| 1. |
- Aeinehband, Shahin, et al.
(författare)
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Complement Component C3 and Butyrylcholinesterase Activity Are Associated with Neurodegeneration and Clinical Disability in Multiple Sclerosis
- 2015
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:4
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Tidskriftsartikel (refereegranskat)abstract
- Dysregulation of the complement system is evident in many CNS diseases but mechanisms regulating complement activation in the CNS remain unclear. In a recent large rat genomewide expression profiling and linkage analysis we found co-regulation of complement C3 immediately downstream of butyrylcholinesterase (BuChE), an enzyme hydrolyzing acetylcholine (ACh), a classical neurotransmitter with immunoregulatory effects. We here determined levels of neurofilament-light (NFL), a marker for ongoing nerve injury, C3 and activity of the two main ACh hydrolyzing enzymes, acetylcholinesterase (AChE) and BuChE, in cerebrospinal fluid (CSF) from patients with MS (n = 48) and non-inflammatory controls (n = 18). C3 levels were elevated in MS patients compared to controls and correlated both to disability and NFL. C3 levels were not induced by relapses, but were increased in patients with >= 9 cerebral lesions on magnetic resonance imaging and in patients with progressive disease. BuChE activity did not differ at the group level, but was correlated to both C3 and NFL levels in individual samples. In conclusion, we show that CSF C3 correlates both to a marker for ongoing nerve injury and degree of disease disability. Moreover, our results also suggest a potential link between intrathecal cholinergic activity and complement activation. These results motivate further efforts directed at elucidating the regulation and effector functions of the complement system in MS, and its relation to cholinergic tone.
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| 2. |
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| 3. |
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| 4. |
- Ardesjö Lundgren, Brita, et al.
(författare)
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Identification of complement C3 as an autoantigen in inflammatory bowel disease.
- 2010
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Ingår i: European journal of gastroenterology & hepatology. - 1473-5687 .- 0954-691X. ; 22:4, s. 429-436
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Autoantibodies against goblet cells in the gastrointestinal mucosa have been described in patients with inflammatory bowel disease (IBD) but a corresponding autoantigen has not yet been identified. The aim of this study was to identify such an antigen. METHODS: First, 10 candidate autoantigens were discarded based on double stainings of appendiceal sections and a mucin-producing cell line (HT29-mtx). Second, an appendiceal cDNA library was immunoscreened with IBD sera. RESULTS: Three out of 48 positive clones were identified as complement C3. Using immunoprecipitation of in vitro transcribed and translated C3, seven of 17 primary sclerosing cholangitis patient sera, 15 of 65 IBD sera, and none out of 54 sera from healthy blood donors showed C3 immunoreactivity. The results were confirmed using western blot and an enzyme-linked immunosorbent assay with alternative sources of C3 protein. CONCLUSION: In conclusion, we have identified complement C3 as a potential autoantigen in IBD and primary sclerosing cholangitis.
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| 5. |
- Bexborn, Fredrik, et al.
(författare)
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Hirudin versus heparin for use in whole blood in vitro biocompatibility models
- 2009
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Ingår i: Journal of Biomedical Materials Research. Part A. - Hoboken, NJ, US : John Wiley & Sons Inc. - 1549-3296 .- 1552-4965. ; 89A:4, s. 951-959
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Tidskriftsartikel (refereegranskat)abstract
- Background: Heparin has traditionally been a widely used anticoagulant in blood research, but has been shown to be inappropriate for work with the complement system because of its complement-interacting properties. In this work, we have compared the effects of heparin with those of the specific thrombin inhibitor hirudin on complement and blood cells in vitro. Methods: Whole blood collected in the presence of hirudin (50 µg/mL) or heparin (1 IU/mL) was incubated in the slide chamber model. The plasma was analyzed for complement activation markers C3a and sC5b-9, and the polyvinylchloride test slides were stained for adhering cells. The integrity of the complement system was tested by incubating serum and hirudin-treated plasma in the presence of various activating agents.Results: In contrast to heparin, the addition of hirudin generally preserved the complement reactivity, and complement activation in hirudin plasma closely resembled that in normal serum. Importantly, immunochemical staining of surface-bound cells demonstrated the inducible expression of tissue factor on bound monocytes from hirudin-treated blood, an effect that was completely abolished in heparin-treated blood.Conclusion: Our results indicate that hirudin as an anticoagulant produces more physiological conditions than heparin, making hirudin well-suited for in vitro studies, especially those addressing the regulation of cellular processes.
