| 1. |
- Havarinasab, Said, 1964-, et al.
(författare)
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Dose and Hg species determine the T-helper cell activation in murine autoimmunity
- 2007
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Ingår i: Toxicology. - : Elsevier BV. - 0300-483X .- 1879-3185. ; 229:1-2, s. 23-32
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Tidskriftsartikel (refereegranskat)abstract
- Inorganic mercury (mercuric chloride-HgCl2) induces in mice an autoimmune syndrome (HgIA) with T cell-dependent polyclonal B cell activation and hypergammaglobulinemia, dose- and H-2-dependent production of autoantibodies targeting the 34 kDa nucleolar protein fibrillarin (AFA), and systemic immune-complex deposits. The organic mercury species methylmercury (MeHg) and ethylmercury (EtHg-in the form of thimerosal) induce AFA, while the other manifestations of HgIA seen after treatment with HgCl2 are present to varying extent. Since these organic Hg species are converted to the autoimmunogen Hg2+ in the body, their primary autoimmunogen potential is uncertain and the subject of this study. A moderate dose of HgCl2 (8 mg/L drinking water - internal dose 148 μg Hg/kg body weight [bw]/day) caused the fastest AFA response, while the induction was delayed after higher (25 mg/L) and lower (1.5 and 3 mg/L) doses. The lowest dose of HgCl2 inducing AFA was 1.5 mg/L drinking water which corresponded to a renal Hg2+ concentration of 0.53 μg/g. Using a dose of 8 mg HgCl2/L this threshold concentration was reached within 24 h, and a consistent AFA response developed after 8-10 days. The time lag for the immunological part of the reaction leading to a consistent AFA response was therefore 7-9 days. A dose of thimerosal close to the threshold dose for induction of AFA (2 mg/L drinking water-internal dose 118 μg Hg/kg bw per day), caused a renal Hg2+ concentration of 1.8 μg/g. The autoimmunogen effect of EtHg might therefore be entirely due to Hg2+ formed from EtHg in the body. The effect of organic and inorganic Hg species on T-helper type 1 and type 2 cells during induction of AFA was assessed as the presence and titre of AFA of the IgG1 and IgG2a isotype, respectively. EtHg induced a persistent Th1-skewed response irrespectively of the dose and time used. A low daily dose of HgCl2 (1.5-3 mg/L) caused a Th1-skewed AFA response, while a moderate dose (8 mg/L) after 2 weeks resulted in a balanced or even Th2-skewed response. Higher daily doses of HgCl2 (25 mg/L) caused a balanced Th2-Th1 response already from onset. In conclusion, while metabolically formed Hg2+ might be the main AFA-inducing factor also after treatment with EtHg, the quality of the Hg-induced AFA response is modified by the species of Hg as well as the dose. © 2006 Elsevier Ireland Ltd. All rights reserved.
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| 2. |
- Havarinasab, Said, et al.
(författare)
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Dose and Hg species determine the T-helper cell activation in murine autoimmunity.
- 2007
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Ingår i: Toxicology. - 0300-483X. ; 229:1-2, s. 23-32
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Tidskriftsartikel (refereegranskat)abstract
- Inorganic mercury (mercuric chloride--HgCl(2)) induces in mice an autoimmune syndrome (HgIA) with T cell-dependent polyclonal B cell activation and hypergammaglobulinemia, dose- and H-2-dependent production of autoantibodies targeting the 34 kDa nucleolar protein fibrillarin (AFA), and systemic immune-complex deposits. The organic mercury species methylmercury (MeHg) and ethylmercury (EtHg--in the form of thimerosal) induce AFA, while the other manifestations of HgIA seen after treatment with HgCl(2) are present to varying extent. Since these organic Hg species are converted to the autoimmunogen Hg(2+) in the body, their primary autoimmunogen potential is uncertain and the subject of this study. A moderate dose of HgCl(2) (8 mg/L drinking water--internal dose 148 micro gHg/kg body weight [bw]/day) caused the fastest AFA response, while the induction was delayed after higher (25 mg/L) and lower (1.5 and 3 mg/L) doses. The lowest dose of HgCl(2) inducing AFA was 1.5 mg/L drinking water which corresponded to a renal