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- Alexander, Gerianne, et al.
(author)
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The sounds of science-a symphony for many instruments and voices
- 2020
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In: Physica Scripta. - : IOP Publishing. - 0031-8949 .- 1402-4896. ; 95:6
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Journal article (peer-reviewed)abstract
- Sounds of Science is the first movement of a symphony for many (scientific) instruments and voices, united in celebration of the frontiers of science and intended for a general audience. John Goodenough, the maestro who transformed energy usage and technology through the invention of the lithium-ion battery, opens the programme, reflecting on the ultimate limits of battery technology. This applied theme continues through the subsequent pieces on energy-related topics-the sodium-ion battery and artificial fuels, by Martin Mansson-and the ultimate challenge for 3D printing, the eventual production of life, by Anthony Atala. A passage by Gerianne Alexander follows, contemplating a related issue: How might an artificially produced human being behave? Next comes a consideration of consciousness and free will by Roland Allen and Suzy Lidstrom. Further voices and new instruments enter as Warwick Bowen, Nicolas Mauranyapin and Lars Madsen discuss whether dynamical processes of single molecules might be observed in their native state. The exploitation of chaos in science and technology, applications of Bose-Einstein condensates and the significance of entropy follow in pieces by Linda Reichl, Ernst Rasel and Roland Allen, respectively. Mikhail Katsnelson and Eugene Koonin then discuss the potential generalisation of thermodynamic concepts in the context of biological evolution. Entering with the music of the cosmos, Philip Yasskin discusses whether we might be able to observe torsion in the geometry of the Universe. The crescendo comes with the crisis of singularities, their nature and whether they can be resolved through quantum effects, in the composition of Alan Coley. The climax is Mario Krenn, Art Melvin and Anton Zeilinger's consideration of how computer code can be autonomously surprising and creative. In a harmonious counterpoint, his 'Guidelines for considering AIs as coauthors', Roman Yampolskiy concludes that code is not yet able to take responsibility for coauthoring a paper. An interlude summarises a speech by Zdenek Papousek. In a subsequent movement, new themes emerge as we seek to comprehend how far we have travelled along the path to understanding, and speculate on where new physics might arise. Who would have imagined, 100 years ago, a global society permeated by smartphones and scientific instruments so sophisticated that genes can be modified and gravitational waves detected?
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- Andersson, Carl-Håkan, et al.
(author)
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Fibre Handleability, Damage Formation, Dust Emission and Morphology
- 1994
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In: Composites Testing and Standardization. - 1855731878 ; , s. 625-632
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Conference paper (peer-reviewed)abstract
- The mechanical stress build up in fibre handling, the dynamical frictional phenomena between fibres and curved surfaces and formation of dust have been studied. Typical are stick slip behavior and threshold stress levels for formation of dust. The emission of dust can be limited by electrostatic charging. The measured coefficients of friction of the fibres depend on the mechanical properties, micro structure, morphology and sizing of the fibres, the friction materials, the deformation rates and applied loads.
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- Ansari, Daniel, et al.
(author)
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Surveillance after surgery for pancreatic cancer : a global scoping review of guidelines and a nordic survey of contemporary practice
- 2024
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In: Scandinavian Journal of Gastroenterology. - : Taylor & Francis. - 0036-5521 .- 1502-7708.
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Research review (peer-reviewed)abstract
- Objectives: Most patients with pancreatic cancer who have undergone surgical resection eventually develop disease recurrence. This study aimed to investigate whether there is evidence to support routine surveillance after pancreatic cancer surgery, with a secondary aim of analyzing the implementation of surveillance strategies in the Nordic countries.Materials and Methods: A scoping review was conducted to identify clinical practice guidelines globally and research studies relating to surveillance after pancreatic cancer resection. This was followed by a survey among 20 pancreatic units from four Nordic countries to assess their current practice of follow-up for operated patients.Results: Altogether 16 clinical practice guidelines and 17 research studies were included. The guidelines provided inconsistent recommendations regarding postoperative surveillance of pancreatic cancer. The clinical research data were mainly based on retrospective cohort studies with low level of evidence and lead-time bias was not addressed. Active surveillance was recommended in Sweden and Denmark, but not in Norway beyond the post-operative/adjuvant period. Finland had no national recommendations for surveillance. The Nordic survey revealed a wide variation in reported practice among the different units. About 75% (15 of 20 units) performed routine postoperative surveillance. Routine CA 19-9 testing was used by 80% and routine CT by 67% as part of surveillance. About 73% of centers continued follow-up until 5 years postoperatively.Conclusion: Evidence for routine long-term (i.e. 5 years) surveillance after pancreatic cancer surgery remains limited. Most pancreatic units in the Nordic countries conduct regular follow-up, but protocols vary.
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- Christensson, Bengt, et al.
