| 1. |
- Atefyekta, Saba, 1987, et al.
(författare)
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Antimicrobial performance of mesoporous titania thin films: role of pore size, hydrophobicity, and antibiotic release
- 2016
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Ingår i: International journal of nanomedicine. - : Informa UK Limited. - 1176-9114 .- 1178-2013. ; 11, s. 977-990
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Tidskriftsartikel (refereegranskat)abstract
- Implant-associated infections are undesirable complications that might arise after implant surgery. If the infection is not prevented, it can lead to tremendous cost, trauma, and even life threatening conditions for the patient. Development of an implant coating loaded with antimicrobial substances would be an effective way to improve the success rate of implants. In this study, the in vitro efficacy of mesoporous titania thin films used as a novel antimicrobial release coating was evaluated. Mesoporous titania thin films with pore diameters of 4, 6, and 7 nm were synthesized using the evaporation-induced self-assembly method. The films were characterized and loaded with antimicrobial agents, including vancomycin, gentamicin, and daptomycin. Staphylococcus aureus and Pseudomonas aeruginosa were used to evaluate their effectiveness toward inhibiting bacterial colonization. Drug loading and delivery were studied using a quartz crystal microbalance with dissipation monitoring, which showed successful loading and release of the antibiotics from the surfaces. Results from counting bacterial colony-forming units showed reduced bacterial adhesion on the drug-loaded films. Interestingly, the presence of the pores alone had a desired effect on bacterial colonization, which can be attributed to the documented nanotopographical effect. In summary, this study provides significant promise for the use of mesoporous titania thin films for reducing implant infections.
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| 2. |
- Bengtsson-Palme, Johan, 1985, et al.
(författare)
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Strategies to improve usability and preserve accuracy in biological sequence databases
- 2016
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Ingår i: Proteomics. - : Wiley. - 1615-9853 .- 1615-9861. ; 16:18, s. 2454-2460
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Tidskriftsartikel (refereegranskat)abstract
- Biology is increasingly dependent on large-scale analysis, such as proteomics, creating a requirement for efficient bioinformatics. Bioinformatic predictions of biological functions rely upon correctly annotated database sequences, and the presence of inaccurately annotated or otherwise poorly described sequences introduces noise and bias to biological analyses. Accurate annotations are, for example, pivotal for correct identifications of polypeptide fragments. However, standards for how sequence databases are organized and presented are currently insufficient. Here, we propose five strategies to address fundamental issues in the annotation of sequence databases: (i) to clearly separate experimentally verified and unverified sequence entries; (ii) to enable a system for tracing the origins of annotations; (iii) to separate entries with high-quality, informative annotation from less useful ones; (iv) to integrate automated quality-control software whenever such tools exist; and (v) to facilitate post-submission editing of annotations and metadata associated with sequences. We believe that implementation of these strategies, for example as requirements for publication of database papers, would enable biology to better take advantage of large-scale data.
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| 3. |
- Karlsson, Johan, 1984, et al.
(författare)
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Stem cell homing using local delivery of plerixafor and stromal derived growth factor-1alpha for improved bone regeneration around Ti-implants
- 2016
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Ingår i: Journal of Biomedical Materials Research - Part A. - : Wiley. - 1552-4965 .- 1549-3296. ; 104:10, s. 2466-2475
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Tidskriftsartikel (refereegranskat)abstract
- Triggering of the early healing events, including the recruitment of progenitor cells, has been suggested to promote bone regeneration. In implantology, local drug release technologies could provide an attractive approach to promote tissue regeneration. In this study, we targeted the chemotactic SDF-1a/CXCR4 axis that is responsible e.g. for the homing of stem cells to trauma sites. This was achieved by local delivery of plerixafor, an antagonist to CXCR4, and/or SDF-1a from titanium implants coated with mesoporous titania thin films with a pore size of 7.5 nm. In vitro drug delivery experiments demonstrated that the mesoporous coating provided a high drug loading capacity and controlled release. The subsequent in vivo study in rat tibia showed beneficial effects with respect to bone-implant anchorage and bone-formation along the surface of the implants when plerixafor and SDF-1a were delivered locally. The effect was most prominent by the finding that the combination of the drugs significantly improved the mechanical bone anchorage. These observations suggest that titanium implants with local delivery of drugs for enhanced local recruitment of progenitor cells have the ability to promote osseointegration. This approach may provide a potential strategy for the development of novel implant treatments.
