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Sökning: WFRF:(Lundin B.)

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1.
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2.
  • Singh, B. P., et al. (författare)
  • Experimental access to Transition Distribution Amplitudes with the PANDA experiment at FAIR
  • 2015
  • Ingår i: European Physical Journal A. Hadrons and Nuclei. - : Springer Science and Business Media LLC. - 1434-6001 .- 1434-601X. ; 51:8
  • Tidskriftsartikel (refereegranskat)abstract
    • Baryon-to-meson Transition Distribution Amplitudes (TDAs) encoding valuable new information on hadron structure appear as building blocks in the collinear factorized description for several types of hard exclusive reactions. In this paper, we address the possibility of accessing nucleon-to-pion (pi N) TDAs from (p) over barp -> e(+)e(-)pi(0) reaction with the future PANDA detector at the FAIR facility. At high center-of-mass energy and high invariant mass squared of the lepton pair q(2), the amplitude of the signal channel (p) over barp -> e(+)e(-)pi(0) admits a QCD factorized description in terms of pi N TDAs and nucleon Distribution Amplitudes (DAs) in the forward aid backward kinematic regimes. Assuming the validity of this factorized description, we perform feasibility studies for measuring (p) over barp -> e(+)e(-)pi(0) with the PANDA detector. Detailed simulations on signal reconstruction efficiency as well as on rejection of the most severe background channel, i.e. (p) over barp -> pi(+)pi(-)pi(0) were performed for the center-of-mass energy squared s = 5 GeV2 and s = 10 GeV2, in the kinematic regions 3.0 < q(2) < 4.3 GeV2 and 5 < q(2) < 9 GeV2, respectively, with a neutral pion scattered in the forward or backward cone vertical bar cos theta(pi 0)vertical bar > 0.5 in the proton-antiproton center-of-mass frame. Results of the simulation show that the particle identification capabilities of the PANDA detector will allow to achieve a background rejection factor of 5 . 10(7) (1 . 10(7)) at low (high) q(2) for s = 5 GeV2, and of 1 . 10(8) (6 . 10(6)) at low (high) q(2) for s = 10 GeV2, while keeping the signal reconstruction efficiency at around 40%. At both energies, a clean lepton signal can be reconstructed with the expected statistics corresponding to 2 of integrated luminosity. The cross sections obtained from the simulations are used to show that a test of QCD collinear factorization can be done at the lowest order by measuring scaling laws and angular distributions. The future measurement of the signal channel cross section with PANDA will provide a new test of the perturbative QCD description of a novel class of hard exclusive reactions and will open the possibility of experimentally accessing pi N TDAs.
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3.
  • Erni, W., et al. (författare)
  • Technical design report for the PANDA (AntiProton Annihilations at Darmstadt) Straw Tube Tracker
  • 2013
  • Ingår i: European Physical Journal A. Hadrons and Nuclei. - : Springer Science and Business Media LLC. - 1434-6001 .- 1434-601X. ; 49:2
  • Tidskriftsartikel (refereegranskat)abstract
    • This document describes the technical layout and the expected performance of the Straw Tube Tracker (STT), the main tracking detector of the PANDA target spectrometer. The STT encloses a Micro-Vertex-Detector (MVD) for the inner tracking and is followed in beam direction by a set of GEM stations. The tasks of the STT are the measurement of the particle momentum from the reconstructed trajectory and the measurement of the specific energy loss for a particle identification. Dedicated simulations with full analysis studies of certain proton-antiproton reactions, identified as being benchmark tests for the whole PANDA scientific program, have been performed to test the STT layout and performance. The results are presented, and the time lines to construct the STT are described.
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4.
