| 1. |
- Kirchhof, Paulus, et al.
(författare)
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Comprehensive risk reduction in patients with atrial fibrillation : emerging diagnostic and therapeutic options - a report from the 3rd Atrial Fibrillation Competence NETwork/European Heart Rhythm Association consensus conference
- 2012
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Ingår i: Europace. - : Oxford University Press (OUP). - 1099-5129 .- 1532-2092. ; 14:1, s. 8-27
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Forskningsöversikt (refereegranskat)abstract
- While management of atrial fibrillation (AF) patients is improved by guideline-conform application of anticoagulant therapy, rate control, rhythm control, and therapy of accompanying heart disease, the morbidity and mortality associated with AF remain unacceptably high. This paper describes the proceedings of the 3rd Atrial Fibrillation NETwork (AFNET)/European Heart Rhythm Association (EHRA) consensus conference that convened over 60 scientists and representatives from industry to jointly discuss emerging therapeutic and diagnostic improvements to achieve better management of AF patients. The paper covers four chapters: (i) risk factors and risk markers for AF; (ii) pathophysiological classification of AF; (iii) relevance of monitored AF duration for AF-related outcomes; and (iv) perspectives and needs for implementing better antithrombotic therapy. Relevant published literature for each section is covered, and suggestions for the improvement of management in each area are put forward. Combined, the propositions formulate a perspective to implement comprehensive management in AF.
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| 2. |
- Bruederle, Daniel, et al.
(författare)
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A comprehensive workflow for general-purpose neural modeling with highly configurable neuromorphic hardware systems
- 2011
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Ingår i: Biological Cybernetics. - : Springer Science and Business Media LLC. - 0340-1200 .- 1432-0770. ; 104:4-5, s. 263-296
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Tidskriftsartikel (refereegranskat)abstract
- In this article, we present a methodological framework that meets novel requirements emerging from upcoming types of accelerated and highly configurable neuromorphic hardware systems. We describe in detail a device with 45 million programmable and dynamic synapses that is currently under development, and we sketch the conceptual challenges that arise from taking this platform into operation. More specifically, we aim at the establishment of this neuromorphic system as a flexible and neuroscientifically valuable modeling tool that can be used by non-hardware experts. We consider various functional aspects to be crucial for this purpose, and we introduce a consistent workflow with detailed descriptions of all involved modules that implement the suggested steps: The integration of the hardware interface into the simulator-independent model description language PyNN; a fully automated translation between the PyNN domain and appropriate hardware configurations; an executable specification of the future neuromorphic system that can be seamlessly integrated into this biology-to-hardware mapping process as a test bench for all software layers and possible hardware design modifications; an evaluation scheme that deploys models from a dedicated benchmark library, compares the results generated by virtual or prototype hardware devices with reference software simulations and analyzes the differences. The integration of these components into one hardware-software workflow provides an ecosystem for ongoing preparative studies that support the hardware design process and represents the basis for the maturity of the model-to-hardware mapping software. The functionality and flexibility of the latter is proven with a variety of experimental results.
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| 3. |
- Brännström, Andreas, et al.
(författare)
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Kite Aerial Photography - Hué
- 2014
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Bok (populärvet., debatt m.m.)abstract
- The Kite Aerial Photography - Hué project started with the intention from Mattias Ericsson and me Micael Norberg to work artistically on a jointly project with students from di erent art schools and from di erent cultures. We had an idea of building bridges both artistically and culturally. We traveled to Hué in Vietnam in order to explore new ways to collaborate and nd new artistic meth- ods. We wanted to use kites and send our cameras up in the air to make aerial pictures. We tried to nd a way to control events and by that also control our artistic outcome and understanding. But in the The Kite Aerial Photography project we had no control. The weather controlled our kites. The place and the language controlled what we knew and understood. What was left was to look into ourself and negate a compromise. The leftovers became documentations of an experience.And now I am looking back at those events, wondering what really happened. I am using words, trying to create an image of my memories and of my experience - hot air, smells and noise. Experi- ences I can’t communicate fully in words. You as a viewer will never feel them and I will only remember them. We will also remember di erently. Every participant have their own image ofwhat happened during those days in Hué. The feeling of being di erent, not understanding and being an outsider made us all meet ourselves in di erent ways. We believed that language would build bridges of understanding, and maybe it did. But here we are now. A long time has passed since we returned from Hué. What we have left are images and memories. I remember smells and emotions and in this state between memory and fact a tension is created. A juxtaposition of con ict- ing feelings. I look at the photographs now with a new understanding. We tried to move out of our comfort-zone looking for the unseen, the enigma, where memory and re ection becomes a liminal state. I now realize that knowledge is not fact or truth, but a state that we can call ”not knowing”. A state which for me is the very basic for understanding, and by that becoming the very essence of art.
