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1.
  • Abbasi, R., et al. (author)
  • The IceCube data acquisition system : Signal capture, digitization, and timestamping
  • 2009
  • In: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 601:3, s. 294-316
  • Journal article (peer-reviewed)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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2.
  • Ahrens, J., et al. (author)
  • Initial results from AMANDA
  • 2001
  • In: 21st Rencontres de Moriond Workshop on Very High-Energy Phenomena in the Universe.
  • Conference paper (peer-reviewed)
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3.
  • Ahrens, J., et al. (author)
  • Limits to the muon flux from WIMP annihilation in the center of the Earth with the AMANDA detector
  • 2002
  • In: Physical Review D. - : American Physical Society. - 1550-7998 .- 1550-2368. ; 66:3, s. 032006-
  • Journal article (peer-reviewed)abstract
    • A search for nearly vertical up-going muon-neutrinos from neutralino annihilations in the center of the Earth has been performed with the AMANDA-B10 neutrino detector. The data collected in 130.1 days of live time in 1997, ∼10 9 events, have been analyzed for this search. No excess over the expected atmospheric neutrino background has been observed. An upper limit at 90% confidence level has been obtained on the annihilation rate of neutralinos in the center of the Earth, as well as the corresponding muon flux limit, both as a function of the neutralino mass in the range 100 GeV-5000 GeV. © 2002 The American Physical Society.
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4.
  • Andrés, E., et al. (author)
  • Observation of high-energy neutrinos using Čerenkov detectors embedded deep in Antarctic ice
  • 2001
  • In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 410:6827, s. 441-443
  • Journal article (peer-reviewed)abstract
    • Neutrinos are elementary particles that carry no electric charge and have little mass. As they interact only weakly with other particles, they can penetrate enormous amounts of matter, and therefore have the potential to directly convey astrophysical information from the edge of the Universe and from deep inside the most cataclysmic high-energy regions. The neutrino's great penetrating power, however, also makes this particle difficult to detect. Underground detectors have observed low-energy neutrinos from the Sun and a nearby supernova2, as well as neutrinos generated in the Earth's atmosphere. But the very low fluxes of high-energy neutrinos from cosmic sources can be observed only by much larger, expandable detectors in, for example, deep water3,4 or ice5. Here we report the detection of upwardly propagating atmospheric neutrinos by the ice-based Antarctic muon and neutrino detector array (AMANDA). These results establish a technology with which to build a kilometre-scale neutrino observatory necessary for astrophysical observations1.
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5.
  • Andrés, E., et al. (author)
  • Recent results from AMANDA
  • 2001
  • In: International Journal of Modern Physics A. - 0217-751X .- 1793-656X. ; 16:1C, s. 1013-1015
  • Journal article (peer-reviewed)abstract
    • We present results based on data taken in 1997 with the 302-PMT Antarctic Muon and Neutrino Detector Array-B10 ("AMANDA-B10") array. Atmospheric neutrinos created in the northern hemisphere are observed indirectly through their charged current interactions which produce relativistic, Cherenkov-light-emitting upgoing muons in the South Pole ice cap. The reconstructed angular distribution of these events is in good agreement with expectation and demonstrates the viability of this ice-based device as a neutrino telescope.
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6.
  • Andres, E., et al. (author)
  • Selected recent results from AMANDA
  • 2001
  • In: ICHEP 2000. Proceedings of the 30th International Conference on High Energy Physics. - : World Scientific. ; , s. 965-968
  • Conference paper (peer-reviewed)abstract
    • We present a selection of results based on data taken in 1997 with the 302-PMT Antarctic Muon and Neutrino Detector Array-B10 ("AMANDA-B10") array. Atmospheric neutrinos created in the northern hemisphere are observed indirectly through their charged current interactions which produce relativistic, Cherenkov-light-emitting upgoing muons in the South Pole ice cap. The reconstructed angular distribution of these events is in good agreement with expectation and demonstrates the viability of this ice-based device as a neutrino telescope. Studies of nearly vertical upgoing muons limit the available parameter space for WIMP dark matter under the assumption that WIMPS are trapped in the earth's gravitational potential well and annihilate with one another near the earth's center.
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7.
  • Bai, X., et al. (author)
  • Status of the Neutrino Telescope AMANDA : Monopoles and WIMPS
  • 2001
  • In: Dark Matter in Astro- and Particle Physics. - Berlin, Heidelberg : Springer. - 9783642626081 ; , s. 699-706
  • Conference paper (peer-reviewed)abstract
    • The neutrino telescope AMANDA has been set up at the geographical South Pole as first step to a neutrino telescope of the scale of one cubic kilometer, which is the canonical size for a detector sensitive to neutrinos from Active Galactic Nuclei (AGN), Gamma Ray Bursts (GRB) and Topological Defects (TD). The location and depth in which the detector is installed is given by the requirement to detect neutrinos by the Cherenkov light produced by their reaction products and to keep the background due to atmospheric muons as small as possible. However, a detector optimized for this purpose is also capable to detect the bright Cherenkov light from relativistic Monopoles and neutrino signals from regions with high gravitational potential, where WIMPS are accumulated and possibly annihilate. Both hypothetical particles might contribute to the amount of dark matter. Therefore here a report about the status of the experiment (autumn 2000) and about the status of the search for these particles with the AMANDA B10 sub-detector is given.
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8.
  • Karle, A., et al. (author)
  • Observation of high energy atmospheric neutrinos with AMANDA
  • 2000
  • In: AIP Conference Proceedings. - : American Institute of Physics (AIP). ; , s. 823-827
  • Conference paper (peer-reviewed)abstract
    • In 1997 the Antarctic Muon and Neutrino Detector Array (AMANDA) started operating with 10 strings. In an analysis of data taken during the first year of operation 188 atmospheric neutrino candidates were found. Their zenith angle distribution agrees with expectations based on Monte Carlo simulations. A preliminary upper limit is given on a diffuse flux of high energy neutrinos of astrophysical origin.
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9.
  • Andres, E., et al. (author)
  • Results from the AMANDA high energy neutrino detector
  • 2000
  • In: Nuclear physics B, Proceedings supplements. - : Elsevier. - 0920-5632 .- 1873-3832. ; 91:1-3, s. 423-430
  • Journal article (peer-reviewed)abstract
    • This paper briefly summarizes the search for astronomical sources of high-energy neutrinos using the AMANDA-B10 detector. The complete data set from 1997 was analyzed. For Eμ > 10 TeV, the detector exceeds 10,000 m2 in effective area between declinations of 25 and 90 degrees. Neutrinos generated in the atmosphere by cosmic ray interactions were used to verify the overall sensitivity of the detector. The absolute pointing accuracy and angular resolution has been confirmed by the analysis of coincident events between the SPASE air shower array and the AMANDA detector. Preliminary flux limits from point source candidates are presented. For declinations larger than +45 degrees, our results compare favorably to existing limits for sources in the Southern sky. We also present the current status of the searches for high energy neutrino emission from diffusely distributed sources, GRBs, and WIMPs from the center of the earth.
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10.
  • Edsjö, Joakim, et al. (author)
  • WIMP searches with AMANDA-B10
  • 2001
  • In: The Identification Of Dark Matter. - : World Scientific. - 9789810246020 ; , s. 499-505
  • Book chapter (other academic/artistic)
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11.
