| 1. |
|
|
| 2. |
- Niemi, MEK, et al.
(författare)
-
- 2021
-
swepub:Mat__t
|
|
| 3. |
- Kanai, M, et al.
(författare)
-
- 2023
-
swepub:Mat__t
|
|
| 4. |
|
|
| 5. |
- Bellenguez, C, et al.
(författare)
-
New insights into the genetic etiology of Alzheimer's disease and related dementias
- 2022
-
Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 54:4, s. 412-436
-
Tidskriftsartikel (refereegranskat)abstract
- Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele.
|
|
| 6. |
|
|
| 7. |
- Marconi, Alessandro, et al.
(författare)
-
ELT-HIRES, the high resolution spectrograph for the ELT : Phase A study and path to construction
- 2020
-
Ingår i: Ground-based and Airborne Instrumentation for Astronomy VIII. - : SPIE - International Society for Optical Engineering. - 9781510636828 - 9781510636811
-
Konferensbidrag (refereegranskat)abstract
- HIRES is the high-resolution spectrograph of the European Extremely Large Telescope at optical and near-infrared wavelengths. It consists of three fibre-fed spectrographs providing a wavelength coverage of 0.4-1.8 µm (goal 0.35-2.4 µm) at a spectral resolution of 100,000. The fibre-feeding allows HIRES to have several, interchangeable observing modes including a SCAO module and a small diffraction-limited IFU in the NIR. Therefore, it will be able to operate both in seeing- and diffraction-limited modes. Its modularity will ensure that HIRES can be placed entirely on the Nasmyth platform, if enough mass and volume is available, or part on the Nasmyth and part in the Coud`e room. ELT-HIRES has a wide range of science cases spanning nearly all areas of research in astrophysics and even fundamental physics. Among the top science cases there are the detection of biosignatures from exoplanet atmospheres, finding the fingerprints of the first generation of stars (PopIII), tests on the stability of Nature’s fundamental couplings, and the direct detection of the cosmic acceleration. The HIRES consortium is composed of more than 30 institutes from 14 countries, forming a team of more than 200 scientists and engineers.
|
|
| 8. |
- Sodergren, Erica, et al.
(författare)
-
The genome of the sea urchin Strongylocentrotus purpuratus.
- 2006
-
Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 314:5801, s. 941-52
-
Tidskriftsartikel (refereegranskat)abstract
- We report the sequence and analysis of the 814-megabase genome of the sea urchin Strongylocentrotus purpuratus, a model for developmental and systems biology. The sequencing strategy combined whole-genome shotgun and bacterial artificial chromosome (BAC) sequences. This use of BAC clones, aided by a pooling strategy, overcame difficulties associated with high heterozygosity of the genome. The genome encodes about 23,300 genes, including many previously thought to be vertebrate innovations or known only outside the deuterostomes. This echinoderm genome provides an evolutionary outgroup for the chordates and yields insights into the evolution of deuterostomes.
|
|
| 9. |
- Bryant, J. M., et al.
(författare)
-
Emergence and spread of a human-transmissible multidrug-resistant nontuberculous mycobacterium
- 2016
-
Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 354:6313, s. 751-757
-
Tidskriftsartikel (refereegranskat)abstract
- Lung infections with Mycobacterium abscessus, a species of multidrug-resistant nontuberculous mycobacteria, are emerging as an important global threat to individuals with cystic fibrosis (CF), in whom M. abscessus accelerates inflammatory lung damage, leading to increased morbidity and mortality. Previously, M. abscessus was thought to be independently acquired by susceptible individuals from the environment. However, using whole-genome analysis of a global collection of clinical isolates, we show that the majority of M. abscessus infections are acquired through transmission, potentially via fomites and aerosols, of recently emerged dominant circulating clones that have spread globally. We demonstrate that these clones are associated with worse clinical outcomes, show increased virulence in cell-based and mouse infection models, and thus represent an urgent international infection challenge.
|
|
| 10. |
- Burke, R. D., et al.
