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Sökning: WFRF:(Flodstrom S)

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  • Palma Medina, LM, et al. (författare)
  • Targeted plasma proteomics reveals signatures discriminating COVID-19 from sepsis with pneumonia
  • 2023
  • Ingår i: Respiratory research. - : Springer Science and Business Media LLC. - 1465-993X. ; 24:1, s. 62-
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundCOVID-19 remains a major public health challenge, requiring the development of tools to improve diagnosis and inform therapeutic decisions. As dysregulated inflammation and coagulation responses have been implicated in the pathophysiology of COVID-19 and sepsis, we studied their plasma proteome profiles to delineate similarities from specific features.MethodsWe measured 276 plasma proteins involved in Inflammation, organ damage, immune response and coagulation in healthy controls, COVID-19 patients during acute and convalescence phase, and sepsis patients; the latter included (i) community-acquired pneumonia (CAP) caused by Influenza, (ii) bacterial CAP, (iii) non-pneumonia sepsis, and (iv) septic shock patients.ResultsWe identified a core response to infection consisting of 42 proteins altered in both COVID-19 and sepsis, although higher levels of cytokine storm-associated proteins were evident in sepsis. Furthermore, microbiologic etiology and clinical endotypes were linked to unique signatures. Finally, through machine learning, we identified biomarkers, such as TRIM21, PTN and CASP8, that accurately differentiated COVID-19 from CAP-sepsis with higher accuracy than standard clinical markers.ConclusionsThis study extends the understanding of host responses underlying sepsis and COVID-19, indicating varying disease mechanisms with unique signatures. These diagnostic and severity signatures are candidates for the development of personalized management of COVID-19 and sepsis.
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  • Soderholm, S, et al. (författare)
  • A photoelectron spectroscopy and x-ray absorption study of Bi2Sr2CaCu2O8 single crystal with adsorbed Cs : On the origin of the states affected by electron doping and evidence for spatially resolved electron doping
  • 1996
  • Ingår i: Journal of Physics. - : IOP Publishing. - 0953-8984 .- 1361-648X. ; 8:9, s. 1307-1320
  • Tidskriftsartikel (refereegranskat)abstract
    • The influence of electron doping, via deposition of small amounts of Cs, on the electronic structure of Bi2Sr2CaCu2O8 has been studied by high-resolution photoelectron spectroscopy (PES) and x-ray absorption spectroscopy (XAS), utilizing synchrotron radiation. The changes in the electronic structure were monitored by PES of the valence band and of the O Is, Bi 4f, Bi 5d, Ca 2p and Sr 3d core levels, and by XAS at the O Is, Cu 2p and Ca 2p edges. The experimental data suggest that the loss of the Fermi edge and the loss of spectral intensity down to about 2 eV below the Fermi level, and the substantial loss of spectral intensity of the pre-edge structure in the O 1s XAS spectrum are mainly due to annihilation of states with O 2p character in the Cu-O layer. It is evident from bulk- and surface-sensitive XAS spectra that the electron doping by Cs affects the electronic structure more strongly close to the surface. This implies that the doping occurs locally and that the charge transfer between the different layers in the unit cell is not uniform. Thus it seems possible to alter the electronic properties of Bi2Sr2CaCu2O8 locally through spatially resolved electron doping. When larger amounts of Cs are deposited, a chemical reaction occurs which causes a disruption of the Bi-O layer. This deposition regime is characterized by the presence of caesium oxide and reduced (metallic) Bi.
