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2.
  • Björklund, J., et al. (författare)
  • Scientific Merits and Analytical Challenges of Tree-Ring Densitometry
  • 2019
  • Ingår i: Reviews of geophysics. - 8755-1209 .- 1944-9208. ; 57:4, s. 1224-1264
  • Forskningsöversikt (refereegranskat)abstract
    • X-ray microdensitometry on annually resolved tree-ring samples has gained an exceptional position in last-millennium paleoclimatology through the maximum latewood density (MXD) parameter, but also increasingly through other density parameters. For 50 years, X-ray based measurement techniques have been the de facto standard. However, studies report offsets in the mean levels for MXD measurements derived from different laboratories, indicating challenges of accuracy and precision. Moreover, reflected visible light-based techniques are becoming increasingly popular, and wood anatomical techniques are emerging as a potentially powerful pathway to extract density information at the highest resolution. Here we review the current understanding and merits of wood density for tree-ring research, associated microdensitometric techniques, and analytical measurement challenges. The review is further complemented with a careful comparison of new measurements derived at 17 laboratories, using several different techniques. The new experiment allowed us to corroborate and refresh long-standing wisdom but also provide new insights. Key outcomes include (i) a demonstration of the need for mass/volume-based recalibration to accurately estimate average ring density; (ii) a substantiation of systematic differences in MXD measurements that cautions for great care when combining density data sets for climate reconstructions; and (iii) insights into the relevance of analytical measurement resolution in signals derived from tree-ring density data. Finally, we provide recommendations expected to facilitate futureinter-comparability and interpretations for global change research.
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3.
  • Björklund, Jesper, 1979, et al. (författare)
  • Scientific Merits and Analytical Challenges ofTree-Ring Densitometry
  • 2019
  • Ingår i: Reviews of Geophysics. - : American Geophysical Union (AGU). - 8755-1209 .- 1944-9208. ; 57:4, s. 1224-1264
  • Tidskriftsartikel (refereegranskat)abstract
    • X-ray microdensitometry on annually resolved tree-ring samples has gained an exceptional position in last-millennium paleoclimatology through the maximum latewood density (MXD) parameter, but also increasingly through other density parameters. For 50 years, X-ray based measurement techniques have been the de facto standard. However, studies report offsets in the mean levels for MXD measurements derived from different laboratories, indicating challenges of accuracy and precision. Moreover, reflected visible light-based techniques are becoming increasingly popular, and wood anatomical techniques are emerging as a potentially powerful pathway to extract density information at the highest resolution. Here we review the current understanding and merits of wood density for tree-ring research, associated microdensitometric techniques, and analytical measurement challenges. The review is further complemented with a careful comparison of new measurements derived at 17 laboratories, using several different techniques. The new experiment allowed us to corroborate and refresh "long-standing wisdom" but also provide new insights. Key outcomes include (i) a demonstration of the need for mass/volume-based recalibration to accurately estimate average ring density; (ii) a substantiation of systematic differences in MXD measurements that cautions for great care when combining density data sets for climate reconstructions; and (iii) insights into the relevance of analytical measurement resolution in signals derived from tree-ring density data. Finally, we provide recommendations expected to facilitate futureinter-comparability and interpretations for global change research.
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4.
  • Babst, F., et al. (författare)
  • When tree rings go global: Challenges and opportunities for retro- and prospective insight
  • 2018
  • Ingår i: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791. ; 197, s. 1-20
  • Tidskriftsartikel (refereegranskat)abstract
    • The demand for large-scale and long-term information on tree growth is increasing rapidly as environmental change research strives to quantify and forecast the impacts of continued warming on forest ecosystems. This demand, combined with the now quasi-global availability of tree-ring observations, has inspired researchers to compile large tree-ring networks to address continental or even global-scale research questions. However, these emergent spatial objectives contrast with paleo-oriented research ideas that have guided the development of many existing records. A series of challenges related to how, where, and when samples have been collected is complicating the transition of tree rings from a local to a global resource on the question of tree growth. Herein, we review possibilities to scale tree-ring data (A) from the sample to the whole tree, (B) from the tree to the site, and (C) from the site to larger spatial domains. Representative tree-ring sampling supported by creative statistical approaches is thereby key to robustly capture the heterogeneity of climate-growth responses across forested landscapes. We highlight the benefits of combining the temporal information embedded in tree rings with the spatial information offered by forest inventories and earth observations to quantify tree growth and its drivers. In addition, we show how the continued development of mechanistic tree-ring models can help address some of the non-linearities and feedbacks that complicate making inference from tree-ring data. By embracing scaling issues, the discipline of dendrochronology will greatly increase its contributions to assessing climate impacts on forests and support the development of adaptation strategies. © 2018 Elsevier Ltd
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8.
  • Buentke, E, et al. (författare)
  • Glucocorticoid-induced cell death is mediated through reduced glucose metabolism in lymphoid leukemia cells
  • 2011
  • Ingår i: Blood Cancer Journal. - : Macmillan Publishers Limited. - 2044-5385. ; 1:e31, s. 9-
  • Tidskriftsartikel (refereegranskat)abstract
    • Malignant cells are known to have increased glucose uptake and accelerated glucose metabolism. Using liquid chromatography and mass spectrometry, we found that treatment of acute lymphoblastic leukemia (ALL) cells with the glucocorticoid (GC) dexamethasone (Dex) resulted in profound inhibition of glycolysis. We thus demonstrate that Dex reduced glucose consumption, glucose utilization and glucose uptake by leukemic cells. Furthermore, Dex treatment decreased the levels of the plasma membrane-associated glucose transporter GLUT1, thus revealing the mechanism for the inhibition of glucose uptake. Inhibition of glucose uptake correlated with induction of cell death in ALL cell lines and in leukemic blasts from ALL patients cultured ex vivo. Addition of di-methyl succinate could partially overcome cell death induced by Dex in RS4;11 cells, thereby further supporting the notion that inhibition of glycolysis contributes to the induction of apoptosis. Finally, Dex killed RS4;11 cells significantly more efficiently when cultured in lower glucose concentrations suggesting that modulation of glucose levels might influence the effectiveness of GC treatment in ALL. In summary, our data show that GC treatment blocks glucose uptake by leukemic cells leading to inhibition of glycolysis and that these effects play an important role in the induction of cell death by these drugs.