  • Andres, E., et al. (author)
  • AMANDA : Status, results and future
  • 1999
  • In: Proceedings, 8th International Workshop, Venice, Italy, February 23-26, 1999. Vol. 1, 2. ; , s. 63-79
  • Conference paper (peer-reviewed)abstract
    • We review the status of the AMANDA neutrino telescope. We present resultsobtained from the four-string prototype array AMANDA-B4 and describe themethods of track reconstruction and neutrino event separation. We give also firstresults of the analysis of the 10-string detector AMANDA-B10, in particular onatmospheric neutrinos and the search for magnetic monopoles. We sketch thefuture schedule on the way to a cube kilometer telescope at the South Pole,ICECUBE.
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12.
  • Wischnewski, R., et al. (author)
  • The AMANDA neutrino detector : Status report
  • 2000
  • In: Nuclear physics B, Proceedings supplements. - 0920-5632 .- 1873-3832. ; 85:1-3, s. 141-145
  • Journal article (peer-reviewed)abstract
    • The first stage of the AMANDA High Energy Neutrino Detector at the South Pole, the 302 PMT array AMANDA-B10, is taking data since 1997. We describe results on atmospheric neutrinos, limits on indirect WIMP detection, seasonal muon flux variation, relativistic monopole flux limits, a search for gravitational collapse neutrinos, and a depth scan of the optical ice properties. The next stage 19-string detector AMANDA-II with ∼650 PMTs will be completed in spring 2000.
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16.
  • McCarthy, Randy J., et al. (author)
  • Registered Replication Report on Srull and Wyer (1979)
  • 2018
  • In: Advances in Methods and Practices in Psychological Science. - : SAGE Publications Inc. - 2515-2459 .- 2515-2467. ; 1:3, s. 321-336
  • Journal article (peer-reviewed)abstract
    • Srull and Wyer (1979) demonstrated that exposing participants to more hostility-related stimuli caused them subsequently to interpret ambiguous behaviors as more hostile. In their Experiment 1, participants descrambled sets of words to form sentences. In one condition, 80% of the descrambled sentences described hostile behaviors, and in another condition, 20% described hostile behaviors. Following the descrambling task, all participants read a vignette about a man named Donald who behaved in an ambiguously hostile manner and then rated him on a set of personality traits. Next, participants rated the hostility of various ambiguously hostile behaviors (all ratings on scales from 0 to 10). Participants who descrambled mostly hostile sentences rated Donald and the ambiguous behaviors as approximately 3 scale points more hostile than did those who descrambled mostly neutral sentences. This Registered Replication Report describes the results of 26 independent replications (N = 7,373 in the total sample; k = 22 labs and N = 5,610 in the primary analyses) of Srull and Wyer?s Experiment 1, each of which followed a preregistered and vetted protocol. A random-effects meta-analysis showed that the protagonist was seen as 0.08 scale points more hostile when participants were primed with 80% hostile sentences than when they were primed with 20% hostile sentences (95% confidence interval, CI = [0.004, 0.16]). The ambiguously hostile behaviors were seen as 0.08 points less hostile when participants were primed with 80% hostile sentences than when they were primed with 20% hostile sentences (95% CI = [?0.18, 0.01]). Although the confidence interval for one outcome excluded zero and the observed effect was in the predicted direction, these results suggest that the currently used methods do not produce an assimilative priming effect that is practically and routinely detectable.
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17.
  • Muus, Christoph, et al. (author)
  • Single-cell meta-analysis of SARS-CoV-2 entry genes across tissues and demographics
  • 2021
  • In: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 27:3, s. 546-559
  • Journal article (peer-reviewed)abstract
    • Angiotensin-converting enzyme 2 (ACE2) and accessory proteases (TMPRSS2 and CTSL) are needed for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cellular entry, and their expression may shed light on viral tropism and impact across the body. We assessed the cell-type-specific expression of ACE2, TMPRSS2 and CTSL across 107 single-cell RNA-sequencing studies from different tissues. ACE2, TMPRSS2 and CTSL are coexpressed in specific subsets of respiratory epithelial cells in the nasal passages, airways and alveoli, and in cells from other organs associated with coronavirus disease 2019 (COVID-19) transmission or pathology. We performed a meta-analysis of 31 lung single-cell RNA-sequencing studies with 1,320,896 cells from 377 nasal, airway and lung parenchyma samples from 228 individuals. This revealed cell-type-specific associations of age, sex and smoking with expression levels of ACE2, TMPRSS2 and CTSL. Expression of entry factors increased with age and in males, including in airway secretory cells and alveolar type 2 cells. Expression programs shared by ACE2(+)TMPRSS2(+) cells in nasal, lung and gut tissues included genes that may mediate viral entry, key immune functions and epithelial-macrophage cross-talk, such as genes involved in the interleukin-6, interleukin-1, tumor necrosis factor and complement pathways. Cell-type-specific expression patterns may contribute to the pathogenesis of COVID-19, and our work highlights putative molecular pathways for therapeutic intervention. An integrated analysis of over 100 single-cell and single-nucleus transcriptomics studies illustrates severe acute respiratory syndrome coronavirus 2 viral entry gene coexpression patterns across different human tissues, and shows association of age, smoking status and sex with viral entry gene expression in respiratory cell populations.
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18.
  • Jonsson, Frida, et al. (author)
  • Mutations in Collagen, Type XVII, Alpha 1 (COL17A1) Cause Epithelial Recurrent Erosion Dystrophy (ERED)
  • 2015
  • In: Human Mutation. - : John Wiley & Sons. - 1059-7794 .- 1098-1004. ; 36:4, s. 463-473
  • Journal article (peer-reviewed)abstract
    • Corneal dystrophies are a clinically and genetically heterogeneous group of inherited disorders that bilaterally affect corneal transparency. They are defined according to the corneal layer affected and by their genetic cause. In this study, we identified a dominantly inherited epithelial recurrent erosion dystrophy (ERED)-like disease that is common in northern Sweden. Whole-exome sequencing resulted in the identification of a novel mutation, c.2816C>T, p.T939I, in the COL17A1 gene, which encodes collagen type XVII alpha 1. The variant segregated with disease in a genealogically expanded pedigree dating back 200 years. We also investigated a unique COL17A1 synonymous variant, c.3156C>T, identified in a previously reported unrelated dominant ERED-like family linked to a locus on chromosome 10q23-q24 encompassing COL17A1. We show that this variant introduces a cryptic donor site resulting in aberrant pre-mRNA splicing and is highly likely to be pathogenic. Bi-allelic COL17A1 mutations have previously been associated with a recessive skin disorder, junctional epidermolysis bullosa, with recurrent corneal erosions being reported in some cases. Our findings implicate presumed gain-of-function COL17A1 mutations causing dominantly inherited ERED and improve understanding of the underlying pathology.
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19.
  • Verschuere, Bruno, et al. (author)
  • Registered Replication Report on Mazar, Amir, and Ariely (2008)
  • 2018
  • In: Advances in Methods and Practices in Psychological Science. - : SAGE Publications. - 2515-2459 .- 2515-2467. ; 1:3, s. 299-317
  • Journal article (peer-reviewed)abstract
    • The self-concept maintenance theory holds that many people will cheat in order to maximize self-profit, but only to the extent that they can do so while maintaining a positive self-concept. Mazar, Amir, and Ariely (2008, Experiment 1) gave participants an opportunity and incentive to cheat on a problem-solving task. Prior to that task, participants either recalled the Ten Commandments (a moral reminder) or recalled 10 books they had read in high school (a neutral task). Results were consistent with the self-concept maintenance theory. When given the opportunity to cheat, participants given the moral-reminder priming task reported solving 1.45 fewer matrices than did those given a neutral prime (Cohen’s d = 0.48); moral reminders reduced cheating. Mazar et al.’s article is among the most cited in deception research, but their Experiment 1 has not been replicated directly. This Registered Replication Report describes the aggregated result of 25 direct replications (total N = 5,786), all of which followed the same preregistered protocol. In the primary meta-analysis (19 replications, total n = 4,674), participants who were given an opportunity to cheat reported solving 0.11 more matrices if they were given a moral reminder than if they were given a neutral reminder (95% confidence interval = [−0.09, 0.31]). This small effect was numerically in the opposite direction of the effect observed in the original study (Cohen’s d = −0.04).
