| 1. |
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| 2. |
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| 3. |
- Wightman, D. P., et al.
(författare)
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A genome-wide association study with 1,126,563 individuals identifies new risk loci for Alzheimer’s disease
- 2021
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 53:9, s. 1276-1282
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Tidskriftsartikel (refereegranskat)abstract
- Late-onset Alzheimer’s disease is a prevalent age-related polygenic disease that accounts for 50–70% of dementia cases. Currently, only a fraction of the genetic variants underlying Alzheimer’s disease have been identified. Here we show that increased sample sizes allowed identification of seven previously unidentified genetic loci contributing to Alzheimer’s disease. This study highlights microglia, immune cells and protein catabolism as relevant to late-onset Alzheimer’s disease, while identifying and prioritizing previously unidentified genes of potential interest. We anticipate that these results can be included in larger meta-analyses of Alzheimer’s disease to identify further genetic variants that contribute to Alzheimer’s pathology.
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| 4. |
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| 5. |
- Gordon, I.E., et al.
(författare)
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The HITRAN2020 molecular spectroscopic database
- 2022
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Ingår i: Journal of Quantitative Spectroscopy and Radiative Transfer. - : Elsevier. - 0022-4073 .- 1879-1352. ; 277
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Tidskriftsartikel (refereegranskat)abstract
- The HITRAN database is a compilation of molecular spectroscopic parameters. It was established in the early 1970s and is used by various computer codes to predict and simulate the transmission and emission of light in gaseous media (with an emphasis on terrestrial and planetary atmospheres). The HITRAN compilation is composed of five major components: the line-by-line spectroscopic parameters required for high-resolution radiative-transfer codes, experimental infrared absorption cross-sections (for molecules where it is not yet feasible for representation in a line-by-line form), collision-induced absorption data, aerosol indices of refraction, and general tables (including partition sums) that apply globally to the data. This paper describes the contents of the 2020 quadrennial edition of HITRAN. The HITRAN2020 edition takes advantage of recent experimental and theoretical data that were meticulously validated, in particular, against laboratory and atmospheric spectra. The new edition replaces the previous HITRAN edition of 2016 (including its updates during the intervening years). All five components of HITRAN have undergone major updates. In particular, the extent of the updates in the HITRAN2020 edition range from updating a few lines of specific molecules to complete replacements of the lists, and also the introduction of additional isotopologues and new (to HITRAN) molecules: SO, CH3F, GeH4, CS2, CH3I and NF3. Many new vibrational bands were added, extending the spectral coverage and completeness of the line lists. Also, the accuracy of the parameters for major atmospheric absorbers has been increased substantially, often featuring sub-percent uncertainties. Broadening parameters associated with the ambient pressure of water vapor were introduced to HITRAN for the first time and are now available for several molecules. The HITRAN2020 edition continues to take advantage of the relational structure and efficient interface available at www.hitran.org and the HITRAN Application Programming Interface (HAPI). The functionality of both tools has been extended for the new edition.
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| 6. |
- Bonham, LW, et al.
(författare)
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Genetic variation across RNA metabolism and cell death gene networks is implicated in the semantic variant of primary progressive aphasia
- 2019
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1, s. 10854-
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Tidskriftsartikel (refereegranskat)abstract
- The semantic variant of primary progressive aphasia (svPPA) is a clinical syndrome characterized by neurodegeneration and progressive loss of semantic knowledge. Unlike many other forms of frontotemporal lobar degeneration (FTLD), svPPA has a highly consistent underlying pathology composed of TDP-43 (a regulator of RNA and DNA transcription metabolism). Previous genetic studies of svPPA are limited by small sample sizes and a paucity of common risk variants. Despite this, svPPA’s relatively homogenous clinicopathologic phenotype makes it an ideal investigative model to examine genetic processes that may drive neurodegenerative disease. In this study, we used GWAS metadata, tissue samples from pathologically confirmed frontotemporal lobar degeneration, and in silico techniques to identify and characterize protein interaction networks associated with svPPA risk. We identified 64 svPPA risk genes that interact at the protein level. The protein pathways represented in this svPPA gene network are critical regulators of RNA metabolism and cell death, such as SMAD proteins and NOTCH1. Many of the genes in this network are involved in TDP-43 metabolism. Contrary to the conventional notion that svPPA is a clinical syndrome with few genetic risk factors, our analyses show that svPPA risk is complex and polygenic in nature. Risk for svPPA is likely driven by multiple common variants in genes interacting with TDP-43, along with cell death,x` working in combination to promote neurodegeneration.
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| 7. |
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| 8. |
- Gao, YX, et al.
(författare)
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Mendelian randomization implies no direct causal association between leukocyte telomere length and amyotrophic lateral sclerosis
- 2020
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1, s. 12184-
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Tidskriftsartikel (refereegranskat)abstract
- We employed Mendelian randomization (MR) to evaluate the causal relationship between leukocyte telomere length (LTL) and amyotrophic lateral sclerosis (ALS) with summary statistics from genome-wide association studies (n = ~ 38,000 for LTL and ~ 81,000 for ALS in the European population; n = ~ 23,000 for LTL and ~ 4,100 for ALS in the Asian population). We further evaluated mediation roles of lipids in the pathway from LTL to ALS. The odds ratio per standard deviation decrease of LTL on ALS was 1.10 (95% CI 0.93–1.31, p = 0.274) in the European population and 0.75 (95% CI 0.53–1.07, p = 0.116) in the Asian population. This null association was also detected between LTL and frontotemporal dementia in the European population. However, we found that an indirect effect of LTL on ALS might be mediated by low density lipoprotein (LDL) or total cholesterol (TC) in the European population. These results were robust against extensive sensitivity analyses. Overall, our MR study did not support the direct causal association between LTL and the ALS risk in neither population, but provided suggestive evidence for the mediation role of LDL or TC on the influence of LTL and ALS in the European population.