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9.
  • Hagey, DW, et al. (författare)
  • Myeloid cells from Langerhans cell histiocytosis patients exhibit increased vesicle trafficking and an altered secretome capable of activating NK cells
  • 2023
  • Ingår i: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 1592-8721 .- 0390-6078. ; 108:9, s. 2422-2434
  • Tidskriftsartikel (refereegranskat)abstract
    • Langerhans cell histiocytosis (LCH) is a potentially life-threatening inflammatory myeloid neoplasia linked to paediatric neurodegeneration, whereby transformed LCH cells form agglomerated lesions in various organs. Although MAP-kinase pathway mutations have been identified in LCH cells, the functional consequences of these mutations and the mechanisms that cause the pathogenic behaviour of LCH cells are not well understood. In our study, we used an in vitro differentiation system and RNA-sequencing to compare monocyte-derived dendritic cells from LCH patients to those derived from healthy controls or patients with Crohn’s disease, a non-histiocytic inflammatory disease. We observed that Interferon-γ treatment exacerbated intrinsic differences between LCH patient and control cells, including strikingly increased endoand exocytosis gene activity in LCH patients. We validated these transcriptional patterns in lesions and functionally confirmed that LCH cells exhibited increased endo- and exocytosis. Furthermore, RNA-sequencing of extracellular vesicles (EV) revealed the enrichment of pathological transcripts involved in cell adhesion, MAP-kinase pathway, vesicle trafficking and T-cell activation in LCH patients. Thus, we tested the effect of the LCH secretome on lymphocyte activity and found significant activation of NK cells. These findings implicate EVs in the pathology of LCH for the first time, in line with their established roles in the formation of various other tumour niches. Thus, we describe novel traits of LCH patient cells and suggest a pathogenic mechanism of potential therapeutic and diagnostic importance.
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11.
  • Horger, B A, et al. (författare)
  • Neurturin exerts potent actions on survival and function of midbrain dopaminergic neurons
  • 1998
  • Ingår i: The Journal of Neuroscience. - 1529-2401. ; 18:13, s. 4929-4937
  • Tidskriftsartikel (refereegranskat)abstract
    • Glial cell line-derived neurotrophic factor (GDNF) exhibits potent effects on survival and function of midbrain dopaminergic (DA) neurons in a variety of models. Although other growth factors expressed in the vicinity of developing DA neurons have been reported to support survival of DA neurons in vitro, to date none of these factors duplicate the potent and selective actions of GDNF in vivo. We report here that neurturin (NTN), a homolog of GDNF, is expressed in the nigrostriatal system, and that NTN exerts potent effects on survival and function of midbrain DA neurons. Our findings indicate that NTN mRNA is sequentially expressed in the ventral midbrain and striatum during development and that NTN exhibits survival-promoting actions on both developing and mature DA neurons. In vitro, NTN supports survival of embryonic DA neurons, and in vivo, direct injection of NTN into the substantia nigra protects mature DA neurons from cell death induced by 6-OHDA. Furthermore, administration of NTN into the striatum of intact adult animals induces behavioral and biochemical changes associated with functional upregulation of nigral DA neurons. The similarity in potency and efficacy of NTN and GDNF on DA neurons in several paradigms stands in contrast to the differential distribution of the receptor components GDNF Family Receptor alpha1 (GFRalpha1) and GFRalpha2 within the ventral mesencephalon. These results suggest that NTN is an endogenous trophic factor for midbrain DA neurons and point to the possibility that GDNF and NTN may exert redundant trophic influences on nigral DA neurons acting via a receptor complex that includes GFRalpha1.
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  • Bassant, M H, et al. (författare)
  • Electrophysiological and pharmacological properties of neurons within solid basal forebrain transplants in the rat brain
  • 1988
  • Ingår i: Brain Research. - : Elsevier BV. - 0006-8993. ; 460:1, s. 8-16
  • Tidskriftsartikel (refereegranskat)abstract
    • Electrophysiological and pharmacological properties of neurons within solid basal forebrain transplants were studied in adult rats anesthetized with urethane. No specific topography of the neurons recorded was observed within the graft. The mean spontaneous activity of the grafted neurons (GNs) was relatively low (4.9 impulses/s) but not unlike that of other central neurons in situ. A large proportion of GNs fired with regular discharges, but other modes of discharge were also observed. A few rhythmically bursting GNs were recorded having a discharge pattern very much like that of the rhythmically bursting medial septal neurons. The responses of GNs to glutamate, gamma-aminobutyric acid, acetylcholine, serotonin and norepinephrine was fairly similar to those described in other central structures.
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16.
  • Björklund, Margereth, 1950-, et al. (författare)
  • Cancer patients' experiences of nurses' behaviour and health promotion activities : a critical incident analysis
  • 1999
  • Ingår i: European Journal of Cancer Care. - Oxford : Blackwell Publishing. - 0961-5423 .- 1365-2354. ; 8:4, s. 204-212
  • Tidskriftsartikel (refereegranskat)abstract
    • Patients with head and neck cancer report several disease- and health-related problems before, during and a long time after completed treatment. Nurses have an important role in educating/supporting these patients about/through the disease and treatment so that they can attain well-being. This study describes the cancer patients' experiences of nurses' behaviour in terms of critical incidents after nurses had given them care to promote health. The study had a qualitative, descriptive design and the method used was the critical incident technique. Twenty-one informants from the Nordic countries diagnosed with head and neck cancer were strategically selected. It was explained to the informants what a critical incident implies before the interviews took place; this was defined as a major event of great importance, an incident, which the informants still remember, due to its great importance for the outcome of their health and well-being. The nurses' behaviour was examined, and critical incidents were involved in 208 cases-150 positive and 58 negative ones-the number of incidents varying between three and 20 per informant. The nurses' health promotion activities or lack of such activities based on the patients' disease, treatment and symptoms, consisted of informing and instructing the patients as well as enabling their participation. Personal consideration and the nurses' cognisance, knowledge, competence, solicitude, demeanour and statements of understanding were found to be important. Continuous health promotion nursing interventions were of considerable value for the majority of this group of cancer patients. Oncology nurses could reconfirm and update the care of head and neck cancer patients by including health promotion activities in individual care plans. By more frequent use of health promotion models, such as the empowerment model, the nurses could identify and focus on those individuals who needed to alter their life-style as well as tailor their approach towards these patient by setting goals for well-being and a healthy life-style.