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20.
  • Bergenstråhle, Ludvig, et al. (author)
  • Super-resolved spatial transcriptomics by deep data fusion
  • 2022
  • In: Nature Biotechnology. - : Nature Research. - 1087-0156 .- 1546-1696. ; 40:4, s. 476-479
  • Journal article (peer-reviewed)abstract
    • Current methods for spatial transcriptomics are limited by low spatial resolution. Here we introduce a method that integrates spatial gene expression data with histological image data from the same tissue section to infer higher-resolution expression maps. Using a deep generative model, our method characterizes the transcriptome of micrometer-scale anatomical features and can predict spatial gene expression from histology images alone. 
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21.
  • Chawchai, Sakonvan, et al. (author)
  • Hydroclimatic shifts in northeast Thailand during the last two millennia - the record of Lake Pa Kho
  • 2015
  • In: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 111, s. 62-71
  • Research review (peer-reviewed)abstract
    • The Southeast Asian mainland is located in the central path of the Asian summer monsoon, a region where paleoclimatic data are still sparse. Here we present a multi-proxy (TOC, C/N, delta C-13, biogenic silica, and XRF elemental data) study of a 1.5 m sediment/peat sequence from Lake Pa Kho, northeast Thailand, which is supported by 20 AMS C-14 ages. Hydroclimatic reconstructions for Pa Kho suggest a strengthened summer monsoon between BC 170-AD 370, AD 800-960, and after AD 1450; and a weakening of the summer monsoon between AD 370-800, and AD 1300-1450. Increased run-off and a higher nutrient supply after AD 1700 can be linked to agricultural intensification and land-use changes in the region. This study fills an important gap in data coverage with respect to summer monsoon variability over Southeast Asia during the past 2000 years and enables the mean position of the Intertropical Convergence Zone (ITCZ) to be inferred based on comparisons with other regional studies. Intervals of strengthened/weaker summer monsoon rainfall suggest that the mean position of the ITCZ was located as far north as 35 degrees N between BC 170-AD 370 and AD 800-960, whereas it likely did not reach above 17 degrees N during the drought intervals of AD 370-800 and AD 1300-1450. The spatial pattern of rainfall variation seems to have changed after AD 1450, when the inferred moisture history for Pa Kho indicates a more southerly location of the mean position of the summer ITCZ.
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22.
  • Dowdeswell, J. A., et al. (author)
  • High-resolution geophysical observations of the Yermak Plateau and northern Svalbard margin : Implications for ice-sheet grounding and deep-keeled icebergs
  • 2010
  • In: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 29:25-26, s. 3518-3531
  • Journal article (peer-reviewed)abstract
    • High-resolution geophysical evidence on the seafloor morphology and acoustic stratigraphy of the Yermak Plateau and northern Svalbard margin between 79°20′ and 81°30′N and 5° and 22°E is presented. Geophysical datasets are derived from swath bathymetry and sub-bottom acoustic profiling and are combined with existing cores to derive chronological control. Seafloor landforms, in the form of ice-produced lineations, iceberg ploughmarks of various dimensions (including features over 80 m deep and down to about 1000 m), and a moat indicating strong currents are found. The shallow stratigraphy of the Yermak Plateau shows three acoustic units: the first with well-developed stratification produced by hemipelagic sedimentation, often draped over a strong and undulating internal reflector; a second with an undulating upper surface and little acoustic penetration, indicative of the action of ice; a third unit of an acoustically transparent facies, resulting from debris flows. Core chronology suggests a MIS 6 age for the undulating seafloor above about 580 m. There are several possible explanations, including: (a) the flow of a major grounded ice sheet across the plateau crest from Svalbard (least likely given the consolidation state of the underlying sediments); (b) the more transient encroachment of relatively thin ice from Svalbard; or (c) the drift across the plateau of an ice-shelf remnant or megaberg from the Arctic Basin. The latter is our favoured explanation given the evidence currently at our disposal.
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25.
  • El-Habta, Roine, et al. (author)
  • Adipose stem cells enhance myoblast proliferation via acetylcholine and extracellular signal-regulated kinase 1/2 signaling
  • 2018
  • In: Muscle and Nerve. - : WILEY. - 0148-639X .- 1097-4598. ; 57:2, s. 305-311
  • Journal article (peer-reviewed)abstract
    • Introduction: In this study we investigated the interaction between adipose tissue-derived stem cells (ASCs) and myoblasts in co-culture experiments. Methods: Specific inductive media were used to differentiate ASCs in vitro into a Schwann cell-like phenotype (differentiated adipose tissuederived stem cells, or dASCs) and, subsequently, the expression of acetylcholine (ACh)-related machinery was determined. In addition, the expression of muscarinic ACh receptors was examined in denervated rat gastrocnemius muscles. Results: In contrast to undifferentiated ASCs, dASCs expressed more choline acetyltransferase and vesicular acetylcholine transporter. When co-cultured with myoblasts, dASCs enhanced the proliferation rate, as did ACh administration alone. Western blotting and pharmacological inhibitor studies showed that phosphorylated extracellular signal-regulated kinase 1/2 signaling mediated these effects. In addition, denervated muscle showed higher expression of muscarinic ACh receptors than control muscle. Discussion: Our findings suggest that dASCs promote proliferation of myoblasts through paracrine secretion of ACh, which could explain some of their regenerative capacity in vivo.
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  • El-Habta, Roine, et al. (author)
  • Anti-apoptotic effect of adipose tissue-derived stromal vascular fraction in denervated rat muscle
  • 2021
  • In: Stem Cell Research & Therapy. - : BioMed Central (BMC). - 1757-6512. ; 12:1
  • Journal article (peer-reviewed)abstract
    • Background: Recovery of muscle function after peripheral nerve injury is often poor, and this can be attributed to muscle fiber atrophy and cell death. In the current study, we have investigated the effects of stromal vascular fraction (SVF) on muscle cell apoptosis and its potential to preserve muscle tissue following denervation.Methods: Rat gastrocnemius muscle was denervated by sciatic nerve transection. At 2 and 4 weeks after injury, muscles were examined histologically and apoptosis was measured using TUNEL assay and PCR array for a range of apoptotic genes. Additionally, an in vitro TNF-α apoptosis model was established using SVF cells co-cultured indirectly with primary rat myoblasts. Annexin V and TUNEL were used together with Western blotting to investigate the signaling pathways.Results: Denervated muscles showed significantly higher TUNEL reactivity at 2 and 4 weeks following nerve injury, and an increased expression of caspase family genes, mitochondria-related apoptotic genes, and tumor necrosis factor family genes. In cultured rat primary myoblasts, Annexin V labeling was significantly increased at 12 h after TNF-α treatment, and this was followed by a significant increase in TUNEL reactivity at 48 h. Western blotting showed that caspase-7 was activated/cleaved as well as the downstream substrate, poly (ADP-ribose) polymerase (PARP). Co-culture of myoblasts with SVF significantly reduced all these measures of apoptosis. Bax and Bcl-2 levels were not changed suggesting that the TNF-α-induced apoptosis occurred via mitochondria-independent pathways. The protective effect of SVF was also shown in vivo; injections of SVF cells into denervated muscle significantly improved the mean fiber area and diameter, as well as reduced the levels of TUNEL reactivity.Conclusions: This study provides new insights into how adipose tissue-derived cells might provide therapeutic benefits by preserving muscle tissue.