(författare)
-
A genomic view of the sea urchin nervous system
- 2006
-
Ingår i: Developmental Biology. - : Elsevier BV. - 0012-1606 .- 1095-564X. ; 300:1, s. 434-460
-
Tidskriftsartikel (refereegranskat)abstract
- The sequencing of the Strongylocentrotus purpuratus genome provides a unique opportunity to investigate the function and evolution of neural genes. The neurobiology of sea urchins is of particular interest because they have a close phylogenetic relationship with chordates, yet a distinctive pentaradiate body plan and unusual neural organization. Orthologues of transcription factors that regulate neurogenesis in other animals have been identified and several are expressed in neurogenic domains before gastrulation indicating that they may operate near the top of a conserved neural gene regulatory network. A family of genes encoding voltage-gated ion channels is present but, surprisingly, genes encoding gap junction proteins (connexins and pannexins) appear to be absent. Genes required for synapse formation and function have been identified and genes for synthesis and transport of neurotransmitters are present. There is a large family of G-protein-coupled receptors, including 874 rhodopsin-type receptors, 28 metabotropic glutamate-like receptors and a remarkably expanded group of 161 secretin receptor-like proteins. Absence of cannabinoid, lysophospholipid and melanocortin receptors indicates that this group may be unique to chordates. There are at least 37 putative G-protein-coupled peptide receptors and precursors for several neuropeptides and peptide hormones have been identified, including SALMFamides, NGFFFamide, a vasotocin-like peptide, glycoprotein hormones and insulin/insulin-like growth factors. Identification of a neurotrophin-like gene and Trk receptor in sea urchin indicates that this neural signaling system is not unique to chordates. Several hundred chemoreceptor genes have been predicted using several approaches, a number similar to that for other animals. Intriguingly, genes encoding homologues of rhodopsin, Pax6 and several other key mammalian retinal transcription factors are expressed in tube feet, suggesting tube feet function as photosensory organs. Analysis of the sea urchin genome presents a unique perspective on the evolutionary history of deuterostome nervous systems and reveals new approaches to investigate the development and neurobiology of sea urchins. (c) 2006 Elsevier Inc. All rights reserved.
|
|
| 11. |
|
|
| 12. |
|
|
| 13. |
- Bulten, W, et al.
(författare)
-
Artificial intelligence for diagnosis and Gleason grading of prostate cancer: the PANDA challenge
- 2022
-
Ingår i: Nature medicine. - : Springer Science and Business Media LLC. - 1546-170X .- 1078-8956. ; 28:1, s. 154-
-
Tidskriftsartikel (refereegranskat)abstract
- Artificial intelligence (AI) has shown promise for diagnosing prostate cancer in biopsies. However, results have been limited to individual studies, lacking validation in multinational settings. Competitions have been shown to be accelerators for medical imaging innovations, but their impact is hindered by lack of reproducibility and independent validation. With this in mind, we organized the PANDA challenge—the largest histopathology competition to date, joined by 1,290 developers—to catalyze development of reproducible AI algorithms for Gleason grading using 10,616 digitized prostate biopsies. We validated that a diverse set of submitted algorithms reached pathologist-level performance on independent cross-continental cohorts, fully blinded to the algorithm developers. On United States and European external validation sets, the algorithms achieved agreements of 0.862 (quadratically weighted κ, 95% confidence interval (CI), 0.840–0.884) and 0.868 (95% CI, 0.835–0.900) with expert uropathologists. Successful generalization across different patient populations, laboratories and reference standards, achieved by a variety of algorithmic approaches, warrants evaluating AI-based Gleason grading in prospective clinical trials.
|
|
| 14. |
- O'Day, S. J., et al.
(författare)
-
Efficacy and safety of ipilimumab monotherapy in patients with pretreated advanced melanoma: a multicenter single-arm phase II study
- 2010
-
Ingår i: Annals of Oncology. - : Elsevier BV. - 1569-8041 .- 0923-7534. ; 21:8, s. 1712-1717
-
Tidskriftsartikel (refereegranskat)abstract
- Background: This phase II study evaluated the safety and activity of ipilimumab, a fully human mAb that blocks cytotoxic T-lymphocyte antigen-4, in patients with advanced melanoma. Patients and methods: Patients with previously treated, unresectable stage III/stage IV melanoma received 10 mg/kg ipilimumab every 3 weeks for four cycles (induction) followed by maintenance therapy every 3 months. The primary end point was best overall response rate (BORR) using modified World Health Organization (WHO) criteria. We also carried out an exploratory analysis of proposed immune-related response criteria (irRC). Results: BORR was 5.8% with a disease control rate (DCR) of 27% (N = 155). One-and 2-year survival rates (95% confidence interval) were 47.2% (39.5% to 55.1%) and 32.8% (25.4% to 40.5%), respectively, with a median overall survival of 10.2 months (7.6-16.3). Of 43 patients with disease progression by modified WHO criteria, 12 had disease control by irRC (8% of all treated patients), resulting in a total DCR of 35%. Adverse events (AEs) were largely immune related, occurring mainly in the skin and gastrointestinal tract, with 19% grade 3 and 3.2% grade 4. Immune-related AEs were manageable and generally reversible with corticosteroids. Conclusion: Ipilimumab demonstrated clinical activity with encouraging long-term survival in a previously treated advanced melanoma population.
|
|
| 15. |
- Strom, Peter, et al.
