| 1. |
- Bian, Caiyun, et al.
(författare)
-
Finding the optimal location for public charging stations - A GIS-based MILP approach
- 2019
-
Ingår i: Energy Procedia. - : Elsevier Ltd. - 1876-6102. ; , s. 6582-6588
-
Konferensbidrag (refereegranskat)abstract
- Electric Vehicles (EVs) have achieved a significant development because of the continuous technology revolution and policy supports in recent years, which leads to a larger demand of charging stations. Strategies about how to find the optimal location for charging facilities are urgently needed in order to further assist the development of EVs. This paper focus on the return of investments on EV charging stations and proposes a Mixed Integer Linear Programming (MILP) model based on Geographic Information System (GIS) to identify the optimal location of charging stations in cities. Traffic flow data and land-use classifications are used as important inputs, and six important constraints are included in the MILP model with the objective function of maximizing the total profits of new charging stations. The effectiveness of the proposed method is then demonstrated by implementing a case study in Västerås, Sweden.
|
|
| 2. |
- Bian, Li, et al.
(författare)
-
Dichloroacetate alleviates development of collagen II-induced arthritis in female DBA/1 mice
- 2009
-
Ingår i: ARTHRITIS RESEARCH and THERAPY. - : BioMed Central. - 1478-6354 .- 1478-6362. ; 11:5
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction Dichloroacetate (DCA) has been in clinical use for the treatment of lactacidosis and inherited mitochondrial disorders. It has potent anti-tumor effects both in vivo and in vitro, facilitating apoptosis and inhibiting proliferation. The proapoptotic and anti-proliferative properties of DCA prompted us to investigate the effects of this compound in arthritis. Methods In the present study, we used DCA to treat murine collagen type II (CII)-induced arthritis (CIA), an experimental model of rheumatoid arthritis. DBA/1 mice were treated with DCA given in drinking water. Results Mice treated with DCA displayed much slower onset of CIA and significantly lower severity (P less than 0.0001) and much lower frequency (36% in DCA group vs. 86% in control group) of arthritis. Also, cartilage and joint destruction was significantly decreased following DCA treatment (P = 0.005). Moreover, DCA prevented arthritis-induced cortical bone mineral loss. This clinical picture was also reflected by lower levels of anti-CII antibodies in DCA-treated versus control mice, indicating that DCA affected the humoral response. In contrast, DCA had no effect on T cell-or granulocyte-mediated responses. The beneficial effect of DCA was present in female DBA/1 mice only. This was due in part to the effect of estrogen, since ovariectomized mice did not benefit from DCA treatment to the same extent as sham-operated controls (day 30, 38.7% of ovarectomized mice had arthritis vs. only 3.4% in sham-operated group). Conclusion Our results indicate that DCA delays the onset and alleviates the progression of CIA in an estrogen-dependent manner.
|
|
| 3. |
|
|
| 4. |
- Bian, Li, 1966
(författare)
-
The role of S100A4 protein as a regulator of inflammation and bone metabolism in experimental arthritis
- 2011
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- S100A4 belongs to the family of calcium-binding S100 proteins and modulates cell proliferation, cytoskeletal rearrangement, cell motility, and angiogenesis. Increased levels of S100A4 expression correlate with high incidence of metastasis of cancers. Up-regulation of S100A4 protein is demonstrated in synovial tissue and in plasma of rheumatoid arthritis (RA) patients compared with osteoarthritis, and the elevated expression of S100A4 is associated with increased disease activity in patients with RA. Dichloroacetate (DCA) was shown to have a potent anti-tumour effect by facilitating apoptosis and inhibiting proliferation. The aims of this thesis are to investigate contributions of S100A4 in experimental models of septic arthritis and antigen-induced arthritis, and in bone formation using S100A4KO mice. In addition, we also aim to find out the impact of DCA on collagen type II-induced arthritis. Our studies showed that S100A4 deficiency resulted in reduced joint inflammation and cartilage/bone destruction in both septic and antigen-induced arthritis in mice. Additionally, in septic arthritis, S100A4KO mice had less bone loss and showed a lower bacterial load in the kidneys. S100A4 deficiency resulted in changed pattern of adhesion molecules. In antigen-induced arthritis, S100A4 deficiency resulted in reduced intensity of arthritis and significantly lower frequency of bone destruction, supported by fewer numbers of CD4+ T cells and CD19+CD5+ B cells accumulated in synovia and spleen compared with