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  • Cromer, M. Kyle, et al. (författare)
  • Neomorphic effects of recurrent somatic mutations in Yin Yang 1 in insulin-producing adenomas
  • 2015
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 112:13, s. 4062-4067
  • Tidskriftsartikel (refereegranskat)abstract
    • Insulinomas are pancreatic islet tumors that inappropriately secrete insulin, producing hypoglycemia. Exome and targeted sequencing revealed that 14 of 43 insulinomas harbored the identical somatic mutation in the DNA-binding zinc finger of the transcription factor Yin Yang 1 (YY1). Chromatin immunoprecipitation sequencing (ChIP-Seq) showed that this T372R substitution changes the DNA motif bound by YY1. Global analysis of gene expression demonstrated distinct clustering of tumors with and without YY1(T372R) mutations. Genes showing large increases in expression in YY1(T372R) tumors included ADCY1 (an adenylyl cyclase) and CACNA2D2 (a Ca2+ channel); both are expressed at very low levels in normal beta-cells and show mutation-specific YY1 binding sites. Both gene products are involved in key pathways regulating insulin secretion. Expression of these genes in rat INS-1 cells demonstrated markedly increased insulin secretion. These findings indicate that YY1(T372R) mutations are neomorphic, resulting in constitutive activation of cAMP and Ca2+ signaling pathways involved in insulin secretion.
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19.
  • Dalemo, M., et al. (författare)
  • ORWARE – A simulation model for organic waste handling systems. : Part 1: Model description
  • 1997
  • Ingår i: Resources, Conservation and Recycling. - 0921-3449 .- 1879-0658. ; 21:1, s. 17-37
  • Tidskriftsartikel (refereegranskat)abstract
    • A simulation model, ORWARE (ORganic WAste REsearch), for the handling of organic waste in urban areas has been constructed. The model provides a comprehensive view of the environmental effects, plant nutrient utilisation and energy turnover for this large and complex system. The ORWARE model consists of several sub-models; sewage plant, incineration, landfill, compost, anaerobic digestion, truck transport, transport by sewers, residue transport and spreading of residues on arable land. The model is intended for simulating different scenarios, and the results are: emissions to air and water, energy turnover and the amount of residues returned to arable land. All results are presented, both as the gross figure for the entire system and figures for each process. Throughout the model all physical flows are described by the same variable vector, consisting of 43 substances. This extensive vector facilitates a thorough analysis of the results, but involves some difficulties in acquiring relevant data. In this paper, the model is described. Results from a hypothetical case study are presented in a companion paper.
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  • Fallath, Thorya, et al. (författare)
  • MEDIATOR18 and MEDIATOR20 confer susceptibility to Fusarium oxysporum in Arabidopsis thaliana
  • 2017
  • Ingår i: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 12:4
  • Tidskriftsartikel (refereegranskat)abstract
    • The conserved protein complex known as Mediator conveys transcriptional signals by acting as an intermediary between transcription factors and RNA polymerase II. As a result, Mediator subunits play multiple roles in regulating developmental as well as abiotic and biotic stress pathways. In this report we identify the head domain subunits MEDIATOR18 and MEDIATOR20 as important susceptibility factors for Fusarium oxysporum infection in Arabidopsis thaliana. Mutants of MED18 and MED20 display down-regulation of genes associated with jasmonate signaling and biosynthesis while up-regulation of salicylic acid associated pathogenesis related genes and reactive oxygen producing and scavenging genes. We propose that MED18 and MED20 form a sub-domain within Mediator that controls the balance of salicylic acid and jasmonate associated defense pathways.
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22.
  • Frost, Robert J. W., et al. (författare)
  • Preliminary results from a study of luminescent materials : For application in the beam imaging system at the ESS
  • 2023
  • Ingår i: Nuclear Instruments and Methods in Physics Research Section B. - : Elsevier. - 0168-583X .- 1872-9584. ; 540, s. 227-233
  • Tidskriftsartikel (refereegranskat)abstract
    • As part of the development of the beam imaging system at the European Spallation Source, luminescent screens have been fabricated by the flame spraying of scintillating materials onto stainless steel backings. A total of seven screens were produced, three of chromia alumina (Al2O3:Cr), two of YAG (Y3Al5O12:Ce) and two of a 50/50 mix of these. The properties of these screens under proton irradiation were evaluated using a2.55 MeV proton beam at currents of up to 10 μA. Irradiation times were up to 25 h per sample, during which luminescence-, spectrographic-, thermal- and current-data was sampled at a rate of 1 Hz. Preliminary results of these measurements are reported here; with a quantitative analysis presented for one of the chromia alumina screens and a qualitative comparison of all three material types. The luminescent yield for chromia alumina was determined to be around 2000 photons/MeV for a virgin screen, and was found to drop to 1.5% after 167 mC of proton irradiation. A recovery of the luminescence of chromia alumina to >60% was observed after beam current was reduced for an 8 h period. Observations indicate that the YAG and mixed composition screens retain higher luminescence than the chromia alumina even at temperatures of over 200 ◦C. It is indicated that the luminescence from YAG feeds the R-lines of chromia alumina in the mixed composition screens. 
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23.