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| 6. |
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| 7. |
- Bexborn, Fredrik, et al.
(författare)
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The tick-over theory revisited : formation and regulation of the soluble alternative complement C3 convertase (C3(H2O)Bb)
- 2008
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Ingår i: Molecular Immunology. - : Elsevier BV. - 0161-5890 .- 1872-9142. ; 45:8, s. 2370-2379
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Tidskriftsartikel (refereegranskat)abstract
- The molecular interactions between the components of the C3 convertase of the alternative pathway (AP) of complement and its regulators, in both surface-bound and fluid-phase form, are still incompletely understood. The fact that the AP convertase is labile makes studies difficult to perform. According to the so called tick-over theory, hydrolyzed C3, called C3(H(2)O), forms the initial convertase in fluid phase together with factor B. In the present study, we have applied western blot analysis and ELISA together with fluorescence resonance energy transfer (FRET) to study the formation of the fluid-phase AP convertases C3(H(2)O)Bb and C3bBb and their regulation by factor H and factor I at specific time points and, with FRET, in real time. In our hands, factor B showed a higher affinity for C3(H(2)O) than for C3b, although in both cases it was readily activated to Bb. However, the convertase activity of C3bBb was approximately twice that of C3(H(2)O)Bb, as monitored by the generation of C3a. But in contrast, the C3(H(2)O)Bb convertase was more resistant to inactivation by factor H and factor I than was the C3bBb convertase. Under conditions that totally inactivated C3bBb, C3(H(2)O)Bb still retained approximately 25% of its initial activity.
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| 8. |
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| 9. |
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| 10. |
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| 11. |
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| 12. |
- Ekdahl, Fredrik, et al.
(författare)
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Experience Report : Using Internal CMMI Appraisals to Institutionalize Software Development Performance Improvement
- 2006
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Ingår i: Proceedings - 32nd Euromicro Conference on Software Engineering and Advanced Applications, SEAA. - 0769525946 ; , s. 216-222
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Konferensbidrag (refereegranskat)abstract
- Critical to any successful performance improvement initiative is to achieve a state of continuous or institutionalized improvement. Some improvement can happen quickly, but long-term improvement is typically a matter of sustaining focus. This requires an infrastructure that keeps activities focused and drives them forward. In ABB, the IDEALSM model is used as a guide for setting up improvement activities in development centers. Central to the IDEALSM model is the diagnostic activity, i.e. the evaluation of current performance in the unit against a suitable reference model. Over the last eight years, ABB has used diagnostics in the form of internal CMM/CMMI appraisals to lay the foundation for improvement activities. In this experience report, the use of internal appraisals as a means for sustaining improvement focus will be discussed. Experiences and lessons learnt, as well as some of the specifics of ABB's internal appraisals will be presented.