(författare)
-
Artificial intelligence for diagnosis and grading of prostate cancer in biopsies : a population-based, diagnostic study
- 2020
-
Ingår i: The Lancet Oncology. - : Elsevier. - 1470-2045 .- 1474-5488. ; 21:2, s. 222-232
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundAn increasing volume of prostate biopsies and a worldwide shortage of urological pathologists puts a strain on pathology departments. Additionally, the high intra-observer and inter-observer variability in grading can result in overtreatment and undertreatment of prostate cancer. To alleviate these problems, we aimed to develop an artificial intelligence (AI) system with clinically acceptable accuracy for prostate cancer detection, localisation, and Gleason grading.MethodsWe digitised 6682 slides from needle core biopsies from 976 randomly selected participants aged 50–69 in the Swedish prospective and population-based STHLM3 diagnostic study done between May 28, 2012, and Dec 30, 2014 (ISRCTN84445406), and another 271 from 93 men from outside the study. The resulting images were used to train deep neural networks for assessment of prostate biopsies. The networks were evaluated by predicting the presence, extent, and Gleason grade of malignant tissue for an independent test dataset comprising 1631 biopsies from 246 men from STHLM3 and an external validation dataset of 330 biopsies from 73 men. We also evaluated grading performance on 87 biopsies individually graded by 23 experienced urological pathologists from the International Society of Urological Pathology. We assessed discriminatory performance by receiver operating characteristics and tumour extent predictions by correlating predicted cancer length against measurements by the reporting pathologist. We quantified the concordance between grades assigned by the AI system and the expert urological pathologists using Cohen's kappa.FindingsThe AI achieved an area under the receiver operating characteristics curve of 0·997 (95% CI 0·994–0·999) for distinguishing between benign (n=910) and malignant (n=721) biopsy cores on the independent test dataset and 0·986 (0·972–0·996) on the external validation dataset (benign n=108, malignant n=222). The correlation between cancer length predicted by the AI and assigned by the reporting pathologist was 0·96 (95% CI 0·95–0·97) for the independent test dataset and 0·87 (0·84–0·90) for the external validation dataset. For assigning Gleason grades, the AI achieved a mean pairwise kappa of 0·62, which was within the range of the corresponding values for the expert pathologists (0·60–0·73).InterpretationAn AI system can be trained to detect and grade cancer in prostate needle biopsy samples at a ranking comparable to that of international experts in prostate pathology. Clinical application could reduce pathology workload by reducing the assessment of benign biopsies and by automating the task of measuring cancer length in positive biopsy cores. An AI system with expert-level grading performance might contribute a second opinion, aid in standardising grading, and provide pathology expertise in parts of the world where it does not exist.
|
|
| 16. |
- Thompson, Luke R., et al.
(författare)
-
A communal catalogue reveals Earth's multiscale microbial diversity
- 2017
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 551:7681, s. 457-463
-
Tidskriftsartikel (refereegranskat)abstract
- © 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved. Our growing awareness of the microbial world's importance and diversity contrasts starkly with our limited understanding of its fundamental structure. Despite recent advances in DNA sequencing, a lack of standardized protocols and common analytical frameworks impedes comparisons among studies, hindering the development of global inferences about microbial life on Earth. Here we present a meta-analysis of microbial community samples collected by hundreds of researchers for the Earth Microbiome Project. Coordinated protocols and new analytical methods, particularly the use of exact sequences instead of clustered operational taxonomic units, enable bacterial and archaeal ribosomal RNA gene sequences to be followed across multiple studies and allow us to explore patterns of diversity at an unprecedented scale. The result is both a reference database giving global context to DNA sequence data and a framework for incorporating data from future studies, fostering increasingly complete characterization of Earth's microbial diversity.
|
|
| 17. |
|
|
| 18. |
- Adrianto, Indra, et al.