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| 4. |
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| 5. |
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| 6. |
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| 7. |
- Christiansson, Lisa, 1983-
(författare)
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Myeloid-Derived Suppressor Cells and Other Immune Escape Mechanisms in Chronic Leukemia
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Chronic myeloid leukemia (CML) is characterized by the Philadelphia chromosome, a minute chromosome that leads to the creation of the fusion gene BCR/ABL and the transcription of the fusion protein BCR/ABL in transformed cells. The constitutively active tyrosine kinase BCR/ABL confers enhanced proliferation and survival on leukemic cells. CML has in only a few decades gone from being a disease with very bad prognosis to being a disease that can be effectively treated with oral tyrosine kinase inhibitors (TKIs). TKIs are drugs inhibiting BCR/ABL as well as other tyrosine kinases. In this thesis, the focus has been on the immune system of CML patients, on immune escape mechanisms present in untreated patients and on how these are affected by TKI therapy. We have found that newly diagnosed, untreated CML patients exert different kinds of immune escape mechanisms. Patients belonging to the Sokal high-risk group had higher levels of myeloid-derived suppressor cells (MDSCs) as well as high levels of the programmed death receptor 1 (PD-1)-expressing cytotoxic T cells compared to control subjects. Moreover, CML patients had higher levels of myeloid cells expressing the ligand for PD-1, PD-L1. CML patients as well as patients with B cell malignacies had high levels of soluble CD25 in blood plasma. In B cell malignacies, sCD25 was found to be released from T regulatory cells (Tregs). Treatment with the TKIs imatinib or dasatinib decreased the levels of MDSCs in peripheral blood. Tregs on the other hand increased during TKI therapy. The immunostimulatory molecule CD40 as well as NK cells increased during therapy, indicating an immunostimulatory effect of TKIs. When evaluating immune responses, multiplex techniques for quantification of proteins such as cytokines and chemokines are becoming increasingly popular. With these techniques a lot of information can be gained from a small sample volume and complex networks can be more easily studied than when using for example the singleplex ELISA. When comparing different multiplex platforms we found that the absolute protein concentration measured by one platform rarely correlated with the absolute concentration measured by another platform. However, relative quantification was better correlated.
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| 8. |
- Dardar, Raghad, et al.
(författare)
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Industrial Experiences of Building a Safety Case in Compliance with ISO 26262
- 2012
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Ingår i: 23RD IEEE INTERNATIONAL SYMPOSIUM ON SOFTWARE RELIABILITY ENGINEERING WORKSHOPS (ISSREW 2012). - 9780769549286 ; , s. 349-354
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Konferensbidrag (refereegranskat)abstract
- The ISO 26262 functional safety standard provides appropriate development processes, requirements and safety integrity levels specific for the automotive domain. One crucial requirement consists of the creation of a safety case, a structured argument, which inter-relates evidence and claims, needed to show that safety-critical systems are acceptably safe. The standard is currently not mandatory to be applied to safety critical systems installed in heavy trucks; however, this is likely to be changed by 2016. This paper describes the experience gathered by applying the standard to the Fuel Level Estimation and Display System, a subsystem that together with other subsystems plays a significant role in terms of global system safety for heavy trucks manufactured by Scania. More specifically, exploratory and laborious work related to the creation of a safety case in compliance with ISO 26262 in an inexperienced industrial setting is described, and the paper ends with presenting some lessons learned together with guidelines to facilitate the adoption of ISO 26262.
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| 9. |
- de Blanche, Andreas, 1975-, et al.
(författare)
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A methodology for estimating co-scheduling slowdowns due to memory bus contention on multicore nodes
- 2014
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Ingår i: Proceedings of the IASTED International Conference on Parallel and Distributed Computing and Networks, PDCN 2014. - : ACTA Press. - 9780889869677 - 9780889869653 ; , s. 216-223
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Konferensbidrag (refereegranskat)abstract
- When two or more programs are co-scheduled on the same multicore computer they might experience a slowdown due to the limited off-chip memory bandwidth. According to our measurements, this slowdown does not depend on the total bandwidth use in a simple way. One thing we observe is that a higher memory bandwidth usage will not always lead to a larger slowdown. This means that relying on bandwidth usage as input to a job scheduler might cause non-optimal scheduling of processes on multicore nodes in clusters, clouds, and grids. To guide scheduling decisions, we instead propose a slowdown based characterization approach. Real slowdowns are complex to measure due to the exponential number of experiments needed. Thus, we present a novel method for estimating the slowdown programs will experience when co-scheduled on the same computer. We evaluate the method by comparing the predictions made with real slowdown data and the often used memory bandwidth based method. This study show that a scheduler relying on slowdown based categorization makes fewer incorrect co-scheduling choices and the negative impact on program execution times is less than when using a bandwidth based categorization method.
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| 10. |
- du Bois, Andreas, et al.
(författare)
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Phase III trial of carboplatin plus paclitaxel with or without gemcitabine in first-line treatment of epithelial ovarian cancer.