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| 9. |
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| 10. |
- Abbasi, R., et al.
(författare)
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The IceCube data acquisition system : Signal capture, digitization, and timestamping
- 2009
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 601:3, s. 294-316
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Tidskriftsartikel (refereegranskat)abstract
- IceCube is a km-scale neutrino observatory under construction at the South Pole with sensors both in the deep ice (InIce) and on the surface (IceTop). The sensors, called Digital Optical Modules (DOMs). detect, digitize and timestamp the signals from optical Cherenkov-radiation photons. The DOM Main Board (MB) data acquisition subsystem is connected to the central DAQ in the IceCube Laboratory (ICL) by a single twisted copper wire-pair and transmits packetized data on demand. Time calibration is maintained throughout the array by regular transmission to the DOMs of precisely timed analog signals, synchronized to a central GPS-disciplined clock. The design goals and consequent features, functional capabilities, and initial performance of the DOM MB, and the operation of a combined array of DOMs as a system, are described here. Experience with the first InIce strings and the IceTop stations indicates that the system design and performance goals have been achieved. (c) 2009 Elsevier B.V. All rights reserved.
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| 11. |
- Achterberg, A., et al.
(författare)
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Detection of atmospheric muon neutrinos with the IceCube 9-string detector
- 2007
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Ingår i: Physical Review D - Particles, Fields, Gravitation and Cosmology. - 1550-7998. ; 76:2, s. 027101-
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Tidskriftsartikel (refereegranskat)abstract
- The IceCube neutrino detector is a cubic kilometer TeV to PeV neutrino detector under construction at the geographic South Pole. The dominant population of neutrinos detected in IceCube is due to meson decay in cosmic-ray air showers. These atmospheric neutrinos are relatively well understood and serve as a calibration and verification tool for the new detector. In 2006, the detector was approximately 10% completed, and we report on data acquired from the detector in this configuration. We observe an atmospheric neutrino signal consistent with expectations, demonstrating that the IceCube detector is capable of identifying neutrino events. In the first 137.4 days of live time, 234 neutrino candidates were selected with an expectation of 211 +/- 76.1(syst)+/- 14.5(stat) events from atmospheric neutrinos.
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| 12. |
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| 13. |
- Achterberg, A., et al.
(författare)
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Multiyear search for a diffuse flux of muon neutrinos with AMANDA-II
- 2007
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Ingår i: Physical Review D - Particles, Fields, Gravitation and Cosmology. - 1550-7998. ; 76:4, s. 042008-
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Tidskriftsartikel (refereegranskat)abstract
- A search for TeV-PeV muon neutrinos from unresolved sources was performed on AMANDA-II data collected between 2000 and 2003 with an equivalent live time of 807 days. This diffuse analysis sought to find an extraterrestrial neutrino flux from sources with nonthermal components. The signal is expected to have a harder spectrum than the atmospheric muon and neutrino backgrounds. Since no excess of events was seen in the data over the expected background, an upper limit of E-2 Phi(90%C.L.)< 7.4x10(-8) GeV cm(-2) s(-1) sr(-1) is placed on the diffuse flux of muon neutrinos with a Phi proportional to E-2 spectrum in the energy range 16 TeV to 2.5 PeV. This is currently the most sensitive Phi proportional to E-2 diffuse astrophysical neutrino limit. We also set upper limits for astrophysical and prompt neutrino models, all of which have spectra different from Phi proportional to E-2.
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| 14. |
- Achterberg, A., et al.
(författare)
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The search for muon neutrinos from northern hemisphere gamma-ray bursts with AMANDA
- 2008
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 674:1, s. 357-370
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Tidskriftsartikel (refereegranskat)abstract
- We present the results of the analysis of neutrino observations by the Antarctic Muon and Neutrino Detector Array (AMANDA) correlated with photon observations of more than 400 gamma-ray bursts (GRBs) in the northern hemisphere from 1997 to 2003. During this time period, AMANDA's effective collection area for muon neutrinos was larger than that of any other existing detector. After the application of various selection criteria to our data, we expect similar to 1 neutrino event and <2 background events. Based on our observations of zero events during and immediately prior to the GRBs in the data set, we set the most stringent upper limit on muon neutrino emission correlated with GRBs. Assuming a Waxman-Bahcall spectrum and incorporating all systematic uncertainties, our flux upper limit has a normalization at 1 PeV of E-2 Phi(nu) <= 6.3 x 10(-9) GeV cm(-2) s(-1) sr(-1), with 90% of the events expected within the energy range of similar to 10 TeV to similar to 3 PeV. The impact of this limit on several theoretical models of GRBs is discussed, as well as the future potential for detection of GRBs by next-generation neutrino telescopes. Finally, we briefly describe several modifications to this analysis in order to apply it to other types of transient point sources.
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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. |
- Abbasi, R., et al.
