| 1. |
- Swat, M. J., et al.
(författare)
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Pharmacometrics Markup Language (PharmML) : Opening New Perspectives for Model Exchange in Drug Development
- 2015
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Ingår i: CPT. - : American Society for Clinical Pharmacology & Therapeutics. - 2163-8306. ; 4:6, s. 316-319
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Tidskriftsartikel (refereegranskat)abstract
- The lack of a common exchange format for mathematical models in pharmacometrics has been a long-standing problem. Such a format has the potential to increase productivity and analysis quality, simplify the handling of complex workflows, ensure reproducibility of research, and facilitate the reuse of existing model resources. Pharmacometrics Markup Language (PharmML), currently under development by the Drug Disease Model Resources (DDMoRe) consortium, is intended to become an exchange standard in pharmacometrics by providing means to encode models, trial designs, and modeling steps.
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| 2. |
- Baklanov, D. V., et al.
(författare)
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Comparison of transendocardial and retrograde coronary venous intramyocardial catheter delivery systems in healthy and infarcted pigs
- 2006
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Ingår i: Catheterization and cardiovascular interventions. - : Wiley-Blackwell. - 1522-1946 .- 1522-726X. ; 68:3, s. 416-423
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Tidskriftsartikel (refereegranskat)abstract
- We compared two routes for myocardial delivery of therapeutics, transendocardial (TE) delivery with an intramyocardial injection catheter, and retrograde coronary venous (RCV) delivery with a balloon occlusion catheter in the interventricular vein. Methods: TE and RCV injection of 15 mu m, neutron-activatable microspheres was compared in healthy pigs (Group I, n = 3), pigs with a 1-week-old myocardial infarction (MI; group II, n = 5), and pigs with a 2-weeks-old MI (group III, n = 4). The MI was induced by a 1-hr balloon occlusion in the LAD. Both methods were compared in the same animal using different microspheres. The RCV catheter allowed for continuous measurement of distal pressure and 2.5 x 10(6) microspheres were injected in 10 ml at 300 mmHg above balloon occlusion pressure. The TE injections were targeted to the infarct zone and 2.5 x 10(6) microspheres were distributed over 10 injections of 200 mu l. Results: The retention of microspheres decreased with increase in MI age, but was comparable between devices within the groups. RCV delivery resulted in (14.3 +/- 0.9)% microsphere retention in Group I, (10.3 +/- 0.2)% in Group II, and (6.4 +/- 0.1)% in group III (P less than 0.05 versus group I). Microsphere retention after TE was (15.1 +/- 0.7)% in group I, (18.9 +/- 0.6)% in group II, (4.1 +/- 0.1)% in Group III (P less than 0.05 versus groups I and II). The RCV catheter delivered primarily to midventricular, antero-septal segments, whereas TE targeted apical areas predominantly. Conclusions: Delivery efficacy was comparable between devices in each group however RCV targeted midventricular areas whereas TE targeted apical areas.
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| 3. |
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| 4. |
- Morf, Andrea, 1968, et al.
(författare)
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Challenges and Enablers to Integrate Land-Sea-Interactions in Cross-Border Marine and Coastal Planning: Experiences from the Pan Baltic Scope Collaboration
- 2022
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Ingår i: Planning Practice and Research. - : Informa UK Limited. - 0269-7459 .- 1360-0583. ; 37:3, s. 333-354
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Tidskriftsartikel (refereegranskat)abstract
- This paper analyses challenges and enablers for integrating a transboundary land-sea interaction (LSI) perspective into marine spatial planning (MSP) practice as experienced in the Baltic Sea Region. Collaborative research results from the Pan Baltic Scope project indicate that LSI remains an amorphous concept, particularly within a transboundary MSP context. Difficulty lies in bridging planning practices across land and sea and between varying uses, administrative settings and governance functions. Addressing LSI requires capacity, time, resources, awareness, reflection, and forums for collaborative learning across sectors and governance levels.
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| 5. |
- Morf, Andrea, 1968, et al.