  • Meech, K. J., et al. (författare)
  • EPOXI: Comet 103P/Hartley 2 Observations from a Worldwide Campaign
  • 2011
  • Ingår i: Astrophysical Journal Letters. - London : IOP. - 2041-8213 .- 2041-8205. ; 734:L1, s. 1-9
  • Tidskriftsartikel (refereegranskat)abstract
    • Earth- and space-based observations provide synergistic information for space mission encounters by providing data over longer timescales, at different wavelengths and using techniques that are impossible with an in situ flyby. We report here such observations in support of the EPOXI spacecraft flyby of comet 103P/Hartley 2. The nucleus is small and dark, and exhibited a very rapidly changing rotation period. Prior to the onset of activity, the period was ~16.4?hr. Starting in 2010 August the period changed from 16.6?hr to near 19?hr in December. With respect to dust composition, most volatiles and carbon and nitrogen isotope ratios, the comet is similar to other Jupiter-family comets. What is unusual is the dominance of CO 2 -driven activity near perihelion, which likely persists out to aphelion. Near perihelion the comet nucleus was surrounded by a large halo of water-ice grains that contributed significantly to the total water production.
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  • Adam, A, et al. (författare)
  • Abstracts from Hydrocephalus 2016.
  • 2017
  • Ingår i: Fluids and Barriers of the CNS. - : Springer Science and Business Media LLC. - 2045-8118. ; 14:Suppl 1
  • Tidskriftsartikel (refereegranskat)
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  • Strandberg, B., et al. (författare)
  • Compton scattering from the deuteron above pion-production threshold
  • 2018
  • Ingår i: Physical Review C. - 2469-9985. ; 98:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The electromagnetic polarizabilities of the nucleon are fundamental nucleon-structure observables that characterize its response to external electromagnetic fields. The neutron polarizabilities can be accessed from Compton-scattering data on light nuclear targets. Recent measurements of the differential cross section for Compton scattering on the deuteron below the pion-production threshold have decreased the uncertainties in the neutron polarizabilities, yet the proton polarizabilities remain known substantially more accurately. As the sensitivity of the cross section to the polarizabilities increases with incident photon energy, measurements above the pion threshold may offer a way for an improved determination of the neutron polarizabilities. In this Rapid Communiciation, the first measurement of the cross section for coherent Compton scattering on the deuteron above the pion-production threshold is presented.
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11.
  • Strandberg, B., et al. (författare)
  • Near-threshold π-photoproduction on the deuteron
  • 2020
  • Ingår i: Physical Review C. - 2469-9985. ; 101:3
  • Tidskriftsartikel (refereegranskat)abstract
    • The first experimental investigation of the near-threshold cross section for incoherent π-photoproduction on the deuteron γd→π-pp is presented. The experimental technique involved detection of the ≈131 MeV γ ray resulting from the radiative capture of photoproduced π-in the target. The total cross section was measured using an unpolarized tagged-photon beam, a liquid-deuterium target, and three very large NaI(Tl) spectrometers. The data are compared to theoretical models that give insight into the elementary reaction γn→π-p and pion-nucleon and nucleon-nucleon final-state interactions.
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12.
  • Wimberger, Sandra, 1987, et al. (författare)
  • Simultaneous inhibition of DNA-PK and Pol ϴ improves integration efficiency and precision of genome editing
  • 2023
  • Ingår i: Nature Communications. ; 14:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Genome editing, specifically CRISPR/Cas9 technology, has revolutionized biomedical research and offers potential cures for genetic diseases. Despite rapid progress, low efficiency of targeted DNA integration and generation of unintended mutations represent major limitations for genome editing applications caused by the interplay with DNA double-strand break repair pathways. To address this, we conduct a large-scale compound library screen to identify targets for enhancing targeted genome insertions. Our study reveals DNA-dependent protein kinase (DNA-PK) as the most effective target to improve CRISPR/Cas9-mediated insertions, confirming previous findings. We extensively characterize AZD7648, a selective DNA-PK inhibitor, and find it to significantly enhance precise gene editing. We further improve integration efficiency and precision by inhibiting DNA polymerase theta (Pol ϴ). The combined treatment, named 2iHDR, boosts templated insertions to 80% efficiency with minimal unintended insertions and deletions. Notably, 2iHDR also reduces off-target effects of Cas9, greatly enhancing the fidelity and performance of CRISPR/Cas9 gene editing. Low efficiency of target DNA integration remains a challenge in genome engineering. Here the authors perform large-scale compound library and genetic screens to identify targets that enhance gene editing: they see that combined DNA-PK and Pol ϴ inhibition with potent compounds increases editing efficiency and precision.
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13.
