| 1. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 2. |
- Li, Shiyu, et al.
(författare)
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Nanoarrays on Passivated Aluminum Surface for Site-Specific Immobilization of Biomolecules
- 2018
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Ingår i: ACS Applied Bio Materials. - : American Chemical Society (ACS). - 2576-6422. ; 1:1, s. 125-135
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Tidskriftsartikel (refereegranskat)abstract
- The rapid development of biosensing platforms for highly sensitive and specific detection raises the desire of precise localization of biomolecules onto various material surfaces. Aluminum has been strategically employed in the biosensor system due to its compatibility with CMOS technology and its optical and electrical properties such as prominent propagation of surface plasmons. Herein, we present an adaptable method for preparation of carbon nanoarrays on aluminum surface passivated with poly(vinylphosphonic acid) (PVPA). The carbon nanoarrays were defined by means of electron beam induced deposition (EBID) and they were employed to realize site-specific immobilization of target biomolecules. To demonstrate the concept, selective streptavidin/neutravidin immobilization on the carbon nanoarrays was achieved through protein physisorption with a significantly high contrast of the carbon domains over the surrounding PVPA-modified aluminum surface. By adjusting the fabrication parameters, local protein densities could be varied on similarly sized nanodomains in a parallel process. Moreover, localization of single 40 nm biotinylated beads was achieved by loading them on the neutravidin-decorated nanoarrays. As a further demonstration, DNA polymerase with a streptavidin tag was bound to the biotin-beads that were immobilized on the nanoarrays and in situ rolling circle amplification (RCA) was subsequently performed. The observation of organized DNA arrays synthesized by RCA verified the nanoscale localization of the enzyme with retained biological activity. Hence, the presented approach could provide a flexible and universal avenue to precise localizing various biomolecules on aluminum surface for potential biosensor and bioelectronic applications.
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| 3. |
- Daniel, Quentin, et al.
(författare)
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Rearranging from 6-to 7-coordination initiates the catalytic activity : An EPR study on a Ru-bda water oxidation catalyst
- 2017
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Ingår i: Coordination chemistry reviews. - : Elsevier. - 0010-8545 .- 1873-3840. ; 346, s. 206-215
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Tidskriftsartikel (refereegranskat)abstract
- The coordination of a substrate water molecule on a metal centered catalyst for water oxidation is a crucial step involving the reorganization of the ligand sphere. This process can occur by substituting a coordinated ligand with a water molecule or via a direct coordination of water onto an open site. In 2009, we reported an efficient ruthenium-based molecular catalyst, Ru-bda, for water oxidation. Despite the impressive improvement in catalytic activity of this type of catalyst over the past years, a lack of understanding of the water coordination still remains. Herein, we report our EPR and DFT studies on Ru-bda (triethylammonium 3-pyridine sulfonate)(2) (1) at its Ru-III oxidation state, which is the initial state in the catalytic cycle for the O-O bond formation. Our investigation suggests that at this III-state, there is already a rearrangement in the ligand sphere where the coordination of a water molecule at the 7th position (open site) takes place under acidic conditions (pH = 1.0) to form a rare 7-coordinated Ru-III species.
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| 4. |
- Daniel, Quentin, et al.
(författare)
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Water Oxidation Initiated by In Situ Dimerization of the Molecular Ru(pdc) Catalyst
- 2018
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Ingår i: ACS Catalysis. - : AMER CHEMICAL SOC. - 2155-5435. ; 8:5, s. 4375-4382
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Tidskriftsartikel (refereegranskat)abstract
- The mononuclear ruthenium complex [Ru(pdc)L-3] (H(2)pdc = 2,6-pyridinedicarboxylic acid, L = N-heterocycles such as 4-picoline) has previously shown promising catalytic efficiency toward water oxidation, both in homogeneous solutions and anchored on electrode surfaces. However, the detailed water oxidation mechanism catalyzed by this type of complex has remained unclear. In order to deepen understanding of this type of catalyst, in the present study, [Ru(pdc)(py)(3)] (py = pyridine) has been synthesized, and the detailed catalytic mechanism has been studied by electrochemistry, UV-vis, NMR, MS, and X-ray crystallography. Interestingly, it was found that once having reached the Ru-IV state, this complex promptly formed a stable ruthenium dimer [Ru-III(pdc)(py)(2)-O-Ru-IV(pdc)(py)(2)](+). Further investigations suggested that the present dimer, after one pyridine ligand exchange with water to form [Ru-III(pdc)(py)(2)-O-Ru-IV(pdc)(py)(H2O)](+), was the true active species to catalyze water oxidation in homogeneous solutions.
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| 5. |
- Henning, Petra, 1974, et al.
(författare)
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Toll-like receptor-2 induced inflammation causes local bone formation and activates canonical Wnt signaling.
