| 1. |
- Nyberg, Lena, 1979, et al.
(författare)
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A single-step competitive binding assay for mapping of single DNA molecules
- 2012
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Ingår i: Biochemical and Biophysical Research Communications - BBRC. - : Elsevier BV. - 0006-291X .- 1090-2104. ; 417:1, s. 404-408
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Tidskriftsartikel (refereegranskat)abstract
- Optical mapping of genomic DNA is of relevance for a plethora of applications such as scaffolding for sequencing and detection of structural variations as well as identification cif pathogens like bacteria and viruses. For future clinical applications it is desirable to have a fast and robust mapping method based on as few steps as possible. We here demonstrate a single-step method to obtain a DNA barcode that is directly visualized using nanofluidic devices and fluorescence microscopy. Using a mixture of YOYO-1, a bright DNA dye, and netropsin, a natural antibiotic with very high AT specificity, we obtain a DNA map with a fluorescence intensity profile along the DNA that reflects the underlying sequence. The netropsin binds to AT-tetrads and blocks these binding sites from YOYO-1 binding which results in lower fluorescence intensity from AT-rich regions of the DNA. We thus obtain a DNA barcode that is dark in AT-rich regions and bright in GC-rich regions with kilobasepair resolution. We demonstrate the versatility of the method by obtaining a barcode on DNA from the phage T4 that captures its circular permutation and agrees well with its known sequence.
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| 2. |
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| 3. |
- Sanchez Heres, Luis Felipe, 1984, et al.
(författare)
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COLREG 3 - Exploring the potential of Large Language Models in marine navigation systems
- 2024
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- This pre-study explores the potential use of Large Language Models (LLM), like ChatGPT and GPT-4, in decision-support systems for maritime navigation. The aim is to determine if these models could be part of decision support systems for identifying and resolving complex traffic situations, as doing so, would enhance maritime safety and efficiency, as well as reduce the environmental impact of shipping. The study benefits from previous research carried out in the COLREG2 project, COLREG 2 - Potential consequences of varying algorithms in traffic situations, which examined the limitations of algorithms meant to support the resolution of complex traffic situations. COLREG2 concluded that the evaluated algorithms had severe limitations and stated scepticism regarding the development of suitable algorithms in the near future. Shortly after the end of the COLREG2 project, large language models demonstrated their uncanny ability to understand, and to some extent, reason about complex texts and tasks. These abilities seemingly address the shortfalls of the algorithms evaluated in the COLREG2 project, making the use of large language models in decision support systems for marine traffic situations thought-provoking.
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| 4. |
- Wadensten, Elisabeth, et al.
(författare)
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Diagnostic Yield From a Nationwide Implementation of Precision Medicine for all Children With Cancer.
- 2023
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Ingår i: JCO Precision Oncology (JCO PO). - : American Society of Clinical Oncology. - 2473-4284. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Several studies have indicated that broad genomic characterization of childhood cancer provides diagnostically and/or therapeutically relevant information in selected high-risk cases. However, the extent to which such characterization offers clinically actionable data in a prospective broadly inclusive setting remains largely unexplored.We implemented prospective whole-genome sequencing (WGS) of tumor and germline, complemented by whole-transcriptome sequencing (RNA-Seq) for all children diagnosed with a primary or relapsed solid malignancy in Sweden. Multidisciplinary molecular tumor boards were set up to integrate genomic data in the clinical decision process along with a medicolegal framework enabling secondary use of sequencing data for research purposes.During the study's first 14 months, 118 solid tumors from 117 patients were subjected to WGS, with complementary RNA-Seq for fusion gene detection in 52 tumors. There was no significant geographic bias in patient enrollment, and the included tumor types reflected the annual national incidence of pediatric solid tumor types. Of the 112 tumors with somatic mutations, 106 (95%) exhibited alterations with a clear clinical correlation. In 46 of 118 tumors (39%), sequencing only corroborated histopathological diagnoses, while in 59 cases (50%), it contributed to additional subclassification or detection of prognostic markers. Potential treatment targets were found in 31 patients (26%), most commonly ALK mutations/fusions (n = 4), RAS/RAF/MEK/ERK pathway mutations (n = 14), FGFR1 mutations/fusions (n = 5), IDH1 mutations (n = 2), and NTRK2 gene fusions (n = 2). In one patient, the tumor diagnosis was revised based on sequencing. Clinically relevant germline variants were detected in 8 of 94 patients (8.5%).Up-front, large-scale genomic characterization of pediatric solid malignancies provides diagnostically valuable data in the majority of patients also in a largely unselected cohort.