  • Berthomier, M., et al. (författare)
  • Alfven : magnetosphere-ionosphere connection explorers
  • 2012
  • Ingår i: Experimental astronomy. - Dordrecht : Springer. - 0922-6435 .- 1572-9508. ; 33:2-3, s. 445-489
  • Tidskriftsartikel (refereegranskat)abstract
    • The aurorae are dynamic, luminous displays that grace the night skies of Earth's high latitude regions. The solar wind emanating from the Sun is their ultimate energy source, but the chain of plasma physical processes leading to auroral displays is complex. The special conditions at the interface between the solar wind-driven magnetosphere and the ionospheric environment at the top of Earth's atmosphere play a central role. In this Auroral Acceleration Region (AAR) persistent electric fields directed along the magnetic field accelerate magnetospheric electrons to the high energies needed to excite luminosity when they hit the atmosphere. The "ideal magnetohydrodynamics" description of space plasmas which is useful in much of the magnetosphere cannot be used to understand the AAR. The AAR has been studied by a small number of single spacecraft missions which revealed an environment rich in wave-particle interactions, plasma turbulence, and nonlinear acceleration processes, acting on a variety of spatio-temporal scales. The pioneering 4-spacecraft Cluster magnetospheric research mission is now fortuitously visiting the AAR, but its particle instruments are too slow to allow resolve many of the key plasma physics phenomena. The Alfv,n concept is designed specifically to take the next step in studying the aurora, by making the crucial high-time resolution, multi-scale measurements in the AAR, needed to address the key science questions of auroral plasma physics. The new knowledge that the mission will produce will find application in studies of the Sun, the processes that accelerate the solar wind and that produce aurora on other planets.
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  • Bhuiyan, Taufiqur Rahman, 1974, et al. (författare)
  • Cholera caused by Vibrio cholerae O1 induces T-cell responses in the circulation.
  • 2009
  • Ingår i: Infection and immunity. - 1098-5522. ; 77:5, s. 1888-93
  • Tidskriftsartikel (refereegranskat)abstract
    • Considerable effort is being made to understand the acute and memory antibody responses in natural cholera infection, while rather less is known about the roles of cellular immune responses involving T and B lymphocytes. We studied responses in adult patients hospitalized with cholera caused by Vibrio cholerae O1. Peripheral blood mononuclear cells from patients (n = 15) were analyzed by flow cytometry after stimulation with V. cholerae O1 membrane protein (MP) or toxin-coregulated pilus antigen (TcpA). The gamma interferon (IFN-gamma) and interleukin-13 (IL-13) responses in stimulated-lymphocyte supernatants were studied. The responses were compared with those of healthy controls (n = 10). Patients responded with increased frequencies of gut-homing CD4(+) T cells (CD4(+) beta7(+)), gut-homing CD8(+) T cells (CD8(+) beta7(+)), and gut-homing B cells (CD19(+) beta7(+)) at the early and/or late convalescent stages compared to the acute stage. After stimulation with MP or TcpA, proliferation of CD4(+) and CD8(+) T cells was increased at the acute stage and/or early convalescent stage compared to healthy controls. Increased IL-13 and IFN-gamma responses were observed after antigenic stimulation at the acute and convalescent stages compared to healthy controls. Thus, increases in the levels of gut-homing T and B cells, as well as involvement of CD8 and CD4 Th1-mediated (IFN-gamma) and CD4 Th2-mediated (IL-13) cytokine responses, take place in acute dehydrating disease caused by V. cholerae O1. Further studies are needed to determine if such responses are also stimulated after immunization with oral cholera vaccines and if these responses play a role in protection following exposure to cholera.
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  • Brudvik, G., et al. (författare)
  • Measurement of d(γ,p) reaction cross sections and asymmetry with linearly polarized coherent bremsstrahlung beam
  • 2018
  • Ingår i: Problems of Atomic Science and Technology. - 1682-9344. ; 115:3, s. 132-139
  • Tidskriftsartikel (refereegranskat)abstract
    • On the base of reaction of deuteron photo-disintegration it was studied possibility of the simultaneous measuring of cross sections and asymmetry of the (γ,p) reactions at the using of the coherent polarized photon beam. Measurements were performed for the proton emission angle 90°. The cross sections well agree with the literary data, obtained on the bremsstrahlung photon beam in the range of energies 45…80 MeV.