(författare)
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Towards sustainability of marine governance: Challenges and enablers for stakeholder integration in transboundary marine spatial planning in the Baltic Sea
- 2019
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Ingår i: Ocean & Coastal Management. - : Elsevier BV. - 0964-5691. ; 177, s. 200-212
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Tidskriftsartikel (refereegranskat)abstract
- Integrating stakeholder knowledge, views and needs in marine or maritime spatial planning (MSP) processes is important from a governance and social sustainability perspective both for MSP practitioners and for the evolving field of MSP research. Transboundary MSP appears particularly challenging for participation, which is why it is important to identify opportunities and address obstacles for stakeholder integration in this specific context. This article examines how stakeholder integration is currently practiced in the Baltic Sea Region (BSR), an enclosed sea where policy coherence and addressing conflicting interests across borders are especially relevant. It synthesises a range of challenges and enablers for stakeholder participation and mobilisation that have emerged from two transboundary MSP research and development projects, BaltSpace and Baltic SCOPE. The article finds that with the exception of statutory authorities, stakeholder engagement in the BSR is mostly limited to self-motivated stakeholders and consultation rather than more inclusive forms of participation. This can reduce the quality and legitimacy of MSP processes and risks to concentrate power in the hands of a small group of actors. For transboundary stakeholder integration to become more interactive and effective, five types of challenges need attention, regarding a) timing, b) governance systems, c) capacity and processes, d) stakeholder characteristics and e) knowledge and language. These obstacles can be addressed by (1) a dedicated research and development agenda that critically reflects on integrative tools and processes, and (2) by encouraging transnational institutions in the BSR to devote more resources to transboundary stakeholder integration and adopt flexible and adaptive strategies and tools that can facilitate stakeholder involvement throughout the MSP policy cycle.
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| 6. |
- Cahill, P. L., et al.
(författare)
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Creating New Antifoulants Using the Tools and Tactics of Medicinal Chemistry
- 2024
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Ingår i: Accounts of Chemical Research. - : American Chemical Society. - 0001-4842 .- 1520-4898. ; 57:3, s. 399-
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Tidskriftsartikel (refereegranskat)abstract
- Conspectus The unwanted accumulation of marine micro- and macroorganisms such as algae and barnacles on submerged man-made structures and vessel hulls is a major challenge for any marine operation. Known as biofouling, this problem leads to reduced hydrodynamic efficiency, significantly increased fuel usage, microbially induced corrosion, and, if not managed appropriately, eventual loss of both performance and structural integrity. Ship hull biofouling in the international maritime transport network conservatively accounts for 0.6% of global carbon emissions, highlighting the global scale and the importance of this problem. Improved antifouling strategies to limit surface colonization are paramount for essential activities such as shipping, aquaculture, desalination, and the marine renewable energy sector, representing both a multibillion dollar cost and a substantial practical challenge. From an ecological perspective, biofouling is a primary contributor to the global spread of invasive marine species, which has extensive implications for the marine environment. Historically, heavy metal-based toxic biocides have been used to control biofouling. However, their unwanted collateral ecological damage on nontarget species and bioaccumulation has led to recent global bans. With expanding human activities within aquaculture and offshore energy, it is both urgent and apparent that environmentally friendly surface protection remains key for maintaining the function of both moving and stationary marine structures. Biofouling communities are typically a highly complex network of both micro- and macroorganisms, representing a broad section of life from bacteria to macrophytes and animals. Given this diversity, it is unrealistic to expect that a single antifouling “silver bullet” will prevent colonization with the exception of generally toxic biocides. For that reason, modern and future antifouling solutions are anticipated to rely on novel coating technologies and “combination therapies” where mixtures of narrow-spectrum bioactive components are used to provide coverage across fouling species. In contrast to the existing cohort of outdated, toxic antifouling strategies, such as copper- and tributyltin-releasing paints, modern drug discovery techniques are increasingly being employed for the rational design of effective yet safe alternatives. The challenge for a medicinal chemistry approach is to effectively account for the large taxonomic diversity among fouling organisms combined with a lack of well-defined conserved molecular targets within most taxa. The current Account summarizes our work employing the tools of modern medicinal chemistry to discover, modify, and develop optimized and scalable antifouling solutions based on naturally occurring antifouling and repelling compounds from both marine and terrestrial sources. Inspiration for rational design comes from targeted studies on allelopathic natural products, natural repelling peptides, and secondary metabolites from sessile marine organisms with clean exteriors, which has yielded several efficient and promising antifouling leads.