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  • El-Habta, Roine, 1988- (author)
  • Cell therapy for denervated tissue
  • 2020
  • Doctoral thesis (other academic/artistic)abstract
    • Background: Peripheral nerve injury results in denervation of tendons and muscles. The biology of denervated muscle has been well studied but little is known about the associated tendons. Denervation of muscle leads to atrophy which includes muscle fiber shrinkage and cell death, a process that is influenced by the lack of acetylcholine (ACh) signaling to the muscle cells. Recovery of long-term denervated muscle function is often poor. This thesis describes how a cell therapy approach using adipose tissue-derived stromal vascular fraction (SVF) may be used to protect and regenerate denervated muscle. Previous studies have shown how adipose tissue-dervied stem cells (ASCs), commonly expanded from the SVF, have pro-regenerative effects on the injured peripheral nervous system, and how ASCs differentiated towards a “Schwann cell-like phenotype” (dASCs) reduce muscle atrophy. In this thesis work, we studied the possible mechanisms underlying the regenerative potential of both SVF and culture expanded dASCs.Hypotheses: We hypothesized that: 1) denervated tendon displays morphological and biochemical properties that resemble the chronic degenerative tendon condition known as tendinosis; 2) denervated muscle up-regulates expression of muscarinic acetylcholine (ACh) receptors and apoptosis-associated signaling mechanisms; 3) dASCs enhance the proliferation of myoblasts in vitro through secretion of ACh; 4) SVF influences the proliferation, differentiation, and survival of myoblasts in vitro via secretion of growth factors; and 5) SVF can preserve denervated muscle tissue. To test our hypotheses, two model systems were used: an in vitro model based on indirect co-culture, and an in vivo rat sciatic nerve transection model.Results: Denervated tendon displayed morphological changes similar to tendinosis, including hypercellularity, disfigurement of cells, and disorganized collagen architecture, along with an increased expression of type I and type III collagen. In addition, levels of neurokinin 1 receptor (NK-1R) were upregulated in the tendon cells. In denervated muscle, there was an increased expression of muscarinic ACh receptors, as well as of genes associated with apoptosis, such as caspases, cytokines (e.g., tumor necrosis factor-alpha; TNF-a), and death domain receptors. We subsequently used TNF-aas an inducer of apoptosis in an in vitrorat primary myoblast culture model. TNF-aactivated/cleaved caspase 7 and increased poly ADP-ribose polymerase (PARP) levels. Moreover, Annexin V and TUNEL were increased after TNF-atreatment. Indirect co-culture with SVF significantly reduced all these measures of apoptosis. Proliferation studies showed that both dASCs and SVF enhanced growth of myoblasts in vitro. With dASCs, the effect was partially explained by secretion of ACh, and for SVF by released growth factors, such as hepatocyte growth factor (HGF). In both cases, the signal was mediated via phosphorylation of ERK1/2 (MAPK). HGF also had an inhibitory effect on the differentiation of myoblasts into myotubes. Finally, the protective effects of SVF were confirmed in vivo: injections of SVF into denervated muscle significantly increased the mean fiber area and diameter, as well as reduced the expression of apoptotic genes and TUNEL reactivity.Conclusions: Denervated tendons undergo severe degenerative changes similar to tendinosis. Furthermore, SVF has the ability to reduce muscle atrophy in vivo. Using in vitro systems, we showed that this might occur through secretion of growth factors which activate MAPK signaling and anti-apoptotic pathways. In conclusion, SVF offers a promising approach for future clinical application in the treatment of denervated muscle.
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  • El-Habta, Roine, et al. (author)
  • The adipose tissue stromal vascular fraction secretome enhances the proliferation but inhibits the differentiation of myoblasts
  • 2018
  • In: Stem Cell Research & Therapy. - : BioMed Central. - 1757-6512. ; 9
  • Journal article (peer-reviewed)abstract
    • Background: Adipose tissue is an excellent source for isolation of stem cells for treating various clinical conditions including injuries to the neuromuscular system. Many previous studies have focused on differentiating these adipose stem cells (ASCs) towards a Schwann cell-like phenotype (dASCs), which can enhance axon regeneration and reduce muscle atrophy. However, the stromal vascular fraction (SVF), from which the ASCs are derived, also exerts broad regenerative potential and might provide a faster route to clinical translation of the cell therapies for treatment of neuromuscular disorders.Methods: The aim of this study was to establish the effects of SVF cells on the proliferation and differentiation of myoblasts using indirect co-culture experiments. A Growth Factor PCR Array was used to compare the secretomes of SVF and dASCs, and the downstream signaling pathways were investigated.Results: SVF cells, unlike culture-expanded dASCs, expressed and secreted hepatocyte growth factor (HGF) at concentrations sufficient to enhance the proliferation of myoblasts. Pharmacological inhibitor studies revealed that the signal is mediated via ERK1/2 phosphorylation and that the effect is significantly reduced by the addition of 100 pM Norleual, a specific HGF inhibitor. When myoblasts were differentiated into multinucleated myotubes, the SVF cells reduced the expression levels of fast-type myosin heavy chain (MyHC2) suggesting an inhibition of the differentiation process.Conclusions: In summary, this study shows the importance of HGF as a mediator of the SVF effects on myoblasts and provides further evidence for the importance of the secretome in cell therapy and regenerative medicine applications.
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29.
  • Erickson, Andrew, et al. (author)
  • The spatial landscape of clonal somatic mutations in benign and malignant tissue
  • Other publication (other academic/artistic)abstract
    • Defining the transition from benign to malignant tissue is fundamental to improve early diagnosis of cancer. Here, we provide an unsupervised approach to study spatial genome integrity in situ to gain molecular insight into clonal relationships. We employed spatially resolved transcriptomics to infer spatial copy number variations in >120 000 regions across multiple organs, in benign and malignant tissues. We demonstrate that genome-wide copy number variation reveals distinct clonal patterns within tumours and in nearby benign tissue. Our results suggest a model for how genomic instability arises in histologically benign tissue that may represent early events in cancer evolution. We highlight the power of an unsupervised approach to capture the molecular and spatial continuums in a tissue context and challenge the rationale for treatment paradigms, including focal therapy.
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31.
  • Kjellsson, Ludvig, et al. (author)
  • Resonant Inelastic X-Ray Scattering Reveals Hidden Local Transitions of the Aqueous OH Radical
  • 2020
  • In: Physical Review Letters. - : AMER PHYSICAL SOC. - 0031-9007 .- 1079-7114. ; 124:23
  • Journal article (peer-reviewed)abstract
    • Resonant inelastic x-ray scattering (RIXS) provides remarkable opportunities to interrogate ultra-fast dynamics in liquids. Here we use RIXS to study the fundamentally and practically important hydroxyl radical in liquid water, OH(aq). Impulsive ionization of pure liquid water produced a short-lived population of OH(aq), which was probed using femtosecond x-rays from an x-ray free-electron laser. We find that RIXS reveals localized electronic transitions that are masked in the ultraviolet absorption spectrum by strong charge-transfer transitions-thus providing a means to investigate the evolving electronic structure and reactivity of the hydroxyl radical in aqueous and heterogeneous environments. First-principles calculations provide interpretation of the main spectral features.
  •  
32.