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| 4. |
- Raphel, J., et al.
(författare)
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Engineered protein coatings to improve the osseointegration of dental and orthopaedic implants
- 2016
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Ingår i: Biomaterials. - : Elsevier BV. - 0142-9612 .- 1878-5905. ; 83, s. 269-282
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Tidskriftsartikel (refereegranskat)abstract
- Here we present the design of an engineered, elastin-like protein (ELP) that is chemically modified to enable stable coatings on the surfaces of titanium-based dental and orthopaedic implants by novel photocrosslinking and solution processing steps. The ELP includes an extended RGD sequence to confer bio-signaling and an elastin-like sequence for mechanical stability. ELP thin films were fabricated on cpTi and Ti6A14V surfaces using scalable spin and dip coating processes with photoactive covalent cross linking through a carbene insertion mechanism. The coatings withstood procedures mimicking dental screw and hip replacement stem implantations, a key metric for clinical translation. They promoted rapid adhesion of MG63 osteoblast-like cells, with over 80% adhesion after 24 h, compared to 38% adhesion on uncoated Ti6A14V. MG63 cells produced significantly more mineralization on ELP coatings compared to uncoated Ti6A14V. Human bone marrow mesenchymal stem cells (hMSCs) had an earlier increase in alkaline phosphatase activity, indicating more rapid osteogenic differentiation and mineral deposition on adhesive ELP coatings. Rat tibia and femur in vivo studies demonstrated that cell -adhesive ELP-coated implants increased bone-implant contact area and interfacial strength after one week. These results suggest that ELP coatings withstand surgical implantation and promote rapid osseointegration, enabling earlier implant loading and potentially preventing micromotion that leads to aseptic loosening and premature implant failure.
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| 5. |
- Sangchoolie, Behrooz, et al.
(författare)
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A Comparison of Inject-on-Read and Inject-on-Write in ISA-Level Fault Injection
- 2016
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Ingår i: Proceedings - 2015 11th European Dependable Computing Conference, EDCC 2015. - : Institute of Electrical and Electronics Engineers Inc.. - 9781467392891 ; , s. 178-189, s. 178-189
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Konferensbidrag (refereegranskat)abstract
- ISA-level fault injection, i.e. the injection of bit-flip faults in Instruction Set Architecture (ISA) registers and main memory words, is widely used for studying the impact of transient and intermittent hardware faults in computer systems. This paper compares two techniques for ISA-level fault injection: inject-on-read, and inject-on-write. The first technique injects bit-flips in a data-item (the content of a register or memory word) just before the data-item is read by a machine instruction, while the second one injects bit-flips in a data-item just after it has been updated by a machine instruction. In addition, the paper compares two variants of inject-on-read, one where all faults are given the same weight and one where weight factors are used to reflect the time a data-item spends in a register or memory word. The weighted injected-on-read aims to accurately model soft errors that occur when an ionizing particle perturbs a data-item while it resides in an ISA register or a memory word. This is in contrast to inject-on-write, which emulates errors that propagate into an ISA register or a memory word. Our experiments show significant differences in the results obtained with the three techniques.
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| 6. |
- Smith, Jennifer A, et al.
(författare)
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Genome-wide association study identifies 74 loci associated with educational attainment
- 2016
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Ingår i: Nature (London). - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 533:7604, s. 539-542
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Tidskriftsartikel (refereegranskat)abstract
- Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals. Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends our earlier discovery sample of 101,069 individuals to 293,723 individuals, and a replication study in an independent sample of 111,349 individuals from the UK Biobank. We identify 74 genome-wide significant loci associated with the number of years of schooling completed. Single-nucleotide polymorphisms associated with educational attainment are disproportionately found in genomic regions regulating gene expression in the fetal brain. Candidate genes are preferentially expressed in neural tissue, especially during the prenatal period, and enriched for biological pathways involved in neural development. Our findings demonstrate that, even for a behavioural phenotype that is mostly environmentally determined, a well-powered GWAS identifies replicable associated genetic variants that suggest biologically relevant pathways. Because educational attainment is measured in large numbers of individuals, it will continue to be useful as a proxy phenotype in efforts to characterize the genetic influences of related phenotypes, including cognition and neuropsychiatric diseases.
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