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- Forslund, Elin, et al.
(author)
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Microchip-Based Single-Cell Imaging Reveals That CD56(dim) CD57(-)KIR(-)NKG2A(+) NK Cells Have More Dynamic Migration Associated with Increased Target Cell Conjugation and Probability of Killing Compared to CD56(dim)CD57(-)KIR(-)NKG2A(-) NK Cells
- 2015
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In: Journal of Immunology. - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 195:7, s. 3374-3381
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Journal article (peer-reviewed)abstract
- NK cells are functionally educated by self-MHC specific receptors, including the inhibitory killer cell Ig-like receptors (KIRs) and the lectin-like CD94/NKG2A heterodimer. Little is known about how NK cell education influences qualitative aspects of cytotoxicity such as migration behavior and efficacy of activation and killing at the single-cell level. In this study, we have compared the behavior of FACS-sorted CD56(dim)CD57(-)KIR(-)NKG2A(+) (NKG2A(+)) and CD56(dim)CD57(-)KIR(-)NKG2A(+) (lacking inhibitory receptors; IR-) human NK cells by quantifying migration, cytotoxicity, and contact dynamics using microchip-based live cell imaging. NKG2A(+) NK cells displayed a more dynamic migration behavior and made more contacts with target cells than IR-NK cells. NKG2A(+) NK cells also more frequently killed the target cells once a conjugate had been formed. NK cells with serial killing capacity were primarily found among NKG2A(+) NK cells. Conjugates involving IR- NK cells were generally more short-lived and IR- NK cells did not become activated to the same extent as NKG2A(+) NK cells when in contact with target cells, as evident by their reduced spreading response. In contrast, NKG2A(+) and IR- NK cells showed similar dynamics in terms of duration of conjugation periods and NK cell spreading response in conjugates that led to killing. Taken together, these observations suggest that the high killing capacity of NKG2A(+) NK cells is linked to processes regulating events in the recognition phase of NK-target cell contact rather than events after cytotoxicity has been triggered.
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- Olsson, E., et al.
(author)
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Assessment and Modelling of Joint Command and Control in Aircraft Maintenance Contexts Using Enterprise Models and Knowledge Graph Representations
- 2022
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In: International Journal of COMADEM. - : COMADEM International. - 1363-7681. ; 25:2, s. 13-22
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Journal article (peer-reviewed)abstract
- The increasingly complex context of dynamic, high-tempo military air operations raise new needs for aircraft maintenance and logistic support systems to more rapidly respond to changes in operational needs and available resources, with retained support resource efficiency. The future maintenance and support system are thus envisioned with improved net-centric capabilities to facilitate matching of tactical needs with aircraft maintenance capabilities. The study addresses this challenge by creating abstract representations and definitions of relevant tactical structures and maintenance structures, processes, and resources using enterprise modelling. By addressing this in a holistic perspective, a better understanding of the matching problem is achieved, enabling efficient matching of operational needs with available resources. Based on these findings, graph models are created from a domain-centric view of two adjacent domain contexts, which includes command and control and aircraft maintenance contexts. The result has the ability to leverage interoperability and collaboration between air- and ground-based systems by facilitating interactions between tactical needs and aircraft maintenance resources.
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| 21. |
- Olsson, E., et al.