- 2024
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Ingår i: Frontiers in immunology. - : Frontiers Media S.A.. - 1664-3224. ; 15:5
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Tidskriftsartikel (refereegranskat)abstract
- It is well established that inflammatory processes in the vicinity of bone often induce osteoclast formation and bone resorption. Effects of inflammatory processes on bone formation are less studied. Therefore, we investigated the effect of locally induced inflammation on bone formation. Toll-like receptor (TLR) 2 agonists LPS from Porphyromonas gingivalis and PAM2 were injected once subcutaneously above mouse calvarial bones. After five days, both agonists induced bone formation mainly at endocranial surfaces. The injection resulted in progressively increased calvarial thickness during 21 days. Excessive new bone formation was mainly observed separated from bone resorption cavities. Anti-RANKL did not affect the increase of bone formation. Inflammation caused increased bone formation rate due to increased mineralizing surfaces as assessed by dynamic histomorphometry. In areas close to new bone formation, an abundance of proliferating cells was observed as well as cells robustly stained for Runx2 and alkaline phosphatase. PAM2 increased the mRNA expression of Lrp5, Lrp6 and Wnt7b, and decreased the expression of Sost and Dkk1. In situ hybridization demonstrated decreased Sost mRNA expression in osteocytes present in old bone. An abundance of cells expressed Wnt7b in Runx2-positive osteoblasts and ß-catenin in areas with new bone formation. These data demonstrate that inflammation, not only induces osteoclastogenesis, but also locally activates canonical WNT signaling and stimulates new bone formation independent on bone resorption.
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| 6. |
- Kurenkova, A. D., et al.
(författare)
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Notch Signaling Regulates the Chondrogenic Potential of Both Articular Chondrocytes and Their Progenitors During Expansion
- 2023
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Ingår i: Stem Cells. - 1066-5099. ; 41:6, s. 658-671
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Tidskriftsartikel (refereegranskat)abstract
- Articular cartilage has a limited capacity for self-repair and clinical approaches to cartilage regeneration are needed. The only such approach developed to date involves an expansion of primary autologous chondrocytes in culture, followed by their reimplantation into a cartilage defect. However, because of the formation of fibrocartilage instead of hyaline cartilage, the outcome is often not satisfactory. It happens due to the de-differentiation of chondrocytes during the expansion step. Indeed, articular chondrocytes are non-proliferative and require partial or complete dedifferentiation before actively proliferating. In recent years stem/progenitor cells in articular cartilage (artSPCs) have been described. These cells maintain their own population and renew articular cartilage in sexually mature mice. artSPCs can, theoretically, be superior to chondrocytes, for repairing damaged cartilage. Accordingly, here, we searched for conditions that allow rapid expansion of both artSPCs and chondrocytes with simultaneous preservation of their ability to form hyaline cartilage. Among the modulators of Wnt, Notch, and FGF signaling and of cell adhesion screened, only fibronectin and modulators of the Notch pathway promoted the rapid expansion of artSPCs. Surprisingly, both inhibition and activation of the pathway had this effect. However, only inhibition of Notch during expansion facilitated the chondrogenic potential of both artSPCs and primary chondrocytes, whereas activation of this pathway abrogated this potential entirely. This effect was the same for murine and human cells. Our present observations indicate that Notch signaling is the major regulator of the chondrogenic capacity of both artSPCs and chondrocytes during their expansion.
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| 7. |
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| 8. |
- Li, Fusheng, 1985-, et al.
(författare)
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Control the O-O bond formation pathways by immobilizing molecular catalysts on glassy carbon via electrochemical polymerization
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Molecular water oxidation catalysts Ru-bda (1) and Ru-pda (2) are electrochemically polymerized on glassy carbon (GC) electrodes. Reaction orders and kinetic isotope effects (KIE) of the corresponding electrodes are studied. Results indicate that poly-1@GC goes through a radical coupling pathway. By adding poly-styrene (PSt) as a “blocking unit” in the poly-1, the radical coupling process of Ru-bda is blocked, and poly-1+PSt@GC catalyzes water oxidation through the water nucleophilic attack pathway. In comparison, catalyst 2, which oxidizes water via water nucleophilic attack path in homogeneous systems, goes through a radical coupling pathway as well when 2 is polymerized on glassy carbon (poly-2@GC).
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| 9. |
- Li, Xixing, et al.