  • Kremer, A., et al. (author)
  • Changes in sea ice cover and ice sheet extent at the Yermak Plateau during the last 160 ka - Reconstructions from biomarker records
  • 2018
  • In: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 182, s. 93-108
  • Journal article (peer-reviewed)abstract
    • The Yermak Plateau is located north of Svalbard at the entrance to the Arctic Ocean, i.e. in an area highly sensitive to climate change. A multi proxy approach was carried out on Core PS92/039-2 to study glacial interglacial environmental changes at the northern Barents Sea margin during the last 160 ka. The main emphasis was on the reconstruction of sea ice cover, based on the sea ice proxy IP25 and the related phytoplankton - sea ice index PIP25. Sea ice was present most of the time but showed significant temporal variability decisively affected by movements of the Svalbard Barents Sea Ice Sheet. For the first time, we prove the occurrence of seasonal sea ice at the eastern Yermak Plateau during glacial intervals, probably steered by a major northward advance of the ice sheet and the formation of a coastal polynya in front of it. Maximum accumulation of terrigenous organic carbon, IP25 and the phytoplankton biomarkers (brassicasterol, dinosterol, HBI III) can be correlated to distinct deglaciation events. More severe, but variable sea ice cover prevailed at the Yermak Plateau during interglacials. The general proximity to the sea ice margin is further indicated by biomarker (GDGT) - based sea surface temperatures below 2.5 degrees C.
  •  
33.
  • Landälv, Ludvig, 1982-, et al. (author)
  • Phase composition and transformations in magnetron-sputtered (Al,V)2O3 coatings
  • 2019
  • In: Thin Solid Films. - : Elsevier BV. - 0040-6090 .- 1879-2731. ; 688
  • Journal article (peer-reviewed)abstract
    • Coatings of (Al1-xVx)2O3, with x ranging from 0 to 1, were deposited by pulsed DC reactive sputter deposition on Si(100) at a temperature of 550 °C. XRD showed three different crystal structures depending on V-metal fraction in the coating: α-V2O3 rhombohedral structure for 100 at.% V, a defect spinel structure for the intermediate region, 63–42 at.% V. At lower V-content, 18 and 7 at.%, a gamma-alumina-like solid solution was observed, shifted to larger d-spacing compared to pure γ-Al2O3. The microstructure changes from large columnar faceted grains for α-V2O3 to smaller equiaxed grains when lowering the vanadium content towards pure γ-Al2O3. Annealing in air resulted in formation of V2O5 crystals on the surface of the coating after annealing to 500 °C for 42 at.% V and 700 °C for 18 at.% V metal fraction respectively. The highest thermal stability was shown for pure γ-Al2O3-coating, which transformed to α-Al2O3 after annealing to 1100 °C. Highest hardness was observed for the Al-rich oxides, ~24 GPa. The latter decreased with increasing V-content, larger than 7 at.% V metal fraction. The measured hardness after annealing in air decreased in conjunction with the onset of further oxidation of the coatings.
  •  
34.
  • Li, Junhong, et al. (author)
  • Secretome from myoblasts statically loaded at low intensity promotes tenocyte proliferation via the IGF-1 receptor pathway
  • 2023
  • In: The FASEB Journal. - : John Wiley & Sons. - 0892-6638 .- 1530-6860. ; 37:10
  • Journal article (peer-reviewed)abstract
    • Exercise is widely recognized as beneficial for tendon healing. Recently, it has been described that muscle-derived molecules secreted in response to static exercise influence tendon healing. In this study, the optimal static loading intensity for tendon healing and the composition of secretome released by myoblasts in response to different intensities of static strain were investigated. In an in vitro coculture model, myoblasts were mechanically loaded using a Flexcell Tension System. Tenocytes were seeded on transwell inserts that allowed communication between the tenocytes and myoblasts without direct contact. Proliferation and migration assays, together with RNA sequencing, were used to determine potential cellular signaling pathways. The secretome from myoblasts exposed to 2% static loading increased the proliferation and migration of the cocultured tenocytes. RNA-seq analysis revealed that this loading condition upregulated the expression of numerous genes encoding secretory proteins, including insulin-like growth factor-1 (IGF-1). Confirmation of IGF-1 expression and secretion was carried out using qPCR and enzyme-linked immunosorbt assay (ELISA), revealing a statistically significant upregulation in response to 2% static loading in comparison to both control conditions and higher loading intensities of 5% and 10%. Addition of an inhibitor of the IGF-1 receptor (PQ401) to the tenocytes significantly reduced myoblast secretome-induced tenocyte proliferation. In conclusion, IGF-1 may be an important molecule in the statically loaded myoblast secretome, which is responsible for influencing tenocytes during exercise-induced healing.
  •  
35.
  • Li, S., et al. (author)
  • Two-dimensional correlation analysis for x-ray photoelectron spectroscopy
  • 2021
  • In: Journal of Physics B. - : Institute of Physics Publishing (IOPP). - 0953-4075 .- 1361-6455. ; 54:14
  • Journal article (peer-reviewed)abstract
    • X-ray photoelectron spectroscopy (XPS) measures the binding energy of core-level electrons, which are well-localised to specific atomic sites in a molecular system, providing valuable information on the local chemical environment. The technique relies on measuring the photoelectron spectrum upon x-ray photoionisation, and the resolution is often limited by the bandwidth of the ionising x-ray pulse. This is particularly problematic for time-resolved XPS, where the desired time resolution enforces a fundamental lower limit on the bandwidth of the x-ray source. In this work, we report a novel correlation analysis which exploits the correlation between the x-ray and photoelectron spectra to improve the resolution of XPS measurements. We show that with this correlation-based spectral-domain ghost imaging method we can achieve sub-bandwidth resolution in XPS measurements. This analysis method enables XPS for sources with large bandwidth or spectral jitter, previously considered unfeasible for XPS measurements.
  •  
36.
  • Loh, Z-H, et al. (author)
  • Observation of the fastest chemical processes in the radiolysis of water
  • 2020
  • In: Science. - : AMER ASSOC ADVANCEMENT SCIENCE. - 0036-8075 .- 1095-9203. ; 367:6474, s. 179-182
  • Journal article (peer-reviewed)abstract
    • Elementary processes associated with ionization of liquid water provide a framework for understanding radiation-matter interactions in chemistry and biology. Although numerous studies have been conducted on the dynamics of the hydrated electron, its partner arising from ionization of liquid water, H2O+, remains elusive. We used tunable femtosecond soft x-ray pulses from an x-ray free electron laser to reveal the dynamics of the valence hole created by strong-field ionization and to track the primary proton transfer reaction giving rise to the formation of OH. The isolated resonance associated with the valence hole (H2O+/OH) enabled straightforward detection. Molecular dynamics simulations revealed that the x-ray spectra are sensitive to structural dynamics at the ionization site. We found signatures of hydrated-electron dynamics in the x-ray spectrum.
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37.