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| 13. |
- Ekdahl, Fredrik
(författare)
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On the Application of Designed Experimentation for Customer Focused Product Development
- 1999
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Today, the use of statistical methods and tools for solving problems in industry is growing steadily. The increased application of statistics in industry is attributable to the many theoretical advancements made by researchers over the years, but also to the increased awareness in industry that statistical methods and tools constitute an important resource of great strategic value. The foundation of this thesis lies in the ideas presented by Walter A. Shewhart in the early 1930s and the influence they have on today's activities in industry. The thesis uses an integrated framework for linking customer satisfaction to product development activities to establish the relationship between Shewhart's statistical perspective and customer focused product development. In particular, the important role of designed experimentation in this framework is highlighted. In detail the following topics are considered.An important challenge facing product developers is to link customer satisfaction to development activities carried out within a company. Success in the marketplace is very much dependent on the ability to translate satisfaction into product properties and to do it as early as possible in the product development process. The use of Quality Function Deployment combined with Customer Satisfaction Modeling is presented as means for linking internal product development and improvement activities to increased customer satisfaction.Separating active factors from inert ones represents an important problem in the analysis of designed experiments. An extensive simulation study comparing eight procedures complementing the normal probability plot for this separation is presented. The study shows that only small differences appear between different procedures, regardless of complexity, when the sparsity assumption is not violated. As the number of active factors increases, so do the differences in the performance of the studied procedures. Among the best performing procedures is one that rests on a Bayesian foundation and utilizes generic a priori knowledge for the selection problem. To further improve its performance a modification is proposed that will allow introduction of more elaborate and foremost less generic domain knowledge. The performance of the modified procedure is evaluated in a simulation study and it is found that considerable improvements can be made unless the introduced domain knowledge strongly contradicts the reality. A procedure for construction of new contrasts supplementing the original experimental design is introduced that will allow more efficient use of the available data. The new contrasts can be defined in various ways and thereby be given different interpretations in order to serve special purposes according to the agenda of the analyst. Apart from an enhanced interpretation of the experimental results, these contrasts contribute to a more elaborate representation of the experimental error when using normal probability plotting.In an effort to encourage use and to illustrate the possible benefits from using Conjoint Analysis, a step-by-step introductory workflow is presented. One of the apparent problems when designing a conjoint analysis study is the conflict between including many product attributes and not overloading the respondents. Non-geometric Plackett-Burman designs represents a class of orthogonal designs that provide an opportunity to resolve this conflict. The use of non-geometric Plackett-Burman designs for conjoint analysis is advocated and a procedure that takes advantage of the special properties of the non-geometric Plackett-Burman designs is proposed and demonstrated.
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| 14. |
- 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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| 15. |
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| 16. |
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| 17. |
- Larsson, Stig, et al.
(författare)
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Are limited non-intrusive CMMI-based appraisals enough?
- 2003
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Ingår i: Proceedings of the ESEIW 2003 Workshop on Empirical Studies in Software Engineering WSESE 2003.
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Konferensbidrag (refereegranskat)abstract
- An integral part of the strategy for performance improvement within the product development at ABB is the use of CMMI-based appraisals. Each appraisal represents an investment by the organization to lay the best possible foundation for improvements. The challenge is to balance the investment, the intrusiveness and the benefits. Depending on different organizational characteristics, different kinds of appraisals should be used. All appraisals are driven by data collection and consequently the quality of an appraisal depends on the data collection methods used. In this paper we outline strategies used in ABB for selection of appropriate CMMI appraisals and data collection methods. Early results indicate that the use of a series of appraisals can be a way to overcome the resistance in an organization. We also claim that a discussion is needed on the reliability and validity of the appraisal methodologies and on the feasibility to base decisions regarding process improvement strategies on appraisal results.
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| 18. |
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| 19. |
- Larsson, Stig, 1958-
(författare)
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Key Elements of Software Product Integration Processes
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The product integration is a particularly critical phase of the software product development process as many problems originating from earlier phases become visible in this phase. Problems in product integration result in delays and rework. One of the measures to decrease the late discovery of problems is the use of development standards and guidelines that define practices to ensure correctness of the product integration. However, even if such standards and reference models exist, they are in not used consistently. One of the reasons is a lack of a proof that they indeed improve the integration process, and even more important, that they are sufficient for performing efficient and correct product integration.The conclusion of the presented research is that the available descriptions in standards and reference models taken one by one are insufficient and must be consolidated to help development organizations improve the product integration process. The research has resulted in a proposed combination of the activities included in the different reference models. This combination has been based on a number of case studies. Through the case studies performed in seven different product development organizations, a relationship between problems that are observed and the failure to follow the recommendations in reference models is identified. The analysis has indicated which practices are necessary, and how other practices support these. The goal with the research is to provide product development organizations with guidelines for how to perform software product integration.One additional finding of the research is the existence of relation between software architecture and the development process. A method for identifying dependencies between evolvement of software architectures and adaptation of integration practices has been demonstrated.