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  • Burdeinyi, D. D., et al. (författare)
  • Cross section asymmetry of the 12C(γ; p0)11B and 12C(γ; p1)11B reactions at photon energies 40...55 MeV
  • 2019
  • Ingår i: Problems of Atomic Science and Technology. - 1682-9344. ; 121:3, s. 26-37
  • Tidskriftsartikel (refereegranskat)abstract
    • The asymmetry of the cross section of the 12C(γ; p0)11B and 12C(γ; p1)11B reactions has been measured in the energy range 40...55MeV using linearly polarized tagged photons of the MAX-lab facility. The asymmetry of the process 12C(γ; p0)11B is Σ ∼ 0:85, that implies one-particle reaction mechanism. The asymmetry of the reaction 12C(γ; p1)11B is smaller, Σ ∼ 0.6...0.7, that may be due to the stronger relative contribution of the 2h − 1p mechanism to the dominant one-particle reaction mechanism.
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17.
  • Ganenko, V. B., et al. (författare)
  • Mechanisms of 200 MeV electron radiation in diamond crystal in the axial orientation
  • 2018
  • Ingår i: Nuclear Instruments and Methods in Physics Research, Section B: Beam Interactions with Materials and Atoms. - : Elsevier BV. - 0168-583X. ; 424, s. 17-25
  • Tidskriftsartikel (refereegranskat)abstract
    • The γ-radiation by electrons with the energy of ∼200 MeV in a 100μm-thick diamond crystal has been measured at the MAX-lab experimental facility, when the electrons are incident on the crystal along the 〈100〉 axis. In this case, the intensity of the -radiation with the energy ∼1–2 MeV is approximately 16 times higher than that in amorphous matter of the same thickness. Theoretical calculations based on the quasi-classical QED approximation are in good agreement with the experimental data. The analysis of the radiation mechanisms has shown that the main contribution to the radiation intensity resulted from electrons, moving in the above-barrier regime and at small angles to the crystal axis.
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18.
  • HULTQVIST, B, et al. (författare)
  • ON THE UPWARD ACCELERATION OF ELECTRONS AND IONS BY LOW-FREQUENCY ELECTRIC-FIELD FLUCTUATIONS OBSERVED BY VIKING
  • 1991
  • Ingår i: JOURNAL OF GEOPHYSICAL RESEARCH-SPACE PHYSICS. - : American Geophysical Union (AGU). - 0148-0227. ; 96:A7, s. 11609-11615
  • Tidskriftsartikel (refereegranskat)abstract
    • The dependence of the generation of upward electron beams in the to side ionosphere on the amplitude of the slow electric field fluctuations and the magnitude of the dc potential difference in the acceleration region is found to agree with the model involving the fluctuating electric field component presented in 1988 by Hultqvist. The ratio between the amplitude of the electric field fluctuations, E(f), determined by the dipole electric field experiment, and the dc acceleration voltage V(acc), given by the energy of the upflowing ion beam, is much higher on average for satellite spins showing an upward electron beam than for the spins without. It is also shown that low plasma density favors the generation of electron beams.
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  • Ameur, Adam, et al. (författare)
  • SweGen : a whole-genome data resource of genetic variability in a cross-section of the Swedish population
  • 2017
  • Ingår i: European Journal of Human Genetics. - : NATURE PUBLISHING GROUP. - 1018-4813 .- 1476-5438. ; 25:11, s. 1253-1260
  • Tidskriftsartikel (refereegranskat)abstract
    • Here we describe the SweGen data set, a comprehensive map of genetic variation in the Swedish population. These data represent a basic resource for clinical genetics laboratories as well as for sequencing-based association studies by providing information on genetic variant frequencies in a cohort that is well matched to national patient cohorts. To select samples for this study, we first examined the genetic structure of the Swedish population using high-density SNP-array data from a nation-wide cohort of over 10 000 Swedish-born individuals included in the Swedish Twin Registry. A total of 1000 individuals, reflecting a cross-section of the population and capturing the main genetic structure, were selected for whole-genome sequencing. Analysis pipelines were developed for automated alignment, variant calling and quality control of the sequencing data. This resulted in a genome-wide collection of aggregated variant frequencies in the Swedish population that we have made available to the scientific community through the website https://swefreq.nbis.se. A total of 29.2 million single-nucleotide variants and 3.8 million indels were detected in the 1000 samples, with 9.9 million of these variants not present in current databases. Each sample contributed with an average of 7199 individual-specific variants. In addition, an average of 8645 larger structural variants (SVs) were detected per individual, and we demonstrate that the population frequencies of these SVs can be used for efficient filtering analyses. Finally, our results show that the genetic diversity within Sweden is substantial compared with the diversity among continental European populations, underscoring the relevance of establishing a local reference data set.