Hg(2+) concentration of 0.53 micro g/g. Using a dose of 8 mg HgCl(2)/L this threshold concentration was reached within 24 h, and a consistent AFA response developed after 8-10 days. The time lag for the immunological part of the reaction leading to a consistent AFA response was therefore 7-9 days. A dose of thimerosal close to the threshold dose for induction of AFA (2 mg/L drinking water--internal dose 118 micro gHg/kg bw per day), caused a renal Hg(2+) concentration of 1.8 micro g/g. The autoimmunogen effect of EtHg might therefore be entirely due to Hg(2+) formed from EtHg in the body. The effect of organic and inorganic Hg species on T-helper type 1 and type 2 cells during induction of AFA was assessed as the presence and titre of AFA of the IgG1 and IgG2a isotype, respectively. EtHg induced a persistent Th1-skewed response irrespectively of the dose and time used. A low daily dose of HgCl(2) (1.5-3 mg/L) caused a Th1-skewed AFA response, while a moderate dose (8 mg/L) after 2 weeks resulted in a balanced or even Th2-skewed response. Higher daily doses of HgCl(2) (25 mg/L) caused a balanced Th2-Th1 response already from onset. In conclusion, while metabolically formed Hg(2+) might be the main AFA-inducing factor also after treatment with EtHg, the quality of the Hg-induced AFA response is modified by the species of Hg as well as the dose.
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| 3. |
- Havarinasab, Said, et al.
(författare)
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Immunosuppressive and autoimmune effects of thimerosal in mice
- 2005
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Ingår i: TOXICOLOGY AND APPLIED PHARMACOLOGY. - : Elsevier BV. - 0041-008X. ; 204:2, s. 109-21
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Tidskriftsartikel (refereegranskat)abstract
- The possible health effects of the organic mercury compound thimerosal (ethylmercurithiosalicylate), which is rapidly metabolized to ethylmercury (EtHg), have recently been much debated and the effect of this compound on the immune system is largely unknown. We therefore studied the effect of thimerosal by treating A.SW (H-2(s)) mice, susceptible to induction of autoimmunity by heavy metals, with 10 mg thimerosal/L drinking water (internal dose ca 590 mu g Hg/kg body weight/day) for up to 30 days. The lymph node expression of IL-2 and IL-15 mRNA was increased after 2 days, and of IL-4 and IFN-gamma rnRNA after 6 and 14 days. During the first 14 days treatment, the number of splenocytes, including T and B cells as well as Ig-secreting cells decreased. A strong immunostimulation superseded after 30 days treatment xvith increase in splenic weight, number of splenocytes including T and B cells and Ig-secreting cells, and Th2- as well as Th-l-dependent serum immunoglobulins. Antinucleolar antibodies (ANoA) targeting the 34-kDa nucleolar protein fibrillarin, and systemic immune-complex deposits developed. The H-2(s) strains SJL and B10.S also responded to thimerosal treatment with ANoA. The A.TL and B10.TL strain, sharing background genes with the A.SW and B10.S strain, respectively, but with a different H-2 haplotype (tl), did not develop ANoA, linking the susceptibility to H-2. Thimerosal-treated H-2(s) mice homozygous for the nu mutation (SJL-nu/nu), or lacking the T-cell costimulatory molecule CD28 (B10.S-CD28(-/-)), did not develop ANoA, which showed that the autoimmune response is T-cell dependent. Using H-2(s) strains with targeted mutations, we found that IFN-gamma and IL-6, but not IL-4, is important for induction of ANoA by thimerosal. The maximum added renal concentration of thimerosal (EtHg) and inorganic mercury occurred after 14 days treatment and was 8 1 mu g Hg/g. EtHg made tip 59% and inorganic mercury 41% of the renal mercury. In conclusion, the organic mercury compound thimerosal (EtHg) has initial immunosuppressive effects similar to those of MeHg. However, in contrast to MeHg, thimerosal treatment leads in genetically susceptible mice to a second phase with strong immunostimulation and autoimmunity, which is T-cell dependent, H-2 linked and may at least partly be due to the inorganic mercury derived from the metabolism of ethyl mercury.
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| 4. |
- Havarinasab, Said, 1964-, et al.