(författare)
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Search for point sources of high energy neutrinos with final data from AMANDA-II
- 2009
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Ingår i: Physical Review D. - 1550-7998 .- 1550-2368. ; 79, s. 062001-
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Tidskriftsartikel (refereegranskat)abstract
- We present a search for point sources of high energy neutrinos using 3.8 yr of data recorded by AMANDA-II during 2000-2006. After reconstructing muon tracks and applying selection criteria designed to optimally retain neutrino-induced events originating in the northern sky, we arrive at a sample of 6595 candidate events, predominantly from atmospheric neutrinos with primary energy 100 GeV to 8 TeV. Our search of this sample reveals no indications of a neutrino point source. We place the most stringent limits to date on E(-2) neutrino fluxes from points in the northern sky, with an average upper limit of E(2)Phi(nu mu)+nu(tau)<= 5.2x10(-11) TeV cm(-2) s(-1) on the sum of nu(mu) and nu(tau) fluxes, assumed equal, over the energy range from 1.9 TeV to 2.5 PeV.
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| 20. |
- Ackermann, M., et al.
(författare)
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Search for ultra-high-energy neutrinos with amanda-II
- 2008
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 675:2, s. 1014-1024
-
Tidskriftsartikel (refereegranskat)abstract
- A search for diffuse neutrinos with energies in excess of 10(5) GeV is conducted with AMANDA-II data recorded between 2000 and 2002. Above 10(7) GeV, the Earth is essentially opaque to neutrinos. This fact, combined with the limited overburden of the AMANDA-II detector ( roughly 1.5 km), concentrates these ultra-high-energy neutrinos at the horizon. The primary background for this analysis is bundles of downgoing, high-energy muons from the interaction of cosmic rays in the atmosphere. No statistically significant excess above the expected background is seen in the data, and an upper limit is set on the diffuse all-flavor neutrino flux of E-2 Phi(90%CL) < 2.7x10(-7) GeV cm(-2) s(-1) sr(-1) valid over the energy range of 2x10(5) to 10(9) GeV. A number of models that predict neutrino fluxes from active galactic nuclei are excluded at the 90% confidence level.
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| 21. |
- Kemmer, D., et al.
(författare)
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Exploring the foundation of genomics : a Northern blot reference set for the comparative analysis of transcript profiling technologies
- 2004
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Ingår i: Comparative and functional genomics. - : Hindawi Limited. - 1531-6912 .- 1532-6268. ; 5:8, s. 584-595
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Tidskriftsartikel (refereegranskat)abstract
- In this paper we aim to create a reference data collection of Northern blot results and demonstrate how such a collection can enable a quantitative comparison of modern expression profiling techniques, a central component of functional genomics studies. Historic ally, Northern blots were the de facto standard for determining RNA transcript levels. However, driven by the demand for analysis of large sets of genes in parallel, high-throughput methods, such as microarrays, dominate modern profiling efforts. To facilitate assessment of these methods, in comparison to Northern blots, we created a database of published Northern results obtained with a standardized commercial multiple tissue blot (dbMTN). In order to demonstrate the utility of the dbMTN collection for technology comparison, we also generated expression profiles for genes across a set of human tissues, using multiple profiling techniques. No method produced profiles that were strongly correlated with the Northern blot data. The highest correlations to the Northern blot data were determined with microarrays for the subset of genes observed to be specifically expressed in a single tissue in the Northern analyses. The database and expression profiling data are available via the project website (http://www.cisreg.ca). We believe that emphasis on multitechnique validation of expression profiles is justified, as the correlation results between platforms are not encouraging on the whole. Supplementary material for this article can be found at: http://www.interscience.wiley.com/jpages/1531-6912/suppmat
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| 22. |
- Langerak, A. W., et al.
(författare)
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EuroClonality/BIOMED-2 guidelines for interpretation and reporting of Ig/TCR clonality testing in suspected lymphoproliferations
- 2012
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 26:10, s. 2159-2171
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Forskningsöversikt (refereegranskat)abstract
- PCR-based immunoglobulin (Ig)/T-cell receptor (TCR) clonality testing in suspected lymphoproliferations has largely been standardized and has consequently become technically feasible in a routine diagnostic setting. Standardization of the pre-analytical and post-analytical phases is now essential to prevent misinterpretation and incorrect conclusions derived from clonality data. As clonality testing is not a quantitative assay, but rather concerns recognition of molecular patterns, guidelines for reliable interpretation and reporting are mandatory. Here, the EuroClonality (BIOMED-2) consortium summarizes important pre- and post-analytical aspects of clonality testing, provides guidelines for interpretation of clonality testing results, and presents a uniform way to report the results of the Ig/TCR assays. Starting from an immunobiological concept, two levels to report Ig/TCR profiles are discerned: the technical description of individual (multiplex) PCR reactions and the overall molecular conclusion for B and T cells. Collectively, the EuroClonality (BIOMED-2) guidelines and consensus reporting system should help to improve the general performance level of clonality assessment and interpretation, which will directly impact on routine clinical management (standardized best-practice) in patients with suspected lymphoproliferations.
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| 23. |
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| 24. |
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| 25. |
- Bååth, L.B. 1948-, et al.
