| 1. |
- Tyden, Gunnar, et al.
(författare)
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A Randomized, Doubleblind, Placebo-Controlled, Study of Single-Dose Rituximab as Induction in Renal Transplantation
- 2009
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Ingår i: Transplantation. - 1534-6080 .- 0041-1337. ; 87:9, s. 1325-1329
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Tidskriftsartikel (refereegranskat)abstract
- We performed a prospective, double blind, randomized, placebo-controlled multicenter study on the efficacy and safety of rituximab as induction therapy, together with tacrolimus, mycophenolate mofetil, and steroids. The primary endpoint was defined as acute rejection, graft loss, or death during the first 6 months. Secondary endpoints were creatinine clearance, incidence of infections, and incidence of rituximab-related adverse event. Results. We enrolled 140 patients (44 living donor and 96 deceased donor), and of those, 68 rituximab and 68 placebo patients fulfilled the study. In all the patients receiving rituximab, there was a complete depiction of CD 19/CD20 cells, whereas there was no change in the number of CD19/CD20 cells in the placebo group. There were 10 treatment failures in the rituximab group versus 14 in the placebo group (P=0.348). There were eight rejection episodes in the rituximab group versus 12 in the placebo group (P=0.317) Creatinine clearance was 66 +/- 22 mL/min in the study group and 67 +/- 23 mL/min in the placebo group. There was no difference in the number of bacterial infections, cytomegalovirus infections, and BK virus infections or fungal infections. Conclusion. We performed a placebo-controlled study of rituximab induction in renal transplantation. There was a tendency toward fewer and milder rejections during the first 6 months in the rituximab group. Although induction with one dose of rituximab induced a complete depletion B cells, there was no increase in the incidence of infectious complications or leukopenia and it seems safe, therefore, to conduct further studies on the use of rituximab in transplantation.
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| 3. |
- André, Ingemar, et al.
(författare)
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Streptococcal M protein: Structural studies of the hypervariable region, free and bound to human C4BP
- 2006
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Ingår i: Biochemistry. - : American Chemical Society (ACS). - 0006-2960 .- 1520-4995. ; 45:14, s. 4559-4568
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Tidskriftsartikel (refereegranskat)abstract
- Streptococcus pyogenes is a Gram-positive bacterium that causes several diseases, including acute tonsillitis and toxic shock syndrome. The surface-localized M protein, which is the most extensively studied virulence factor of S. pyogenes, has an similar to 50-residue N-terminal hypervariable region (HVR) that plays a key role in the escape of the host immunity. Despite the extensive sequence variability in this region, many HVRs specifically bind human C4b-binding protein (C4BP), a plasma protein that inhibits complement activation. Although the more conserved parts of M protein are known to have dimeric coiled-coil structure, it is unclear whether the HVR also is a coiled coil. Here, we use nuclear magnetic resonance (NMR) to study the conformational properties of HVRs from M4 and M22 proteins in isolation and in complex with the M protein binding portion of C4BP. We conclude that the HVRs of M4 and M22 are folded as coiled coils and that the folded nucleus of the M4 HVR has a length of similar to 27 residues. Moreover, we demonstrate that the C4BP binding surface of M4-N is found within a region of four heptad repeats. Using molecular modeling, we propose a model for the structure of the M4 HVR that is consistent with our experimental information from NMR spectroscopy.
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| 6. |
- Bivall Persson, Petter, 1979-, et al.
(författare)
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Improved Feature Detection over Large Force Ranges Using History Dependent Transfer Functions
- 2009
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Ingår i: Third Joint Eurohaptics Conference and Symposium on Haptic Interfaces for Virtual Environments and Teleoperator Systems, WorldHaptics 2009. - : IEEE. - 9781424438587 ; , s. 476-481
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Konferensbidrag (refereegranskat)abstract
- In this paper we present a history dependent transfer function (HDTF) as a possible approach to enable improved haptic feature detection in high dynamic range (HDR) volume data. The HDTF is a multi-dimensional transfer function that uses the recent force history as a selection criterion to switch between transfer functions, thereby adapting to the explored force range. The HDTF has been evaluated using artificial test data and in a realistic application example, with the HDTF applied to haptic protein-ligand docking. Biochemistry experts performed docking tests, and expressed that the HDTF delivers the expected feedback across a large force magnitude range, conveying both weak attractive and strong repulsive protein-ligand interaction forces. Feature detection tests have been performed with positive results, indicating that the HDTF improves the ability of feature detection in HDR volume data as compared to a static transfer function covering the same range.
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| 7. |
- Björnsson, Gunnar, 1969-, et al.
(författare)
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Judgments of moral responsibility - a unified account
- 2009
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Ingår i: Conferences and Volumes: [2009] Society for Philosophy and Psychology, 35th Annual Meeting (Bloomington, IN; June 12-14) (5). ; 2009
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Konferensbidrag (refereegranskat)abstract
- Recent work in experimental philosophy shows that folk intuitions about moral responsibility are sensitive to a surprising variety of factors. Studies by Nichols and Knobe (2007) suggest that whether people take agents to be responsible for their actions in a deterministic scenario depends on whether these actions are described abstractly or concretely, and on how serious moral transgression these actions seem to represent. Studies by Nahmias et. al. (2007) show that the kind of determinism involved affects assignments of responsibility. When deterministic scenarios are described using reductionist explanations of action, subjects were significantly less prone to ascribe responsibility than when the deterministic laws are described as involving ordinary psychological concepts. Finally, a study by Knobe (2003) suggests that people are significantly more inclined to hold an agent responsible for bringing about bad side effects than for bringing about good side effects when the agent just doesn’t care about these side effects. Elsewhere, we have presented an analysis of our everyday concept of moral responsibility that provides a unified explanation of paradigmatic cases of moral responsibility, and accounts for the force of both typical excuses and the most influential skeptical arguments against moral responsibility or for incompatibilism. In this article, we suggest that it also explains the divergent and apparently incoherent set of intuitions revealed by these new studies. If our hypothesis is correct, the surprising variety of judgments stems from a unified concept of moral responsibility. Knobe, J. (2003) Intentional Action and Side Effects in Ordinary Language. Analysis 63, pp.190–93. Nahmias, E.; Coates, J.; Kvaran. T. (2007) Free will, moral responsibility, and mechanism: experiments on folk intuitions. Midwest studies in Philosophy XXXI Nichols, S.; Knobe, J. (2007) Moral responsibility and determinism: the cognitive science of folk intuitions, Noûs 41:4, 663-685
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| 8. |
- Björnsson, Gunnar, 1969-, et al.