  • Löwemark, Ludvig, et al. (author)
  • Late Quaternary spatial and temporal variability in Arctic deep-sea bioturbation and its relation to Mn cycles
  • 2012
  • In: Palaeogeography, Palaeoclimatology, Palaeoecology. - : Elsevier BV. - 0031-0182 .- 1872-616X. ; 365-366, s. 192-208
  • Journal article (peer-reviewed)abstract
    • Changes in intensity and composition of bioturbation and trace fossils in deep-sea settings are directly related to changes in environmental parameters such as food availability, bottom water oxygenation, or substrate consistency. Because trace fossils are practically always preserved in situ, and are often present in environments where other environmental indicators are scarce or may have been compromised or removed by diagenetic processes, the trace fossils provide an important source of paleoenvironmental information in regions such as the deep Arctic Ocean. Detailed analysis of X-ray radiographs from 12 piston and gravity cores from a transect spanning from the Makarov Basin to the Yermak Plateau via the Lomonosov Ridge, the Morris Jesup Rise, and the Gakkel Ridge reveal both spatial and temporal variations in an ichnofauna consisting of Chondrites, Nereites, Phycosiphon, Planolites, Scolicia, Trichichnus, Zoophycos, as well as deformational biogenic structures. The spatial variability in abundance and diversity is in close correspondence to observed patterns in the distribution of modern benthos, suggesting that food availability and food flux to the sea floor are the most important parameters controlling variations in bioturbation in the Arctic Ocean. The most diverse ichnofaunas were observed at sites on the central Lomonosov Ridge that today have partially ice free conditions and relatively high summer productivity. In contrast, the most sparse ichnofauna was observed in the ice-infested region on the Lomonosov Ridge north of Greenland. Since primary productivity, and therefore also the food flux at a certain location, is ultimately controlled by the geographical position in relation to ice margin and the continental shelves, temporal variations in abundance and diversity of trace fossils have the potential to reveal changes in food flux, and consequently sea ice conditions on glacial–interglacial time scales. Down core analysis reveal clearly increased abundance and diversity during interglacial/interstadial intervals that were identified through strongly enhanced Mn levels and the presence of micro- and nannofossils. Warm stages are characterized by larger trace fossils such as Scolicia, Planolites or Nereites, while cold stages typically display an ichnofauna dominated by small deep penetrating trace fossils such as Chondrites or Trichichnus. The presence of biogenic structures in glacial intervals clearly show that the Arctic deep waters must have remained fairly well ventilated also during glacials, thereby lending support to the hypothesis that the conspicuous brown layers rich in Mn which are found ubiquitously over the Arctic basins are related to input from rivers and coastal erosion during sea level high-stands rather than redox processes in the water column and on the sea floor. However, the X-ray radiograph study also revealed the presence of apparently post-sedimentary, diagenetically formed Mn-layers which are not directly related to Mn input from rivers and shelves. These observations thus bolster the hypothesis that the bioturbated, brownish Mn-rich layers can be used for stratigraphic correlation over large distances in the Arctic Ocean, but only if post sedimentary diagenetic layers can be identified and accounted for in the Mn-cycle stratigraphy.
  •  
38.
  • Löwemark, Ludvig, 1969-, et al. (author)
  • New evidence for a glacioeustatic influence on deep watercirculation, bottom water ventilation and primaryproductivity in the South China Sea
  • 2009
  • In: Dynamics of atmospheres and oceans (Print). - : Elsevier. - 0377-0265 .- 1872-6879. ; 47:1-3, s. 138-153
  • Journal article (peer-reviewed)abstract
    • We provide new evidence for the development of a stable estuarinecirculation characterized by stagnating water bodies, nutrientrecycling and increased primary productivity in the South ChinaSea (SCS) during glacial intervals. This circulation was caused bythe closure of the shallow and narrow straits connecting the SCSin the south and west. Our main evidence is derived from newlymeasured Mn concentrations and Mn/Al ratios in two sedimentcores from the northern and southeastern SCS covering the last500 ky. Concentrations and Mn/Al ratios of the redox sensitive elementMnshowclearglacial–interglacial cycles with maxima duringinterglacial periods and minima during glacial periods. These cyclesindicate ventilation cycles of the bottom water, and are connectedto the glacial–interglacial changes in sea level. In contrast, totalorganic carbon (TOC) concentrations display an opposite patternwith pronounced maxima during glacial times, especially in thesouthern part of the basin. The variations in TOC can be ascribed totwo factors. Firstly, variations in primary productivity are controlledby variations in the intensity of the winter monsoon. Secondlyto the degree of preservation of TOC controlled by variations inventilation, which in turn is ultimately controlled by sea level. Consequently, variations in TOC represent a superimposition ofprimarily sea level influenced preservation control and wintermonsoon driven variations in primary productivity intensity. Thedecrease in Mn correspond to times when sea level dropped40–60m below the present level. The larger amplitude of the variationsin TOC and Mn in the southern part of the basin compared tothe northern site suggest that oxygen depletion and nutrient recyclingwas stronger in the parts of the basin situated the furthest away from the only remaining opening to the open Pacific, the LuzonStrait.
  •  
39.
  • Löwemark, Ludvig, et al. (author)
  • Practical guidelines and recent advances in the Itrax XRF core-scanning procedure
  • 2019
  • In: Quaternary International. - : Elsevier BV. - 1040-6182 .- 1873-4553. ; 514, s. 16-29
  • Journal article (peer-reviewed)abstract
    • XRF core scanning has evolved to become a standard analytical technique for the rapid assessment of elemental, density and textural variations in a wide range of sediments and other materials, with applications ranging from palaeoceanography, paleoclimatology, geology, and environmental forensics to environmental protection. In general, scanning provides rapid, non-destructive acquisition of elemental and textural variations at sub-millimetre resolution for a wide range of materials. Numerous procedural adaptations have been developed for the growing number of applications, such as analyses of unconsolidated, water-rich sediments, powdered soil samples, or resin bags. Here, practical expertise and guidance from the Itrax community, gained over 15 years, is presented that should provide insights for new and experienced users.
  •  
40.
  • Löwemark, Ludvig, et al. (author)
  • Variations in glacial and interglacial marine conditions over the last two glacial cycles off northern Greenland
  • 2016
  • In: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 147:SI, s. 164-177
  • Journal article (peer-reviewed)abstract
    • Five sediment cores from the Lomonosov Ridge and the Morris Jesup Rise north of Greenland show the history of sea-ice coverage and primary productivity over the last two glacial cycles. Variations in Manganese content, benthic and planktonic foraminifera, bioturbation, and trace fossil diversity are interpreted to reflect differences in sea-ice cover and sediment depositional conditions between the identified interglacials. Marine Isotope Stage (MIS) 1 and MIS 2 are represented by thin (<< 5 cm) sediment units while the preceding interglacial MIS 5 and glacial MIS 6 are characterized by thick (10 -20 cm) deposits. Foraminiferal abundances and bioturbation suggest that MIS 1 was generally characterized by severe sea-ice conditions north of Greenland while MISS appears to have been considerably warmer with more open water, higher primary productivity, and higher sedimentation rates. Strengthened flow of Atlantic water along the northern continental shelf of Greenland rather than development of local polynyas is here suggested as a likely cause for the relatively warmer marine conditions during MIS 5 compared to MIS 1. The cores also suggest distinct differences between the glacial intervals MIS 2 and MIS 6. While MIS 6 is distinguished by a relatively thick sediment unit poor in foraminifera and with low Mn values, MIS 2 is practically missing. We speculate that this could be the effect from a paleocrystic sea-ice cover north of Greenland during MIS 2 that prevented sediment delivery from sea ice and icebergs. In contrast, the thick sequence deposited during MIS 6 indicates a longer glacial period with dynamic intervals characterized by huge drifting icebergs delivering ice rafted debris (IRD). A drastic shift from thinner sedimentary cycles where interglacial sediment parameters indicate more severe sea-ice conditions gave way to larger amplitude cycles with more open water indicators was observed around the boundary between MIS 7/8. This shift is in agreement with a sedimentary regime shift previously identified in the Eurasian Basin and may be an indicator for the growth of larger ice sheets on the Eurasian landmass during the penultimate glacial period.
  •  
41.