  • Genevskiy, Vladislav, et al. (författare)
  • Water sorption properties and nanostructures of airway mucus in patients with COPD and cystic fibrosis
  • 2022
  • Ingår i: European Respiratory Journal. - : EUROPEAN RESPIRATORY SOC JOURNALS LTD. - 0903-1936 .- 1399-3003. ; 60:Suppl 66
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Background: Muco-obstructive diseases lead to hypersecretion, changing the airway mucus properties, and impairing mucociliary transport, resulting in mucostasis, and increasing infection likelihood. Mucin structure may determine the water sorption properties of mucus and play a role in chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF).Objectives: Investigate the sorption properties and mucin nanostructures in mucus collected from healthy, COPD and CF airways.Methods: To investigate mucin nanostructures, small-angle X-ray scattering (SAXS) and atomic force microscopy (AFM) were used. Sorption properties were determined by quartz crystal microbalance with dissipation (QCM-D). Cell-culture (cc) samples from healthy airway mucus (HAM), COPD and CF cultures, and patient HAM from endotracheal tubes and COPD from bronchoscopy were used. Patient mucus was oven-dried at 80°C for the solids content.Results: SAXS and AFM revealed mucin monomers with typical dumbbell structures and varying chain lengths, CF mucins having the shortest chain lengths. Dry-weight solids reached 11wt% in COPD mucus. From QCM-D analysis, cc-COPD and COPD mucus had the highest water content (67 and 75%) during sorption at 99% humidity compared with cc-HAM and HAM (63 and 56%). The overall sorption isotherm for cc-CF mucus was notably lower than HAM and COPD. In low-humidity environments, no hydration-induced glass transition was observed, suggesting mucus remains in a rubbery state.Conclusions: Mucin nanostructures observed in disease could explain the sorption properties where mucin chains affect water content in high humidity environments, which may play a role in protecting the epithelium.
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24.
  • Jakobsson, Lotta, 1967, et al. (författare)
  • Rear-End impact-Crash prevention and occupant protection
  • 2015
  • Ingår i: 2015 IRCOBI Conference Proceedings - International Research Council on the Biomechanics of Injury. ; , s. 803-813
  • Konferensbidrag (refereegranskat)abstract
    • This study presents the enhancements of knowledge as well as countermeasures addressing crash prevention and occupant protection in rear-end impact situations. It includes the second-generation Whiplash Protection System (WHIPS) together with occupant pre-positioning by tightening the electrical reversible safety belts, acceleration reduction by applying the brakes when the car is at a standstill and rearward flashing lights triggered by sensors identifying a potential rear-end impact. Significant steps towards whiplash injury reduction through rear-end impact crash prevention and occupant protection are taken by integrating pre-crash sensing and crash performance to address real-world safety needs. The pre-crash sensing information, with safety belt tightening, addresses some of the main high-risk situations in rear-end impacts, such as extensive head to head-restraint distance. By adjusting the occupants to sit closer to the seat at time of impact, the full benefit of the seat protection can be achieved. The WHIPS has been further improved by focusing energy absorption together with even and close support, and by addressing small and large occupants, both male and female, thus adding to overall occupant protection potential. Through the use of pre-crash sensing, opponent warning system and a braking functionality, additional injury reductions can be achieved and some crashes avoided altogether. Further studies are needed to quantify these effects.
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25.
  • Kotur, M, et al. (författare)
  • PHOTOCATHODE LASER PULSE SHAPING FOR IMPROVED EMITTANCE
  • 2018
  • Ingår i: Proceedings of the 29th Linear Accelerator Conference, LINAC 2018. - 9783954501946 ; , s. 84-86
  • Konferensbidrag (refereegranskat)abstract
    • We present a setup for producing and characterizing picosecond ultraviolet laser pulses for use in the MAX IV photocathode electron gun preinjector. Frequency-tripled laser pulses from a commercial laser system are shaped directly in the ultraviolet domain using a Fourier-domain pulse shaper. The pulses were characterized using a transient grating FROG. We discuss a proposed upgrade of the pulse shaper, as well as its limitations.
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26.
  • Kotur, M, et al. (författare)
  • Pulse shaping at the MAX IV photoelectron gun laser
  • 2017
  • Ingår i: IPAC 2017 - Proceedings of the 8th International Particle Accelerator Conference. - 9783954501823 - 9783954501823 ; , s. 1541-1543
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • A motivation for the development of a versatile, programmable source of shaped picosecond pulses for use in photocathode electron gun preinjectors is presented. We present the experimental setup for arbitrary longitudinal pusle shaping of the MAX IV photocathode gun laser. The setup consists of a grating-based Fourier-domain shaper capable of stretching the pulses directly in the UV domain. Preliminary results are presented and discussed.
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27.
  • Kuter, Katarzyna Z., et al. (författare)
  • The role of glia in Parkinson's disease : Emerging concepts and therapeutic applications
  • 2020
  • Ingår i: Recent Advances in Parkinson's Disease. - : Elsevier. - 0079-6123 .- 1875-7855. - 9780444642608 ; 252, s. 131-168
  • Bokkapitel (refereegranskat)abstract
    • Originally believed to primarily affect neurons, Parkinson's disease (PD) has recently been recognized to also affect the functions and integrity of microglia and astroglia, two cell categories of fundamental importance to brain tissue homeostasis, defense, and repair. Both a loss of glial supportive-defensive functions and a toxic gain of glial functions are implicated in the neurodegenerative process. Moreover, the chronic treatment with L-DOPA may cause maladaptive glial plasticity favoring a development of therapy complications. This chapter focuses on the pathophysiology of PD from a glial point of view, presenting this rapidly growing field from the first discoveries made to the most recent developments. We report and compare histopathological and molecular findings from experimental models of PD and human studies. We moreover discuss the important role played by astrocytes in compensatory adaptations taking place during presymptomatic disease stages. We finally describe examples of potential therapeutic applications stemming from an increased understanding of the important roles of glia in PD.
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28.
  • Lindau, F, et al. (författare)
  • MAX IV Photocathode Gun Laser System Specification and Diagnostics
  • 2017
  • Ingår i: IPAC 2017 - Proceedings of the 8th International Particle Accelerator Conference. - 9783954501823 - 9783954501823 ; , s. 1544-1546
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • The MAXIV injector has two guns - a thermionic used for ring injections, and a photocathode used for short pulse facility operation. A commercial Ti:sapphire laser from KMLabs drives the copper based photocathode gun. It has been running without major issues for more than 3 years. The laser delivers up to §I{500}{\textmu J} on the cathode at the third harmonic, §I{263}{nm}, via a vacuum laser transport system. To achieve the desired pulse duration of 2–§I10{ps} the laser pulses, originally ~§I{100}{fs} long, are stretched with a prism pair and the resulting §I{1.5}{ps} pulses stacked by a series of birefringent \textalpha -BBO crystals. Diagnostics consist of photodiodes, spectrometers, and cameras. Longitudinal pulse characterization is done with a cross correlator and a UV FROG.