(author)
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Enterprise Modeling for Dynamic Matching of Tactical Needs and Aircraft Maintenance Capabilities
- 2022
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In: Lecture Notes in Mechanical Engineering. - Cham : Springer Science and Business Media Deutschland GmbH. - 9783030936389 ; , s. 370-383
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Conference paper (peer-reviewed)abstract
- The increasingly complex context of dynamic, high-tempo military air operations raises new needs for airbase aircraft maintenance and logistic support systems to more rapidly respond to changes in operational needs, with retained support resource efficiency. The future maintenance and support system are thus envisioned with improved net-centric capabilities to facilitate matching of tactical needs with aircraft maintenance capabilities. Today military Command and Control (C2) of tactical needs against airbase aircraft maintenance capabilities contain many manual activities. This constrains speed of execution as well as drives manning requirements, and there is a need to further develop existing IS and IT support. Thus the studied matching capability address these limitations through an approach based on improved integration of the air vehicle on-board health management system with corresponding ground-based functions, and exploitation of technologies such as big-data analytics, diagnostic-prognostics, Artificial Intelligence (AI), machine learning and reasoning systems in a system-of-system-wide service architecture. However, understanding the concept of matching of tactical needs and aircraft maintenance capabilities requires insights of complex multi-domain C2 interactions and interrelations between the tactical domain and the aircraft maintenance domain. Whereas each domain is quite well understood, the more detailed interrelations between the domains is less studied. This paper present an approach to this problem by creating useful representations of the underpinning insights, by enterprise modeling of abstract representations and definitions of relevant tactical and maintenance structures, processes, and resources, in the airbase context, to better understand the matching problem, and to address this problem through a holistic perspective.
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| 22. |
- Olsson, E., et al.
(author)
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Using a Drone Swarm/Team for Safety, Security and Protection Against Unauthorized Drones
- 2024
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In: Lecture Notes in Mechanical Engineering. - : Springer Science and Business Media Deutschland GmbH. - 9783031396182 ; , s. 263-277
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Conference paper (peer-reviewed)abstract
- There is an increased need for protection against unauthorized entry of drones as there has been an increased number of reports of UAV’s entering restricted areas. In this paper we explore an approach of using a swarm/team of drones that are able to cooperate, to autonomously engage and disable one or more unauthorized drones entering a restricted area. In our approach, we have investigated technologies for distributed decision-making and task allocation in real-time, in a dynamic simulated environment and developed descriptive models for how such technologies may be exploited in a mission designed for a drone swarm. This includes the definition of discrete tasks, how they interact and how they are composed to form such a mission, as well as the realization and execution of these tasks using machine learning models combined with behaviour trees. To evaluate our approach, we use a simulated environment for mission execution where relevant KPI’s related to the design of the mission have been used to measure how efficient our approach is in deterring or incapacitating unauthorized drones. The evaluation has been performed using Monte-Carlo simulations on a batch of randomized scenarios and measures of effectiveness has been used to measure each scenario instance and later compiled into a final assessment for the main scenario as well as each ingoing task. The results show a mission success in 93% of the simulated scenarios. Of these 93%, 58% of the scenarios resulted in the threat being neutralized and in 35% of the scenarios the threat was driven away from the critical area. We believe that the application of such measurements aids to validate the applicability of this capability in a real-world scenario and in order to assert the relevance of these parameters, future validations in real-world operational scenarios are warranted.
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- Rasul, Abu E., et al.
(author)
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Simultaneous detection of the two main proliferation driving EBV encoded proteins, EBNA-2 and LMP-1 in single B cells
- 2012
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In: JIM - Journal of Immunological Methods. - : Elsevier BV. - 0022-1759 .- 1872-7905. ; 385:1-2, s. 60-70
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Journal article (peer-reviewed)abstract
