative non-Hermitian realm where the knotted nodal lines are generic and thus stable towards any small perturbation. We show that these nodal structures, taking the forms of Turk's head knots, appear in both continuum- and lattice models with relatively short-ranged hopping that is within experimental reach. To determine the topology of the nodal structures, we devise an efficient algorithm for computing the Alexander polynomial, linking numbers and higher order Milnor invariants based on an approximate and well controlled parameterisation of the knot.
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