(författare)
-
Association of a functional variant downstream of TNFAIP3 with systemic lupus erythematosus
- 2011
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 43:3, s. 253-258
-
Tidskriftsartikel (refereegranskat)abstract
- Systemic lupus erythematosus (SLE, MIM152700) is an autoimmune disease characterized by self-reactive antibodies resulting in systemic inflammation and organ failure. TNFAIP3, encoding the ubiquitin-modifying enzyme A20, is an established susceptibility locus for SLE. By fine mapping and genomic re-sequencing in ethnically diverse populations, we fully characterized the TNFAIP3 risk haplotype and identified a TT>A polymorphic dinucleotide (deletion T followed by a T to A transversion) associated with SLE in subjects of European (P = 1.58 x 10(-8), odds ratio = 1.70) and Korean (P = 8.33 x 10(-10), odds ratio = 2.54) ancestry. This variant, located in a region of high conservation and regulatory potential, bound a nuclear protein complex composed of NF-kappa B subunits with reduced avidity. Further, compared with the non-risk haplotype, the haplotype carrying this variant resulted in reduced TNFAIP3 mRNA and A20 protein expression. These results establish this TT>A variant as the most likely functional polymorphism responsible for the association between TNFAIP3 and SLE.
|
|
| 19. |
- Ambrosi, D., et al.
(författare)
-
Perspectives on biological growth and remodeling
- 2011
-
Ingår i: Journal of the mechanics and physics of solids. - : Elsevier BV. - 0022-5096 .- 1873-4782. ; 59:4, s. 863-883
-
Forskningsöversikt (refereegranskat)abstract
- The continuum mechanical treatment of biological growth and remodeling has attracted considerable attention over the past fifteen years. Many aspects of these problems are now well-understood, yet there remain areas in need of significant development from the standpoint of experiments, theory, and computation. In this perspective paper we review the state of the field and highlight open questions, challenges, and avenues for further development.
|
|
| 20. |
|
|
| 21. |
|
|
| 22. |
|
|
| 23. |
|
|
| 24. |
|
|
| 25. |
|
|
| 26. |
|
|
| 27. |
|
|
| 28. |
|
|
| 29. |
|
|
| 30. |
|
|
| 31. |
|
|
| 32. |
|
|
| 33. |
|
|
| 34. |
- Humphrey, Madeleine, et al.
(författare)
-
Colistin resistance in Escherichia coli confers protection of the cytoplasmic but not outer membrane from the polymyxin antibiotic
- 2021
-
Ingår i: Microbiology. - : Microbiology Society. - 1350-0872 .- 1465-2080. ; 167:11
-
Tidskriftsartikel (refereegranskat)abstract
- Colistin is a polymyxin antibiotic of last resort for the treatment of infections caused by multi-drug-resistant Gram-negative bacteria. By targeting lipopolysaccharide (LPS), the antibiotic disrupts both the outer and cytoplasmic membranes, leading to bacterial death and lysis. Colistin resistance in Escherichia coli occurs via mutations in the chromosome or the acquisition of mobilized colistin-resistance (mcr) genes. Both these colistin-resistance mechanisms result in chemical modifications to the LPS, with positively charged moieties added at the cytoplasmic membrane before the LPS is transported to the outer membrane. We have previously shown that MCR-1-mediated LPS modification protects the cytoplasmic but not the outer membrane from damage caused by colistin, enabling bacterial survival. However, it remains unclear whether this observation extends to colistin resistance conferred by other mcr genes, or resistance due to chromosomal mutations. Using a panel of clinical E. coli that had acquired mcr −1, –1.5, −2, –3, −3.2 or −5, or had acquired polymyxin resistance independently of mcr genes, we found that almost all isolates were susceptible to colistin-mediated permeabilization of the outer, but not cytoplasmic, membrane. Furthermore, we showed that permeabilization of the outer membrane of colistin-resistant isolates by the polymyxin is in turn sufficient to sensitize bacteria to the antibiotic rifampicin, which normally cannot cross the LPS monolayer. These findings demonstrate that colistin resistance in these E. coli isolates is due to protection of the cytoplasmic but not outer membrane from colistin-mediated damage, regardless of the mechanism of resistance.
|
|
| 35. |
|
|
| 36. |
|
|
| 37. |
|
|
| 38. |
|
|
| 39. |
- Liebenberg, L., et al.
(författare)
-
Tracking science : An alternative for those excluded by citizen science
- 2021
-
Ingår i: Citizen Science: Theory and Practice. - : Ubiquity Press. - 2057-4991. ; 6:1, s. 1-16
-
Tidskriftsartikel (refereegranskat)abstract
- In response to recent discussion about terminology, we propose "tracking science" as a term that is more inclusive than citizen science. Our suggestion is set against a post-colonial political background and large-scale migrations, in which "citizen" is becoming an increasingly contentious term. As a diverse group of authors from several continents, our priority is to deliberate a term that is all-inclusive, so that it could be adopted by everyone who participates in science or contributes to scientific knowledge, regardless of socio-cultural background. For example, current citizen science terms used for Indigenous knowledge imply that such practitioners belong to a sub-group that is other, and therefore marginalized. Our definition for "tracking science" does not exclude Indigenous peoples and their knowledge contributions and may provide a space for those who currently participate in citizen science, but want to contribute, explore, and/or operate beyond its confinements. Our suggestion is not that of an immediate or complete replacement of terminology, but that the notion of tracking science can be used to complement the practice and discussion of citizen science where it is contextually appropriate or needed. This may provide a breathing space, not only to explore alternative terms, but also to engage in robust, inclusive discussion on what it means to do science or create scientific knowledge. In our view, tracking science serves as a metaphor that applies broadly to the scientific community-from modern theoretical physics to ancient Indigenous knowledge.
|
|
| 40. |
- Linke, H, et al.