- 2010
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Ingår i: Journal of Clinical Oncology. - : American society of clinical oncology. - 0732-183X .- 1527-7755. ; 28:27, s. 4162-4169
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: One attempt to improve long-term survival in patients with advanced ovarian cancer was thought to be the addition of more non-cross-resistant drugs to platinum-paclitaxel combination regimens. Gemcitabine was among the candidates for a third drug.PATIENTS AND METHODS: We performed a prospective, randomized, phase III, intergroup trial to compare carboplatin plus paclitaxel (TC; area under the curve [AUC] 5 and 175 mg/m(2), respectively) with the same combination and additional gemcitabine 800 mg/m(2) on days 1 and 8 (TCG) in previously untreated patients with advanced epithelial ovarian cancer. TC was administered intravenously (IV) on day 1 every 21 days for a planned minimum of six courses. Gemcitabine was administered by IV on days 1 and 8 of each cycle in the TCG arm.RESULTS: Between 2002 and 2004, 1,742 patients were randomly assigned; 882 and 860 patients received TC and TCG, respectively. Grades 3 to 4 hematologic toxicity and fatigue occurred more frequently in the TCG arm. Accordingly, quality-of-life analysis during chemotherapy showed a disadvantage in the TCG arm. Although objective response was slightly higher in the TCG arm, this did not translate into improved progression-free survival (PFS) or overall survival (OS). Median PFS was 17.8 months for the TCG arm and 19.3 months for the TC arm (hazard ratio [HR], 1.18; 95% CI, 1.06 to 1.32; P = .0044). Median OS was 49.5 for the TCG arm and 51.5 months for the TC arm (HR, 1.05; 95% CI, 0.91 to 1.20; P = .5106).CONCLUSION: The addition of gemcitabine to carboplatin plus paclitaxel increased treatment burden, reduced PFS time, and did not improve OS in patients with advanced epithelial ovarian cancer. Therefore, we recommend no additional clinical use of TCG in this population.
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| 11. |
- Galon, Jerome, et al.
(författare)
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Cancer classification using the Immunoscore : a worldwide task force
- 2012
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Ingår i: Journal of Translational Medicine. - : Springer Science and Business Media LLC. - 1479-5876. ; 10, s. 205-
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Forskningsöversikt (refereegranskat)abstract
- Prediction of clinical outcome in cancer is usually achieved by histopathological evaluation of tissue samples obtained during surgical resection of the primary tumor. Traditional tumor staging (AJCC/UICC-TNM classification) summarizes data on tumor burden (T), presence of cancer cells in draining and regional lymph nodes (N) and evidence for metastases (M). However, it is now recognized that clinical outcome can significantly vary among patients within the same stage. The current classification provides limited prognostic information, and does not predict response to therapy. Recent literature has alluded to the importance of the host immune system in controlling tumor progression. Thus, evidence supports the notion to include immunological biomarkers, implemented as a tool for the prediction of prognosis and response to therapy. Accumulating data, collected from large cohorts of human cancers, has demonstrated the impact of immune-classification, which has a prognostic value that may add to the significance of the AJCC/UICC TNM-classification. It is therefore imperative to begin to incorporate the ` Immunoscore' into traditional classification, thus providing an essential prognostic and potentially predictive tool. Introduction of this parameter as a biomarker to classify cancers, as part of routine diagnostic and prognostic assessment of tumors, will facilitate clinical decision-making including rational stratification of patient treatment. Equally, the inherent complexity of quantitative immunohistochemistry, in conjunction with protocol variation across laboratories, analysis of different immune cell types, inconsistent region selection criteria, and variable ways to quantify immune infiltration, all underline the urgent requirement to reach assay harmonization. In an effort to promote the Immunoscore in routine clinical settings, an international task force was initiated. This review represents a follow-up of the announcement of this initiative, and of the J Transl Med. editorial from January 2012. Immunophenotyping of tumors may provide crucial novel prognostic information. The results of this international validation may result in the implementation of the Immunoscore as a new component for the classification of cancer, designated TNM-I (TNM-Immune).
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| 12. |
- Ginks, Matthew R., et al.
(författare)
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Relationship between intracardiac impedance and left ventricular contractility in patients undergoing cardiac resynchronization therapy
- 2011
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Ingår i: Europace. - : Oxford University Press (OUP). - 1099-5129 .- 1532-2092. ; 13:7, s. 984-991
-
Tidskriftsartikel (refereegranskat)abstract
- Aims Cardiac resynchronization therapy (CRT) has dramatically improved the symptoms and prognosis of patients with heart failure in large randomized clinical trials. Optimization of device settings may maximize benefit on an individual basis, although the best method for this is not yet established. We evaluated the use of cardiogenic impedance measurements (derived from intracardiac impedance signals) in CRT device optimization, using invasive left ventricular (LV) dP/dt(max) as the reference. Methods and results Seventeen patients underwent invasive haemodynamic assessment using a pressure wire placed in the LV cavity at the time of CRT device implantation. Intracardiac impedance measurements were made at different atrioventricular (AV) and interventricular (VV) delays and compared with LV dP/dt(max). We assessed the performance of patient-specific and generic impedance-based models in predicting acute haemodynamic response to CRT. In two patients, LV catheterization with the pressure wire was unsuccessful and in two patients LV lead delivery was unsuccessful; therefore, data were acquired for 13 out of 17 patients. Left ventricular dP/dt(max) was 919 +/- 182 mmHg/s at baseline and this increased acutely (by 24%) to 1121 +/- 226 mmHg/s as a result of CRT. The patient-specific impedance-based model correctly predicted the optimal haemodynamic response (to within 5% points) for AV and VV delays in 90 and 92% of patients, respectively. Conclusion Cardiogenic impedance measurements are capable of correctly identifying the maximum achievable LV dP/dt(max) as measured by invasive haemodynamic assessment. This study suggests that cardiogenic impedance can potentially be used for CRT optimization and may have a role in ambulatory assessment of haemodynamics.
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| 13. |
- Götherström, Cecilia, et al.