(författare)
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Mercury species in lymphoid and non-lymphoid tissues after exposure to methyl mercury: Correlation with autoimmune parameters during and after treatment in susceptible mice
- 2007
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Ingår i: Toxicology and Applied Pharmacology. - : Elsevier BV. - 0041-008X .- 1096-0333. ; 221:1, s. 21-8
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Tidskriftsartikel (refereegranskat)abstract
- Methylmercury (MeHg) is present in the environment as a result of the global cycling of mercury, although anthropogenic sources may dramatically increase the availability in confined geographical areas. Accumulation of MeHg in the aquatic food chain is the dominating way of exposure in mammals, which accumulate MeHg in all organs, including the brain. Demethylation has been described in the organs, especially in phagocytic cells, but mainly in the flora of the intestinal tract. While most of the inorganic mercury (Hg2+) formed in the intestine is excreted, a fraction is reabsorbed which together with the local demethylation increases the organ Hg2+ concentration. MeHg is a well-known immunosuppressive agent, while Hg2+ is associated with immunostimulation and autoimmunity especially in genetically susceptible rodents, creating a syndrome, i.e. mercury-induced autoimmunity (HgIA). This study aimed at exploring the effect of MeHg with regard to HgIA, and especially the immunological events after stopping treatment, correlated with the presence of MeHg and Hg2+ in the organs.Treatment of A.SW mice for 30 days with 4.2 mg MeHg/L drinking water (corresponding to approximately 420 μg Hg/kg body weight/day) caused all the HgIA features observed after primary treatment with inorganic Hg, except systemic immune complex deposits. The total Hg concentration was 5-fold higher in the kidneys as compared with lymph nodes, but the fraction of Hg2+ was similar (17–20%). After stopping treatment, the renal and lymph node MeHg concentration declined according to first order kinetics during the initial 4–6 weeks, but then slower. A similar decline in the organ Hg2+ concentration occurred during the initial 2 weeks after stopping treatment but then ceased, causing the Hg2+ concentration to exceed that of MeHg in the lymph nodes and kidneys after 3 and 8 weeks, respectively. The selective increase in lymph node Hg2+ fraction is likely to be due to demethylation of MeHg in the macrophage-rich lymphoid tissue. The major autoantibody in HgIA, anti-fibrillarin antibodies, tended to increase during the initial 6 weeks after stopping treatment, while all other HgIA features including antichromatin antibodies declined to control levels after 2–4 weeks. This indicates differences in either dose requirement or induction mechanisms for the different HgIA parameters.The selective accumulation of Hg2+ in lymph nodes following MeHg treatment should be taken into account when the effect of MeHg on the immune system is evaluated.
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| 5. |
- Häggqvist, Bo, 1962-, et al.
(författare)
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The immunosuppressive effect of methylmercury does not preclude development of autoimmunity in genetically susceptible mice
- 2005
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Ingår i: TOXICOLOGY. - : Elsevier BV. - 0300-483X .- 1879-3185. ; 208:1, s. 149-64
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Tidskriftsartikel (refereegranskat)abstract
- Methylmercury (MeHg) is a common environmental pollutant due to both natural and anthropogenic sources. Although the central nervous system (CNS) is considered the critical organ for the toxic effect of MeHg, it has recently been suggested that the immune system might be at least as sensitive as the CNS.We have examined the effects of MeHg on the immune system in genetically metal-susceptible mice. Subcutaneous (sc) injections of 2 mg MeHg/kg body weight (bw) every third day (internal dose ca. 540 μg Hg/kg bw/day) to A.SW mice of the H-2s haplotype, caused during the first week a 47 and 9% reduction of B- and T-cells, respectively, which indicates immunosuppression. Subsequently, an autoimmune syndrome developed which shared certain features with the syndrome induced by inorganic mercury in H-2s mice, including antibodies targeting the 34 kDa nucleolar protein fibrillarin, increased expression of IL-4 mRNA, increase of Th2-type of immunoglobulins (IgE and IgG1), and increased MHC class II expression on B-cells. However, the response using MeHg was attenuated compared with even lower doses of Hg in the form of inorganic mercury, and specifically lacked the increased expression of IL-2 and IFN-γ mRNA, the polyclonal B-cell activation (PBA), and the systemic immune-complex (IC) deposits which are induced by inorganic mercury. Increasing the dose of MeHg increased the titre of anti-nucleolar antibodies and shortened the induction time, but did not lead to stronger immunostimulation or systemic IC-deposits. The kidney and liver selectively accumulated MeHg, while the blood, spleen and lymph nodes showed lower levels of MeHg. The accumulation of MeHg and Hg2+ increased throughout the 30-day period. The fraction of Hg2+ in the kidney varied between 4 and 22%, and the lymph nodes showed a maximum of 30% Hg2+.We conclude first that MeHg has quantitatively different effect on the immune system compared with inorganic mercury, and secondly that an initial immunosuppression induced by a xenobiotic does not preclude subsequent immunostimulation and autoimmunity.