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  • Hankaniemi, MM, et al. (författare)
  • Structural Insight into CVB3-VLP Non-Adjuvanted Vaccine
  • 2020
  • Ingår i: Microorganisms. - : MDPI AG. - 2076-2607. ; 8:9
  • Tidskriftsartikel (refereegranskat)abstract
    • Coxsackievirus B (CVB) enteroviruses are common pathogens that can cause acute and chronic myocarditis, dilated cardiomyopathy, aseptic meningitis, and they are hypothesized to be a causal factor in type 1 diabetes. The licensed enterovirus vaccines and those currently in clinical development are traditional inactivated or live attenuated vaccines. Even though these vaccines work well in the prevention of enterovirus diseases, new vaccine technologies, like virus-like particles (VLPs), can offer important advantages in the manufacturing and epitope engineering. We have previously produced VLPs for CVB3 and CVB1 in insect cells. Here, we describe the production of CVB3-VLPs with enhanced production yield and purity using an improved purification method consisting of tangential flow filtration and ion exchange chromatography, which is compatible with industrial scale production. We also resolved the CVB3-VLP structure by Cryo-Electron Microscopy imaging and single particle reconstruction. The VLP diameter is 30.9 nm on average, and it is similar to Coxsackievirus A VLPs and the expanded enterovirus cell-entry intermediate (the 135s particle), which is ~2 nm larger than the mature virion. High neutralizing and total IgG antibody levels, the latter being a predominantly Th2 type (IgG1) phenotype, were detected in C57BL/6J mice immunized with non-adjuvanted CVB3-VLP vaccine. The structural and immunogenic data presented here indicate the potential of this improved methodology to produce highly immunogenic enterovirus VLP-vaccines in the future.
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  • Jacobson, S., et al. (författare)
  • Alloreactivity but Failure to Reject Human Islet Transplants by Humanized Balb/c/Rag2(-/-)gc(-/-) Mice
  • 2010
  • Ingår i: Scandinavian Journal of Immunology. - : Wiley. - 0300-9475 .- 1365-3083. ; 71:2, s. 83-90
  • Tidskriftsartikel (refereegranskat)abstract
    • A human islet transplant can cure patients with type 1 diabetes. A drawback of islet transplantation is the life-long immunosuppressive medication, often associated with severe side effects. Moreover, in spite of the immunosuppressive therapy, islets are lost in the majority of transplanted patients over time. An improved small animal model for studies on human islet allograft rejection mechanisms and the development of new measures for its prevention is clearly warranted. Here, we evaluated the potential of Balb/cRag2(-/-)gamma c(-/-) mice carrying a human-like immune system (so-called humanized mice) as a tool for studies on the rejection of transplanted human islets. Human T cells from Balb/cRag2(-/-)gamma c(-/-) mice, which as neonates had been transplanted with CD34(+) human cord blood haematopoietic stem cells (HIS mice), proliferated in response to allogeneic human dendritic cells, but failed to reject a human islet allograft transplanted to the renal subcapsular space as assessed by immunohistochemistry and analysis of human serum C-peptide levels. Histological analysis revealed that few if any T cells had migrated to the grafted tissue. These observations question the usefulness of the HIS mouse model for studies on human islet allograft rejection mechanisms and highlight the need for further improvements.
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  • Khan, D, et al. (författare)
  • Short-term CFTR inhibition reduces islet area in C57BL/6 mice
  • 2019
  • Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1, s. 11244-
  • Tidskriftsartikel (refereegranskat)abstract
    • Cystic fibrosis-related diabetes (CFRD) worsens CF lung disease leading to early mortality. Loss of beta cell area, even without overt diabetes or pancreatitis is consistently observed. We investigated whether short-term CFTR inhibition was sufficient to impact islet morphology and function in otherwise healthy mice. CFTR was inhibited in C57BL/6 mice via 8-day intraperitoneal injection of CFTRinh172. Animals had a 7-day washout period before measures of hormone concentration or islet function were performed. Short-term CFTR inhibition increased blood glucose concentrations over the course of the study. However, glucose tolerance remained normal without insulin resistance. CFTR inhibition caused marked reductions in islet size and in beta cell and non-beta cell area within the islet, which resulted from loss of islet cell size rather than islet cell number. Significant reductions in plasma insulin concentrations and pancreatic insulin content were also observed in CFTR-inhibited animals. Temporary CFTR inhibition had little long-term impact on glucose-stimulated, or GLP-1 potentiated insulin secretion. CFTR inhibition has a rapid impact on islet area and insulin concentrations. However, islet cell number is maintained and insulin secretion is unaffected suggesting that early administration of therapies aimed at sustaining beta cell mass may be useful in slowing the onset of CFRD.