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| 20. |
- Larsson, Stig, et al.
(författare)
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On the expected synergies between component-based software engineering and best practices in production integration
- 2004
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Ingår i: Proceeding EUROMICRO '04 Proceedings of the 30th EUROMICRO Conference. - 0769521991 ; , s. 430-436, s. 430-436
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Konferensbidrag (refereegranskat)abstract
- The expectations for a well working integration process are described in the Capability Maturity Model Integration (CMMI). Often during the integration process, weaknesses of the entire development process become visible. This is usually too late and too costly. Particular development processes and use of particular technologies may help to improve the performance of the integration process by providing proper input to it. For example, by the use of a component-based approach, the development process changes. Some of these changes may help in performing according to the process expectations. In this paper, examples of problems that have been observed in the integration process are described. Through a case study we describe a number of practical problems in current development projects. Based on this case study, we analyze how a component-based approach could help and lead to a more effective integration process.
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| 21. |
- Larsson, Stig, et al.
(författare)
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Product integration improvement based on analysis of build statistics
- 2007
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Ingår i: 6th Joint Meeting of the European Software Engineering Conference and the ACM SIGSOFT Symposium on the Foundations of Software Engineering, ESEC/FSE 2007. - New York, NY, USA : ACM. - 9781595938114 ; , s. 505-508
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Process improvement efforts based on best practices and standards such as the CMMI use appraisal results as input and focus on implementing processes as described in reference models. Since these models are of a general character the conclusions from the assessments could easily overlook problems experienced in the daily work. In addition, process improvement programs often fail to engage practitioners. To improve this, data that can be related to the daily work can help. This paper reports on the results from a study performed to understand how process data can complement project appraisals in finding improvement possibilities. A method for mapping process data to different practices and combining this with project appraisals to form a basis for focused performance improvement is proposed and a study including four projects from three organizations is presented.
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| 22. |
- Larsson, Stig, et al.
(författare)
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Selecting CMMI appraisal classes based on maturity and openness
- 2004
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Ingår i: Product Focused Software Process Improvement. - Berlin, Heidelberg : Springer. - 9783540214212 ; , s. 457-470
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Bokkapitel (refereegranskat)abstract
- Over the last eight years, different approaches have been used to diagnose the performance in ABB organizations developing software. The efforts build to a large degree on methods from the Software Engineering Institute (SEI). In this paper we examine the experiences from five organizations through a description of the pathways that we have observed in the maturity development. We also propose a way to classify organizations based on two organizational characteristics, maturity and openness. Based on this classification, a simple method for the selection of how to collect performance data from the organizations is described.
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| 23. |
- Larsson, Stig, et al.
(författare)
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Software product integration : A case study-based synthesis of reference models
- 2009
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Ingår i: Information and Software Technology. - : Elsevier BV. - 0950-5849 .- 1873-6025. ; 51:6, s. 1066-1080
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Tidskriftsartikel (refereegranskat)abstract
- In software intensive systems the integration becomes complex since both software and hardware components are integrated and run in the execution environment for the first time. Support for this stage is thus essential. Practices for Product Integration are described in different reference models. We have investigated these and compared them with activities performed in seven product development projects. Our conclusion is that descriptions of best practices in product integration are available in different reference models, but need to be merged into one set of practices. Through case studies we see that the described practices are insufficiently used in industry, and that organizations would benefit from adhering to them. Our investigations indicate that a set of practices are necessary to be successful in software product integration: define and check criteria for integration, review interface descriptions and ensure coordination of interface changes, and deliver components as agreed. In addition to these, a set of practices are supporting the integration activities, including the definition of an integration strategy, and the establishment of a suitable integration environment.
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| 24. |
- Lindblom, Rickard, 1981-, et al.