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| 6. |
- Kakanakova-Georgieva, Anelia, 1970-, et al.
(författare)
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AlGaInN metal-organic-chemical-vapor-deposition gas-phase chemistry in hydrogen and nitrogen diluents : First-principles calculations
- 2006
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Ingår i: Chemical Physics Letters. - : Elsevier BV. - 0009-2614 .- 1873-4448. ; 431:4-6, s. 346-351
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Tidskriftsartikel (refereegranskat)abstract
- Direct impact of H2 and N2 diluents on the metal-organic-chemical-vapor-deposition gas-phase chemistry in M(CH3)3/NH3 (M = Al, Ga, In) systems is identified in the framework of Density Functional Theory in terms of cohesive energy differences. While both diluents destabilize model reaction species, i.e. adducts, transition states and chain complexes, the effect is particularly strong with respect to N2 in the Al(CH3)3/NH3 system, and can be a factor to restrain the expansion of chain complexes that deplete the gas-phase from precursors. Theoretical results are supported by experimental evidences of higher growth rate and superior optical properties of AlN grown in N2 vs. H2 diluent. © 2006 Elsevier B.V. All rights reserved.
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| 7. |
- Kakanakova-Georgieva, Anelia, 1970-, et al.
(författare)
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Superior material properties of AlN on vicinal 4H-SiC
- 2006
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Ingår i: Journal of Applied Physics. - : AIP Publishing. - 0021-8979 .- 1089-7550. ; 100:3
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Tidskriftsartikel (refereegranskat)abstract
- The crystal structure and optical properties of thick (>100 nm) AlN layers grown by hot-wall metalorganic chemical vapor deposition are characterized by infrared spectroscopic ellipsometry, cathodoluminescence, and transmission electron microscopy. The choice of substrates among the available SiC wafer polytype modifications (4H/6H) and misorientations (on-/off-axis cut) is found to determine the AlN defect interaction, stress homogeneity, and luminescence. The growth of thick AlN layers benefits by performing the epitaxy on off-axis substrates because, due to stacking faults, the propagation of threading defects in AlN layers is stopped in a narrow interface region. © 2006 American Institute of Physics.
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| 8. |
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| 9. |
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| 10. |
- Levlin, Erik, 1951-, et al.
(författare)
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Phosphorus recovery from sewage sludge : Ideas for further studies to improve leaching
- 2007
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Ingår i: Integration and optimisation of urban sanitation systems. - 9789171788252 ; , s. 61-70
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Development of methods to recover phosphorus will make handling of sewage sludge moresustainable. In earlier studies sludge incineration ash and SCWO-residues have been leached withacid and base. Acid leaching gives a high degree of recovery but releases besides phosphate alsothe main part of other metals (including heavy metals). This gives a large separation problem andgives a complicated process technology. Leaching with base (NaOH) gives a lower degree ofrecovery (up to about 50 %) however with less dissolution of metals. When leaching with base, thecalcium content in the sludge probably binds phosphorus as calcium phosphate.To improve leaching different possibilities can be studied such as use of a two-step leachingprocess. In a first step acid leaching dissolves calcium and magnesium. Treating the leachate withsulphuric acid, calcium sulphate (gypsum) is precipitated and phosphoric acid is obtained.Remaining ash or SCWO-residual product can afterwards be treated by alkaline leaching. Anotheralternative is to study leaching at anaerobic conditions. Since ferrous iron(II) phosphate is moresoluble than ferric iron(III) phosphate the phosphate is more easily dissolved and the heavy metalcontamination will be lower.
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| 11. |
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| 12. |
- Lewin, Erik, et al.