  • Rogerson, Mike, et al. (author)
  • Enhanced Mediterranean-Atlantic exchange during Atlantic freshening phases
  • 2010
  • In: Geochemistry Geophysics Geosystems. - : AGU. - 1525-2027. ; 11:8, s. Q08013-
  • Journal article (peer-reviewed)abstract
    • The Atlantic-Mediterranean exchange of water at Gibraltar represents a significant heat and freshwater sink for the North Atlantic and is a major control on the heat, salt and freshwater budgets of the Mediterranean Sea. Consequently, an understanding of the response of the exchange system to external changes is vital to a full comprehension of the hydrographic responses in both ocean basins. Here, we use a synthesis of empirical (oxygen isotope, planktonic foraminiferal assemblage) and modeling (analytical and general circulation) approaches to investigate the response of the Gibraltar Exchange system to Atlantic freshening during Heinrich Stadials (HSs). HSs display relatively flat W–E surface hydrographic gradients more comparable to the Late Holocene than the Last Glacial Maximum. This is significant, as it implies a similar state of surface circulation during these periods and a different state during the Last Glacial Maximum. During HS1, the gradient may have collapsed altogether, implying very strong water column stratification and a single thermal and δ18Owater condition in surface water extending from southern Portugal to the eastern Alboran Sea. Together, these observations imply that inflow of Atlantic water into the Mediterranean was significantly increased during HS periods compared to background glacial conditions. Modeling efforts confirm that this is a predictable consequence of freshening North Atlantic surface water with iceberg meltwater and indicate that the enhanced exchange condition would last until the cessation of anomalous freshwater supply into to the northern North Atlantic. The close coupling of dynamics at Gibraltar Exchange with the Atlantic freshwater system provides an explanation for observations of increased Mediterranean Outflow activity during HS periods and also during the last deglaciation. This coupling is also significant to global ocean dynamics, as it causes density enhancement of the Atlantic water column via the Gibraltar Exchange to be inversely related to North Atlantic surface salinity. Consequently, Mediterranean enhancement of the Atlantic Meridional Overturning Circulation will be greatest when the overturning itself is at its weakest, a potentially critical negative feedback to Atlantic buoyancy change during times of ice sheet collapse.
  •  
42.
  • Ruggeri, Kai, et al. (author)
  • The globalizability of temporal discounting
  • 2022
  • In: Nature Human Behaviour. - : Springer Nature. - 2397-3374. ; 6:10, s. 1386-1397
  • Journal article (peer-reviewed)abstract
    • Economic inequality is associated with preferences for smaller, immediate gains over larger, delayed ones. Such temporal discounting may feed into rising global inequality, yet it is unclear whether it is a function of choice preferences or norms, or rather the absence of sufficient resources for immediate needs. It is also not clear whether these reflect true differences in choice patterns between income groups. We tested temporal discounting and five intertemporal choice anomalies using local currencies and value standards in 61 countries (N = 13,629). Across a diverse sample, we found consistent, robust rates of choice anomalies. Lower-income groups were not significantly different, but economic inequality and broader financial circumstances were clearly correlated with population choice patterns. Ruggeri et al. find in a study of 61 countries that temporal discounting patterns are globally generalizable. Worse financial environments, greater inequality and high inflation are associated with extreme or inconsistent long-term decisions.
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43.
  •  
44.
  • Virtasalo, Joonas J., et al. (author)
  • Pyritic and baritic burrows and microbial filaments in postglacial lacustrine clays in the northern Baltic Sea
  • 2010
  • In: Journal of the Geological Society. - : Geological Society of London. - 0016-7649 .- 2041-479X. ; 167:6, s. 1185-1198
  • Journal article (peer-reviewed)abstract
    • Holocene postglacial lacustrine clays in the northern Baltic Sea were studied for ichnofossils,petrography, and microscale elemental and 34S/32S composition to understand the impact of benthos-producedorganic matrices on the early diagenesis of sediments. X-radiographs of these clays display intense burrowmottling with discrete Palaeophycus, ‘Mycellia’ and rare Arenicolites. Small burrow-like and irregularlyshaped concretions were separated from these clays. The burrow-like concretions are composed of framboidalpyrite and poorly crystalline FeS2 cement. They formed within worm-produced burrows by the decompositionof mucous coatings on the burrow walls by sulphate reduction. 34SCDT composition of the framboidsindicates saline inflows from the North Sea as the sulphate source. The irregular concretions are microcrystallinepyritic masses that formed in pore spaces with less reactive organic compounds. Their 34SCDT valuesreflect precipitation from the ambient porewater sulphate by sulphate reduction. The burrow-like and irregularconcretions are microcrystalline barite in the lower parts of the clays. ‘Mycellia’ are mineral-replacedfilaments produced by large sulphur-oxidizing bacteria or mycelial fungi. They concentrate in monosulphidebands in the lower substrate levels, but are associated with organic patches upward. This study demonstratesthat substantial amounts of pyrite formed within organic matrices close to the sediment–water interface. Thisdiffers from previous studies that proposed a deeper-burial origin and allochthonous sulphur source.
  •  
45.
  • Zhou, Xin, et al. (author)
  • Secretome from in vitro mechanically loaded myoblasts induces tenocyte migration, transition to a fibroblastic phenotype and suppression of collagen production
  • 2021
  • In: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 22:23
  • Journal article (peer-reviewed)abstract
    • It is known that mechanical loading of muscles increases the strength of healing tendon tissue, but the mechanism involved remains elusive. We hypothesized that the secretome from myoblasts in co-culture with tenocytes affects tenocyte migration, cell phenotype, and collagen (Col) production and that the effect is dependent on different types of mechanical loading of myoblasts. To test this, we used an in vitro indirect transwell co-culture system. Myoblasts were mechanically loaded using the FlexCell® Tension system. Tenocyte cell migration, proliferation, apoptosis, collagen production, and several tenocyte markers were measured. The secretome from myoblasts decreased the Col I/III ratio and increased the expression of tenocyte specific markers as compared with tenocytes cultured alone. The secretome from statically loaded myoblasts significantly enhanced tenocyte migration and Col I/III ratio as compared with dynamic loading and controls. In addition, the secretome from statically loaded myoblasts induced tenocytes towards a myofibroblast-like phenotype. Taken together, these results demonstrate that the secretome from statically loaded myoblasts has a profound influence on tenocytes, affecting parameters that are related to the tendon healing process.
  •  
46.
  • Adlercreutz, Ludvig, et al. (author)
  • Optimizing the Natural Gas Engine for CO2 reduction
  • 2016
  • In: SAE Technical Papers. - 400 Commonwealth Drive, Warrendale, PA, United States : SAE International. - 0148-7191.
  • Conference paper (peer-reviewed)abstract
    • With alternative fuels having moved more into market in light of their reduction of emissions of CO2 and other air pollutants, the spark ignited internal combustion engine design has only been affected to small extent. The development of combustion engines running on natural gas or Biogas have been focused to maintain driveability on gasoline, creating a multi fuel platform which does not fully utilise the alternative fuels' potential. However, optimising these concepts on a fundamental level for gas operation shows a great potential to increase the level of utilisation and effectiveness of the engine and thereby meeting the emissions legislation. The project described in this paper has focused on optimising a combustion concept for CNG combustion on a single cylinder research engine. The ICE's efficiency at full load and the fuels characteristics, including its knock resistance, is of primary interest - together with part load performance and overall fuel consumption. In the process of increasing the efficiency of the engine the following areas have been of primary interest, increased compression ratio, thermal load at high cylinder pressure and the use of EGR to further increase efficiency. The overall goal in the project was to reduce the CO2-emissions while maintaining the performance and characteristics of the engine. The ambition is to reduce specific tail-pipe CO2-emissions in g/kWh by 50% compared to a modern gasoline engine. The goal was close to being reached at 45% reduction at full load and 25-34% on part load. This was done by theoretically downsizing the engine and increasing the specific performance of the engine.