WT mice. Smaller populations of CD4+ and CD8+ T cells in spleen of S100A4 deficient mice were accompanied by reduced productions of INF-γ and IL-17A, and lower expression of Th17 transcription factor RORγt. Difference in the severity of arthritis was observed in female mice in septic arthritis and in male mice in antigen-induced arthritis. To assess the role of sex hormone on bone, we analysed BMD in S100A4KO and WT mice. S100A4KO mice had higher total BMD and female mice displayed more cortical bone content compared with WT mice. Following ovariectomy (OVX), both S100A4KO and WT mice lost BMD. However, cortical bone loss was more pronounced in S100A4KO mice than in WT supported by high CTX-I level. The loss of trabecular bone was similar in S100A4KO and WT mice. DHEA treatment resulted in a significant increase in the trabecular and cortical BMD both in WT and S100A4KO mice. This increase of BMD was lower in S100A4KO mice. The collagen-type II arthritis model was employed to study the potential effect of dichloroacetate (DCA) treatment on experimental arthritis. Our results showed that mice treated with DCA had a slower onset of CIA, and significantly lower severity and frequency of joint inflammation and cartilage/bone destruction compared with water-treated controls. Moreover, DCA prevented arthritis-induced loss of cortical mineral density. The beneficial effect of DCA was present only in female DBA/1 mice. DCA treatment on the OVX mice did not protect from the development of arthritis, indicating that effect of DCA is potentially estrogen-dependent. In conclusion, our studies demonstrate that S100A4 plays an important role in inflammation and bone metabolism in experimental arthritis. S100A4 deficiency protects against inflammation and cartilage/bone destruction in staphylococcal and antigen-induced arthritis by changing the expression of adhesion molecules, affecting lymphocyte maturation and functions. S100A4 is a regulator of bone formation in both estrogen sufficient and deficient mice. Our studies indicate that S100A4 protein can be a therapeutic target in arthritis and osteoporosis. We also demonstrate that DCA can be a potential anti-arthritis drug for female patients with RA.
|
|
| 5. |
- Brisslert, Mikael, 1974, et al.
(författare)
-
S100A4 regulates the Src-tyrosine kinase dependent differentiation of Th17 cells in rheumatoid arthritis
- 2014
-
Ingår i: Biochimica Et Biophysica Acta-Molecular Basis of Disease. - : Elsevier BV. - 0925-4439. ; 1842:11, s. 2049-2059
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives: To evaluate the role of S100A4, a calcium-binding regulator of nonmuscle myosin assembly, for T-cell responses in rheumatoid arthritis. Methods: Arthritis was induced in the methylated bovine serum albumin (mBSA)-immunized mice lacking the entire S100A4 protein (S100A4KO) and in wild-type counterparts treated with short hairpin ribonucleic acid (shRNA)-lentiviral constructs targeting S100A4 (S100A4-shRNA). The severity of arthritis was evaluated morphologically. T-cell subsets were characterized by the expression of master transcription factors, and functionally by proliferation activity and cytokine production. The activity of the Scr-kinases Fyn and Lck was assessed by the autophosphorylation of C-terminal thyrosine and by the phosphorylation of the CD5 cytodomain. The interaction between S100A4 and the CD5 cytodomain was analysed by nuclear magnetic resonance spectrophotometry. Results: S100A4-deficient mice (S100A4KO and S100A4-shRNA) had significantly alleviated morphological signs of arthritis and joint damage. Leukocyte infiltrates in the arthritic joints of S100A4-deficient mice accumulated Foxp3(+) Treg cells, while the number of ROR gamma t(+) and (pTyr705)STAT3(+) cells was reduced. S100A4-deficient mice had a limited formation of Th17-cells with low retinoic acid orphan receptor gamma t (ROR gamma t) mRNA and IL17 production in T-cell cultures. S100A4-deficient mice had a low expression and activity of T-cell receptor (TCR) inhibitor CD5 and low (pTyr705)STAT3 (signal transducer and activator of transcription 3), which led to increased (pTyr352)ZAP-70 (theta-chain associated protein kinase of 70 kDa), lymphocyte proliferation and production of IL2. In vitro experiments showed that S100A4 directly binds Lck and Fyn and reciprocally regulates their kinase activity towards the CD5 cytodomain. Spectrometry demonstrates an interaction between the CD5 cytodomain and EF2-binding sites of S100A4. Conclusion: The present. study demonstrates that S100A4 plays an important part in the pathogenesis of arthritis. It controls CD5-dependent differentiation of Th17 cells by regulating the activity of the Src-family kinases Lck and Fyn. (C) 2014 Elsevier B.V. All rights reserved.
|
|
| 6. |
|
|
| 7. |
- Erlandsson, Malin, 1972, et al.