(författare)
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Fetal and adult multipotent mesenchymal stromal cells are killed by different pathways
- 2011
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Ingår i: Cytotherapy. - : Elsevier BV. - 1465-3249 .- 1477-2566. ; 13:3, s. 269-278
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Tidskriftsartikel (refereegranskat)abstract
- Background aims. Multipotent mesenchymal stromal cells, also known as mesenchymal stem cells (MSC), can be isolated from adult and fetal tissues. Recently, there has been considerable interest in MSC because they have features favorable for transplantation, namely their multipotency and non-immunogenic properties. Methods. We analyzed how human MSC derived from first-trimester fetal liver and adult bone marrow interact with naive and activated innate natural killer (NK) cells. NK cell function was studied by measuring killing of MSC, as well as degranulation (CD107a) induced by MSC. To assess the importance of NK cell killing, expression of surface epitopes was analyzed by flow cytometry on MSC before and after stimulation with interferon (IFN)gamma gamma. Results. Fetal and adult MSC express several ligands to activating NK cell receptors as well as low levels of HLA class I, with large inter-individual variation. Naive peripheral blood NK cells did not lyse fetal or adult MSC, whereas interleukin (IL)2 activated allogeneic as well as autologous NK cells did. Pre-incubation of MSC with IFN-gamma gamma increased their levels of HLA class I, protecting them from NK cell recognition. Fetal and adult MSC were preferably killed via the tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and Fas ligand (FasL) pathways, respectively. Blocking NKG2D reduced NK cell degranulation in both fetal and adult MSC. Conclusions. Fetal and adult MSC differ in their interactions with NK cells. Both fetal and adult MSC are susceptible to lysis by activated NK cells, which may have implications for the use of MSC in cell therapy.
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| 14. |
- Hanning, Andreas, 1982, et al.
(författare)
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Are we educating engineers for sustainability? Comparison between obtained competences and Swedish industry's needs
- 2012
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Ingår i: International Journal of Sustainability in Higher Education. - : Emerald. - 1467-6370. ; 13:3, s. 305-320
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Tidskriftsartikel (refereegranskat)abstract
- Purpose – The aim of this study is to contribute to the quality improvement and long-term strategic development of education for sustainable development (ESD) in engineering education curricula.Design/methodology/approach – The content in 70 courses in environment and SD were characterized and quantified using course document text analysis. Additionally, two questionnaires were sent to students and alumni at Chalmers, and interviews and focus group discussions were conducted with representatives from 16 Swedish companies and five organizations.Findings – It was found that industry demands a broader range of competences in SD amongst engineers in general than what is currently provided. In total, 35 per cent of alumni claim they encounter sustainability issues from sometimes to daily in their work. However, only half of them believe they possess enough competences to make decisions from a sustainability perspective. Quantity, coverage and the level of integration in the educational programme all appear to be important for the students' perceived competences on SD and for the importance that they put on achieving SD.Originality/value – Earlier research has reported on how to further develop the idea and design of ESD and on competence needs in general. Few attempts have been made to assess industry's needs of competences in SD. This paper sheds light on how engineering universities educate for SD and benchmarks this to industry's needs in an exploratory case study, using Chalmers as an example.
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| 15. |
- Johnsen, Andreas, et al.
(författare)
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An Architecture-Based Verification Technique for AADL Specifications
- 2011
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Konferensbidrag (refereegranskat)abstract
- Quality assurance processes of software-intensive systems are an increasing challenge as the complexity of these systems dramatically increases. The use of Architecture Description Languages (ADLs) provide an important basis for evaluation. The Architecture Analysis and Design Language (AADL) is an ADL developed for designing software intensive systems. In this paper, we propose an architecture-based verification technique covering the entire development process by adapting a combination of model-checking and model-based testing approaches to AADL specifications. The technique reveals inconsistencies of early design decisions and ensures a system's conformity with its AADL specification. The objective and criteria (test-selection) of the verification technique is derived from traditional integration testing.
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| 16. |
- Johnsen, Andreas
(författare)
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Architecture-Based Verification of Dependable Embedded Systems
- 2013
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Quality assurance of dependable embedded systems is becoming increasingly difficult, as developers are required to build more complex systems on tighter budgets. As systems become more complex, system architects must make increasingly complex architecture design decisions. The process of making the architecture design decisions of an intended system is the very first, and the most significant, step of ensuring that the developed system will meet its requirements, including requirements on its ability to tolerate faults. Since the decisions play a key role in the design of a dependable embedded system, they have a comprehensive effect on the development process and the largest impact on the developed system. Any faulty architecture design decision will, consequently, propagate throughout the development process, and is likely to lead to a system not meeting the requirements, an unacceptable level of dependability and costly corrections.Architecture design decisions are in turn critical with respect to quality and dependability of a system, and the cost of the development process. It is therefore crucial to prevent faulty architecture design decisions and, as early as practicable, detect and remove faulty decisions that have not successfully been prevented. The use of Architecture Description Languages (ADLs) helps developers to cope with the increasing complexity by formal and standardized means of communication and understanding. Furthermore, the availability of a formal description enables automated and formal analysis of the architecture design.The contribution of this licentiate thesis is an architecture quality assurance framework for safety-critical, performance-critical and mission-critical embedded systems specified by the Architecture Analysis and Design Language (AADL). The framework is developed through the adaption of formal methods, in particular traditional model checking and model-based testing techniques, to AADL, by defining formal verification criteria for AADL, and a formal AADL-semantics. Model checking of AADL models provides evidence of the completeness, consistency and correctness of the model, and allows for automated avoidance of faulty architecture design decisions, costly corrections and threats to quality and dependability. In addition, the framework can automatically generate test suites from AADL models to test a developed system with respect to the architecture design decisions. A successful test suite execution provides evidence that the architecture design has been implemented correctly. Methods for selective regression verification are included in the framework to cost-efficiently re-verify a modified architecture design, such as after a correction of a faulty design decision.