(författare)
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Judgments of moral responsibility –a unified account II
- 2009
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Ingår i: ESPP 2009 Budapest, Book of abstracts. ; , s. 16-
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Konferensbidrag (refereegranskat)abstract
- Recent work in experimental philosophy shows that folk intuitions about moral responsibility are sensitive to a surprising variety of factors. Whether people take agents to be responsible for their actions in deterministic scenarios depends on whether the deterministic laws are couched in neurological or psychological terms (Nahmias et. al. 2007), on whether actions are described abstractly or concretely, and on how serious moral transgression they seem to represent (Nichols & Knobe 2007). Finally, people are more inclined to hold an agent responsible for bringing about bad than for bringing about good side effects that the agent is indifferent about (Knobe 2003). Elsewhere, we have presented an analysis of the everyday concept of moral responsibility that provides a unified explanation of paradigmatic cases of moral responsibility, and accounts for the force of both typical excuses and the most influential skeptical arguments against moral responsibility or for incompatibilism. In this article, we suggest that it also explains the divergent and apparently incoherent set of intuitions revealed by these new studies. If our hypothesis is correct, the surprising variety of judgments stems from a unified concept of moral responsibility. Knobe, J. (2003) Intentional Action and Side Effects in Ordinary Language. Analysis 63, pp.190–93. Nahmias, E.; Coates, J.; Kvaran. T. (2007) Free will, moral responsibility, and mechanism: experiments on folk intuitions. Midwest studies in Philosophy XXXI Nichols, S.; Knobe, J. (2007) Moral responsibility and determinism: the cognitive science of folk intuitions, Noûs 41:4, 663-685
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| 9. |
- Björnsson, Gunnar, 1969-, et al.
(författare)
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The Explanatory Component of Moral Responsibility
- 2008
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Ingår i: The Fifth Interuniversity Workshop on Art, Mind and Morals, Palma de Mallorca.
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Konferensbidrag (refereegranskat)abstract
- Conflicting judgments and intuitions are commonplace in philosophical debates about moral responsibility. Some participants think that if an agent does not fully control a decision, then she has no or little responsibility for that decision; others think that some degrees of luck are entirely compatible with full responsibility. Some think that in order for an agent to be responsible for an action, she must have been capable of doing something else instead; others think that what is important is merely that the action was brought about by the agent in the right way. Some feel quite strongly that responsibility for an action is undermined by determinism; others think that what is relevant is how that action relates to the agent at the time of choice, not how the agent came to be such that she chose the way she did. Many of the arguments supplied in these controversies urge us to focus on one aspect or view of the cases discussed at the expense of others. These arguments seem effective in that various differences in focus do tend to affect intuitions of responsibility, for professional philosophers and laymen alike. The fact that changes of focus affect intuitions of responsibility raises questions: On what factors should we focus our attention? What focus makes for reliable intuitions? It is not clear that such questions can be answered by providing further cases or thought experiments to consider, as reactions to such cases are likely to be subject to the same sort of focus relativity. This paper approaches the problem from a new angle. It would be easier to determine what to think about moral responsibility if we were clearer about why we react the way we do to these arguments, and why our reactions vary. To this end, we will do three things. First, we will present a general model of our judgments of moral responsibility, a model according to which such judgments are, essentially, explanatory judgments. Second, we will explain how this model can account for not only factors that affect the degrees to which we assign moral responsibility in ordinary life, but also the sometimes contradictory judgments that people make about one of the most important thought experiments in the philosophical debate about moral responsibility. Finally, we will argue that this has important methodological consequences for that debate.
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| 10. |
- Engberg, Anna E., 1982-, et al.
(författare)
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Inhibition of complement activation on a model biomaterial surface by streptococcal M protein-derived peptides
- 2009
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Ingår i: Biomaterials. - : Elsevier. - 0142-9612 .- 1878-5905. ; 30:13, s. 2653-2659
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to evaluate a new approach to inhibit complement activation triggered by biomaterial surfaces in contact with blood. In order to inhibit complement activation initiated by the classical pathway (CP), we used streptococcal M protein-derived peptides that specifically bind human C4BP, an inhibitor of the CP. The peptides were used to coat polystyrene microtiter wells which served as a model biomaterial. The ability of coated peptides to bind C4BP and to attenuate complement activation via the CP (monitored as generation of fluid-phase C3a and binding of fragments of C3 and C4 to the surface) was investigated using diluted normal human serum, where complement activation by the AP is minimal, as well as serum from a patient lacking alternative pathway activation. Complement activation (all parameters) was significantly decreased in serum incubated in well surfaces coated with peptides. Total inhibition of complement activation was obtained at peptide coating concentrations as low as 1-5 mu g/mL. Successful use of Streptococcus-derived peptides shows that it is feasible to control complement activation at a model biomaterial surface by capturing autologous complement regulatory molecules from plasma. (C) 2009 Elsevier Ltd. All rights reserved.
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