(author)
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Friction and Damage Accumulation, Formation, Morphology and Transport of Dust from Fibre Handling
- 1993
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In: Developments in the Science and Technology of Composite Materials. ; , s. 89-94
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Conference paper (peer-reviewed)abstract
- The mechanical stress build up in fibre handling, the dynamical frictional phenomena between fibres and curves surfaces and formation of dust have been studied. Typical are stick slip behaviour and threshold stress levels for formation of dust. The emissions of dust can be limited by electrostatic charging. The measured coefficients of friction of the fibres depend on the mechanical properties, micro structure, morphology and sizing of the fibres, the friction materials, the deformation rates and applied loads.
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- Hansson, Magnus, et al.
(author)
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Calcium-induced generation of reactive oxygen species in brain mitochondria is mediated by permeability transition.
- 2008
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In: Free Radical Biology & Medicine. - : Elsevier BV. - 0891-5849. ; 45, s. 284-294
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Journal article (peer-reviewed)abstract
- Mitochondrial uptake of calcium in excitotoxicity is associated with subsequent increase in reactive oxygen species (ROS) generation and delayed cellular calcium deregulation in ischemic and neurodegenerative insults. The mechanisms linking mitochondrial calcium uptake and ROS production remain unknown but activation of the mitochondrial permeability transition (mPT) may be one such mechanism. In the present study, calcium increased ROS generation in isolated rodent brain and human liver mitochondria undergoing mPT despite an associated loss of membrane potential, NADH and respiration. Unspecific permeabilization of the inner mitochondrial membrane by alamethicin likewise increased ROS independently of calcium, and the ROS increase was further potentiated if NAD(H) was added to the system. Importantly, calcium per se did not induce a ROS increase unless mPT was triggered. Twenty-one cyclosporin A analogs were evaluated for inhibition of calcium-induced ROS and their efficacy clearly paralleled their potency of inhibiting mPT-mediated mitochondrial swelling. We conclude that while intact respiring mitochondria possess powerful antioxidant capability, mPT induces a dysregulated oxidative state with loss of GSH- and NADPH-dependent ROS detoxification. We propose that mPT is a significant cause of pathological ROS generation in excitotoxic cell death.
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- Morota, Saori, et al.
(author)
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Evaluation of putative inhibitors of mitochondrial permeability transition for brain disorders - Specificity vs. toxicity.
- 2009
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In: Experimental Neurology. - : Elsevier BV. - 0014-4886. ; 218, s. 353-362
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Journal article (peer-reviewed)abstract
- Inhibition of mitochondrial permeability transition (mPT) has emerged as a promising approach for neuroprotection and development of well-tolerated mPT inhibitors with favorable blood-brain barrier penetration is highly warranted. In a recent study, 28 clinically available drugs with a common heterocyclic structure were identified as mPT inhibitors e.g. trifluoperazine, promethazine and nortriptyline. In addition, neuroprotection by structurally unrelated drugs e.g. neurosteroids, 4-hydroxy-tamoxifen and trimetazidine has been attributed to direct inhibition of mPT. The regulation of mPT is complex and highly dependent on the prevailing experimental conditions. Several features of mPT, such as swelling, depolarization or NADH oxidation, can also occur independently of the mPT phenomenon. Here, in isolated rodent brain-derived and human liver mitochondria, we re-evaluate drugs promoted as potent mPT inhibitors. We address the definition of an mPT inhibitor and present strategies to reliably detect mPT inhibition in vitro. Surprisingly, none of the 12 compounds tested displayed convincing mPT inhibition or effects comparable to cyclophilin D inhibition by the non-immunosuppressive cyclophilin inhibitor D-MeAla(3)-EtVal(4)-Cyclosporin (Debio 025). Propofol and 2-aminoethoxydiphenyl borate (2-APB) inhibited swelling in de-energized mitochondria but did not increase calcium retention capacity (CRC). Progesterone, trifluoperazine, allopregnanolone and 4-hydroxy-tamoxifen dose-dependently reduced CRC and respiratory control and were thus toxic rather than beneficial to mitochondrial function. Interestingly, topiramate increased CRC at high concentrations likely by a mechanism separate from direct mPT inhibition. We conclude that a clinically relevant mPT inhibitor should have a mitochondrial target and increase mitochondrial calcium retention at concentrations which can be translated to human use.