(författare)
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Joint scheduling optimisation method for the machining and heat-treatment of hydraulic cylinders based on improved multi-objective migrating birds optimisation
- 2024
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Ingår i: Journal of manufacturing systems. - : Elsevier BV. - 0278-6125 .- 1878-6642. ; 73, s. 170-191
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Tidskriftsartikel (refereegranskat)abstract
- For the hydraulic cylinder parts manufacturing shop scheduling problem (HCPMS), which integrates a parallel batch processor hybrid flow shop scheduling problem with the flexible job shop scheduling problem, this paper establishes a multi-objective scheduling model with makespan, total energy consumption, and total machine workload as the optimisation objectives, and proposes an improved multi-objective migrating birds optimisation (IMOMBO) algorithm to solve the problem. First, considering the characteristics of the combination of single-piece and batch processing in the workshop, a double-layer coding rule based on the operation and processing equipment is proposed, and the corresponding decoding rule is designed according to whether the workpiece requires quenching and tempering. Second, a multi-population co-evolution mechanism is developed to enhance the diversity of solutions by conducting different evolutionary strategies. Additionally, six neighborhood structures are introduced to perform local searches for the leader and follower birds, thereby improving the quality of the solutions. Finally, the effectiveness of the IMOMBO algorithm is demonstrated by comparing its results with those of four other algorithms through comparative experiments and a practical case.
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| 10. |
- Moverare-Skrtic, Sofia, et al.
(författare)
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B4GALNT3 regulates glycosylation of sclerostin and bone mass
- 2023
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Ingår i: eBioMedicine. - 2352-3964. ; 91
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Tidskriftsartikel (refereegranskat)abstract
- Background Global sclerostin inhibition reduces fracture risk efficiently but has been associated with cardiovascular side effects. The strongest genetic signal for circulating sclerostin is in the B4GALNT3 gene region, but the causal gene is unknown. B4GALNT3 expresses the enzyme beta-1,4-N-acetylgalactosaminyltransferase 3 that transfers N-acetylgalactosamine onto N-acetylglucosaminebeta-benzyl on protein epitopes (LDN-glycosylation). Methods To determine if B4GALNT3 is the causal gene, B4galnt3 / mice were developed and serum levels of total sclerostin and LDN-glycosylated sclerostin were analysed and mechanistic studies were performed in osteoblast-like cells. Mendelian randomization was used to determine causal associations. Findings B4galnt3 / mice had higher circulating sclerostin levels, establishing B4GALNT3 as a causal gene for circulating sclerostin levels, and lower bone mass. However, serum levels of LDN-glycosylated sclerostin were lower in B4galnt3 / mice. B4galnt3 and Sost were co-expressed in osteoblast-lineage cells. Overexpression of B4GALNT3 increased while silencing of B4GALNT3 decreased the levels of LDN-glycosylated sclerostin in osteoblast-like cells. Mendelian randomization demonstrated that higher circulating sclerostin levels, genetically predicted by variants in the B4GALNT3 gene, were causally associated with lower BMD and higher risk of fractures but not with higher risk of myocardial infarction or stroke. Glucocorticoid treatment reduced B4galnt3 expression in bone and increased circulating sclerostin levels and this may contribute to the observed glucocorticoid-induced bone loss. Interpretation B4GALNT3 is a key factor for bone physiology via regulation of LDN-glycosylation of sclerostin. We propose that B4GALNT3-mediated LDN-glycosylation of sclerostin may be a bone-specific osteoporosis target, separating the anti-fracture effect of global sclerostin inhibition, from indicated cardiovascular side effects. Funding Found in acknowledgements.
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| 11. |
- Nethander, Maria, 1980, et al.
(författare)
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An atlas of genetic determinants of forearm fracture.
- 2023
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Ingår i: Nature genetics. - : Springer Nature. - 1546-1718 .- 1061-4036. ; 55:11, s. 1820-1830
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Tidskriftsartikel (refereegranskat)abstract
- Osteoporotic fracture is among the most common and costly of diseases. While reasonably heritable, its genetic determinants have remained elusive. Forearm fractures are the most common clinically recognized osteoporotic fractures with a relatively high heritability. To establish an atlas of the genetic determinants of forearm fractures, we performed genome-wide association analyses including 100,026 forearm fracture cases. We identified 43 loci, including 26 new fracture loci. Although most fracture loci associated with bone mineral density, we also identified loci that primarily regulate bone quality parameters. Functional studies of one such locus, at TAC4, revealed that Tac4-/- mice have reduced mechanical bone strength. The strongest forearm fracture signal, at WNT16, displayed remarkable bone-site-specificity with no association with hip fractures. Tall stature and low body mass index were identified as new causal risk factors for fractures. The insights from this atlas may improve fracture prediction and enable therapeutic development to prevent fractures.
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| 12. |
- Trompet, Dana, 1993, et al.
