| 1. |
- Ahmadi, Alireza, et al.
(author)
-
Inspection Optimization under imperfect maintenance performance
- 2017
-
In: Proceedings of MPMM 2016. - Luleå : Luleå tekniska universitet. - 9789175838410 ; , s. 139-
-
Conference paper (peer-reviewed)abstract
- Scheduled maintenance and inspection development is one of the main requirements for emergency equipment and safety devices. These types of devices have hidden functions which are used intermittently or infrequently, so their failure will not be evident to the operating crew. The analytical model presented in this paper deals with the periodically tested units with overhauls (preventive maintenance) after certain number of inspections and a renewal after a series of overhauls. The cost based optimization method presented in this paper identifies the optimum interval and frequency of Failure Finding Inspection (FFI) and restoration. In the proposed model, repair due to failures found by inspection makes the unit As Bad As Old, and restoration/overhaul action rejuvenates the unit to any condition between As Good As New and As Bad As Old. As Good As New effectiveness also is considered for renewal action. It considers inspection and repair times, and takes into account the costs associated with inspection, repair, restoration, and also the cost of accidents due to the occurrence of multiple failure. The results show that when the unit is not under aging process, the optimal alternative for each inspection interval is the one with highest possible number of inspection without restoration. Finally, it is observed that when the cost of accident is quite high it is needed to perform inspections at smaller intervals to control the risk of accident.
|
|
| 2. |
- Ahmadi, Alireza, et al.
(author)
-
Optimum failure management strategy for periodically inspected units with imperfect maintenance
- 2016
-
In: IFAC-PapersOnLine. - : Elsevier BV. - 2405-8963. ; 49:12, s. 799-804
-
Journal article (peer-reviewed)abstract
- The aim of this paper is to develop a reliability-based cost model for periodically inspected units subject to hidden functions, with imperfect restoration (overhaul) action after a certain number of inspections. In the model, effectiveness of the consecutive restoration actions is considered, and possible alternative maintenance strategies are identified and compared. The method is based on the Total Cost and identifies the optimum interval and frequency of inspections, as well as restoration that minimize the total life cycle cost. In the proposed model, repair due to failures found by inspection is considered as minimal repair, and restoration/overhaul action is considered as normal repair. The result also shows that for a specific value of restoration effectiveness (θ0), when θ> θ0, the behavior of alternatives tends to as-bad-as-old and for θ< θ0 tends to an as-good-as-new. It is also observed that when the cost of accident is high it is needed to perform inspections at smaller intervals.
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
- Ahmadi, Alireza, et al.
(author)
-
Risk based maintenance deferral for components subject to hidden failure
- 2012
-
In: 2012 proceedings. - Piscataway, NJ : IEEE Communications Society. - 9781457718496
-
Conference paper (peer-reviewed)abstract
- In the aviation industry, it may be necessary to employ a combination of Failure Finding Inspection (FFI) and a scheduled discard task at a specific threshold, when a component is aging and its failures are hidden and exert a “safety effect”. This is to ensure an adequate level of availability of hidden functions, and to reduce the risk of multiple failures to an acceptable level. However, in some situations, operators prefer to extend the discard life of components beyond their recommended life limit, due to operational needs or logistic issues. This necessitates the definition of an optimal Failure Finding Inspection interval for the extended life period. The main purpose of this paper is to develop analytical and graphical methodologies to identify the optimal FFI interval for extension of the discard life of aircraft components. The paper considers repairable components which are periodically tested. The methodology assumes that the inspection and repair actions lead to as-bad-as-old (ABAO) reliability characteristics.The graphical approach proposed in this paper considers inspection and repair times, as well as the costs associated with accidents, inspection, and repair, and it takes into account the opportunity losses due to the maintenance downtime. The analytical approach for calculating the unavailability of the hidden function is based on the Mean Fractional Dead Time (MFDT).
|
|
| 6. |
- Block, Jan, et al.