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- Månsson, Roland
(author)
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Calcium-induced mitochondrial permeability transition in CNS-derived mitochondria - Pharmacological aspects of specificity and toxicity in neuroprotection
- 2010
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Doctoral thesis (other academic/artistic)abstract
- Mitochondria are the main site for energy conversion in the cell. Under certain circumstances, such as excess calcium retention or production of reactive oxygen species, a pore forms at contact sites between the outer and the normally impermeable inner mitochondrial membrane. The ensuing osmotic mitochondrial swelling and loss of bioenergetic function is referred to as the mitochondrial permeability transition (mPT). Certain drugs of the cyclosporine family, such as cyclosporin A (CsA), are reversible inhibitors of mPT via direct interaction with cyclophilin D, which is a known part of the pore forming complex. The limited blood-brain barrier penetration by these drugs has instigated a search for mPT modulating effects among already clinically available compounds with better access to the central nervous system. In the present study we show that the choice of methods used to evaluate swelling in vitro of mitochondria derived from the CNS could lead to an underestimation of the ability of brain mitochondria to undergo mPT. We have also re-evaluated minocycline, a semisynthetic antibiotic, which has been reported as a direct mPT inhibitor and found that the previously stated mitochondrial effects (depolarization of the mitochondrial membrane potential and inhibition of calcium-induced swelling) are likely secondary or related to mitochondrial toxicity. In a successive evaluation of 12 putative mPT inhibiting compounds, none displayed effects comparable to cyclophilin D inhibition by the non-immunosuppressive cyclophilin inhibitor D-MeAla3-EtVal4-Cyclosporin (Debio 025). Mitochondrial effects were often related to a compromised mitochondrial respiratory capacity. Drugs that uncouple or inhibit mitochondrial respiration will decrease mitochondrial calcium uptake but simultaneously reduce calcium retention capacity (CRC) and thus sensitize mitochondria towards mPT. In addition, a compromised respiratory function will impede ATP generation of mitochondria. It is concluded that screening for putative inhibitors of mPT in complex disease models (such as cellular systems or in vivo models) is extremely prone to confounding influence, the most important being uncoupling and respiratory inhibition. It is suggested that the minimal requirement for a direct mPT inhibitor should include evidence for a specific mitochondrial target and an increased mitochondrial CRC at concentrations that can be translated to safe clinical use.
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- Månsson, Roland, et al.
(author)
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Re-evaluation of mitochondrial permeability transition as a primary neuroprotective target of minocycline.
- 2007
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In: Neurobiology of Disease. - : Elsevier BV. - 0969-9961. ; 25, s. 198-205
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Journal article (peer-reviewed)abstract
- Minocycline has been shown to be neuroprotective in ischemic and neurodegenerative disease models and could potentially be relevant for clinical use. We revisited the hypothesis that minocycline acts through direct inhibition of calcium-induced mitochondrial permeability transition (mPT) resulting in reduced release of cytochrome c (cyt c). Minocycline, at high dosage, was found to prevent calcium-induced mitochondrial swelling under energized conditions similarly to the mPT inhibitor cyclosporin A (CsA) in rodent mitochondria derived from the CNS. In contrast to CsA, minocycline dose-dependently reduced mitochondrial calcium retention capacity (CRC) and respiratory control ratios and was ineffective in the de-energized mPT assay. Further, minocycline did not inhibit calcium- or tBid-induced cyt c release. We conclude that the neuroprotective mechanism of minocycline is likely not related to direct inhibition of mPT and propose that the mitochondrial effects of minocycline may contribute to toxicity rather than tissue protection at high dosing in animals and humans.
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- Nag, Abhishek, et al.
(author)
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Origin of the Spin-Orbital Liquid State in a Nearly J=0 Iridate Ba3ZnIr2O9
- 2016
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In: Physical Review Letters. - : American Physical Society. - 0031-9007 .- 1079-7114. ; 116:9
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Journal article (peer-reviewed)abstract
- We show using detailed magnetic and thermodynamic studies and theoretical calculations that the ground state of Ba3ZnIr2O9 is a realization of a novel spin-orbital liquid state. Our results reveal that Ba3ZnIr2O9 with Ir5+ (5d(4)) ions and strong spin-orbit coupling (SOC) arrives very close to the elusive J = 0 state but each Ir ion still possesses a weak moment. Ab initio density functional calculations indicate that this moment is developed due to superexchange, mediated by a strong intradimer hopping mechanism. While the Ir spins within the structural Ir2O9 dimer are expected to form a spin-orbit singlet state (SOS) with no resultant moment, substantial frustration arising from interdimer exchange interactions induce quantum fluctuations in these possible SOS states favoring a spin-orbital liquid phase down to at least 100 mK.
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- Yu, Jian-Lin, et al.
(author)
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Fibronectin binding by Propionibacterium acnes
- 1997
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In: Pathogens and Disease. - 2049-632X. ; 19:3, s. 247-253
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Journal article (peer-reviewed)abstract
- Strains of Propionibacterium acnes, isolated from different kinds of orthopaedic and biomaterial-associated infections and from skin flora were shown to express binding of soluble as well as immobilized fibronectin. Among these 7 strains isolated from orthopaedic infections, 2 from breast prostheses, and 9 skin isolates, 2, 2, and 5 strains respectively bound immobilized fibronectin. The fibronectin binding was sensitive to protease and heat treatment, and was inhibited by a cell surface extract from one of the binding strains. In SDS-PAGE and autoradiography of cell surface extracts, a band corresponding to a MW of about 80 kD reacted with fibronectin and the 150 kD fragment of fibronectin. Binding to fibronectin and the 150 kD fragment of fibronectin could be inhibited with heparin. We thus present a first Fn binding protein of P. acnes, a surface exposed protein of 80 kD. None of the strains bound soluble collagen, and only one strain expressed weak binding of vitronectin and bone sialoprotein II.
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