(författare)
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Stimulation of skeletal stem cells in the growth plate promotes linear bone growth
- 2024
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Ingår i: JCI INSIGHT. - 2379-3708. ; 9:6
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Tidskriftsartikel (refereegranskat)abstract
- Recently, skeletal stem cells were shown to be present in the epiphyseal growth plate (epiphyseal skeletal stem cells, epSSCs), but their function in connection with linear bone growth remains unknown. Here, we explore the possibility that modulating the number of epSSCs can correct differences in leg length. First, we examined regulation of the number and activity of epSSCs by Hedgehog (Hh) signaling. Both systemic activation of Hh pathway with Smoothened agonist (SAG) and genetic activation of Hh pathway by Patched1 (Ptch1) ablation in Pthrp-creER Ptch1(fl/fl )tdTomato mice promoted proliferation of epSSCs and clonal enlargement. Transient intra-articular administration of SAG also elevated the number of epSSCs. When SAG-containing beads were implanted into the femoral secondary ossification center of 1 leg of rats, this leg was significantly longer 1 month later than the contralateral leg implanted with vehicle-containing beads, an effect that was even more pronounced 2 and 6 months after implantation. We conclude that Hh signaling This opens therapeutic possibilities for the treatment of differences in leg length.
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| 13. |
- Törnqvist, Anna E, et al.
(författare)
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Induced inactivation of Wnt16 in young adult mice has no impact on osteoarthritis development.
- 2022
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 17:11
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Tidskriftsartikel (refereegranskat)abstract
- Osteoarthritis (OA) is a common disorder and a major cause of disability in the elderly population. WNT16 has been suggested to play important roles in joint formation, bone homeostasis and OA development, but the mechanism of action is not clear. Transgenic mice lacking Wnt16 expression (Wnt16-/-) have a more severe experimental OA than control mice. In addition, Wnt16-/- mice have a reduced cortical thickness and develop spontaneous fractures. Herein, we have used Cre-Wnt16flox/flox mice in which Wnt16 can be conditionally ablated at any age through tamoxifen-inducible Cre-mediated recombination. Wnt16 deletion was induced in 7-week-old mice to study if the Cre-Wnt16flox/flox mice have a more severe OA phenotype after destabilizing the medial meniscus (DMM surgery) than littermate controls with normal Wnt16 expression (Wnt16flox/flox). WNT16 deletion was confirmed in articular cartilage and cortical bone in Cre-Wnt16flox/flox mice, shown by immunohistochemistry and reduced cortical bone area compared to Wnt16flox/flox mice. After DMM surgery, there was no difference in OA severity in the articular cartilage in the knee joint between the Cre-Wnt16flox/flox and Wnt16flox/flox mice in neither female nor male mice. In addition, there was no difference in osteophyte size in the DMM-operated tibia between the genotypes. In conclusion, inactivation of Wnt16 in adult mice do not result in a more severe OA phenotype after DMM surgery. Thus, presence of WNT16 in adult mice does not have an impact on experimental OA development. Taken together, our results from Cre-Wnt16flox/flox mice and previous results from Wnt16-/- mice suggest that WNT16 is crucial during synovial joint establishment leading to limited joint degradation also later in life, after onset of OA. This may be important when developing new therapeutics for OA treatment.
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| 14. |
- Wei, Shupeng, et al.
(författare)
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An improved memetic algorithm for multi-objective resource-constrained flexible job shop inverse scheduling problem : An application for machining workshop
- 2024
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Ingår i: Journal of manufacturing systems. - : Elsevier BV. - 0278-6125 .- 1878-6642. ; 74, s. 264-290
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Tidskriftsartikel (refereegranskat)abstract
- Resource -constrained flexible job shop scheduling problems are commonly encountered in some manufacturing industries, and have been widely studied in recent years. However, traditional resource constrained flexible job shop scheduling problem rarely consider the uncertainties in actual manufacturing systems, which may make the original schedule become suboptimal or even unfeasible. Therefore, a resource constrained flexible job shop inverse scheduling problem (RCFJISP) is proposed in this paper, which aims to cope with uncertain events by simultaneously adjusting the machine, worker and process parameters of the original schedule. A multi -objective optimization model is constructed to minimize the makespan, worker cost, machine energy consumption and deviation index. Furthermore, an improved memetic algorithm (IMA) is developed for solving the proposed problem. In IMA, a novel double -layer encoding mechanism is designed to enhance the capacity in exploring new solution's domains. Three initialization strategies utilizing original scheduling information are designed to improve the quality of initial solutions. An adaptive mutation strategy and a local search mechanism are designed to enhance exploration and exploitation ability of the algorithm. And a crowding operator is proposed to reflect the diversity of the population effectively. In computational experiments, 28 extended benchmarks are constructed, and the effectiveness of the proposed strategy and algorithm is verified by comparing IMA with its 4 variants and other 4 widely used algorithms. Finally, two inverse scheduling problems of a real -world hydraulic cylinder machining workshop under two uncertain situations are studied. The results demonstrate that IMA can effectively solve the actual inverse scheduling problem. With a slight adjustment to the original scheduling, it can reduce the makespan by 11.5%, the worker cost by 8.1% and the machine energy consumption by 27.9% on average.
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