(författare)
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The microarcsecond structure of 3C 273 at 3 MM
- 1991
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Ingår i: Astronomy and Astrophysics. - Les Ulis : EDP Sciences. - 0004-6361 .- 1432-0746. ; 241:1, s. L1-L4
-
Tidskriftsartikel (refereegranskat)abstract
- Recent improvements in data analysis and receiver techniques have allowed us to produce a map of the 100GHz emission from the compact radio source 3C273 with the unsurpassed resolution of 50-mu-as (microarcseconds). Our map shows that the structure within 300-mu-as (approximately 1.5.10(18).h-1 cm) has a position angle significantly different from the position angle of the jet observed at lower frequencies. There are also indications in our map that the inner structure has a more pronounced wiggling structure than has been observed on larger scales. The observations were made about 60 days from the start of the outburst of 1988. Most of the flux from the outburst is concentrated in a component which is elongated approximately (56 x 5).10(16).h-1 cm perpendicular to the overall jet-axis. The distance between this component and the core is approximately 128-mu-as, which corresponds to the distance expected from an apparent velocity of approximately 800-mu-as year-1.
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| 26. |
- Bååth, L.B. 1948-, et al.
(författare)
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VLBI observations of active galactic nuclei at 3 MM
- 1992
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Ingår i: Astronomy and Astrophysics. - Les Ulis : EDP Sciences. - 0004-6361 .- 1432-0746. ; 257:1, s. 31-46
-
Tidskriftsartikel (refereegranskat)abstract
- Recent improvements in data analysis and receiver techniques have allowed us to produce maps of the 100 GHz emission from the compact cores of active galactic nuclei with the unsurpassed resolution of 50-mu-as (microarcseconds). We present here hybrid maps of a set of compact radio sources observed at two epochs with a global VLBI array. The high resolution enables us to show details of active galactic nuclei on size scales of 10(16)-10(17) cm. Jets are shown to be more curved in these inner parts than further out in the areas mapped with VLBI at lower frequencies. Our maps of the quasar 3C345 show that the curvature seen with lower resolution instruments continues very close to the core. New components are seen separating from the cores of 3C84 and BL Lac. We observe a component in 3C84 separating from the core with an apparent speed approximately 21000 km sec-1. The radio source OJ287 is still unresolved with our array, having a core size of less-than-or-similar-to 10(17) cm. There is no indication of any compact component in 3C279 which would be associated with the outburst in integrated flux density which happened some months before our observation. The flux density of the most compact component we observe in 3C279 agrees well with that of the quiet core as extrapolated from its radio spectrum at lower frequencies. The inner part of the radio jet of the giant elliptical galaxy M87 also shows a continuation of the structure on a larger size scale, with a structure we interpret as parts of a helical pattern. No fringes were found for 4C39.25 or Sgr A.
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| 27. |
- Ferrari, Raffaele, et al.
(författare)
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Frontotemporal dementia and its subtypes: a genome-wide association study.
- 2014
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Ingår i: Lancet Neurology. - 1474-4465. ; 13:7, s. 686-699
-
Tidskriftsartikel (refereegranskat)abstract
- Frontotemporal dementia (FTD) is a complex disorder characterised by a broad range of clinical manifestations, differential pathological signatures, and genetic variability. Mutations in three genes-MAPT, GRN, and C9orf72-have been associated with FTD. We sought to identify novel genetic risk loci associated with the disorder.
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| 28. |
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| 29. |
- Jansen, Willemijn J, et al.
(författare)
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Prevalence Estimates of Amyloid Abnormality Across the Alzheimer Disease Clinical Spectrum.
- 2022
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Ingår i: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 79:3, s. 228-243
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Tidskriftsartikel (refereegranskat)abstract
- One characteristic histopathological event in Alzheimer disease (AD) is cerebral amyloid aggregation, which can be detected by biomarkers in cerebrospinal fluid (CSF) and on positron emission tomography (PET) scans. Prevalence estimates of amyloid pathology are important for health care planning and clinical trial design.To estimate the prevalence of amyloid abnormality in persons with normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia and to examine the potential implications of cutoff methods, biomarker modality (CSF or PET), age, sex, APOE genotype, educational level, geographical region, and dementia severity for these estimates.This cross-sectional, individual-participant pooled study included participants from 85 Amyloid Biomarker Study cohorts. Data collection was performed from January 1, 2013, to December 31, 2020. Participants had normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia. Normal cognition and subjective cognitive decline were defined by normal scores on cognitive tests, with the presence of cognitive complaints defining subjective cognitive decline. Mild cognitive impairment and clinical AD dementia were diagnosed according to published criteria.Alzheimer disease biomarkers detected on PET or in CSF.Amyloid measurements were dichotomized as normal or abnormal using cohort-provided cutoffs for CSF or PET or by visual reading for PET. Adjusted data-driven cutoffs for abnormal amyloid were calculated using gaussian mixture modeling. Prevalence of amyloid abnormality was estimated according to age, sex, cognitive status, biomarker modality, APOE carrier status, educational level, geographical location, and dementia severity using generalized estimating equations.Among the 19097 participants (mean [SD] age, 69.1 [9.8] years; 10148 women [53.1%]) included, 10139 (53.1%) underwent an amyloid PET scan and 8958 (46.9%) had an amyloid CSF measurement. Using cohort-provided cutoffs, amyloid abnormality prevalences were similar to 2015 estimates for individuals without dementia and were similar across PET- and CSF-based estimates (24%; 95% CI, 21%-28%) in participants with normal cognition, 27% (95% CI, 21%-33%) in participants with subjective cognitive decline, and 51% (95% CI, 46%-56%) in participants with mild cognitive impairment, whereas for clinical AD dementia the estimates were higher for PET than CSF (87% vs 79%; mean difference, 8%; 95% CI, 0%-16%; P=.04). Gaussian mixture modeling-based cutoffs for amyloid measures on PET scans were similar to cohort-provided cutoffs and were not adjusted. Adjusted CSF cutoffs resulted in a 10% higher amyloid abnormality prevalence than PET-based estimates in persons with normal cognition (mean difference, 9%; 95% CI, 3%-15%; P=.004), subjective cognitive decline (9%; 95% CI, 3%-15%; P=.005), and mild cognitive impairment (10%; 95% CI, 3%-17%; P=.004), whereas the estimates were comparable in persons with clinical AD dementia (mean difference, 4%; 95% CI, -2% to 9%; P=.18).This study found that CSF-based estimates using adjusted data-driven cutoffs were up to 10% higher than PET-based estimates in people without dementia, whereas the results were similar among people with dementia. This finding suggests that preclinical and prodromal AD may be more prevalent than previously estimated, which has important implications for clinical trial recruitment strategies and health care planning policies.