(författare)
-
Expression of metastasin S100A4 is essential for bone resorption and regulates osteoclast function.
- 2013
-
Ingår i: Biochimica et biophysica acta. - : Elsevier BV. - 0006-3002. ; 1833:12, s. 2653-2663
-
Tidskriftsartikel (refereegranskat)abstract
- S100A4 is a Ca-binding protein that regulates cell growth, survival, and motility. The abundant expression of S100A4 in rheumatiod arthritis contributes to the invasive growth of joint tissue and to bone damage. In the present study, we analysed the role of S100A4 in bone homeostasis.
|
|
| 8. |
- Erlandsson, Malin, 1972, et al.
(författare)
-
Metastasin S100A4 is a mediator of sex hormone-dependent formation of the cortical bone.
- 2013
-
Ingår i: Molecular endocrinology (Baltimore, Md.). - : The Endocrine Society. - 1944-9917 .- 0888-8809. ; 27:8, s. 1311-21
-
Tidskriftsartikel (refereegranskat)abstract
- S100A4 is a Ca-binding protein participating in regulation of cell growth, survival, and motility. Here we studied the role of S100A4 protein in sex hormone-regulated bone formation. Bone mineral density in the trabecular and cortical compartments was evaluated in female S100A4 knockout (KO), in matched wild-type (WT) counterparts, and in WT mice treated with lentiviral small hairpin RNA construct inhibiting the S100A4 gene transcription or with a nontargeting construct, by peripheral quantitative computed tomography. The effect of sex hormones on bone was measured 5 weeks after ovariectomy (OVX) and/or dehydroepiadrosterone treatment. S100A4KO had an excessive trabecular and cortical bone formation compared with the age- and sex-matched WT mice. S100A4KO had an increased periosteal circumference (P = .001), cortical thickness (P = .056), and cortical area (P = .003), which predicted 20% higher bone strength in S100A4KO (P = .013). WT mice treated with small hairpin RNA-S100A4 showed an increase of the cortical bone parameters in a fashion identical with S100A4KO mice, indicating the key role of S100A4 in the changed bone formation. S100A4KO mice had higher serum levels of osteocalcin and a higher number of osteocalcin-positive osteoblasts under the periosteum. OVX-S100A4 resulted in the loss of the cortical bone supported by high CTX-I levels, whereas no such changes were observed in OVX-WT mice. S100A4KO mice resisted the dehydroepiadrosterone -induced bone formation observed in the WT counterparts. Our study indicates that S100A4 is a regulator of bone formation, which inhibits bone excess in the estrogen-sufficient mice and prevents the cortical bone loss in the estrogen-deprived mice.
|
|
| 9. |
- Svensson, Mattias, 1982, et al.
(författare)
-
Fms-like tyrosine kinase 3 ligand controls formation of regulatory T cells in autoimmune arthritis.
- 2013
-
Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 8:1
-
Tidskriftsartikel (refereegranskat)abstract
- Fms-like tyrosine kinase 3 ligand (Flt3L) is known as the primary differentiation and survival factor for dendritic cells (DCs). Furthermore, Flt3L is involved in the homeostatic feedback loop between DCs and regulatory T cell (Treg). We have previously shown that Flt3L accumulates in the synovial fluid in rheumatoid arthritis (RA) and that local exposure to Flt3L aggravates arthritis in mice, suggesting a possible involvement in RA pathogenesis. In the present study we investigated the role of Flt3L on DC populations, Tregs as well as inflammatory responses in experimental antigen-induced arthritis. Arthritis was induced in mBSA-immunized mice by local knee injection of mBSA and Flt3L was provided by daily intraperitoneal injections. Flow cytometry analysis of spleen and lymph nodes revealed an increased formation of DCs and subsequently Tregs in mice treated with Flt3L. Flt3L-treatment was also associated with a reduced production of mBSA specific antibodies and reduced levels of the pro-inflammatory cytokines IL-6 and TNF-α. Morphological evaluation of mBSA injected joints revealed reduced joint destruction in Flt3L treated mice. The role of DCs in mBSA arthritis was further challenged in an adoptive transfer experiment. Transfer of DCs in combination with T-cells from mBSA immunized mice, predisposed naïve recipients for arthritis and production of mBSA specific antibodies. We provide experimental evidence that Flt3L has potent immunoregulatory properties. Flt3L facilitates formation of Treg cells and by this mechanism reduces severity of antigen-induced arthritis in mice. We suggest that high systemic levels of Flt3L have potential to modulate autoreactivity and autoimmunity.
|
|