(författare)
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Complement Receptor 2 is increased in cerebrospinal fluid of multiple sclerosis patients and regulates C3 function
- 2016
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Ingår i: Clinical Immunology. - : Elsevier BV. - 1521-6616 .- 1521-7035. ; 166, s. 89-95
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Tidskriftsartikel (refereegranskat)abstract
- Besides its vital role in immunity, the complement system also contributes to the shaping of the synaptic circuitry of the brain. We recently described that soluble Complement Receptor 2 (sCR2) is part of the nerve injury response in rodents. We here study CR2 in context of multiple sclerosis (MS) and explore the molecular effects of CR2 on 0 activation. Significant increases in sCR2 levels were evident in cerebrospinal fluid (CSF) from both patients with relapsing remitting MS (n = 33; 6.2 ng/mL) and secondary-progressive MS (n = 9; 7.0 ng/mL) as compared to controls (n = 18; 4.1 ng/mL). Furthermore, CSF sCR2 levels correlated significantly both with CSF C3 and C1q as well as to a disease severity measure. In vitro, sCR2 inhibited the cleavage and down regulation of Cab to iC3b, suggesting that it exerts a modulatory role in complement activation downstream of C3. These results propose a novel function for CR2/sCR2 in human neuroinflammatory conditions.
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| 25. |
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| 26. |
- Lindblom, Rickard P. F., et al.
(författare)
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Complement receptor 2 is up regulated in the spinal cord following nerve root injury and modulates the spinal cord response
- 2015
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Ingår i: Journal of Neuroinflammation. - : Springer Science and Business Media LLC. - 1742-2094. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Activation of the complement system has been implicated in both acute and chronic states of neurodegeneration. However, a detailed understanding of this complex network of interacting components is still lacking. Methods: Large-scale global expression profiling in a rat F2(DAxPVG) intercross identified a strong cis-regulatory influence on the local expression of complement receptor 2 (Cr2) in the spinal cord after ventral root avulsion (VRA). Expression of Cr2 in the spinal cord was studied in a separate cohort of DA and PVG rats at different time-points after VRA, and also following sciatic nerve transection (SNT) in the same strains. Consequently, Cr2(-/-) mice and Wt controls were used to further explore the role of Cr2 in the spinal cord following SNT. The in vivo experiments were complemented by astrocyte and microglia cell cultures. Results: Expression of Cr2 in naive spinal cord was low but strongly up regulated at 5-7 days after both VRA and SNT. Levels of Cr2 expression, as well as astrocyte activation, was higher in PVG rats than DA rats following both VRA and SNT. Subsequent in vitro studies proposed astrocytes as the main source of Cr2 expression. A functional role for Cr2 is suggested by the finding that transgenic mice lacking Cr2 displayed increased loss of synaptic nerve terminals following nerve injury. We also detected increased levels of soluble CR2 (sCR2) in the cerebrospinal fluid of rats following VRA. Conclusions: These results demonstrate that local expression of Cr2 in the central nervous system is part of the axotomy reaction and is suggested to modulate subsequent complement mediated effects.
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| 27. |
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| 28. |
- Mattsson, Jenny, et al.
(författare)
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Accelerating target deconvolution for therapeutic antibody candidates using highly parallelized genome editing
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12, s. 1-8
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Tidskriftsartikel (refereegranskat)abstract
- Therapeutic antibodies are transforming the treatment of cancer and autoimmune diseases. Today, a key challenge is finding antibodies against new targets. Phenotypic discovery promises to achieve this by enabling discovery of antibodies with therapeutic potential without specifying the molecular target a priori. Yet, deconvoluting the targets of phenotypically discovered antibodies remains a bottleneck; efficient deconvolution methods are needed for phenotypic discovery to reach its full potential. Here, we report a comprehensive investigation of a target deconvolution approach based on pooled CRISPR/Cas9. Applying this approach within three real-world phenotypic discovery programs, we rapidly deconvolute the targets of 38 of 39 test antibodies (97%), a success rate far higher than with existing approaches. Moreover, the approach scales well, requires much less work, and robustly identifies antibodies against the major histocompatibility complex. Our data establish CRISPR/Cas9 as a highly efficient target deconvolution approach, with immediate implications for the development of antibody-based drugs.