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| 30. |
- Lerner, M.S., et al.
(författare)
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A 100 GHZ map of 3C 446
- 1993
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Ingår i: Astronomy and Astrophysics. - Les Ulis : EDP Sciences. - 0004-6361 .- 1432-0746. ; 280:1, s. 117-120
-
Tidskriftsartikel (refereegranskat)abstract
- The first map made from 100 GHz VLBI observations of the quasar/BL Lac object 3C446 is presented. This map represents a 25-fold increase in resolution compared to earlier maps. Our main conclusions are that the core of 3C 446 is still almost unresolved (less than or similar to 30 muas) at this frequency and that a jet extends several hundred microarcseconds at position angle almost-equal-to -142-degrees. A comparison is also made with observations at other size scales.
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| 31. |
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| 32. |
- Rantakyrö, F.T., et al.
(författare)
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50 μas resolution VLBI images of AGN’s at λ3 mm
- 1998
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Ingår i: Astronomy and Astrophysics. - Berlin : Springer-Verlag. - 0004-6361 .- 1432-0746. ; 131, s. 451-467
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Tidskriftsartikel (refereegranskat)abstract
- We present 15 images from the global mm-VLBI sessions in 1990 April at 100 GHz and 1993 April at 86 GHz. These observations probe the central engines of the 16 observed AGN's with up to 50 mu as resolution. Among other sources previously observed with lambda 3 mm VLBI we present the first lambda 3 mm maps of 0735+178, 0748+126, 1055+018, 2145+067, and CTA102, in total we have been able to image 13 out of the 16 observed sources. 6 out of the 13 imaged sources observed exhibit curvature and rapid structural changes, although the low dynamic range in two thirds of the maps limits the detection of weak features. Most of the sources have unresolved cores even at this high resolution. There is substantial evidence that the observed sources can be grouped into two general groups: A misaligned population with parsec scale jets in the form of low pitch helices and an aligned population with straight jets with small changes in PA due to intrinsic bends.
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| 33. |
- Albert, F. W., et al.
(författare)
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Targeted resequencing of a genomic region influencing tameness and aggression reveals multiple signals of positive selection
- 2011
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Ingår i: Heredity. - : Springer Science and Business Media LLC. - 0018-067X .- 1365-2540. ; 107:3, s. 205-214
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Tidskriftsartikel (refereegranskat)abstract
- The identification of the causative genetic variants in quantitative trait loci (QTL) influencing phenotypic traits is challenging, especially in crosses between outbred strains. We have previously identified several QTL influencing tameness and aggression in a cross between two lines of wild-derived, outbred rats (Rattus norvegicus) selected for their behavior towards humans. Here, we use targeted sequence capture and massively parallel sequencing of all genes in the strongest QTL in the founder animals of the cross. We identify many novel sequence variants, several of which are potentially functionally relevant. The QTL contains several regions where either the tame or the aggressive founders contain no sequence variation, and two regions where alternative haplotypes are fixed between the founders. A re-analysis of the QTL signal showed that the causative site is likely to be fixed among the tame founder animals, but that several causative alleles may segregate among the aggressive founder animals. Using a formal test for the detection of positive selection, we find 10 putative positively selected regions, some of which are close to genes known to influence behavior. Together, these results show that the QTL is probably not caused by a single selected site, but may instead represent the joint effects of several sites that were targets of polygenic selection.
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| 34. |
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| 35. |
- He, Min, et al.