(författare)
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On the origin of a third spectral component of C1s XPS-spectra for nc-TiC/a-C nanocomposite thin films
- 2008
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Ingår i: Surface & Coatings Technology. - : Elsevier BV. - 0257-8972 .- 1879-3347. ; 202:15, s. 3563-3570
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Tidskriftsartikel (refereegranskat)abstract
- X-ray photoelectron spectroscopy (XPS) spectra of sputter-etched nc-TiC/a-C nanocomposite thin films published in literature show an extra feature of unknown origin in the C1s region. This feature is situated between the contributions of carbide and the carbon matrix. We have used high kinetic energy XPS (HIKE-XPS) on magnetron-sputtered nc-TiC/a-C thin films to show that this feature represents a third chemical environment in the nanocomposites, besides the carbide and the amorphous carbon. Our results show that component is present in as-deposited samples, and that the intensity is strongly enhanced by Ar+-ion etching. This third chemical environment may be due to interface or disorder effects. The implications of these observations on the XPS analysis of nanocomposites are discussed in the light of overlap problems for ternary carbon based systems.
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| 13. |
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| 14. |
- Magnuson, Martin, et al.
(författare)
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Electronic structure and chemical bonding of nanocrystalline-TiC/amorphous-C nanocomposites
- 2009
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Ingår i: Physical Review B Condensed Matter. - 0163-1829 .- 1095-3795. ; 80:235108
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Tidskriftsartikel (refereegranskat)abstract
- The electronic structure of nanocrystalline (nc-) TiC/amorphous C nanocomposites has been investigated bysoft x-ray absorption and emission spectroscopy. The measured spectra at the Ti 2p and C 1s thresholds of thenanocomposites are compared to those of Ti metal and amorphous C. The corresponding intensities of theelectronic states for the valence and conduction bands in the nanocomposites are shown to strongly depend onthe TiC carbide grain size. An increased charge transfer between the Ti 3d-eg states and the C 2p states hasbeen identified as the grain size decreases, causing an increased ionicity of the TiC nanocrystallites. It issuggested that the charge transfer occurs at the interface between the nanocrystalline-TiC and the amorphous-Cmatrix and represents an interface bonding which may be essential for the understanding of the properties ofnc-TiC/amorphous C and similar nanocomposites.
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| 15. |
- Moqvist, Louise, 1971-
(författare)
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Ledarskap i vardagsarbetet : en studie av högre chefer i statsförvaltningen
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The study aim at describing and analysing the practices of and conditions for senior managers in public administration, as well as which similarities and differences are in existence both within and between authorities in this respect. The practices of senior managers are studied in the light of two dimensions, one explicit that comprises the values, ideologies, interests, knowledge and feelings that senior managers express, as well as an executed dimension that encompasses physical activities, what managers do, how the work is executed, where work is done and with whom they work. These dimensions of managerial practices are studied with a special focus on leadership. The aim of this study can also be understood as to describe and analyse pedagogical processes (influence processes as well as learning and development processes) in a senior manager's work.The study has a multiple case study design comprising eight different authorities. Two sub-studies have been performed, one interview study consisting of 31 senior managers and one observation study comprised of six of these managers.The results show that leadership is a well-known concept, that great value is ascribed to it, that there is unanimity on the meaning of leadership as well as this meaning having changed over time. The results in the form of descriptions of managers' work show that there are many similarities between the managers in the study. For example, the work to a great extent is a question of interplay with other individuals and that in this social dimension the prerequisites for learning and developing processes exist. The study shows too that managers have a certain amount of room for action and that in their work managers take into consideration several different dimensions of contexts in the performance of their work. The managerial work is finally described in terms of an explicit and an implicit context with regard to the public character of the work involved.One conclusion is that there are differences between managers' conceptions of leadership that is executed. These differences can be understood by considering the background consisting of the simultaneous existence of normative respective experiential patterns of practice described in the study as the non-uniform work.Furthermore, the results indicate differences among the authorities but that these are small in relation to differences within the authorities. Thus the results can be interpreted as the immediate context in the form of a number of personal/local preconditions to a greater extent being formed for managerial work in relation to a more peripheral context.In this light, leadership is defined as a social, influence, learning and developmental process, which is executed as implicit and explicit work within the framework for a structural, an institutional and a subjective fields.