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| 6. |
- Bridel, Claire, et al.
(författare)
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Diagnostic Value of Cerebrospinal Fluid Neurofilament Light Protein in Neurology : A Systematic Review and Meta-analysis
- 2019
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Ingår i: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157. ; 76:9, s. 1035-1048
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Forskningsöversikt (refereegranskat)abstract
- Importance Neurofilament light protein (NfL) is elevated in cerebrospinal fluid (CSF) of a number of neurological conditions compared with healthy controls (HC) and is a candidate biomarker for neuroaxonal damage. The influence of age and sex is largely unknown, and levels across neurological disorders have not been compared systematically to date.Objectives To assess the associations of age, sex, and diagnosis with NfL in CSF (cNfL) and to evaluate its potential in discriminating clinically similar conditions.Data Sources PubMed was searched for studies published between January 1, 2006, and January 1, 2016, reporting cNfL levels (using the search terms neurofilament light and cerebrospinal fluid) in neurological or psychiatric conditions and/or in HC.Study Selection Studies reporting NfL levels measured in lumbar CSF using a commercially available immunoassay, as well as age and sex.Data Extraction and Synthesis Individual-level data were requested from study authors. Generalized linear mixed-effects models were used to estimate the fixed effects of age, sex, and diagnosis on log-transformed NfL levels, with cohort of origin modeled as a random intercept.Main Outcome and Measure The cNfL levels adjusted for age and sex across diagnoses.Results Data were collected for 10 059 individuals (mean [SD] age, 59.7 [18.8] years; 54.1% female). Thirty-five diagnoses were identified, including inflammatory diseases of the central nervous system (n = 2795), dementias and predementia stages (n = 4284), parkinsonian disorders (n = 984), and HC (n = 1332). The cNfL was elevated compared with HC in a majority of neurological conditions studied. Highest levels were observed in cognitively impaired HIV-positive individuals (iHIV), amyotrophic lateral sclerosis, frontotemporal dementia (FTD), and Huntington disease. In 33.3% of diagnoses, including HC, multiple sclerosis, Alzheimer disease (AD), and Parkinson disease (PD), cNfL was higher in men than women. The cNfL increased with age in HC and a majority of neurological conditions, although the association was strongest in HC. The cNfL overlapped in most clinically similar diagnoses except for FTD and iHIV, which segregated from other dementias, and PD, which segregated from atypical parkinsonian syndromes.Conclusions and Relevance These data support the use of cNfL as a biomarker of neuroaxonal damage and indicate that age-specific and sex-specific (and in some cases disease-specific) reference values may be needed. The cNfL has potential to assist the differentiation of FTD from AD and PD from atypical parkinsonian syndromes.
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| 7. |
- Chursa, Urszula, et al.
(författare)
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Overexpression of protein kinase STK25 in mice exacerbates ectopic lipid accumulation, mitochondrial dysfunction and insulin resistance in skeletal muscle.
- 2017
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 60:3, s. 553-567
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Tidskriftsartikel (refereegranskat)abstract
- Understanding the molecular networks controlling ectopic lipid deposition and insulin responsiveness in skeletal muscle is essential for developing new strategies to treat type 2 diabetes. We recently identified serine/threonine protein kinase 25 (STK25) as a critical regulator of liver steatosis, hepatic lipid metabolism and whole body glucose and insulin homeostasis. Here, we assessed the role of STK25 in control of ectopic fat storage and insulin responsiveness in skeletal muscle.Skeletal muscle morphology was studied by histological examination, exercise performance and insulin sensitivity were assessed by treadmill running and euglycaemic-hyperinsulinaemic clamp, respectively, and muscle lipid metabolism was analysed by ex vivo assays in Stk25 transgenic and wild-type mice fed a high-fat diet. Lipid accumulation and mitochondrial function were also studied in rodent myoblasts overexpressing STK25. Global quantitative phosphoproteomics was performed in skeletal muscle of Stk25 transgenic and wild-type mice fed a high-fat diet to identify potential downstream mediators of STK25 action.We found that overexpression of STK25 in transgenic mice fed a high-fat diet increases intramyocellular lipid accumulation, impairs skeletal muscle mitochondrial function and sarcomeric ultrastructure, and induces perimysial and endomysial fibrosis, thereby reducing endurance exercise capacity and muscle insulin sensitivity. Furthermore, we observed enhanced lipid accumulation and impaired mitochondrial function in rodent myoblasts overexpressing STK25, demonstrating an autonomous action for STK25 within cells. Global phosphoproteomic analysis revealed alterations in the total abundance and phosphorylation status of different target proteins located predominantly to mitochondria and sarcomeric contractile elements in Stk25 transgenic vs wild-type muscle, respectively, providing a possible molecular mechanism for the observed phenotype.STK25 emerges as a new regulator of the complex interplay between lipid storage, mitochondrial energetics and insulin action in skeletal muscle, highlighting the potential of STK25 antagonists for type 2 diabetes treatment.