(författare)
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Artificial Polymeric Scaffolds as Extracellular Matrix Substitutes for Autologous Conjunctival Goblet Cell Expansion
- 2016
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Ingår i: Investigative Ophthalmology and Visual Science. - : ASSOC RESEARCH VISION OPHTHALMOLOGY INC. - 0146-0404 .- 1552-5783. ; 57:14, s. 6134-6146
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE. We fabricated and investigated polymeric scaffolds that can substitute for the conjunctival extracellular matrix to provide a substrate for autologous expansion of human conjunctival goblet cells in culture. METHODS. We fabricated two hydrogels and two silk films: (1) recombinant human collagen (RHC) hydrogel, (2) recombinant human collagen 2-methacryloylxyethyl phosphorylcholine (RHC-MPC) hydrogel, (3) arginine-glycine-aspartic acid (RGD) modified silk, and (4) poly-D-lysine (PDL) coated silk, and four electrospun scaffolds: (1) collagen, (2) poly(acrylic acid) (PAA), (3) poly(caprolactone) (PCL), and (4) poly(vinyl alcohol) (PVA). Coverslips and polyethylene terephthalate (PET) were used for comparison. Human conjunctival explants were cultured on scaffolds for 9 to 15 days. Cell viability, outgrowth area, and the percentage of cells expressing markers for stratified squamous epithelial cells (cytokeratin 4) and goblet cells (cytokeratin 7) were determined. RESULTS. Most of cells grown on all scaffolds were viable except for PCL in which only 3.6 +/- 2.2% of the cells were viable. No cells attached to PVA scaffold. The outgrowth was greatest on PDL-silk and PET. Outgrowth was smallest on PCL. All cells were CK7-positive on RHCMPC while 84.7 +/- 6.9% of cells expressed CK7 on PDL-silk. For PCL, 87.10 +/- 3.17% of cells were CK7-positive compared to PET where 67.10 +/- 12.08% of cells were CK7-positive cells. CONCLUSIONS. Biopolymer substrates in the form of hydrogels and silk films provided for better adherence, proliferation, and differentiation than the electrospun scaffolds and could be used for conjunctival goblet cell expansion for eventual transplantation once undifferentiated and stratified squamous cells are included. Useful polymer scaffold design characteristics have emerged from this study.
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| 36. |
- Imlay, Hannah, et al.
(författare)
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Consensus Definitions of BK Polyomavirus Nephropathy in Renal Transplant Recipients for Clinical Trials
- 2022
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Ingår i: Clinical Infectious Diseases. - : Oxford University Press (OUP). - 1058-4838 .- 1537-6591. ; 75:7, s. 1210-1216
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Tidskriftsartikel (refereegranskat)abstract
- Background BK polyomavirus (BKPyV) infection and BK polyomavirus nephropathy (BKPyVAN) are important causes of allograft dysfunction and premature allograft loss in renal transplant recipients. Results and Discussion Controlled clinical trials to evaluate new agents for prevention and treatment are needed but are hampered by the lack of outcome measures that accurately assess the effect of the intervention, are clinically relevant, and are acceptable from a regulatory perspective. Methods To facilitate consistent end points in clinical trials and to support clinical research and drug development, definitions of BKPyV infection and disease have been developed by the BK Disease Definitions Working Group of the Transplantation Associated Virus Infection Forum with the Forum for Collaborative Research, which consists of scientists, clinicians, regulators, and industry representatives. Conclusions These definitions refine established principles of "proven" BKPyV disease and introduce a "probable" disease category that could be used in clinical trials to prevent or treat BKPyVAN in renal transplant recipients. Standardized BK polyomavirus nephropathy (BKPyVAN) definitions are needed to evaluate therapeutics. We refine established criteria for "proven" BKPyVAN and introduce a "probable disease" category based on allograft dysfunction and plasma DNAemia. Plasma DNAemia thresholds for BKPyVAN are needed.
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| 37. |
- Manzoni, Claudia, et al.
(författare)
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Genome-wide analyses reveal a potential role for the MAPT, MOBP, and APOE loci in sporadic frontotemporal dementia
- 2024
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Ingår i: American Journal of Human Genetics. - 0002-9297. ; 111:7, s. 1316-1329
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Tidskriftsartikel (refereegranskat)abstract
- Frontotemporal dementia (FTD) is the second most common cause of early-onset dementia after Alzheimer disease (AD). Efforts in the field mainly focus on familial forms of disease (fFTDs), while studies of the genetic etiology of sporadic FTD (sFTD) have been less common. In the current work, we analyzed 4,685 sFTD cases and 15,308 controls looking for common genetic determinants for sFTD. We found a cluster of variants at the MAPT (rs199443; p = 2.5 × 10−12, OR = 1.27) and APOE (rs6857; p = 1.31 × 10−12, OR = 1.27) loci and a candidate locus on chromosome 3 (rs1009966; p = 2.41 × 10−8, OR = 1.16) in the intergenic region between RPSA and MOBP, contributing to increased risk for sFTD through effects on expression and/or splicing in brain cortex of functionally relevant in-cis genes at the MAPT and RPSA-MOBP loci. The association with the MAPT (H1c clade) and RPSA-MOBP loci may suggest common genetic pleiotropy across FTD and progressive supranuclear palsy (PSP) (MAPT and RPSA-MOBP loci) and across FTD, AD, Parkinson disease (PD), and cortico-basal degeneration (CBD) (MAPT locus). Our data also suggest population specificity of the risk signals, with MAPT and APOE loci associations mainly driven by Central/Nordic and Mediterranean Europeans, respectively. This study lays the foundations for future work aimed at further characterizing population-specific features of potential FTD-discriminant APOE haplotype(s) and the functional involvement and contribution of the MAPT H1c haplotype and RPSA-MOBP loci to pathogenesis of sporadic forms of FTD in brain cortex.
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| 38. |
- Shraim, M. A., et al.