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30.
  • Lyphout, Christophe, 1981-, et al. (författare)
  • Screening Design of Supersonic Air Fuel Processing for Hard Metal Coatings
  • 2014
  • Ingår i: Journal of thermal spray technology (Print). - : Springer Science and Business Media LLC. - 1059-9630 .- 1544-1016. ; 23:8, s. 1323-1332
  • Tidskriftsartikel (refereegranskat)abstract
    • Replacement of electrolytic hard chromium method by thermal spray technology has shown a growing interest in the past decades, mainly pioneered by depositing WC-based material by conventional HVOF processes. Lower thermal energy and higher kinetic energy of sprayed particles achieved by newly developed Supersonic Air Fuel system, so-called HVAF-M3, significantly reduces decarburization, and increases wear and corrosion resistance properties, making HVAF-sprayed coatings attractive both economically and environmentally. In the present work, full factorial designs of experiments have been extensively utilized to establish relationships between hardware configurations, process and engineering variables, and coatings properties. The relevance of those process factors is emphasized and their significance is discussed in the optimization of coatings for improved abrasion wear and corrosion performances. © 2014 ASM International.
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32.
  • Masarapu, Yuvarani, et al. (författare)
  • Spatially resolved multiomics on the neuronal effects induced by spaceflight in mice
  • 2024
  • Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 15:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Impairment of the central nervous system (CNS) poses a significant health risk for astronauts during long-duration space missions. In this study, we employed an innovative approach by integrating single-cell multiomics (transcriptomics and chromatin accessibility) with spatial transcriptomics to elucidate the impact of spaceflight on the mouse brain in female mice. Our comparative analysis between ground control and spaceflight-exposed animals revealed significant alterations in essential brain processes including neurogenesis, synaptogenesis and synaptic transmission, particularly affecting the cortex, hippocampus, striatum and neuroendocrine structures. Additionally, we observed astrocyte activation and signs of immune dysfunction. At the pathway level, some spaceflight-induced changes in the brain exhibit similarities with neurodegenerative disorders, marked by oxidative stress and protein misfolding. Our integrated spatial multiomics approach serves as a stepping stone towards understanding spaceflight-induced CNS impairments at the level of individual brain regions and cell types, and provides a basis for comparison in future spaceflight studies. For broader scientific impact, all datasets from this study are available through an interactive data portal, as well as the National Aeronautics and Space Administration (NASA) Open Science Data Repository (OSDR).
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33.
  • Nikkhah, G, et al. (författare)
  • A microtransplantation approach for cell suspension grafting in the rat Parkinson model : a detailed account of the methodology
  • 1994
  • Ingår i: Neuroscience. - : Elsevier BV. - 0306-4522. ; 63:1, s. 57-72
  • Tidskriftsartikel (refereegranskat)abstract
    • Shortcomings of current techniques used for the intracerebral transplantation of ventral mesencephalic dopamine neurons include low graft survival, high variability, considerable implantation trauma and suboptimal graft integration. In order to overcome these limitations, we have adopted a microtransplantation approach which allows precise and reproducible implantation of ventral mesencephalon cell suspensions at single or multiple sites with minimal trauma and improved survival and integration of the grafted neurons [Nikkhah et al. (1994) Brain Res. 633, 133-143]. The present study was undertaken to determine the influence of different grafting parameters as well as the time-course of development of micrografted dopaminergic neurons and to devise an optimal microtransplantation procedure in the rat Parkinson model, Rats with unilateral 6-hydroxydopamine lesions of the nigrostriatal pathway received four graft deposits of either 0.25, 0.5, 1.0 or 2.0 microliters along four injection tracts (150,000 cells/microliters) using either a glass capillary (o.d. 50-70 microns) or a regular cannula (o.d. 0.50 mm, metal cannula grafts). At one, two and 12 weeks postgrafting (capillary grafts) and at 12 weeks postgrafting (metal cannula grafts) dopamine neuron survival and graft volumes were measured and the implantation trauma assessed by glial fibrillary acidic protein expression. The results demonstrate that single deposits of 50,000-75,000 cells in 0.5 microliter, implanted with a glass capillary, provide the best environment both for dopaminergic and non-dopaminergic neuron survival. Grafts implanted with the glass capillary showed much weaker long-term glial fibrillary acidic protein expression along the injection tract and around the implants than was the case in grafts implanted with the thicker metal cannula. Optimal graft integration and minimal disturbances of host brain structures can reliably be achieved by small-sized implants (20,000-35,000 cells/deposit). Tyrosine hydroxylase-positive fiber outgrowth from micrografted dopaminergic neurons was seen not only in the surrounding caudate-putamen, but also along white matter tracts into the nucleus accumbens and the overlying cerebral cortex. Spreading of dopaminergic micrografts over multiple small deposits rather than increasing the volume of single grafts gave more extensive reinnervation of the entire host striatum. The micrografting technique provides a useful tool to improve graft-host interactions in the rat Parkinson model, and it allows more precise and reproducible quantitative studies on dopamine neuron survival and growth in intrastriatal ventral mesencephalon transplants. This technique should also be highly useful for the intracerebral implantation of cells derived from primary cultures or cell lines [Gage and Fisher (1991) Neuron 6, 1-12].
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34.
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35.