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| 17. |
- Johnsen, Andreas, et al.
(författare)
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Automated Verification of AADL-Specifications Using UPPAAL
- 2012
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Ingår i: Proceedings of the 14th IEEE International Symposium on High Assurance Systems Engineering (HASE). - 9781467347426 ; , s. 130-138
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Konferensbidrag (refereegranskat)abstract
- The Architecture Analysis and Design Language (AADL) is used to represent architecture design decisions of safety-critical and real-time embedded systems. Due to the far-reaching effects these decisions have on the development process, an architecture design fault is likely to have a significant deteriorating impact through the complete process. Automated fault avoidance of architecture design decisions therefore has the potential to significantly reduce the cost of the development while increasing the dependability of the end product. To provide means for automated fault avoidance when developing systems specified in AADL, a formal verification technique has been developed to ensure completeness and consistency of an AADL specification as well as its conformity with the end product. The approach requires the semantics of AADL to be formalized and implemented. We use the methodology of semantic anchoring to contribute with a formal and implemented semantics of a subset of AADL through a set of transformation rules to timed automata constructs. In addition, the verification technique, including the transformation rules, is validated using a case study of a safety-critical fuel-level system developed by a major vehicle manufacturer.
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| 18. |
- Johnsen, Andreas, et al.
(författare)
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Developing dependable software-intensive systems : AADL vs. EAST-ADL
- 2011
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Ingår i: Lecture Notes in Computer Science, vol. 6652. - Berlin, Heidelberg : Springer. - 9783642213373 ; , s. 103-117
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Bokkapitel (refereegranskat)abstract
- Dependable software-intensive systems, such as embedded systems for avionics and vehicles are often developed under severe quality, schedule and budget constraints. As the size and complexity of these systems dramatically increases, the architecture design phase becomes more and more significant in order to meet these constraints. The use of Architecture Description Languages (ADLs) provides an important basis for mutual communication, analysis and evaluation activities. Hence, selecting an ADL suitable for such activities is of great importance. In this paper we compare and investigate the two ADLs - AADL and EAST-ADL. The level of support provided to developers of dependable software-intensive systems is compared, and several critical areas of the ADLs are highlighted. Results of using an extended comparison framework showed many similarities, but also one clear distinction between the languages regarding the perspectives and the levels of abstraction in which systems are modeled. © 2011 Springer-Verlag.
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| 19. |
- Johnsen, Andreas, et al.
(författare)
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Regression verification of AADL models through slicing of system dependence graphs
- 2014
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Ingår i: QoSA 2014 - Proceedings of the 10th International ACM SIGSOFT Conference on Quality of Software Architectures (Part of CompArch 2014). - New York, NY, USA : ACM. - 9781450325769 ; , s. 103-112
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Konferensbidrag (refereegranskat)abstract
- Design artifacts of embedded systems are subjected to a number of modifications during the development process. Verified artifacts that subsequently are modified must nec- essarily be re-Verified to ensure that no faults have been introduced in response to the modification. We collectively call this type of verification as regression verification. In this paper, we contribute with a technique for selective regression verification of embedded systems modeled in the Architec- ture Analysis and Design Language (AADL). The technique can be used with any AADL-based verification technique to eficiently perform regression verification by only selecting verification sequences that cover parts that are afiected by the modification for re-execution. This allows for the avoid- ance of unnecessary re-verification, and thereby unnecessary costs. The selection is based on the concept of specification slicing through system dependence graphs (SDGs) such that the efiect of a modification can be identified.
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| 20. |
- Kienle, Holger, et al.
(författare)
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Liability for Software in Safety-Critical Mechatronic Systems : An Industrial Questionnaire
- 2012
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Ingår i: 2012 2nd International Workshop on Software Engineering for Embedded Systems, SEES 2012 - Proceedings. - 9781467318532 ; , s. 44-50
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Konferensbidrag (refereegranskat)abstract
- There is very little research on how industry is dealing with the risk of legal liability when constructing safety- critical mechatronic systems that are also software intensive. In this paper we propose a case study approach with the goal to understand how liability concerns in this setting impact software development in industry. The approach takes into account that software development is embedded into a complex socio-technical context involving stakeholders from technical, managerial and legal backgrounds. We present first results of our case study from a questionnaire involving six companies that develop software- intensive, safety-critical systems in the vehicular and avionics domains. The results of the questionnaire shed light on current industrial practices and concerns. The results indicate that liability seems indeed a concern and that a more in-depth analysis of this topic would be desirable to better understand the strategies that are used by industry to address liability risks.
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| 21. |
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| 22. |
- Kirchhof, Paulus, et al.