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24.
  • Brudvik, Jason, et al. (författare)
  • Improvement of energy resolution of ΔE-E CsI/SSD- telescope at measurement of (γ,p)-Reactions using strip information of SSD
  • 2016
  • Ingår i: Problems of Atomic Science and Technology. - 1682-9344. ; 103:3, s. 111-115
  • Tidskriftsartikel (refereegranskat)abstract
    • Information on the triggered strips of silicon strip detectors of a MAX-lab ΔE-E CsI/SSD-telescope was used to determination the angular range of emitted reaction particles. It allowed an improvement in the energy resolution of the telescope by decreasing the kinematical broadening of the missing energy spectra of12C(γ,p)11B reaction, and enabling more accurate separation of exited states of residual nucleus.
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  • Carr, C., et al. (författare)
  • RPC : The rosetta plasma consortium
  • 2007
  • Ingår i: Space Science Reviews. - : Springer Science and Business Media LLC. - 0038-6308 .- 1572-9672. ; 128:1-4, s. 629-647
  • Forskningsöversikt (refereegranskat)abstract
    • The Rosetta Plasma Consortium (RPC) will make in-situ measurements of the plasma enviromnent of comet 67P/Churyumov-Gerasimenko. The consortium will provide the complementary data sets necessary for an understanding of the plasma processes in the inner coma, and the structure and evolution of the coma with the increasing cometary activity. Five sensors have been selected to achieve this: the Ion and Electron Sensor (IES), the Ion Composition Analyser (ICA), the Langmuir Probe (LAP), the Mutual Impedance Probe (MIP) and the Magnetometer (MAG). The sensors interface to the spacecraft through the Plasma Interface Unit (PIU). The consortium approach allows for scientific, technical and operational coordination, and makes Optimum use of the available mass and power resources.
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  • Dobrydnjov, Igor, et al. (författare)
  • Improved analgesia with clonidine when added to local anesthetic during combined spinal-epidural anesthesia for hip arthroplasty : a double-blind, randomized and placebo-controlled study
  • 2005
  • Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 49:4, s. 538-545
  • Tidskriftsartikel (refereegranskat)abstract
    • Background:  The perioperative effects of intrathecal and epidural clonidine combined with local anesthetic were evaluated in 60 patients undergoing hip arthroplasty.Methods:  This was a double-blinded study and the patients were randomized into three groups, with 20 patients in each group. All patients received spinal anesthesia with 17.5 mg of plain bupivacaine with 15 µg of clonidine (Group BC-RC) or without clonidine (Groups B-R and B-RC). Postoperatively, epidural infusion was administered in the following way: Group B-R – ropivacaine 4 mg h−1; Groups B-RC and BC-RC: ropivacaine 4 mg h−1 and clonidine 40 µg h−1. Sensory block was assessed with light touch, pinprick, transcutaneous electrical stimulation at T12 and L2 dermatomes, and perception of thermal stimuli.Results:  The maximal upper level of sensory block measured by pin-prick (T6–T7) did not differ between the groups while the partial sensory block for cold and warmth were increased two dermatomes above pin-prick level in the group with intrathecal clonidine compared to the other two groups (P < 0.05). Duration of anesthesia, analgesia and motor block were longer in Group BC-RC compared to Groups B-R and B-RC (P < 0.02). Postoperatively, both VAS score on movement and PCA-morphine consumption were higher in Group B-R than in Groups B-RC and BC-RC (P < 0.01). The arterial pressure and heart rate in Groups B-RC and BC-RC were significantly lower than in Group B-R at 10–24 and 15–24 h, respectively, after spinal injection.Conclusion:  Low-dose intrathecal clonidine provided a better quality of anesthesia and longer-lasting analgesia. Epidural clonidine-ropivacaine infusion resulted in improved postoperative analgesia but was associated with a moderate decrease in blood pressure.