  • Philips, Matthew F., et al. (författare)
  • Neuroprotective and behavioral efficacy of nerve growth factor-transfected hippocampal progenitor cell transplants after experimental traumatic brain injury
  • 2001
  • Ingår i: Journal of Neurosurgery. - 0022-3085. ; 94:5, s. 765-765
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECT: Immortalized neural progenitor cells derived from embryonic rat hippocampus (HiB5), were transduced ex vivo with the gene for mouse nerve growth factor (NGF) to secrete NGF (NGF-HiB5) at 2 ng/hr/10(5) cells in culture. METHODS: Fifty-nine male Wistar rats weighing 300 to 370 g each were anesthetized with 60 mg/kg sodium pentobarbital and subjected to lateral fluid-percussion brain injury of moderate severity (2.3-2.4 atm, 34 rats) or sham injury (25 rats). At 24 hours postinjury, 2 microl (150,000 cells/microl) of [3H]thymidine-labeled NGF-HiB5 cells were transplanted stereotactically into three individual sites in the cerebral cortex adjacent to the injury site (14 rats). Separate groups of brain-injured rats received nontransfected (naive [n])-HiB5 cells (12 animals) or cell suspension vehicle (eight animals). One week postinjury, animals underwent neurological evaluation for motor function and cognition (Morris water maze) and were killed for histological, autoradiographic, and immunocytochemical analysis. Viable HiB5 cell grafts were identified in all animals, together with reactive microglia and macrophages located throughout the periinjured parenchyma and grafts (OX-42 immunohistochemistry). Brain-injured animals transplanted with either NGF-HiB5 or n-HiB5 cells displayed significantly improved neuromotor function (p < 0.05) and spatial learning behavior (p < 0.005) compared with brain-injured animals receiving microinjections of vehicle alone. A significant reduction in hippocampal CA3 cell death was observed in brain-injured animals receiving transplants of NGF-HiB5 cells compared with those receiving n-HiB5 cells or vehicle (p < 0.025). CONCLUSIONS: This study demonstrates that immortalized neural stem cells that have been retrovirally transduced to produce NGF can markedly improve cognitive and neuromotor function and rescue hippocampal CA3 neurons when transplanted into the injured brain during the acute posttraumatic period.
  •  
36.
  • Rosenblad, Carl, et al. (författare)
  • Vector-mediated l-3,4-dihydroxyphenylalanine delivery reverses motor impairments in a primate model of Parkinson's disease
  • 2019
  • Ingår i: Brain : a journal of neurology. - : Oxford University Press (OUP). - 1460-2156. ; , s. 2402-2416
  • Tidskriftsartikel (refereegranskat)abstract
    • Ever since its introduction 40 years ago l-3,4-dihydroxyphenylalanine (l-DOPA) therapy has retained its role as the leading standard medication for patients with Parkinson's disease. With time, however, the shortcomings of oral l-DOPA treatment have become apparent, particularly the motor fluctuations and troublesome dyskinetic side effects. These side effects, which are caused by the excessive swings in striatal dopamine caused by intermittent oral delivery, can be avoided by delivering l-DOPA in a more continuous manner. Local gene delivery of the l-DOPA synthesizing enzymes, tyrosine hydroxylase and guanosine-tri-phosphate-cyclohydrolase-1, offers a new approach to a more refined dopaminergic therapy where l-DOPA is delivered continuously at the site where it is needed i.e. the striatum. In this study we have explored the therapeutic efficacy of adeno-associated viral vector-mediated l-DOPA delivery to the putamen in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated rhesus monkeys, the standard non-human primate model of Parkinson's disease. Viral vector delivery of the two enzymes, tyrosine hydroxylase and guanosine-5'-tri-phosphate-cyclohydrolase-1, bilaterally into the dopamine-depleted putamen, induced a significant, dose-dependent improvement of motor behaviour up to a level identical to that obtained with the optimal dose of peripheral l-DOPA. Importantly, this improvement in motor function was obtained without any adverse dyskinetic effects. These results provide proof-of-principle for continuous vector-mediated l-DOPA synthesis as a novel therapeutic strategy for Parkinson's disease. The constant, local supply of l-DOPA obtained with this approach holds promise as an efficient one-time treatment that can provide long-lasting clinical improvement and at the same time prevent the appearance of motor fluctuations and dyskinetic side effects associated with standard oral dopaminergic medication.
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37.
  • Schönning, A., et al. (författare)
  • Venous thrombosis in children and adolescents with Hodgkin lymphoma in Sweden
  • 2017
  • Ingår i: Thrombosis Research. - : Elsevier BV. - 0049-3848 .- 1879-2472. ; 152, s. 64-68
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction Pediatric patients with Hodgkin lymphoma (HL) have several risk factors for venous thromboembolism (VTE). Although these patients are occasionally treated with thromboprophylaxis, no guidelines are implemented in Sweden. Scarce data from adult patients indicate an increased risk of VTE, but pediatric data is largely missing. Given the favorable overall survival of HL, there should reasonably be more focus on preventing complications. Materials and methods We conducted a retrospective cohort study, including all patients registered in the Childhood Cancer Registry under the age of 18 years diagnosed with HL between January 2005 and December 2015 in Sweden. Results Data was retrieved from the medical records of all 163 patients (100%) at six Swedish pediatric cancer centers. The incidence of VTE was 7.7% (symptomatic VTE 3.9%). The median follow-up was 3.4 years (range 0.3–10.5). Only five patients (3.1%) were treated with thromboprophylaxis. All VTE events occurred in the older age category (11–17 years) and all but one (92.7%) had a mediastinal mass. While the VTE did not significantly affect the treatment of HL, it caused increased morbidity and 2/12 developed a post-thrombotic syndrome. No significant risk factors for VTE were identified. Conclusions VTE is a relatively common complication of HL and its treatment, causing increased acute and long-term morbidity. However, due to limited number of events we could not demonstrate risk-factors for VTE that would identify patients who might benefit from thromboprophylaxis.
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38.
  • Silveira, L. L., et al. (författare)
  • Study of the corrosion and cavitation resistance of HVOF and HVAF FeCrMnSiNi and FeCrMnSiB coatings
  • 2019
  • Ingår i: Surface & Coatings Technology. - : Elsevier BV. - 0257-8972 .- 1879-3347. ; 374, s. 910-922
  • Tidskriftsartikel (refereegranskat)abstract
    • Cavitation and corrosion on hydrodynamic components and systems reduces the operational efficiency. The use of wear resistant coatings has been studied as a solution to the problem of corrosion and cavitation in industrial environments. The high velocity oxy-fuel process (HVOF) can produce coatings with high density and bond strength. High velocity air-fuel (HVAF) is an alternative process, which can deposit coatings with higher velocity and lower temperatures, compared to the HVOF process, resulting in lower oxide content. This paper analyzes the HVOF and HVAF processes to deposit FeCrMnSiNi and FeCrMnSiB coatings, comparing their cavitation and corrosion resistance. HVAF coatings presented lower porosity and oxide levels, as well as higher hardness values. The HVAF process presented better cavitation and corrosion resistance, due to lower porosity and oxide contents of the coatings. The amount of oxides and pores in the coatings was crucial in their corrosive behavior, by facilitating the penetration of the chloride ions through the pores, leading to a higher corrosion rate and pitting formation. © 2019 Elsevier B.V.