(författare)
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Personalized management of atrial fibrillation : Proceedings from the fourth Atrial Fibrillation competence NETwork/European Heart Rhythm Association consensus conference
- 2013
-
Ingår i: Europace. - : Oxford University Press (OUP). - 1099-5129 .- 1532-2092. ; 15:11, s. 1540-1556
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Tidskriftsartikel (refereegranskat)abstract
- The management of atrial fibrillation (AF) has seen marked changes in past years, with the introduction of new oral anticoagulants, new antiarrhythmic drugs, and the emergence of catheter ablation as a common intervention for rhythm control. Furthermore, new technologies enhance our ability to detect AF. Most clinical management decisions in AF patients can be based on validated parameters that encompass type of presentation, clinical factors, electrocardiogram analysis, and cardiac imaging. Despite these advances, patients with AF are still at increased risk for death, stroke, heart failure, and hospitalizations. During the fourth Atrial Fibrillation competence NETwork/European Heart Rhythm Association (AFNET/EHRA) consensus conference, we identified the following opportunities to personalize management of AF in a better manner with a view to improve outcomes by integrating atrial morphology and damage, brain imaging, information on genetic predisposition, systemic or local inflammation, and markers for cardiac strain. Each of these promising avenues requires validation in the context of existing risk factors in patients. More importantly, a new taxonomy of AF may be needed based on the pathophysiological type of AF to allow personalized management of AF to come to full fruition. Continued translational research efforts are needed to personalize management of this prevalent disease in a better manner. All the efforts are expected to improve the management of patients with AF based on personalized therapy.
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| 23. |
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| 24. |
- Pujade-Lauraine, Eric, et al.
(författare)
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Pegylated liposomal Doxorubicin and Carboplatin compared with Paclitaxel and Carboplatin for patients with platinum-sensitive ovarian cancer in late relapse.
- 2010
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Ingår i: Journal of Clinical Oncology. - : American Society of Clinical Oncology. - 0732-183X .- 1527-7755. ; 28:20, s. 3323-3329
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: This randomized, multicenter, phase III noninferiority trial was designed to test the efficacy and safety of the combination of pegylated liposomal doxorubicin (PLD) with carboplatin (CD) compared with standard carboplatin and paclitaxel (CP) in patients with platinum-sensitive relapsed/recurrent ovarian cancer (ROC).PATIENTS AND METHODS: Patients with histologically proven ovarian cancer with recurrence more than 6 months after first- or second-line platinum and taxane-based therapies were randomly assigned by stratified blocks to CD (carboplatin area under the curve [AUC] 5 plus PLD 30 mg/m(2)) every 4 weeks or CP (carboplatin AUC 5 plus paclitaxel 175 mg/m(2)) every 3 weeks for at least 6 cycles. Primary end point was progression-free survival (PFS); secondary end points were toxicity, quality of life, and overall survival.RESULTS: Overall 976 patients were recruited. With median follow-up of 22 months, PFS for the CD arm was statistically superior to the CP arm (hazard ratio, 0.821; 95% CI, 0.72 to 0.94; P = .005); median PFS was 11.3 versus 9.4 months, respectively. Although overall survival data are immature for final analysis, we report here a total of 334 deaths. Overall severe nonhematologic toxicity (36.8% v 28.4%; P < .01) leading to early discontinuation (15% v 6%; P < .001) occurred more frequently in the CP arm. More frequent grade 2 or greater alopecia (83.6% v 7%), hypersensitivity reactions (18.8% v 5.6%), and sensory neuropathy (26.9% v 4.9%) were observed in the CP arm; more hand-foot syndrome (grade 2 to 3, 12.0% v 2.2%), nausea (35.2% v 24.2%), and mucositis (grade 2-3, 13.9% v 7%) in the CD arm.CONCLUSION: To our knowledge, this trial is the largest in recurrent ovarian cancer and has demonstrated superiority in PFS and better therapeutic index of CD over standard CP.
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| 25. |
- Reed, Nicholas Simon, et al.
(författare)
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Gynecologic Cancer InterGroup (GCIG) consensus review for ovarian small cell cancers.
- 2014
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Ingår i: International Journal of Gynecological Cancer. - : Lippincott Williams & Wilkins. - 1048-891X .- 1525-1438. ; 24:9, s. S30-S34
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Forskningsöversikt (refereegranskat)abstract
- Small cell carcinomas of the ovary are uncommon and account for less than 1% of ovarian cancers. They were first recognized in 1979, and a number of reports appeared during the next 2 decades. They are highly aggressive tumors and usually carry a poor prognosis, although this may reflect that most are diagnosed at advanced stage; however, those diagnosed as stage 1A have only 30% to 40% of long-term survivors. More reports followed extending our experience in the diagnosis and management of these rare cancers. The classification is described below and shown in Table 1, but a revision is expected to be published from the World Health Organization in 2014.
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| 26. |
- Sarhan, Dhifaf, et al.
(författare)
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A novel inhibitor of proteasome deubiquitinating activity renders tumor cells sensitive to TRAIL-mediated apoptosis by natural killer cells and T cells
- 2013
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Ingår i: Cancer Immunology, Immunotherapy. - Stockholm : Karolinska Institutet, Dept of Oncology-Pathology. - 1432-0851 .- 0340-7004.