(författare)
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Features and methods to discriminate between mechanism-based categories of pain experienced in the musculoskeletal system: a Delphi expert consensus study
- 2022
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Ingår i: Pain. - : Ovid Technologies (Wolters Kluwer Health). - 0304-3959 .- 1872-6623. ; 163:9, s. 1812-1828
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Tidskriftsartikel (refereegranskat)abstract
- Classification of musculoskeletal pain based on underlying pain mechanisms (nociceptive, neuropathic, and nociplastic pain) is challenging. In the absence of a gold standard, verification of features that could aid in discrimination between these mechanisms in clinical practice and research depends on expert consensus. This Delphi expert consensus study aimed to: (1) identify features and assessment findings that are unique to a pain mechanism category or shared between no more than 2 categories and (2) develop a ranked list of candidate features that could potentially discriminate between pain mechanisms. A group of international experts were recruited based on their expertise in the field of pain. The Delphi process involved 2 rounds: round 1 assessed expert opinion on features that are unique to a pain mechanism category or shared between 2 (based on a 40% agreement threshold); and round 2 reviewed features that failed to reach consensus, evaluated additional features, and considered wording changes. Forty-nine international experts representing a wide range of disciplines participated. Consensus was reached for 196 of 292 features presented to the panel (clinical examination-134 features, quantitative sensory testing-34, imaging and diagnostic testing-14, and pain-type questionnaires-14). From the 196 features, consensus was reached for 76 features as unique to nociceptive (17), neuropathic (37), or nociplastic (22) pain mechanisms and 120 features as shared between pairs of pain mechanism categories (78 for neuropathic and nociplastic pain). This consensus study generated a list of potential candidate features that are likely to aid in discrimination between types of musculoskeletal pain.
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| 39. |
- Sood, Sanjana, et al.
(författare)
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A novel multi-tissue RNA diagnostic of healthy ageing relates to cognitive health status
- 2015
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Ingår i: Genome Biology. - : Springer Science and Business Media LLC. - 1465-6906 .- 1474-760X. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- Background: Diagnostics of the human ageing process may help predict future healthcare needs or guide preventative measures for tackling diseases of older age. We take a transcriptomics approach to build the first reproducible multi-tissue RNA expression signature by gene-chip profiling tissue from sedentary normal subjects who reached 65 years of age in good health. Results: One hundred and fifty probe-sets form an accurate classifier of young versus older muscle tissue and this healthy ageing RNA classifier performed consistently in independent cohorts of human muscle, skin and brain tissue (n = 594, AUC = 0.83-0.96) and thus represents a biomarker for biological age. Using the Uppsala Longitudinal Study of Adult Men birth-cohort (n = 108) we demonstrate that the RNA classifier is insensitive to confounding lifestyle biomarkers, while greater gene score at age 70 years is independently associated with better renal function at age 82 years and longevity. The gene score is 'up-regulated' in healthy human hippocampus with age, and when applied to blood RNA profiles from two large independent age-matched dementia case-control data sets (n = 717) the healthy controls have significantly greater gene scores than those with cognitive impairment. Alone, or when combined with our previously described prototype Alzheimer disease (AD) RNA 'disease signature', the healthy ageing RNA classifier is diagnostic for AD. Conclusions: We identify a novel and statistically robust multi-tissue RNA signature of human healthy ageing that can act as a diagnostic of future health, using only a peripheral blood sample. This RNA signature has great potential to assist research aimed at finding treatments for and/or management of AD and other ageing-related conditions.
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| 40. |
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| 41. |
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| 42. |
- Chang, Dan, et al.
(författare)
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The evolutionary and phylogeographic history of woolly mammoths : a comprehensive mitogenomic analysis
- 2017
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Near the end of the Pleistocene epoch, populations of the woolly mammoth (Mammuthus primigenius) were distributed across parts of three continents, from western Europe and northern Asia through Beringia to the Atlantic seaboard of North America. Nonetheless, questions about the connectivity and temporal continuity of mammoth populations and species remain unanswered. We use a combination of targeted enrichment and high-throughput sequencing to assemble and interpret a data set of 143 mammoth mitochondrial genomes, sampled from fossils recovered from across their Holarctic range. Our dataset includes 54 previously unpublished mitochondrial genomes and significantly increases the coverage of the Eurasian range of the species. The resulting global phylogeny confirms that the Late Pleistocene mammoth population comprised three distinct mitochondrial lineages that began to diverge ~1.0–2.0 million years ago (Ma). We also find that mammoth mitochondrial lineages were strongly geographically partitioned throughout the Pleistocene. In combination, our genetic results and the pattern of morphological variation in time and space suggest that male-mediated gene flow, rather than large-scale dispersals, was important in the Pleistocene evolutionary history of mammoths.
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| 43. |
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| 44. |
- Hodges, Paul W, et al.
(författare)
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Intra-abdominal pressure increases stiffness of the lumbar spine
- 2005
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Ingår i: Journal of Biomechanics. - Oxford : Elsevier. - 0021-9290 .- 1873-2380. ; 38:9, s. 1873-1880
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Tidskriftsartikel (refereegranskat)abstract
- Intra-abdominal pressure (IAP) increases during many tasks and has been argued to increase stability and stiffness of the spine. Although several studies have shown a relationship between the IAP increase and spinal stability, it has been impossible to determine whether this augmentation of mechanical support for the spine is due to the increase in IAP or the abdominal muscle activity which contributes to it. The present study determined whether spinal stiffness increased when IAP increased without concurrent activity of the abdominal and back extensor muscles. A sustained increase in IAP was evoked by tetanic stimulation of the phrenic nerves either. unilaterally or bilaterally at 20 Hz (for 5 s) via percutaneous electrodes in three subjects. Spinal stiffness was measured as the force required to displace an indentor over the L4 or L2 spinous process with the subjects lying prone. Stiffness was measured as the slope of the regression line fitted to the linear region of the force-displacement curve. Tetanic stimulation of the diaphragm increased IAP by 27-61% of a maximal voluntary pressure increase and increased the stiffness of the spine by 8-31% of resting levels. The increase in spinal stiffness was positively correlated with the size of the IAP increase. IAP increased stiffness at L2 and L4 level. The results of this:study provide evidence that the stiffness of the lumbar spine is increased when IAP is elevated.