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  • Lozano, IMD, et al. (författare)
  • Proteome profiling of whole plasma and plasma-derived extracellular vesicles facilitates the detection of tissue biomarkers in the non-obese diabetic mouse
  • 2022
  • Ingår i: Frontiers in endocrinology. - : Frontiers Media SA. - 1664-2392. ; 13, s. 971313-
  • Tidskriftsartikel (refereegranskat)abstract
    • The mechanism by which pancreatic beta cells are destroyed in type 1 diabetes (T1D) remains to be fully understood. Recent observations indicate that the disease may arise because of different pathobiological mechanisms (endotypes). The discovery of one or several protein biomarkers measurable in readily available liquid biopsies (e.g. blood plasma) during the pre-diabetic period may enable personalized disease interventions. Recent studies have shown that extracellular vesicles (EVs) are a source of tissue proteins in liquid biopsies. Using plasma samples collected from pre-diabetic non-obese diabetic (NOD) mice (an experimental model of T1D) we addressed if combined analysis of whole plasma samples and plasma-derived EV fractions increases the number of unique proteins identified by mass spectrometry (MS) compared to the analysis of whole plasma samples alone. LC-MS/MS analysis of plasma samples depleted of abundant proteins and subjected to peptide fractionation identified more than 2300 proteins, while the analysis of EV-enriched plasma samples identified more than 600 proteins. Of the proteins detected in EV-enriched samples, more than a third were not identified in whole plasma samples and many were classified as either tissue-enriched or of tissue-specific origin. In conclusion, parallel profiling of EV-enriched plasma fractions and whole plasma samples increases the overall proteome depth and facilitates the discovery of tissue-enriched proteins in plasma. If applied to plasma samples collected longitudinally from the NOD mouse or from models with other pathobiological mechanisms, the integrated proteome profiling scheme described herein may be useful for the discovery of new and potentially endotype specific biomarkers in T1D.
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  • Nyholm, R., et al. (författare)
  • ELECTRONIC AND STRUCTURAL-PROPERTIES OF THE CU-BI2CASR2CU2O8 INTERFACE
  • 1991
  • Ingår i: Physica. C, Superconductivity. - 0921-4534 .- 1873-2143. ; 180:1-4, s. 120-123
  • Tidskriftsartikel (refereegranskat)abstract
    • The formation of the Cu-Bi2CaSr2Cu2O8 interface has been studied by photoelectron spectroscopy using synchrotron radiation. Photon energies in the range 20-1000 eV were utilized in order to probe both the valence band and to monitor chemical changes upon Cu deposition, as revealed by the core-level shifts. A strong chemical reaction between Bi2CaSr2CuO8 and Cu is manifested by the formation of metallic Bi. From the intensity variations as a function of electron emission angle it is shown that the metallic Bi segregates to the top surface layer.
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  • Nyholm, R., et al. (författare)
  • PHOTOEMISSION-STUDY OF THE BI2CASR2CU2O8 SUPERCONDUCTOR WITH CU, AG AND AU OVERLAYERS
  • 1993
  • Ingår i: Physica. C, Superconductivity. - 0921-4534 .- 1873-2143. ; 218:1-2, s. 103-108
  • Tidskriftsartikel (refereegranskat)abstract
    • In this paper, we present a photoemission study of the interaction of Cu, Ag and Au with clean single-crystal Bi2CaSr2Cu2O8 superconductor surfaces. Both the valence-band and the Bi 5d, O 1 s and Sr 3d core levels were monitored for all overlayers. Cu, Ag and Au were deposited as consecutively thicker layers starting with a third of a monolayer and progressing in steps up to a deposition in the range of eight monolayers. Comparing the results for the different overlayers reveals the Ag overlayer to be less reactive than Au which causes the formation of metallic Bi on cleaved Bi2CaSr2Cu2O8 surface. Cu is shown to be the most reactive of the three metals. The Au and Ag overlayers display an island-growth mode, while Cu grows in a layer-by-layer fashion.