  •  
47.
  • Andersson, Gustav, et al. (author)
  • Nerve distributions in insertional Achilles tendinopathy - a comparison of bone, bursae and tendon
  • 2017
  • In: Histology and Histopathology. - 0213-3911 .- 1699-5848. ; 32:3, s. 263-270
  • Journal article (peer-reviewed)abstract
    • Background/Aim. In a condition of pain in the Achilles tendon insertion there are multiple structures involved, such as the Achilles tendon itself, the retrocalcaneal bursa and a bony protrusion at the calcaneal tuberosity called Haglund's deformity. The innervation patterns of these structures are scarcely described, and the subcutaneous calcaneal bursa is traditionally not considered to be involved in the pathology. This study aimed at describing the innervation patterns of the four structures described above to provide a better understanding of possible origins of pain at the Achilles tendon insertion.Methods. Biopsies were taken from 10 patients with insertional Achilles tendinopathy, which had pathological changes in the subcutaneous and retrocalcaneal bursae, a Haglund deformity and Achilles tendon tendinopathy as verified by ultrasound. The biopsies were stained using immunohistochemistry in order to delineate the innervation patterns in the structures involved in insertional Achilles tendinopathy.Results. Immunohistochemical examinations found that the subcutaneous bursa scored the highest using a semi-quantitative evaluation of the degree of innervation when compared to the retrocalcaneal bursa, the Achilles tendon, and the calcaneal bone.Conclusions. These findings suggest that the subcutaneous bursa, which is traditionally not included in surgical treatment, may be a clinically important factor in insertional Achilles tendinopathy.
  •  
48.
  • Backman, Ludvig J, 1983-, et al. (author)
  • Akt-mediated anti-apoptotic effects of substance P in Anti-Fas-induced apoptosis of human tenocytes
  • 2013
  • In: Journal of Cellular and Molecular Medicine (Print). - : Wiley-Blackwell. - 1582-1838 .- 1582-4934. ; 17:6, s. 723-733
  • Journal article (peer-reviewed)abstract
    • Substance P (SP) and its receptor, the neurokinin-1 receptor (NK-1 R), are expressed by human tenocytes, and they are both up-regulated incases of tendinosis, a condition associated with excessive apoptosis. It is known that SP can phosphorylate/activate the protein kinase Akt,which has anti-apoptotic effects. This mechanism has not been studied for tenocytes. The aims of this study were to investigate if Anti-Fastreatment is a good apoptosis model for human tenocytes in vitro, if SP protects from Anti-Fas-induced apoptosis, and by which mechanismsSP mediates an anti-apoptotic response. Anti-Fas treatment resulted in a time- and dose-dependent release of lactate dehydrogenase (LDH), i.e.induction of cell death, and SP dose-dependently reduced the Anti-Fas-induced cell death through a NK-1 R specific pathway. The same trendwas seen for the TUNEL assay, i.e. SP reduced Anti-Fas-induced apoptosis via NK-1 R. In addition, it was shown that SP reduces Anti-Fas-induced decrease in cell viability as shown with crystal violet assay. Protein analysis using Western blot confirmed that Anti-Fas inducescleavage/activation of caspase-3 and cleavage of PARP; both of which were inhibited by SP via NK-1 R. Finally, SP treatment resulted in phosphorylation/activation of Akt as shown with Western blot, and it was confirmed that the anti-apoptotic effect of SP was, at least partly, inducedthrough the Akt-dependent pathway. In conclusion, we show that SP reduces Anti-Fas-induced apoptosis in human tenocytes and that this antiapoptoticeffect of SP is mediated through NK-1 R and Akt-specific pathways.
  •  
49.
  • Backman, Ludvig J, et al. (author)
  • Alpha-2 adrenergic stimulation triggers Achilles tenocyte hypercellularity : comparison between two model systems
  • 2013
  • In: Scandinavian Journal of Medicine and Science in Sports. - : John Wiley & Sons. - 0905-7188 .- 1600-0838. ; 23:6, s. 687-696
  • Journal article (peer-reviewed)abstract
    • The histopathology of tendons with painful tendinopathy is often tendinosis, a fibrosis-like condition of unclear pathogenesis characterized by tissue changes including hypercellularity. The primary tendon cells (tenocytes) have been shown to express adrenoreceptors (mainly alpha-2A) as well as markers of catecholamine production, particularly in tendinosis. It is known that adrenergic stimulation can induce proliferation in other cells. The present study investigated the effects of an exogenously administered alpha-2 adrenergic agonist in an established in vivo Achilles tendinosis model (rabbit) and also in an in vitro human tendon cell culture model. The catecholamine producing enzyme tyrosine hydroxylase and the alpha-2A-adrenoreceptor (α(2A) AR) were expressed by tenocytes, and alpha-2 adrenergic stimulation had a proliferative effect on these cells, in both models. The proliferation was inhibited by administration of an α(2A) AR antagonist, and the in vitro model further showed that the proliferative alpha-2A effect was mediated via a mitogenic cell signaling pathway involving phosphorylation of extracellular-signal-regulated kinases 1 and 2. The results indicate that catecholamines produced by tenocytes in tendinosis might contribute to the proliferative nature of the pathology through stimulation of the α(2A) AR, pointing to a novel target for future therapies. The study furthermore shows that animal models are not necessarily required for all aspects of this research.
  •  
50.
  • Backman, Ludvig J, et al. (author)
  • Low range of ankle dorsiflexion predisposes for patellar tendinopathy in junior elite basketball players : a 1-year prospective study
  • 2011
  • In: American Journal of Sports Medicine. - : SAGE Publications. - 0363-5465 .- 1552-3365. ; 39:12, s. 2626-2633
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Patellar tendinopathy (PT) is one of the most common reasons for sport-induced pain of the knee. Low ankle dorsiflexion range might predispose for PT because of load-bearing compensation in the patellar tendon. PURPOSE: The purpose of this 1-year prospective study was to analyze if a low ankle dorsiflexion range increases the risk of developing PT for basketball players. STUDY DESIGN: Cohort study (prognosis); Level of evidence, 2. METHODS: Ninety junior elite basketball players were examined for different characteristics and potential risk factors for PT, including ankle dorsiflexion range in the dominant and nondominant leg. Data were collected over a 1-year period and follow-up, including reexamination, was made at the end of the year. RESULTS: Seventy-five players met the inclusion criteria. At the follow-up, 12 players (16.0%) had developed unilateral PT. These players were found to have had a significantly lower mean ankle dorsiflexion range at baseline than the healthy players, with a mean difference of -4.7° (P = .038) for the dominant limb and -5.1° (P = .024) for the nondominant limb. Complementary statistical analysis showed that players with dorsiflexion range less than 36.5° had a risk of 18.5% to 29.4% of developing PT within a year, as compared with 1.8% to 2.1% for players with dorsiflexion range greater than 36.5°. Limbs with a history of 2 or more ankle sprains had a slightly less mean ankle dorsiflexion range compared to those with 0 or 1 sprain (mean difference, -1.5° to -2.5°), although this was only statistically significant for nondominant legs. CONCLUSION: This study clearly shows that low ankle dorsiflexion range is a risk factor for developing PT in basketball players. In the studied material, an ankle dorsiflexion range of 36.5° was found to be the most appropriate cutoff point for prognostic screening. This might be useful information in identifying at-risk individuals in basketball teams and enabling preventive actions. A history of ankle sprains might contribute to reduced ankle dorsiflexion range.
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