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| 45. |
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| 46. |
- Komarova, Lena, et al.
(författare)
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Haro 11 : The Spatially Resolved Lyman Continuum Sources
- 2024
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 967:2
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Tidskriftsartikel (refereegranskat)abstract
- As the nearest confirmed Lyman continuum (LyC) emitter, Haro 11 is an exceptional laboratory for studying LyC escape processes crucial to cosmic reionization. Our new Hubble Space Telescope/Cosmic Origins Spectrograph G130M/1055 observations of its three star-forming knots now reveal that the observed LyC originates in Knots B and C, with 903–912 Å luminosities of 1.9 ± 1.5 × 1040 erg s−1 and 0.9 ± 0.7 × 1040 erg s−1, respectively. We derive local escape fractions fesc,912 = 3.4% ± 2.9% and 5.1% ± 4.3% for Knots B and C, respectively. Our Starburst99 modeling shows dominant populations on the order of ∼1–4 Myr and 1–2 × 107M⊙ in each knot, with the youngest population in Knot B. Thus, the knot with the strongest LyC detection has the highest LyC production. However, LyC escape is likely less efficient in Knot B than in Knot C due to higher neutral gas covering. Our results therefore stress the importance of the intrinsic ionizing luminosity, and not just the escape fraction, for LyC detection. Similarly, the Lyα escape fraction does not consistently correlate with LyC flux, nor do narrow Lyα red peaks. High observed Lyα luminosity and low Lyα peak velocity separation, however, do correlate with higher LyC escape. Another insight comes from the undetected Knot A, which drives the Green Pea properties of Haro 11. Its density-bounded conditions suggest highly anisotropic LyC escape. Finally, both of the LyC-leaking Knots, B and C, host ultraluminous X-ray sources (ULXs). While stars strongly dominate over the ULXs in LyC emission, this intriguing coincidence underscores the importance of unveiling the role of accretors in LyC escape and reionization.
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| 47. |
- Leonard, Jennifer, et al.
(författare)
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Animal DNA in PCR reagents plagues ancient DNA research
- 2007
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Ingår i: Journal of Archaeological Science. - : Elsevier BV. - 0305-4403 .- 1095-9238. ; 34:9, s. 1361-1366
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Tidskriftsartikel (refereegranskat)abstract
- Molecular archaeology brings the tools of molecular biology to bear on fundamental questions in archaeology, anthropology, evolution, and ecology. Ancient DNA research is becoming widespread as evolutionary biologists and archaeologists discover the power of the polymerase chain reaction (PCR) to amplify DNA from ancient plant and animal remains. However, the extraordinary susceptibility of PCR to contamination by extraneous DNA is not widely appreciated. We report the independent observation of DNA from domestic animals in PCR reagents and ancient samples in four separate laboratories. Since PCR conditions used in ancient DNA analyses are extremely sensitive, very low concentrations of contaminating DNA can cause false positives. Previously unidentified animal DNA in reagents can confound ancient DNA research on certain domestic animals, especially cows, pigs, and chickens.
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| 48. |
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| 49. |
- Röijezon, Ulrik, et al.
(författare)
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Deep and superficial cervical muscles respond differently to unstable motor skill tasks
- 2021
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Ingår i: Human Movement Science. - : Elsevier. - 0167-9457 .- 1872-7646. ; 80
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Tidskriftsartikel (refereegranskat)abstract
- Biomechanical modelling and physiological studies suggest that various spinal muscle layers differ in their contribution to spine movement and stiffness. This study aimed to investigate the activation of deep and superficial muscles in stable and unstable task conditions. Nine healthy participants performed a task of controlling a metal ball on a plate fixed to the head in seated position. In unstable tasks, visual feedback was provided by mirrors to move the ball to the centre of the plate by small head movements and maintain the position for 3 s. Task difficulty was adjusted in a stepwise progression of difficulty using five surfaces with materials of decreasing resistance. In the stable condition, the ball was fixed to the plate's centre. EMG was recorded with surface (sternocleidomastoid, anterior scalenes, upper trapezius) and fine-wire electrodes (rectus capitis posterior major, obliquus inferior, multifidus, semispinalis cervicis, splenius capitis). The outcome variable was root mean square (RMS) EMG during the part of the task when the ball was maintained in the centre position. Results revealed greater cervical muscle activity in the unstable than stable conditions (p < 0.001, ηp2 = 0.746). Control of deep and superficial cervical muscles differed (p = 0.003, ηp2 = 0.354). Deep cervical muscle activity was greater with unstable tasks, but did not differ with task difficulty. In contrast, superficial cervical muscle activity increased in a stepwise manner with increasing challenge. These results support the notion that the central nervous system uses different strategies for control of deep versus superficial muscle layers of the cervical spine in association with instability.
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