(author)
-
Changes in items' failure pattern during maintenance : an investigation of the perfect repair assumption
- 2008
-
In: Annual Reliability and Maintainability Symposium, 2008. - Piscataway, NJ : IEEE Communications Society. - 9781424414604 ; , s. 117-122
-
Conference paper (peer-reviewed)abstract
- It is clear that the simple ‘perfect repair' assumption is not immediately applicable to any of the studied types of hardware, i.e. Cooling Turbine, High-Voltage Generator, Hydraulic Accumulator, and Radar Transmitter. Hence, the assumption of ‘perfect repair' needs to be validated for each specific type of item. Assumptions based on the type of physical hardware (e.g. mechanical item or avionics item) are not always trustworthy.Strangely enough the ‘perfect repair' assumption fits best for the Cooling Turbine, which is a highly stressed mechanical item, while the fit is much poorer for the Radar Transmitter, which is an avionics item and for the Hydraulic Accumulator.For the Radar Transmitter the trend seems to be very scattered. For items with a large number of failures early in their life-cycle, repair is ‘better than perfect', i.e. the items become more reliable after repair, presumably by elimination of less reliable subcomponents. However, this effect is not seen for items with few failures early in their life-cycle. For these items ‘perfect repair' initially seems to be a valid model. However, in many cases repair becomes ‘less than perfect' later in the life-cycle. For the Hydraulic Accumulator this trend is even more accentuated and individual items seem to fall into two distinct subpopulations with opposite reliability trends.
|
|
| 7. |
- Block, Jan
(author)
-
Dependability analysis of military aircraft fleet performance in a lifecycle perspective
- 2009
-
Licentiate thesis (other academic/artistic)abstract
- Today's highly advanced technological flying platforms, such as aircraft, helicopters and Unmanned Air Vehicles (UAVs), are characterised by a high degree of complexity. Simultaneously, they are used in different operational and mission profiles, and also in multiple operational environments and geographical settings. In addition, the interaction between major stakeholders, such as operators and support providers, has been drastically changed by concepts such as Performance-Based Logistics (PBL), where the support providers' commitment increases through the offering of availability performance at a fixed price. These changes put new and stringent requirements on dependability analysis to make efficient use of field data (e.g. generated by built-in tests, operation and maintenance) to sustain, improve and predict the availability performance of flying platform fleets. The purpose of the research presented in this thesis is to explore and describe methodologies and tools for dependability analysis, modelling and simulation of fleets of complex systems, in order to support improvement decisions throughout the fleets' whole lifecycle. More specifically, the objective of the research is to contribute to the development of a tool for modelling and simulation of multiple parallel lifecycle phases of complex technical systems in a fleet. The focus is on the assessment of field data and the extraction and prediction of information for continuous improvement of subsystem reliability performance, organisational maintenance support performance and fleet availability performance. The empirical work focuses on the Swedish military aeronautics community. The data has been collected through interviews, observations, document studies and archival records, such as recordings of in-flight parameters and maintenance actions. The data has been analysed to investigate critical aspects, such as the perfect repair assumption, the appropriateness of decisions about changes of maintenance intervals and of the No Fault Found (NFF) phenomenon. Through a literature study and practical efforts, this thesis also outlines and exemplifies methodologies and tools that support dependability analysis of an aircraft fleet. In addition, modelling and simulation efforts have been made to enable prediction of aircraft fleet performance and beneficial adjustments of support resources during the fleet retirement phase. The results act as input to a conceptual model that describes the phasing-in, operation and retirement of an aircraft fleet. The model aims to identify when it is cost-effective to consider the Remaining Useful Life (RUL) of individual repairable components comprising aircraft being retired, and utilise these components as spare parts for the aircraft staying in service. In summary, the performed work indicates that, in today's context with PBL and excessive amount of available data, dependability analysis, modelling and simulation must become more transparent, traceable and intersubjective.
|
|
| 8. |
- Block, Jan, et al.
(author)
-
Fleet-Level Reliability Analysis of Repairable Units: A Non-Parametric Approach using the Mean Cumulative Function
- 2013
-
In: International Journal of Performability Engineering. - 0973-1318. ; 9:3, s. 333-344
-
Journal article (peer-reviewed)abstract
- Complex technical systems are normally repaired rather than replaced when they fail. It is often desirable to analyze the reliability characteristics of these systems based on data generated in a customer use environment, in order to assess the reliability, frequency of failure or other parameters which may be influenced by the systems’ age and usage. Despite the advantages of continuously analyzing reliability data to be able to improve the maintenance programme continuously, methods such as parametric and non-parametric analysis are often ignored due to a belief that the mean time between failures (MTBF) is sufficient to describe the reliability pattern of repairable units. This paper describes the use of the mean cumulative function (MCF) and linear estimates based on the recurrence rate to predict the expected number of failures in the future. Reliability data from two repairable units are used to verify the procedure and comparison. The empirical data used in the paper is based on field data gathered during the operational life of the Swedish military aircraft system FPL 37 Viggen from 1977 to 2006, which essentially is the whole life cycle of the system.
|
|
| 9. |
- Block, Jan, et al.