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Tidskriftsartikel (refereegranskat)abstract
- The proteasome inhibitor bortezomib simultaneously renders tumor cells sensitive to killing by natural killer (NK) cells and resistant to killing by tumor-specific T cells. Here, we show that b-AP15, a novel inhibitor of proteasome deubiquitinating activity, sensitizes tumors to both NK and T cell-mediated killing. Exposure to b-AP15 significantly increased the susceptibility of tumor cell lines of various origins to NK (p<0.0002) and T cell (p=0.02) –mediated cytotoxicity. Treatment with b-AP15 resulted in increased TRAIL [tumor necrosis factor-related apoptosis-inducing ligand] receptor-2 expression (p=0.03) and decreased cFLIP expression in tumor cells in vitro. In tumor-bearing SCID/Beige mice, treatment with b-AP15 followed by infusion of either human NK cells or tumor-specific T cells resulted in a significantly delayed tumor progression compared with mice treated with NK cells (p=0.006), T cells (p<0.0001), or b-AP15 alone (p=0.003). Combined infusion of NK and T cells in tumor-bearing BALB/c mice following treatment with b-AP15 resulted in a significantly prolonged long-term survival compared with mice treated with b-AP15 and NK or T cells (p≤0.01). Our findings show that b-AP15-induced sensitization to TRAIL-mediated apoptosis could be used as a novel strategy to augment the anti-cancer effects of adoptively infused NK and T cells in patients with cancer.
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| 27. |
- Sarhan, Dhifaf, et al.
(författare)
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Activated monocytes augment TRAIL-mediated cytotoxicity by human NK cells through release of IFN-gamma
- 2013
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Ingår i: European Journal of Immunology. - Stockholm : Karolinska Institutet, Dept of Oncology-Pathology. - 1521-4141 .- 0014-2980.
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Natural killer (NK) cells are innate lymphocytes that are able to directly kill tumor cells through different mechanisms including ligation of TNF-related apoptosis-inducing ligand (TRAIL) receptors. Zoledronic acid (ZA) is a bisphosphonate known to upregulate the expression of TRAIL on human γδ T cells. Here, we investigated whether exposure to ZA would upregulate TRAIL expression on human NK cells and augment their cytotoxicity against tumor cells. When cocultured with monocytes, treatment with ZA and IL-2 resulted in a significant upregulation of TRAIL expression on human NK cells (p = 0.002). Consequently, ZA-primed NK cells were significantly more cytotoxic against TRAIL sensitive tumor cells (p < 0.0001). In the presence of ZA and IL-2, monocytes produced high levels of IFN-γ; when cultured in the presence of neutralizing antibodies to IFN-γ, TRAIL expression and TRAIL-mediated cytotoxicity of NK cells were significantly reduced. Furthermore, in tumor-bearing SCID/Beige mice, a significant delayed tumor progression and prolonged survival was observed after infusion of ZA-primed NK cells compared with that observed in mice infused with unprimed NK cells. These findings represent a novel approach to potentiate TRAIL-mediated apoptosis by adoptively infused NK cells that could improve the outcome in patients with cancer.
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| 28. |
- Sciaraffia, Elena, 1977-, et al.
(författare)
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The reliability of cardiogenic impedance and correlation with echocardiographic and plethysmographic parameters for predicting CRT time intervals post implantation
- 2013
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Ingår i: Journal of Interventional Cardiac Electrophysiology. - : Springer Science and Business Media LLC. - 1383-875X .- 1572-8595. ; 37:2, s. 155-162
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Tidskriftsartikel (refereegranskat)abstract
- AimsEncouraging data have been reported on the use of cardiogenic impedance (CI) in cardiac reshynchronization therapy (CRT) optimization. The purpose of this study was to: evaluate the stability of certain CI vectors 24 hours post implantation, study the correlation between these CI signals and selected echocardiographic parameters, examine the possibility of non-invasive calibration of patient-specific impedance-based prediction models.Methods and resultsThirteen patients received a CRT-D device with monitor capability of the dynamic impedance between several electrodes. At implantations patient-specific impedance-based prediction models were created for identification of optimal atrioventricular (AV) and interventricular (VV) delays and calibrated on invasive measurements of left ventricular contractility (LV dP/dtmax). Simultaneously non-invasive measurements of LV dP/dtmax and stroke volume (SV) were obtained using a finger plethysmograph. Patients were re-evaluated with echocardiography and new CI measurements the day after implantation.The haemodynamic benefit achieved by optimal VV setting according to the patient-specific impedance-based prediction models at follow-up was not as large as the one obtained at implantation. In a multivariate partial least square regression analysis a correlation was found between aortic VTI and a generic linear combination of CI features (P<0,005). No correlation was found between the patient-specific impedance-based prediction models and the non-invasive measurements of LV dP/dtmax and SV.ConclusionsCardiogenic impedance signals can be used to optimize CRT settings but seems less feasible as an ambulatory tool since calibration is required. The positive correlation between aortic-VTI and CI measurements seems promising; although a larger cohort is required to create an echocardiography-based patient-specific model.
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| 29. |
- Svendsen, Jesper Hastrup, et al.
(författare)
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Outpatient evaluation and management of patients with ventricular premature beats or non-sustained ventricular tachycardia
- 2012
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Ingår i: Europace. - : Oxford University Press (OUP). - 1099-5129 .- 1532-2092. ; 14:2, s. 294-296
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Tidskriftsartikel (refereegranskat)abstract
- In this survey, European physicians who deal with arrhythmia patients gave their opinions about diagnostic work up when they see patients with ventricular premature beats (VPBs) or non-sustained ventricular tachycardia (NSVT). In general, similar work-up regimens were used for these two arrhythmias except for coronary angiography, which was considered by one in four physicians when dealing with NSVT but by almost none for VPBs. The majority of physicians believe that it is acceptable to abstain from pharmacological therapy in an asymptomatic patient with VPBs. When considering second-line therapy almost half of the respondents would consider amiodarone in patients with NSVT whereas almost none would when dealing with VPBs. When the effect of therapy was evaluated, its influence on symptoms and arrhythmia burden were ranked highest.