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39.
  • Sonesson, U., et al. (författare)
  • Environmental and economic analysis of management systems for biodegradable waste
  • 2000
  • Ingår i: Resources, Conservation and Recycling. - 0921-3449 .- 1879-0658. ; 28:02-jan, s. 29-53
  • Tidskriftsartikel (refereegranskat)abstract
    • The management system for solid and liquid organic waste affects the environment and surrounding technical systems in several ways. In order to decrease the environmental impact and resource use, biological waste treatment and alternative solutions for sewage treatment are often advocated. These alternatives include increased agricultural use of waste residuals. To analyse whether such proposed systems indicate improvements for the environment and its sustainability, systems analysis is a useful method The changes in environmental impact and resource use is not only a result of changes in waste treatment methods, but also largely a result of changes in surrounding systems (energy and agriculture) caused by changes in waste management practices. In order to perform a systems analysis, a substance-flow simulation model, the organic waste research model (ORWARE), has been used. The results are evaluated by using methodology from life cycle assessment (LCA). An economic analysis was also performed on three of the studied scenarios. The management system for solid organic waste and sewage in the municipality of Uppsala, Sweden, was studied. Three scenarios for different treatments of solid waste were analysed: incineration with heat recovery, composting, and anaerobic digestion. These three scenarios included conventional sewage treatment. A fourth scenario reviewed was anaerobic digestion of solid waste, using urine-separating toilets and separate handling of the urine fraction. The results are only valid for the case study and under the assumptions made. In this case study anaerobic digestion result in the lowest environmental impact of all the solid waste management systems, but is costly. Economically, incineration with heat recovery is the cheapest way to treat solid waste. Composting gives environmental advantages compared to incineration methods, without significantly increased costs. Urine separation, which may be implemented together with any solid waste treatment, has great advantages, particularly in its low impact on the environment. However, there is a large increase in acidification.
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40.
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41.
  • Tordo, Julie, et al. (författare)
  • A novel adeno-associated virus capsid with enhanced neurotropism corrects a lysosomal transmembrane enzyme deficiency
  • 2018
  • Ingår i: Brain. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 141:7, s. 2014-2031
  • Tidskriftsartikel (refereegranskat)abstract
    • Recombinant adeno-associated viruses (AAVs) are popular in vivo gene transfer vehicles. However, vector doses needed to achieve therapeutic effect are high and some target tissues in the central nervous system remain difficult to transduce. Gene therapy trials using AAV for the treatment of neurological disorders have seldom led to demonstrated clinical efficacy. Important contributing factors are low transduction rates and inefficient distribution of the vector. To overcome these hurdles, a variety of capsid engineering methods have been utilized to generate capsids with improved transduction properties. Here we describe an alternative approach to capsid engineering, which draws on the natural evolution of the virus and aims to yield capsids that are better suited to infect human tissues. We generated an AAV capsid to include amino acids that are conserved among natural AAV2 isolates and tested its biodistribution properties in mice and rats. Intriguingly, this novel variant, AAV-TT, demonstrates strong neurotropism in rodents and displays significantly improved distribution throughout the central nervous system as compared to AAV2. Additionally, sub-retinal injections in mice revealed markedly enhanced transduction of photoreceptor cells when compared to AAV2. Importantly, AAV-TT exceeds the distribution abilities of benchmark neurotropic serotypes AAV9 and AAVrh10 in the central nervous system of mice, and is the only virus, when administered at low dose, that is able to correct the neurological phenotype in a mouse model of mucopolysaccharidosis IIIC, a transmembrane enzyme lysosomal storage disease, which requires delivery to every cell for biochemical correction. These data represent unprecedented correction of a lysosomal transmembrane enzyme deficiency in mice and suggest that AAV-TT-based gene therapies may be suitable for treatment of human neurological diseases such as mucopolysaccharidosis IIIC, which is characterized by global neuropathology.
  •  
42.
  • Unger, M. M., et al. (författare)
  • Unimpaired postprandial pancreatic polypeptide secretion in Parkinson's disease and REM sleep behavior disorder
  • 2013
  • Ingår i: Movement Disorders. - : Wiley. - 0885-3185. ; 28:4, s. 529-533
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Pancreatic polypeptide is released immediately after food ingestion. The release is operated by vagal-abdominal projections and has therefore been suggested as a test for vagal nerve integrity. Pathoanatomical and clinical studies indicate vagal dysfunction in early Parkinson's disease (PD). Methods: We assessed the postprandial secretion of pancreatic polypeptide and motilin in healthy controls (n = 18) and patients with idiopathic rapid-eye-movement sleep behavior disorder (iRBD, n = 10), a potential premotor stage of PD, as well as in drug-naive (n = 19) and treated (n = 19) PD patients. Results: The postprandial pancreatic polypeptide secretion showed a physiological pattern in all groups and even an enhanced response in drug-naive PD and iRBD. Motilin concentrations correlated with pancreatic polypeptide concentrations. Conclusions: Postprandial pancreatic polypeptide secretion is not a suitable test for vagal nerve integrity in PD. The unimpaired pancreatic polypeptide response in iRBD and PD might be explained by partially intact vagal-abdominal projections or compensatory mechanisms substituting a defective neuronal brain–gut axis.
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43.
  •  
44.