(author)
-
Fleet-level Reliability of Multiple Repairable Units: a Parametric Approach using the Power Law Process
- 2014
-
In: International Journal of Performability Engineering. - 0973-1318. ; 10:3, s. 239-250
-
Journal article (peer-reviewed)abstract
- The application of parametric reliability analysis methods for repairable units, such as Power law process, is quite clear and straightforward for a single repairable unit. However, in practice, the analyst needs to know the reliability characteristics of units at a fleet level. The application of parametric reliability analysis methods at the fleet level, even if it is limited in scope, is quite complex. The aim of this paper is to describe the use of the power law process for multiple repairable units with differing reliability characteristics, to predict the expected number of failures at fleet level. The empirical data used in the paper are based on field data gathered during the operational life of two types of multi repairable units used in the Swedish military aircraft system FPL 37 Viggen from 1977 to 2006. The paper performs the trend test using TTT-based MIL-HDBK-189 and Laplace tests, and assesses the equality of shape-parameters for the intensity function of the power law process for multiple units. Estimation of the scale- and shape-parameters using maximum likelihood estimation is also performed. The parametric approach using power law process was found to yield relatively accurate estimations of number of failures, compared to empirical data
|
|
| 10. |
- Block, Jan, et al.
(author)
-
No Fault Found events during the operational life of military aircraft items
- 2009
-
In: 8th International Conference on Reliability, Maintainability and Safety, 2009. - Piscataway, NJ : IEEE Communications Society. - 9781424449040 ; , s. 920-924
-
Conference paper (peer-reviewed)abstract
- No fault found (NFF) events are critical and well-known problems for certain aircraft items. This paper presents a study of these events for repairable items with on-condition maintenance, based on operational data from a military aircraft. Some findings are that: the number of NFF events is influenced by item type and number of repairs; most NFF events are initiated by faults recognized during operation; and different inspections contribute to NFF events. Hence, item design and tests at different operational modes and maintenance echelons should be better aligned to reduce the number of NFF events
|
|
| 11. |
- Block, Jan, 1973-
(author)
-
Part-out Based Spares Provisioning and Management : A Study for Aircraft Retirement
- 2017
-
Doctoral thesis (other academic/artistic)abstract
- The operation and maintenance phase of a complex technical system may deal with strategicdecisions for asset retirement and end-of-life management. When a fleet of aircraft reachesthe retirement phase, the operation of remaining fleet should still be kept at a defined level ofavailability. Obviously, the provisioning of spares is a key issue to support the maintenanceand operation of the remaining fleet. The best practice within the aviation industry is to re-usethe spares of retired aircraft to support the operational fleet. This is referred to parting-out.The purpose of the research conducted for this thesis has been to develop decision supportmethodologies, models and tools for the management of a sustainable part-out-based sparesprovisioning for an aircraft fleet during its retirement period. The proposed methodology willbe used to support the retirement process of aircraft fleet and enhance the organisation’scapability of making efficient and cost-effective decisions concerning the re-use of spare partsduring the retirement period. To achieve the purpose of this research, literature studies, casestudies, algorithm development and simulations have been conducted. Empirical data havebeen collected through document studies, interviews, and the perusal of archival records fromSaab Support and Services AB. The data analysis performed for this research has been basedon theories and methodologies within reliability analysis, cost modelling, spares forecasting,stock provisioning and decision making, in combination with the best practices implementedby the aviation industry for the end-of-life management and retirement of aircraft.In the present thesis, part-out-based spares provisioning (PBSP) program is proposed to utiliseretired aircraft units effectively as spare parts. The proposed approach is illustrated andverified through a case study performed on the “Saab-105” military aircraft fleet withinSwedish air force fleet. A PBSP programme is proposed, associated management activitiesare described, the key decision criteria are presented, and a functional framework for aneffective PBSP is suggested. The proposed PBSP program provides a foundation for furthermeasures and tasks to be performed within the retirement period, such as terminatingmaintenance contracts, discarding internal maintenance capabilities, reviewing stocks, scalingdown administrative processes (e.g. spares procurement and obsolescence monitoring), etc.An important part of the PBSP programme is the reliability analysis of multiple repairableunits, and this has been investigated, using parametric and non-parametric reliabilityapproaches. The aim is to identify a practical approach for estimation of the future sparedemand at fleet level. Furthermore, a set of computational models and search algorithm havebeen developed for the identification of applicable termination times, of both the parting-outprocess and the maintenance and repair actions performed on the units. This includestermination of the parting-out process (PO), the sending of parted-out units directly to storage(POS), and repair actions performed on the units received at the repair shops owing tocorrective (CM) and preventive (PM) maintenance, as well as the parted-out units that need tobe repaired (POM). The feasible termination alternatives are compared with regard to theirrespective costs and the most cost-effective solutions are identified.The results of the research study show that a PBSP programme can yield large reductions inmaintenance and spares procurement costs, while supporting operation of existing fleet athighest required availability. It also contributes positively to implement a green supply chainduring the retirement phase. The methodology and approaches introduced within the thesiscan be applied in other civil applications, such as energy, mining, process industry andtransportation sectors.