- Epstein Barr virus (EBV) is carried by almost all adults, mostly without clinical manifestations. Latent virus infection of B lymphocytes induces activation and proliferation that can be demonstrated in vitro. In healthy individuals, generation of EBV induced malignant proliferation is avoided by continuous immunological surveillance. The proliferation inducing set of the virally encoded genes is expressed exclusively in B cells in a defined differentiation window. It comprises nine EBV encoded nuclear proteins, EBNA 1-6, and three cell membrane associated proteins, LMP-1,2A and 2B, designated as latency Type III. Outside this window the expression of the viral genes is limited. Healthy carriers harbor a low number of B lymphocytes in which the viral genome is either silent or expresses one virally encoded protein, EBNA-1, latency Type I. In addition, EBV genome carrying B cells can lack either EBNA-2 or LMP-1, latency Type IIa or Type IIb respectively. These cells have no inherent proliferation capacity. Detection of both EBNA-2 and LMP-1 can identify B cells with growth potential. We devised therefore a method for their simultaneous detection in cytospin deposited cell populations. Simultaneous detection of EBNA-2 and LMP-1 was reported earlier in tissues derived from infectious mononucleosis (IM), postransplantation lymphoproliferative disorders (PTLD) and from humanized mice infected with EBV. We show for the first time the occurrence of Type IIa and Type IIb cells in cord blood lymphocyte populations infected with EBV in vitro. Further, we confirm the variation of EBNA-2 and LMP-1 expression in several Type III lines and that they vary independently in individual cells. We visualize that in Type III LCL, induced for plasmacytoid differentiation by IL-21 treatment, EBV protein expression changes to Type ha (EBNA-2 negative LMP-1 positive). We also show that when the proliferation of EBV infected cord blood lymphocyte culture is inhibited by the immunomodulator, PSK the majority of the cells express latency Type IIa pattern. These results show that by modifying the differentiation state, the proliferating EBV positive B cells can be curbed. Type IIa expression is a characteristic for EBV positive Reed-Sternberg (R/S) cells in EBV positive Hodgkin's lymphomas. For survival and proliferation, the R/S cells require the contribution of the in vivo microenvironment Consequently, Type IIa lines could not be established from Hodgkin's lymphoma in vitro. We propose that these experimental cultures can be exploited for study of the Type IIa cells.
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- Sohlberg, Björn, et al.
(author)
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Model based fault detection and isolation by fault parameter elimination
- 2010
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Conference paper (peer-reviewed)abstract
- This paper deals with model based fault detection and isolation of a pickling process within the steel industry. The model is based on the grey box methodology and reflects the physical behaviour of the process. Possible faults are included in the model as parameters, which are estimated on line. The estimation is based on minimizing a loss function using past data from a defined moving time window. The procedure of finding the faults starts by estimate all defined fault parameters. One fault parameter is removed from the set of prospective list of faults by removing the parameter with the smallest saliency. The saliency is defined as the quote between the parameter estimate and the corresponding element of the inverse of the hessian matrix. The parameter with the smallest saliency gives a measure of the relevance of the estimated parameters relative all estimated parameters. The procedure is repeated until all fault parameters are eliminated from the list. To isolate the faults, the Akaike's Information Criterion (AIC) is used to detect faults. This gives the threshold when a fault relevant parameter is removed from the list of prospective faults. © 2010 IFAC.
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| 30. |
- Sohlberg, E, et al.
(author)
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Perturbed NK-cell homeostasis associated with disease severity in chronic neutropenia
- 2022
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In: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 139:5, s. 704-716
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Journal article (peer-reviewed)abstract
- Neutrophils have been thought to play a critical role in terminal differentiation of NK cells. Whether this effect is direct or a consequence of global immune changes with effects on NK-cell homeostasis remains unknown. In this study, we used high-resolution flow and mass cytometry to examine NK-cell repertoires in 64 patients with neutropenia and 27 healthy age- and sex-matched donors. A subgroup of patients with chronic neutropenia showed severely disrupted NK-cell homeostasis manifesting as increased frequencies of CD56bright NK cells and a lack of mature CD56dim NK cells. These immature NK-cell repertoires were characterized by expression of the proliferation/exhaustion markers Ki-67, Tim-3, and TIGIT and displayed blunted tumor target cell responses. Systems-level immune mapping revealed that the changes in immunophenotypes were confined to NK cells, leaving T-cell differentiation intact. RNA sequencing of NK cells from these patients showed upregulation of a network of genes, including TNFSF9, CENPF, MKI67, and TOP2A, associated with apoptosis and the cell cycle, but different from the conventional CD56bright signatures. Profiling of 249 plasma proteins showed a coordinated enrichment of pathways related to apoptosis and cell turnover, which correlated with immature NK-cell repertoires. Notably, most of these patients exhibited severe-grade neutropenia, suggesting that the profoundly altered NK-cell homeostasis was connected to the severity of their underlying etiology. Hence, although our data suggest that neutrophils are dispensable for NK-cell development and differentiation, some patients displayed a specific gap in the NK repertoire, associated with poor cytotoxic function and more severe disease manifestations.
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