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| 8. |
- Cui, Qiao-Yu, et al.
(författare)
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Evaluating fossil charcoal representation in small peat bogs : Detailed Holocene fire records from southern Sweden
- 2020
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Ingår i: The Holocene. - : Sage Publications. - 0959-6836 .- 1477-0911. ; 30:11, s. 1540-1551
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Tidskriftsartikel (refereegranskat)abstract
- In this study, we assess how representative a single charcoal record from a peat profile in small bogs (1.5-2 ha in area) is for the reconstruction of Holocene fire history. We use high-resolution macrocharcoal (>250 mu m) analysis of continuous series of 2 cm(3)samples from two small bogs in southern Sweden. We compare (1) duplicate charcoal records from the same core, (2) duplicate charcoal records from profiles in the same site (10 m apart), and (3) charcoal records from two sites within the same region (15 km apart). Comparisons are made for charcoal counts and area expressed as accumulation rates. The results suggest that (a) charcoal counts and area are highly correlated in all records; (b) duplicate charcoal records within the same core are very similar, although some charcoal peaks are found in only one of the two records; (c) although long-term trends in fire regimes are similar between duplicate charcoal records from nearby profiles within the same site and between charcoal records from sites within the same region, some individual charcoal peaks/fire events are asynchronous between records. The known historical fires of the town of Vaxjo (1570 and 1612 CE) are recorded at the two study sites, which indicates a macrocharcoal source area of minimum 15 km in diameter. The 2 cm(3)peat samples contained relatively low amounts of macrocharcoal; we therefore recommend to analyse larger samples from small peat bogs with comparable peat accumulation rates. This will improve the reliability of the macrocharcoal record and its interpretation.
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| 9. |
- Diaz-Tendero, S., et al.
(författare)
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Electron propagation along Cu nanowires supported on a Cu(111) surface
- 2008
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Ingår i: Nano Letters. - : American Chemical Society (ACS). - 1530-6992 .- 1530-6984. ; 8:9, s. 2712-2717
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Tidskriftsartikel (refereegranskat)abstract
- We present a joint experimental-theoretical study of the one-dimensional band of excited electronic states with sp character localized on Cu nanowires supported on a Cu(III) surface. Energy dispersion and lifetime of these states have been obtained, allowing the determination of the mean distance traveled by an excited electron along the nanowire before it escapes into the substrate. We show that a Cu nanowire supported on a Cu(III) surface can guide a one-dimensional electron flux over a short distance and thus can be considered as a possible component for nanoelectronics devices.
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| 10. |
- Diaz-Tendero, S., et al.
(författare)
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Excited electron dynamics in Cu nanowires supported on a Cu(111) surface
- 2009
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Ingår i: Physical Review B - Condensed Matter and Materials Physics. - 2469-9950 .- 2469-9969. ; 79:11, s. 115438 (artno)-
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Tidskriftsartikel (refereegranskat)abstract
- We present a theoretical study of the excited electron dynamics in infinite Cu monoatomic chains (nanowires) supported on a Cu(111) surface. A joint approach based on the wave packet propagation and the density functional theory is used. The nanowire-induced potential obtained from ab initio density functional theory calculations serves as an input for the wave-packet propagation study of the excited electron dynamics. The energy dispersion and the lifetime of an unoccupied one-dimensional (1D) nanowire-localized electronic band with sp character are obtained. From the group velocity and lifetime of the 1D sp-band states, it follows that an excited electron can travel about four to five atomic sites along the nanowire before its escape into the bulk. We show that the surface projected band gap and the surface Brillouin zone backfolding of the substrate states play a fundamental role in the lifetime of the nanowire-localized states.
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