(författare)
-
Quantum ratchets and quantum heat pumps
- 2002
-
Ingår i: Applied Physics A: Materials Science & Processing. - : Springer Science and Business Media LLC. - 1432-0630. ; 75:2, s. 237-246
-
Tidskriftsartikel (refereegranskat)abstract
- Quantum ratchets are Brownian motors in which the quantum dynamics of particles induces qualitatively new behavior. We review a series of experiments in which asymmetric semiconductor devices of sub-micron dimensions are used to study quantum ratchets for electrons. In rocked quantum-dot ratchets electron-wave interference is used to create a non-linear voltage response, leading to a ratchet effect. The direction of the net ratchet current in this type of device can be sensitively controlled by changing one of the following experimental variables: a small external magnetic field, the amplitude of the rocking force, or the Fermi energy. We also describe a tunneling ratchet in which the current direction depends on temperature. In our discussion of the tunneling ratchet we distinguish between three contributions to the non-linear current-voltage characteristics that lead to the ratchet effect: thermal excitation over energy barriers, tunneling through barriers, and wave reflection from barriers. Finally, we discuss the operation of adiabatically rocked tunneling ratchets as heat pumps.
|
|
| 41. |
- Löfgren, Anneli, et al.
(författare)
-
Symmetry of magnetoconductance fluctuations of quantum dots in the nonlinear response regime
- 2006
-
Ingår i: Physical Review B (Condensed Matter and Materials Physics). - 1098-0121. ; 73:23
-
Tidskriftsartikel (refereegranskat)abstract
- We investigate the symmetry of magnetoconductance fluctuations of phase-coherent, two-terminal quantum dots in the nonlinear regime of transport. Specifically, we consider open, ballistic quantum dots (electron billiards) with and without symmetry axes parallel and perpendicular to the current direction and formulate a set of novel symmetry relations not observed in devices with lower symmetry. We experimentally confirm these relations, demonstrating that high-quality materials and modern semiconductor technology allow the fabrication of devices with almost perfect symmetry. Small deviations from the intended symmetry, presumably due to impurities and fabrication limitations, do exist and can be detected. We also take into account circuit-induced asymmetries of the measured conductance due to bias-dependent depletion and demonstrate that this effect can be experimentally distinguished from rectification effects that are due to a lack of device symmetry. Some open questions regarding the role of a magnetic field in the nonlinear regime of transport are highlighted.
|
|
| 42. |
|
|
| 43. |
|
|
| 44. |
|
|
| 45. |
|
|
| 46. |
- Samoc, Marek, et al.
(författare)
-
Nonlinear absorption and nonlinear refraction: Maximizing the merit factors
- 2012
-
Ingår i: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE. - 0277-786X .- 1996-756X. - 9780819489012 ; 8258, s. Art. no. 82580V-
-
Konferensbidrag (refereegranskat)abstract
- Both nonlinear absorption and nonlinear refraction are effects that are potentially useful for a plethora of applications in photonics, nanophotonics and biophotonics. Despite substantial attention given to these phenomena by researchers studying the merits of disparate systems such as organic materials, hybrid materials, metal-containing molecules and nanostructures, it is virtually impossible to compare the results obtained on different materials when varying parameters of the light beams and different techniques are employed. We have attempted to address the problem by studying the properties of various systems in a systematic way, within a wide range of wavelengths, and including the regions of onephoton, two-photon and three-photon absorption. The objects of our studies have been typical nonlinear chromophores, such as π-conjugated molecules, oligomers and polymers, organometallics and coordination complexes containing transition metals, organometallic dendrimers, small metal-containing clusters, and nanoparticles of various kinds, including semiconductor quantum dots, plasmonic particles and rare-earth doped nanocrystals. We discuss herein procedures to quantify the nonlinear response of all of these systems, by defining and comparing the merit factors relevant for various applications.
|
|
| 47. |
|
|
| 48. |
|
|
| 49. |
|
|
| 50. |
|
|