  • Wang, T., et al. (författare)
  • Change of apheresis device decreased the incidence of severe acute graft-versus-host disease among patients after allogeneic stem cell transplantation with sibling donors
  • 2018
  • Ingår i: Transfusion. - : WILEY. - 0041-1132 .- 1537-2995. ; 53, s. 765-765
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The composition of the graft used for allogeneic hematopoietic stem cell transplantation (HSCT) is important for the treatment outcome. Different apheresis devices may yield significant differences in peripheral blood stem cell graft cellular composition. We compared stem cell grafts produced by Cobe Spectra (Cobe) and Spectra Optia (Optia) with use of the mononuclear cell (MNC) protocol, and evaluated clinical outcome parameters such as graft-versus-host disease (GvHD), transplant-related mortality (TRM), relapse, and overall survival.STUDY DESIGN AND METHODS: During 5 years, 31 Cobe Spectra and 40 Spectra Optia grafts were analyzed for CD34, CD3, CD4, CD8, CD19, and CD56 cell content. Clinical outcome parameters were correlated and compared between the two patient groups using different apheresis devices.RESULTS: Optia grafts contained fewer lymphocytes compared to Cobe (p<0.001). Optia grafts had a significantly lower incidence of acute GvHD Grades II through IV (Cobe 45% vs. Optia 23%; p=0.039) and TRM (16% vs. 2.5%; p<0.05) but higher chronic GvHD (32% vs. 67%; p=0.005) compared to Cobe grafts. Finally, the multivariate analysis showed a significant correlation among the different apheresis devices and both acute GvHD II through IV and severe chronic GvHD. The multivariate analysis also showed a significant correlation between the CD3+ cell dose and the incidence of severe acute GvHD.CONCLUSION: Optia-obtained grafts yielded a lower acute GvHD Grades II-IV and TRM risk, but had no impact on relapse or overall survival in this study. Understanding and further improvement of peripheral blood stem cell (PBSC) apheresis techniques may be used in the future to personalize HSCT by, for example, fine-tuning the GvHD incidence.
  •  
45.
  • Zhou, Junhua, et al. (författare)
  • Somatic mutations of GNA11 and GNAQ in CTNNB1-mutant aldosterone-producing adenomas presenting in puberty, pregnancy or menopause
  • 2021
  • Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 53:9, s. 1360-1372
  • Tidskriftsartikel (refereegranskat)abstract
    • Sequence analysis identifies gain-of-function somatic mutations in GNA11 or GNAQ in CTNNB1-mutant aldosterone-producing adenomas. Most patients with these mutations presented during puberty, pregnancy or menopause, with elevated LHCGR expression. Most aldosterone-producing adenomas (APAs) have gain-of-function somatic mutations of ion channels or transporters. However, their frequency in aldosterone-producing cell clusters of normal adrenal gland suggests a requirement for codriver mutations in APAs. Here we identified gain-of-function mutations in both CTNNB1 and GNA11 by whole-exome sequencing of 3/41 APAs. Further sequencing of known CTNNB1-mutant APAs led to a total of 16 of 27 (59%) with a somatic p.Gln209His, p.Gln209Pro or p.Gln209Leu mutation of GNA11 or GNAQ. Solitary GNA11 mutations were found in hyperplastic zona glomerulosa adjacent to double-mutant APAs. Nine of ten patients in our UK/Irish cohort presented in puberty, pregnancy or menopause. Among multiple transcripts upregulated more than tenfold in double-mutant APAs was LHCGR, the receptor for luteinizing or pregnancy hormone (human chorionic gonadotropin). Transfections of adrenocortical cells demonstrated additive effects of GNA11 and CTNNB1 mutations on aldosterone secretion and expression of genes upregulated in double-mutant APAs. In adrenal cortex, GNA11/Q mutations appear clinically silent without a codriver mutation of CTNNB1.
  •  
46.
  • Adli, Erik, et al. (författare)
  • Progress Of The Ess Proton Beam Imaging Systems
  • 2022
  • Ingår i: LINAC2022. - : ACoW Publishing. ; , s. 395-398
  • Konferensbidrag (refereegranskat)abstract
    • The ESS Target Proton Beam Imaging Systems has the objective to image the 5 MW ESS proton beam as it entersthe spallation target. The imaging systems has to operate in a harsh radiation environment, leading to a number of challenges : development of radiation hard photon sources, long and aperture-restricted optical paths and fast electronics required to provide rapid information in case of beam anomalies. This paper outlines how main challenges of the imaging systems have been addressed, and the status of deployment as ESS gets closer to beam.
  •  
47.
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48.
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49.
  • Alexanderson, H., et al. (författare)
  • FATIGUE IN ADULT IDIOPATHIC INFLAMMATORY MYOPATHIES
  • 2015
  • Ingår i: Annals of the Rheumatic Diseases. - : BMJ PUBLISHING GROUP. - 0003-4967 .- 1468-2060. ; 74, s. 106-106
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
  •  
50.
  • Andersson-Gunnerås, Sara, et al. (författare)
  • Asymmetric expression of a poplar ACC oxidase controls ethylene production during gravitational induction of tension wood
  • 2003
  • Ingår i: The Plant Journal. - : Blackwell Publishing. - 0960-7412 .- 1365-313X. ; 34:3, s. 339-349
  • Tidskriftsartikel (refereegranskat)abstract
    • Ethylene is produced in wood-forming tissues, and when applied exogenously, it has been shown to cause profound effects on the pattern and rate of wood development. However, the molecular regulation of ethylene biosynthesis during wood formation is poorly understood. We have characterised an abundant 1-aminocyclopropane-1-carboxylic acid (ACC) oxidase gene (PttACO1) in the wood-forming tissues of Populus tremula (L.) × P. tremuloides (Michx). PttACO1 is primarily expressed in developing secondary xylem, and is specifically upregulated during secondary wall formation. Nevertheless, according to GC–MS analysis combined with tangential cryosectioning, the distribution of ACC was found to be fairly uniform across the cambial-region tissues. Gravitational stimulation, which causes tension wood to form on the upper side of the stem, resulted in a strong induction of PttACO1 expression and ACC oxidase activity in the tension wood-forming tissues. The ACC levels increased in parallel to the PttACO1 expression. However, the increase on the upper (tension wood) side was only minor, whereas large amounts of both ACC and its hydrolysable conjugates accumulated on the lower (opposite) side of the stem. This suggests that the relatively low level of ACC on the tension wood side is a result of its conversion to ethylene by the highly upregulated PttACO1, and the concurrent accumulation of ACC on the opposite side of the wood is because of the low PttACO1 levels. We conclude that PttACO1 and ACC oxidase activity, but not ACC availability, are important in the control of the asymmetric ethylene production within the poplar stem when tension wood is induced by gravitational stimulation.
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