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| 29. |
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| 30. |
- Neff, Jeniffer, et al.
(författare)
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A biomimetic stent coating to reduce thrombosis and inflammation
- 2005. - 2
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Ingår i: Medical Device Materials II. - : ASM International. - 9780871708243 ; , s. 290-295
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Bokkapitel (refereegranskat)abstract
- Coronary stenting has a high rate of failure, with 10-40% of patients developing restenosis within 6 months. Activation of the complement system and subsequent inflammation play a pivotal role in this process. The aim of this work was to develop a biomimetic stent coating that inhibits complement activation and prevents restenosis. A two part coating was developed using End Group Activated Pluronic (EGAP) in conjunction with factor H, a potent complement regulator. EGAP was applied to pretreated, stainless steel and nitinol stents and factor H was subsequently coupled through activation sites on EGAP. Coatings were characterized by ELISA for factor H. The coating reduced complement activation in human serum as measured by assays for C3a and surface bound complement convertase. The coating was also nonthrombogenic as measured by reduced platelet adhesion and low thrombin anti-thrombin levels. This approach should prove useful for reducing restenosis associated with stenting.
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| 31. |
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| 32. |
- Strand, Anna-Karin, et al.
(författare)
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Is there a relationship between anaesthesia and dementia?
- 2019
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley-Blackwell Publishing Inc.. - 0001-5172 .- 1399-6576. ; 63:4, s. 440-447
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundLong‐term cognitive problems are common among elderly patients after surgery, and it has been suggested that inhalation anaesthetics play a role in the development of dementia. This study aims to investigate the hypothesis that patients with dementia have been more exposed to surgery and inhalational anaesthetics than individuals without dementia.MethodsUsing 457 cases from a dementia‐registry and 420 dementia‐free controls, we performed a retrospective case‐control study. The medical records were reviewed to determine exposure to anaesthesia occurring within a 20‐year timeframe before the diagnosis or inclusion in the study. Data were analysed using multivariate logistic regression and propensity score analysis.ResultsAdvanced age (70 years and older, with the highest risk in ages 80‐84 years) and previous head trauma were risk factors for dementia. History of exposure to surgery with anaesthesia was a risk factor for dementia (OR = 2.23, 95% CI 1.66‐3.00, P < 0.01). Exposure to inhalational anaesthetics with halogenated anaesthetics was associated with an increased risk of dementia, compared to no exposure to anaesthesia (OR = 2.47, 95% CI 1.17‐5.22, P = 0.02). Exposure to regional anaesthesia was not significantly associated with increased risk of dementia (P = 0.13).ConclusionIn this 20‐year retrospective case‐control study, we found a potential association between dementia and prior anaesthesia. Exposure to general anaesthetics with halogenated anaesthetic gases was associated with an increased risk of dementia.
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| 33. |
- Ulf, Forsberg, et al.
(författare)
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A high blood level in the venous chamber and a wet-stored dialyzer help to reduce exposure for microemboli during hemodialysis
- 2013
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Ingår i: Hemodialysis International. - : Wiley. - 1492-7535 .- 1542-4758. ; 17:4, s. 612-617
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Tidskriftsartikel (refereegranskat)abstract
- During hemodialysis (HD), microemboli develop in the blood circuit of the apparatus. These microemboli can pass through the venous chamber and enter into the patient's circulation. The aim of this study was to investigate whether it is possible to reduce the risk for exposure of microemboli by altering of the treatment mode. Twenty patients on chronic HD were randomized to a prospective cross-over study of three modes of HD: (a) a dry-stored dialyzer (F8HPS, Fresenius, steam sterilized) with a low blood level in the venous chamber (DL), (b) the same dialyzer as above, but with a high level in the venous chamber (DH), and (c) a wet-stored dialyzer (Rexeed, Asahi Kasei Medical, gamma sterilized) with a high blood level (WH). Microemboli measurements were obtained in a continuous fashion during 180 minutes of HD for all settings. A greater number of microemboli were detected during dialysis with the setting DL vs. WH (odds ratio [OR] 4.07, 95% confidence interval [CI] 4.03-4.11, P<0.0001) and DH vs. WH (OR 1.18, 95% CI 1.17-1.19, P<0.0001) and less for DH vs. DL (OR 0.290, 95% CI 0.288-0.2930.288-0.293, P<0.0001). These data indicate that emboli exposure was least when using WH, greater with DH, and most with DL. This study shows that using a high blood level in the venous chamber and wet-stored dialyzers may reduce the number of microemboli.CallSend SMSAdd to SkypeYou'll need Skype CreditFree via Skype
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| 34. |
- Vijayaraghavan, Swetha, et al.