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| 7. |
- Mandinov, L., et al.
(författare)
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Inhibition of in-stent restenosis by oral copper chelation in porcine coronary arteries
- 2006
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Ingår i: American Journal of Physiology. Heart and Circulatory Physiology. - : American Physiological Society. - 0363-6135 .- 1522-1539. ; 291:6, s. H2692-H2697
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Tidskriftsartikel (refereegranskat)abstract
- Stress-induced release of IL-1 alpha and fibroblast growth factor-1 is dependent on intracellular copper and is a major driver of neointimal hyperplasia. Therefore, we assessed the effect of tetrathiomolybdate (TTM), a clinically proven copper chelator, on in-stent restenosis. Nine pigs were treated with TTM (5 mg/kg po) twice daily for 2 wk before stent implantation and for 4 wk thereafter, and nine pigs served as controls. In-stent restenosis was assessed by quantitative coronary angiography (QCA), intravascular ultrasound (IVUS), and histomorphometry. Serum ceruloplasmin activity was used as a surrogate marker of copper bioavailability. In TTM-treated animals, ceruloplasmin dropped 70 +/- 10% below baseline levels. Baseline characteristics were comparable in TTM-treated and control animals. At 4-wk follow-up, all parameters relevant to in-stent restenosis were significantly reduced in TTM-treated animals: minimal lumen diameter by QCA was 2.03 +/- 0.57 and 1.47 +/- 0.45 mm in TTM-treated and control animals, respectively (P less than 0.05), percent stenosis diameter was 39% less in TTM-treated animals (27.1 +/- 16.6% vs. 44.5 +/- 16.1%, P less than 0.05), minimal lumen area by IVUS was 60% larger in TTM-treated animals (4.27 +/- 1.56 vs. 2.67 +/- 1.19 mm(2), P less than 0.05), and neointimal volume by histomorphometry was 37% less in TTM-treated animals (34.9 +/- 11.5 vs. 55.2 +/- 19.6 mm(3), P less than 0.05). We conclude that systemic copper chelation with a clinically approved chelator significantly inhibits in-stent restenosis.
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| 8. |
- Rodrigues, Leticia, et al.
(författare)
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Cellular uptake of self-assembled phytantriol-based hexosomes is independent of major endocytic machineries
- 2019
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Ingår i: Journal of Colloid and Interface Science. - : Elsevier. - 0021-9797 .- 1095-7103. ; 553, s. 820-833
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Tidskriftsartikel (refereegranskat)abstract
- Despite increasing interests in non-lamellar liquid crystalline dispersions, such as hexosomes, for drug delivery, little is known about their interactions with cells and mechanism of cell entry. Here we examine the cellular uptake of hexosomes based on phytantriol and mannide monooleate by HeLa cells using live cell microscopy in comparison to conventional liposomes. To investigate the importance of specific endocytosis pathways upon particle internalization, we silenced regulatory proteins of major endocytosis pathways using short interfering RNA. While endocytosis plays a significant role in liposome internalization, hexosomes are not taken up via endocytosis but through a mechanism that is dependent on cell membrane tension. Biophysical studies using biomembrane models highlighted that hexosomes have a high affinity for membranes and an ability to disrupt lipid layers. Our data suggest that direct biomechanical interactions of hexosomes with membrane lipids play a crucial role and that the unique morphology of hexosomes is vital for their membrane activity. Based on these results, we propose a mechanism, where hexosomes destabilize the bilayer, allowing them to "phase through" the membrane. Understanding parameters that influence the uptake of hexosomes is critical to establish them as carrier systems that can potentially deliver therapeutics efficiently to intracellular sites of action.
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