| 1. |
- Watanabe, A, et al.
(författare)
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Gunnar Fant 60 years
- 1979
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Ingår i: TMH-QPSR. ; 20:2, s. 1-45
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Tidskriftsartikel (refereegranskat)
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| 2. |
- 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. |
- Banefelt, J., et al.
(författare)
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Survival and clinical metastases among prostate cancer patients treated with androgen deprivation therapy in Sweden
- 2014
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Ingår i: Cancer Epidemiology. - : Elsevier BV. - 1877-7821 .- 1877-783X. ; 38:4, s. 442-447
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To examine the incidence of metastases and clinical course of prostate cancer patients who are without confirmed metastasis when initiating androgen deprivation therapy (ADT). Methods: Retrospective cohort study conducted using electronic medical records from Swedish outpatient urology clinics linked to national mandatory registries to capture medical and demographic data. Prostate cancer patients initiating ADT between 2000 and 2010 were followed from initiation of ADT to metastasis, death, and/or end of follow-up. Results: The 5-year cumulative incidence (CI) of metastasis was 18%. Survival was 60% after 5 years; results were similar for bone metastasis-free survival. The 5-year CI of castration-resistant prostate cancer (CRPC) was 50% and the median survival from CRPC development was 2.7 years. Serum prostate-specific antigen (PSA) levels and PSA doubling time were strong predictors of bone metastasis, any metastasis, and death. Conclusion: This study provides understanding of the clinical course of prostate cancer patients without confirmed metastasis treated with ADT in Sweden. Greater PSA values and shorter PSA doubling time (particularly <= 6 months) were associated with increased risk of bone metastasis, any metastasis, and death.
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| 4. |
- Yang, Kang, et al.
(författare)
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Homotopy, Symmetry, and Non-Hermitian Band Topology
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Non-Hermitian matrices are ubiquitous in the description of nature ranging from classical dissipative systems, including optical, electrical, and mechanical metamaterials, to scattering of waves and open quantum many-body systems. Seminal K-theory classifications of non-Hermitian systems based on line and point gaps have deepened the understanding of many physical phenomena. However, ample systems remain beyond this description; reference points and lines are in general unable to distinguish whether multiple non-Hermitian bands exhibit band crossings and braids. To remedy this we consider the complementary notions of non-Hermitian band gaps and separation gaps that crucially include a broad class of multi-band scenarios, enabling the description of generic band structures with symmetries. With these concepts, we provide a unified and systematic classification of both gapped and nodal systems in the presence of physically relevant parity-time (PT) and pseudo-Hermitian symmetries using homotopy theory. This uncovers new fragile phases and, remarkably, also implies new stable phenomena stemming from the topology of both eigenvalues and eigenvectors. In particular, we reveal different Abelian and non-Abelian phases in PT-symmetric systems, described by frame and braid topology. The corresponding invariants are robust to symmetry-preserving perturbations that do not close band gaps, and they also predict the deformation rules of nodal phases. We further demonstrate that spontaneous PT symmetry breaking is captured by a Chern-Euler description, a fingerprint of unprecedented non-Hermitian topology. These results open the door for theoretical and experimental exploration of a rich variety of novel topological phenomena in a wide range of physical platforms.
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| 5. |
- Berggård, Karin, et al.