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  • Nyholm, R., et al. (författare)
  • SYNCHROTRON-RADIATION SOFT-X-RAY PHOTOEMISSION-STUDY OF LEAD ON BI2CASR2CU2O8
  • 1992
  • Ingår i: Physical Review B Condensed Matter. - 0163-1829 .- 1095-3795. ; 46:10, s. 6488-6494
  • Tidskriftsartikel (refereegranskat)abstract
    • In this paper we present a study of the interaction of Pb with a clean single-crystal Bi2CaSr2Cu2O8 superconductor surface based on photoemission and low-energy electron diffraction (LEED). Deposition of Pb on a Bi2CaSr2Cu2O8 Crystal kept at room temperature gives rise to the formation of metallic Bi and oxidized Pb at the interface. This behavior could not be observed when the crystal was kept at 100 K during Pb deposition. For all investigated Pb overlayers on a cold crystal (100 K), surface-sensitive photoelectron spectroscopy revealed the growth of a covering metallic Pb overlayer film. The growth at 100 K, contrary to the growth at room temperature, preserved the original LEED 5 X 1 pattern even for Pb depositions corresponding to a 24-angstrom thick overlayer indicating epitaxial growth. Furthermore, a rigid 0.4-eV shift of the valence band and the Bi 5d core levels is observed upon initial Pb deposition and is tentatively attributed to electron doping.
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  • QVARFORD, M, et al. (författare)
  • X-RAY-ABSORPTION AND RESONANT-PHOTOEMISSION STUDY OF CA IN THE HIGH-TEMPERATURE SUPERCONDUCTOR BI2SR2CACU2O8
  • 1992
  • Ingår i: Physical Review B Condensed Matter. - 0163-1829 .- 1095-3795. ; 46:21, s. 14126-14133
  • Tidskriftsartikel (refereegranskat)abstract
    • The electronic structure of Ca in the high-temperature superconductor Bi2Sr2CaCu2O8 has been studied by x-ray-absorption spectroscopy and resonant-photoemission at the Ca L2,3 absorption edge. In the x-ray-absorption spectrum no edge structure is seen at the energy corresponding to the Ca 2p3/2 core-level binding energy, in agreement with the very low Ca density of states at the Fermi level predicted by band-structure calculations. Furthermore, the crystal-field splitting of the Ca 3d level, which is characteristic of ionic Ca compounds, is clearly observed in the x-ray-absorption spectrum. The photoemission spectra display strong resonant enhancements of the Ca 3s and 3p core levels as well as strong changes in the intensity and the line shape of the Ca L2,3M2,3M2,3 Auger structure at the Ca L2,3 threshold, showing the localized nature of the 3d states in core ionized Ca. The 3d induced spectator shift of the Ca L2,3M2,3M2,3 complex is fairly small as compared to what has been reported for CaF2, indicating that the screening of the normal Auger final state by the charge carriers in the surrounding Cu-O2 layers is quite efficient. From the Ca L2,3M2,3M2,3 data it is also suggested that, at the Ca L2 threshold, the excited 3d electron participates in a Coster-Kronig-type decay resulting in a 2p3/2 core hole followed by a normal L3M2,3M2,3 Auger decay.
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  • ROGELET, T, et al. (författare)
  • ELECTRONIC-STRUCTURE OF NIO(1 0 0) WITH ADSORBED NA
  • 1993
  • Ingår i: Solid State Communications. - 0038-1098 .- 1879-2766. ; 85:7, s. 657-660
  • Tidskriftsartikel (refereegranskat)abstract
    • Adsorption of Na on single crystals of NiO(1 0 0) at room temperature has been investigated via angle-resolved photoemission spectroscopy and measurements of work-function changes. The drastic changes in the valence band spectra upon Na deposition are assigned to a chemical reaction between Na and O where metallic Ni is left as by-product. At short deposition times, Na mainly acts as an inert electron donor, and at these coverages no dispersion is observed in the angle-resolved photoemission spectra which indicates that the electronic states are localized. The measurements were performed both for a polished and an in-situ cleaved NiO crystal.
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