(författare)
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Regulated Extracellular Choline Acetyltransferase Activity : The Plausible Missing Link of the Distant Action of Acetylcholine in the Cholinergic Anti-Inflammatory Pathway
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:6
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Tidskriftsartikel (refereegranskat)abstract
- Acetylcholine (ACh), the classical neurotransmitter, also affects a variety of nonexcitable cells, such as endothelia, microglia, astrocytes and lymphocytes in both the nervous system and secondary lymphoid organs. Most of these cells are very distant from cholinergic synapses. The action of ACh on these distant cells is unlikely to occur through diffusion, given that ACh is very short-lived in the presence of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), two extremely efficient ACh-degrading enzymes abundantly present in extracellular fluids. In this study, we show compelling evidence for presence of a high concentration and activity of the ACh-synthesizing enzyme, choline-acetyltransferase (ChAT) in human cerebrospinal fluid (CSF) and plasma. We show that ChAT levels are physiologically balanced to the levels of its counteracting enzymes, AChE and BuChE in the human plasma and CSF. Equilibrium analyses show that soluble ChAT maintains a steady-state ACh level in the presence of physiological levels of fully active ACh-degrading enzymes. We show that ChAT is secreted by cultured human-brain astrocytes, and that activated spleen lymphocytes release ChAT itself rather than ACh. We further report differential CSF levels of ChAT in relation to Alzheimer's disease risk genotypes, as well as in patients with multiple sclerosis, a chronic neuroinflammatory disease, compared to controls. Interestingly, soluble CSF ChAT levels show strong correlation with soluble complement factor levels, supporting a role in inflammatory regulation. This study provides a plausible explanation for the long-distance action of ACh through continuous renewal of ACh in extracellular fluids by the soluble ChAT and thereby maintenance of steady-state equilibrium between hydrolysis and synthesis of this ubiquitous cholinergic signal substance in the brain and peripheral compartments. These findings may have important implications for the role of cholinergic signaling in states of inflammation in general and in neurodegenerative disease, such as Alzheimer's disease and multiple sclerosis in particular.
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| 35. |
- Wallin, Peter, 1979-
(författare)
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Key Challenges in Decision Making for Automotive E/E Architectures
- 2008
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The amount of electronics in vehicles is growing quickly, thus systems are becoming increasingly complex making the engineering of these software intensive systems more and more difficult. In particular, an architecture supporting the business goals is a prerequisite for successful design.In this thesis two case studies have been made including three automotive companies with purpose to investigate the key issues related to real-world decisions when developing Electrical and Electronic (E/E) system architectures in the automotive industry.The results show that many of the identified issues relate to non technical areas such as organization, process, methods and tools, and management. Examples of identified issues are the deficient understanding of the electrical system and software at management level, and the lack of a specific process for architecture development. To cope with these issues we suggest the following actions: Educate management, increase the use of structured decision making, improve the architecture development process, clarify responsibilities in the organization and clarify development strategies.As a possible solution to one of the suggested actions we have developed a method to evaluate how new functionality is successfully integrated into an existing architecture. Themethod is a combination of the Architecture Tradeoff Analysis Method, ATAM, and the Analytical Hierarchy Process, AHP. The method firstly supports a structured way of listing system goals, and secondly, it also supports the making of design decisions.
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