(författare)
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Binding of human C4BP to the hypervariable region of M protein: a molecular mechanism of phagocytosis resistance in Streptococcus pyogenes
- 2001
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Ingår i: Molecular Microbiology. - : Wiley. - 1365-2958 .- 0950-382X. ; 42:2, s. 539-551
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Tidskriftsartikel (refereegranskat)abstract
- The amino-terminal hypervariable region (HVR) of streptococcal M protein is required for the ability of this virulence factor to confer phagocytosis resistance. The function of the HVR has remained unknown, but the finding that many HVRs with extremely divergent sequences bind the human complement regulator C4b-binding protein (C4BP) has suggested that this ligand may play a role in phagocytosis resistance. We used the M22 system to study the function of bound C4BP and provide several lines of evidence that C4BP indeed contributes to phagocytosis resistance. First, the ability of anti-HVR antibodies to cause opsonization correlated with their ability to inhibit binding of C4BP. Secondly, a short deletion in the HVR eliminated C4BP binding and also reduced the ability of M22 to confer phagocytosis resistance. Thirdly, the addition of an excess of pure C4BP to a phagocytosis system almost completely blocked the effect of opsonizing anti-HVR antibodies. Together, our data indicate that binding of C4BP to the HVR of M22 plays an important role in phagocytosis resistance, but other properties of M22 also contribute. This study provides the first molecular insight into the mechanisms by which the HVR of an M protein confers phagocytosis resistance.
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| 6. |
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| 7. |
- 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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| 8. |
- Catton, Erin A., et al.
(författare)
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Human CEACAM1 is targeted by a Streptococcus pyogenes adhesin implicated in puerperal sepsis pathogenesis
- 2023
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Ingår i: Nature Communications. - 2041-1723. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Life-threatening bacterial infections in women after childbirth, known as puerperal sepsis, resulted in classical epidemics and remain a global health problem. While outbreaks of puerperal sepsis have been ascribed to Streptococcus pyogenes, little is known about disease mechanisms. Here, we show that the bacterial R28 protein, which is epidemiologically associated with outbreaks of puerperal sepsis, specifically targets the human receptor CEACAM1. This interaction triggers events that would favor the development of puerperal sepsis, including adhesion to cervical cells, suppression of epithelial wound repair and subversion of innate immune responses. High-resolution structural analysis showed that an R28 domain with IgI3-like fold binds to the N-terminal domain of CEACAM1. Together, these findings demonstrate that a single adhesin-receptor interaction can drive the pathogenesis of bacterial sepsis and provide molecular insights into the pathogenesis of one of the most important infectious diseases in medical history.
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| 9. |
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| 10. |
- Gustavsson, Simon T., et al.
(författare)
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Nicotinamide prevents retinal vascular dropout in a rat model of ocular hypertension and supports ocular blood supply in glaucoma patients
- 2023
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Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 64
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE. To investigate whether nicotinamide (NAM) modulates retinal vasculature in glaucoma.METHODS. This was a prospective controlled clinical trial investigating animal and human histopathology. Participants included normotensive and ocular hypertensive rats, postmortem human ocular tissue, glaucoma patients (n = 90), and healthy controls (n = 30). The study utilized histopathology, computer-assisted retinal vasculature analysis, optical coherence tomography angiography (OCTA), and NAM treatment. The main outcome measures included retinal vascular parameters in rats as assessed by AngioTool; retinal vasculature integrity in rats and humans as assessed by histopathology, antibody-staining, and ImageJ-based measurements; and retinal perfusion density (PD) and flux index in humans as assessed by OCTA.RESULTS. A number of vessel parameters were altered in ocular hypertension/glaucoma compared to healthy controls. NAM treatment improved the retinal vasculature in ocular hypertensive rats, with an increase in mean vessel area, percentage area covered by vessels, total vessel length, total junctions, and junction density as assessed by AngioTool (all P < 0.05); vessel wall integrity as assessed by VE-cadherin antibody staining was also improved (P < 0.01). In humans, as assessed by OCTA, increases in PD in the optic nerve head and macula complete image (0.7%, P = 0.04 and 1.0%, P = 0.002, respectively) in healthy controls, and an increase in the temporal quadrant of the macula (0.7%, P = 0.02) in glaucoma patients was seen after NAM treatment.CONCLUSIONS. NAM can prevent retinal vascular damage in an animal model of glaucoma. After NAM treatment, glaucoma patients and healthy controls demonstrated a small increase in retinal vessel parameters as assessed by OCTA.
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