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29.
  • Fissum, K., et al. (författare)
  • Radiation Spectra of 200 MeV Electrons in Diamond and Silicon Crystals at Axial and Planar Orientations
  • 2010
  • Ingår i: Charged and Neutral Particles Channeling Phenomena : Proceedings of the 51st Workshop of the INFN ELOISATRON Project , Erice, Italy , 25 October – 1 November 2008 - Proceedings of the 51st Workshop of the INFN ELOISATRON Project , Erice, Italy , 25 October – 1 November 2008. - : WORLD SCIENTIFIC. ; , s. 331-334
  • Konferensbidrag (refereegranskat)abstract
    • Results of the first experiment on studying the radiation spectra of electrons with energy 192 7 MeV in diamond and silicon crystals at axial and plane orientation performed at the MAX-lab facility were presented. At these orientation the particle's motion can be both regular, when axial and planar channeling are possible, and chaotic, when the coherent electron interaction with single strings reveals itself. Essential increase of the radiation intensity at low photon energy region, less than 15 MeV, is observed.
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  • Giang, Tony, et al. (författare)
  • Outflowing protons and heavy ions as a source for the sub-keV ringcurrent
  • 2009
  • Ingår i: Annales Geophysicae. - : Copernicus GmbH. - 0992-7689 .- 1432-0576. ; 27:2, s. 839-849
  • Tidskriftsartikel (refereegranskat)abstract
    • Data from the Cluster CIS instrument have been used for studying proton and heavy ion (O+ and He+ ) char- acteristics of the sub-keV ring current. Thirteen events with dispersed heavy ions (O+ and He+ ) were identified out of two years (2001 and 2002) of Cluster data. Allevents took place during rather geomagnetically quiet periods. Three of those events have been investigated in detail: 21 August 2001, 26 November 2001 and 20 February 2002. These events were chosen from varying magnetic local times (MLT), and they showed different characteristics. In this article, we discuss the potential source for sub-keV ring current ions. We show that: (1) outflows of terrestrialsub-keV ions are supplied to the ring current also during quiet geomagnetic conditions; (2) the composition of the out-flow implies an origin that covers an altitude interval from the low-altitude ionosphere to the plasmasphere, and (3) terrestrial ions are moving upward along magnetic field lines, at times forming narrow collimated beams, but  frequently also as broad beams. Over time, the ion beams are expected to gradually become isotropised as a result of wave-particleinteraction, eventually taking the form of isotropic drifting sub-keV ion signatures. We argue that the sub-keV energy-time dispersed signatures originate from field-aligned terrestrial ion energising and outflow, which may occur at all local times and persist also during quiet times.
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35.
  • Hicks, J, et al. (författare)
  • Novel patterns of genome rearrangement and their association with survival in breast cancer
  • 2006
  • Ingår i: Genome research. - : Cold Spring Harbor Laboratory. - 1088-9051. ; 16:12, s. 1465-1479
  • Tidskriftsartikel (refereegranskat)abstract
    • Representational Oligonucleotide Microarray Analysis (ROMA) detects genomic amplifications and deletions with boundaries defined at a resolution of ∼50 kb. We have used this technique to examine 243 breast tumors from two separate studies for which detailed clinical data were available. The very high resolution of this technology has enabled us to identify three characteristic patterns of genomic copy number variation in diploid tumors and to measure correlations with patient survival. One of these patterns is characterized by multiple closely spaced amplicons, or “firestorms,” limited to single chromosome arms. These multiple amplifications are highly correlated with aggressive disease and poor survival even when the rest of the genome is relatively quiet. Analysis of a selected subset of clinical material suggests that a simple genomic calculation, based on the number and proximity of genomic alterations, correlates with life-table estimates of the probability of overall survival in patients with primary breast cancer. Based on this sample, we generate the working hypothesis that copy number profiling might provide information useful in making clinical decisions, especially regarding the use or not of systemic therapies (hormonal therapy, chemotherapy), in the management of operable primary breast cancer with ostensibly good prognosis, for example, small, node-negative, hormone-receptor-positive diploid cases.