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| 30. |
- Wennerberg, Erik, et al.
(författare)
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Doxorubicin sensitizes human tumor cells to NK and T cell-mediated killing by augmented TRAIL-receptor signaling
- 2013
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Ingår i: International Journal of Cancer. - Stockholm : Karolinska Institutet, Dept of Oncology-Pathology. - 1097-0215 .- 0020-7136.
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Doxorubicin (DOX) is an anthracycline antibiotic that is widely used to treat different types of malignancy. In this study, it was studied whether DOX could be used to render tumor cells susceptible to apoptosis by NK and T cells. Pretreatment with subapoptotic doses of DOX sensitized tumor cell lines of various histotypes to both NK and T cells resulting in a 3.7 to 32.7% increase in lysis (2.5 mean fold increase, p < 0.0001) and a 2.9 to 14.2% increase in lysis (3.0 mean-fold increase, p < 0.05), respectively. The sensitizing effect of the drug was primarily dependent on the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)/TRAIL-receptor signaling, but not on Fas-ligand, perforin, NKG2D or DNAM-1. The central role of the TRAIL signaling pathway was further supported by an increased expression of TRAIL-R2 on DOX-treated tumor cells and by downregulation of cellular FLICE inhibitory protein, the inhibitors of death receptor-mediated apoptosis. Compared to untreated cells, pretreatment of tumor cells with DOX showed increased processing and activation of caspase-8 on coculture with NK or T cells. The significance of this treatment strategy was confirmed using a xenogeneic tumor-bearing mouse model. Tumor progression was delayed in mice that received either NK cells (p < 0.05) or T cells (p < 0.0001) following DOX treatment compared to mice receiving either cell type alone. Moreover, combined infusion of both NK and T cells following DOX treatment not only delayed tumor progression but also significantly improved the long-term survival (p < 0.01). Based on these findings, it was proposed that DOX can be used to improve the efficacy of adoptive cell therapy in patients with cancer.
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| 31. |
- Wennerberg, Erik, et al.
(författare)
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Human anaplastic thyroid carcinoma cells are sensitive to NK cell-mediated lysis via ULBP2/5/6 and chemoattract NK cells
- 2014
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Ingår i: Clinical Cancer Research. - 1078-0432. ; 20:22, s. 5733-5744
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Anaplastic thyroid carcinoma (ATC) is one of the most aggressive forms of cancer with no curative therapies available. To date, strategies to target ATC by immunotherapy have not been evaluated. We investigated whether ATC would be a suitable target for natural killer (NK) cell-based immunotherapy.EXPERIMENTAL DESIGN: We first established seven new cell lines from ATC tumors, three from papillary thyroid carcinoma tumors and analyzed them together with eight additional ATC cell lines. Cells were analyzed for sensitivity to lysis by NK cells and their ability to chemoattract and regulate the activity of NK cells. In addition, fresh tumor samples and peripheral blood from six patients with ATC were analyzed for NK cell infiltration and phenotype.RESULTS: We observed that ATC cell lines are sensitive to lysis by ex vivo expanded NK cells and that the lysis was abrogated upon blockade of NKG2D. Sensitivity of thyroid cancer cell lines to NK cell-mediated lysis correlated with surface expression of UL16-binding protein 2 on tumor cells. Moreover, ATC cell lines produced high levels of CXCL10 and stimulated migration of expanded NK cells and ATC tumors were enriched for NK cells expressing the cognate chemokine receptor CXCR3. However, compared with NK cells in peripheral blood, ATC tumor-derived NK cells displayed a suppressed phenotype with a downregulated expression of NKG2D. In vitro, suppression of NK cell-mediated lysis and NKG2D expression by ATC cells was restored upon neutralization of prostaglandin-E2.CONCLUSIONS: ATC cell lines are sensitive to NK cell-mediated lysis via ULBP2/5/6 and chemoattract CXCR3-positive NK cells. Patients with ATC may benefit from NK cell-based immunotherapy.
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| 32. |
- Zhou, Jiale, et al.
(författare)
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Formal Execution Semantics for Asynchronous Constructs of AADL
- 2013
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Ingår i: MODELS 2012 Innsbruck - Proceedings of the 5th International Workshop on Model Based Architecting and Construction of Embedded Systems, ACES-MB 2012. - New York, NY, USA : ACM. ; , s. 43-48
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Konferensbidrag (refereegranskat)abstract
- The Architecture Analysis and Design Language (AADL) has been widely accepted to support the development process of Distributed Real-time and Embedded (DRE) systems and ease the tension of analyzing the systems’ non-functional properties. The AADL standard prescribes the dispatching and scheduling semantics for the thread components in the system using natural language. The lack of formal semantics limits the possibility to perform formal verification of AADL specifications. The main contribution of this paper is a mapping from a substantial asynchronous subset of AADL into the TASM language, allowing us to perform resource consumption and schedulability analysis of AADL models. A small case study is presented as a validation of the usefulness of this work.
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