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| 16. |
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| 17. |
- Pozina, Galia, et al.
(författare)
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Time-resolved photoluminescence properties of AlGaN/AlN/GaN high electron mobility transistor structures grown on 4H-SiC substrate
- 2008
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Ingår i: Journal of Applied Physics. - : AIP Publishing. - 0021-8979 .- 1089-7550. ; 104:11, s. 113513-
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Tidskriftsartikel (refereegranskat)abstract
- AlGaN/AlN/GaN high electron mobility transistor heterostructures grown by metal-organic chemical vapor deposition have been studied by temperature dependent time-resolved photoluminescence. The AlGaN-related emission is found to be sensitive to the excitation power and to the built-in internal electric field. In addition, this emission shows a shift to higher energy with the reduction in the excitation density, which is rather unusual. Using a self-consistent calculation of the band potential profile, we suggest a recombination mechanism for the AlGaN-related emission involving electrons confined in the triangular AlGaN quantum well and holes weakly localized due to potential fluctuations.
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| 18. |
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| 19. |
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| 20. |
- Wennström, Erik, 1952-
(författare)
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The Camberwell Assessment of Need as an Outcome Measure in Community Mental Health Care
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this thesis was to critically examine the current use of the Camberwell Assessment of Need (CAN) in outcome assessment for service evaluation. A further aim was to propose a metric for assessing the adequacy of community mental health services in meeting ongoing needs over longer stretches of time. We made four prospective follow-up studies of CAN assessments of patients with severe mental illness in community-based mental health care. A factor analysis (n=741) gave support for a three-factor model, comprising only 60% of the CAN items. Need assessments (n= 92) in 1997 and 2003 were compared at both the summed total and the underlying item levels of the CAN. The mean total scores did not change, yet there were significant changes in the underlying items. Changes in mean number of needs between 1997 and 1999 were measured (n=262) with both total scores, summed over all CAN items, and with sub-total scores, summed over two sets of items reflecting the social services and the psychiatric services respectively. As indicated by the sub-total scores, all significant changes occurred within the psychiatric services, a result not possible to discern from the total scores. The Met Needs Index (MNI), defined by us as the aggregate measure of beneficial outcome, indicated that needs in general were met during 71% of the intervals between the annuals assessments from 1997 through 2004. However, the variation among particular items was large. In conclusion, the summary scores typically used as outcome measures are likely to conceal meaningful variation at the item level. Nevertheless, sub-total scores, being more transparent, might be more useful in outcome assessment. The MNI is a continuous, normally distributed metric, estimable over any number of consecutive assessments, which seems suitable for assessing the achieved benefit of services for patients with long-term ongoing needs.
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| 21. |
- Wilhelmsson, O., et al.
(författare)
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Deposition and characterization of ternary thin films within the Ti-Al-C system by DC magnetron sputtering
- 2006
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Ingår i: Journal of Crystal Growth. - : Elsevier BV. - 0022-0248 .- 1873-5002. ; 291:1, s. 290-300
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Tidskriftsartikel (refereegranskat)abstract
- The formation of ternary compounds within the Ti-Al-C system was studied by magnetron sputtering for thin-film deposition and first-principles calculations for phase stability. As-deposited films were characterized with X-ray diffraction (XRD) and high-resolution transmission electron microscopy (TEM). The hardness and Young's moduli of the material were studied by nanoindentation. Epitaxial and phase-pure films of Mn+1AXn phases Ti3AlC2 and Ti2AlC as well as the perovskite phase Ti3AlC were deposited on Al2O3(00l) wafers kept at temperatures between 800 and 900 °C. The only ternary phases observed at low temperatures (300 °C) were Ti3AlC and cubic (Ti,Al)C, the latter can be described as a metastable solid solution of Al in TiC similar to the more studied (Ti,Al)N system. The difficulties to form MAX phases at low substrate temperatures were attributed of requirement for a sufficient diffusivity to partition the elements corresponding to the relatively complex crystal structures with long c-axes. While MAX-phase synthesis at 800 °C is significantly lower than contemporary bulk sintering processes, a reduction of the substrate temperature towards 300 °C in the present thin-film deposition experiments resulted in stacking sequence variations and the intergrowth of (Ti,Al)C. © 2006 Elsevier B.V. All rights reserved.
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