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38.
  • Jungebluth, P, et al. (författare)
  • Retraction Statement
  • 2023
  • Ingår i: Respiration. - : S. Karger AG. - 1423-0356 .- 0025-7931. ; 102:5, s. 402-404
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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  • Li, S. Y., et al. (författare)
  • Universal toxin-based selection for precise genome engineering in human cells
  • 2021
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Prokaryotic restriction enzymes, recombinases and Cas proteins are powerful DNA engineering and genome editing tools. However, in many primary cell types, the efficiency of genome editing remains low, impeding the development of gene- and cell-based therapeutic applications. A safe strategy for robust and efficient enrichment of precisely genetically engineered cells is urgently required. Here, we screen for mutations in the receptor for Diphtheria Toxin (DT) which protect human cells from DT. Selection for cells with an edited DT receptor variant enriches for simultaneously introduced, precisely targeted gene modifications at a second independent locus, such as nucleotide substitutions and DNA insertions. Our method enables the rapid generation of a homogenous cell population with bi-allelic integration of a DNA cassette at the selection locus, without clonal isolation. Toxin-based selection works in both cancer-transformed and non-transformed cells, including human induced pluripotent stem cells and human primary T-lymphocytes, as well as it is applicable also in vivo, in mice with humanized liver. This work represents a flexible, precise, and efficient selection strategy to engineer cells using CRISPR-Cas and base editing systems. Genome engineering in cell lines or human stem cells often has poor efficiency, limiting the development of research and therapeutic applications. Here, the authors use a toxin-based selection system for precise bi-allelic engineering in cells and in vivo.
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  • Nookaew, Intawat, 1977, et al. (författare)
  • Transcriptome signatures in Helicobacter pylori-infected mucosa identifies acidic mammalian chitinase loss as a corpus atrophy marker
  • 2013
  • Ingår i: BMC Medical Genomics. - : Springer Science and Business Media LLC. - 1755-8794. ; 6:41
  • Tidskriftsartikel (refereegranskat)abstract
    • The majority of gastric cancer cases are believed to be caused by chronic infection with the bacterium Helicobacter pylori, and atrophic corpus gastritis is a predisposing condition to gastric cancer development. We aimed to increase understanding of the molecular details of atrophy by performing a global transcriptome analysis of stomach tissue. Biopsies from patients with different stages of H. pylori infection were taken from both the antrum and corpus mucosa and analyzed on microarrays. The stages included patients without current H. pylori infection, H. pylori-infected without corpus atrophy and patients with current or past H. pylori-infection with corpus-predominant atrophic gastritis. Using clustering and integrated analysis, we found firm evidence for antralization of the corpus mucosa of atrophy patients. This antralization harbored gain of gastrin expression, as well as loss of expression of corpus-related genes, such as genes associated with acid production, energy metabolism and blood clotting. The analyses provided detailed molecular evidence for simultaneous intestinal metaplasia (IM) and spasmolytic polypeptide expressing metaplasia (SPEM) in atrophic corpus tissue. Finally, acidic mammalian chitinase, a chitin-degrading enzyme produced by chief cells, was shown to be strongly down-regulated in corpus atrophy. Transcriptome analysis revealed several gene groups which are related to development of corpus atrophy, some of which were increased also in H. pylori-infected non-atrophic patients. Furthermore, loss of acidic chitinase expression is a promising marker for corpus atrophy.
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  • Sebat, J, et al. (författare)
  • Large-scale copy number polymorphism in the human genome
  • 2004
  • Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 305:5683, s. 525-528
  • Tidskriftsartikel (refereegranskat)abstract
    • The extent to which large duplications and deletions contribute to human genetic variation and diversity is unknown. Here, we show that large-scale copy number polymorphisms (CNPs) (about 100 kilobases and greater) contribute substantially to genomic variation between normal humans. Representational oligonucleotide microarray analysis of 20 individuals revealed a total of 221 copy number differences representing 76 unique CNPs. On average, individuals differed by 11 CNPs, and the average length of a CNP interval was 465 kilobases. We observed copy number variation of 70 different genes within CNP intervals, including genes involved in neurological function, regulation of cell growth, regulation of metabolism, and several genes known to be associated with disease.
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