|
|
| 12. |
- Block, Jan, et al.
(author)
-
Part-out-based spares provisioning management : A military aviation maintenance case study
- 2014
-
In: Journal of Quality in Maintenance Engineering. - 1355-2511 .- 1758-7832. ; 20:1, s. 76-95
-
Journal article (peer-reviewed)abstract
- Purpose – The purpose of this paper is to present the prerequisites for a part-out-based spares provisioning (PBSP) programme during the phase-out of an aircraft fleet. Furthermore, associated key decision criteria are identified and a framework for the phase-out management process is presented. Design/methodology/approach – Once a decision has been taken to phase-out an aircraft fleet, a number of routines for operations, maintenance and storage are affected and new tasks and functions must be introduced before initiating the actual parting-out process. A decision-making system and a management framework is needed to manage spares planning during the end-of-life phase to ensure availability at minimum cost and to ensure a manageable risk of backorders. Findings – For PBSP programme during the phase-out of an aircraft fleet to succeed and be cost-effective, a number of linked processes, tasks and decisions are required, e.g., those included in the framework proposed in this paper (see Figure 3). A successful implementation of PBSP also requires that these processes and tasks are carried out in a timely manner and that the communications between the concerned parties are prompt, clear and direct. One experience from the studied case is that close and trustful contacts and cooperation between the operator and maintenance provider(s) will greatly facilitate the process. Originality/value – Although the PBSP method is fairly commonly applied within both the military and the civilian sector, somewhat surprisingly very literature has been published on the subject. Indeed, remarkably little has been published on any aspects of maintenance during the end-of-life period.
|
|
| 13. |
- Block, Jan, et al.
(author)
-
Spares Provisioning Strategy for Periodically Replaced Units within the Fleet Retirement Period
- 2019
-
In: International Journal of Systems Assurance Engineering and Management. - : Springer. - 0975-6809 .- 0976-4348. ; 10:3, s. 299-315
-
Journal article (peer-reviewed)abstract
- Within aviation enterprises, the process of dismantling an aircraft at the end of its life is referred to as parting-out. Obviously, the asset value of the units and materials parted out from the retired airframes can be considerable. The benchmarked best practice within the aviation industry is to dismantle the retired aircraft and use the parted-out spares to support the remaining fleet or to offer them on the surplus market. Part-out-based spares provisioning (PBSP) has been a major focus of attention for aviation companies. The PBSP approach is a complex task that requires a multidisciplinary and integrated decision-making process. In order to control the stock level and fulfil the decision criteria within PBSP, it is necessary to make decisions on the termination, at specific times, of both the parting-out process and the maintenance and repair actions performed on the units.This paper considers repairable units and introduces a computational model to identify the applicable alternatives for repair termination times that will minimize the number of remaining spares at the end of the retirement period, while fulfilling the availability requirement for spares during the PBSP period, at the lowest possible cost. The feasible alternatives are compared with regard to their respective costs, and the most cost-effective solution is selected. The cost model uses estimates of future maintenance requirements, the turn-around times, the cost of the various maintenance tasks, the future spares consumption, and the estimated salvage of spares from retired aircraft. The output of the model is a set of applicable alternatives which satisfy the availability requirements for spares for the active fleet. The method is illustrated using a case study performed on the Saab-105 training aircraft. The results show that the proposed PBSP approach and computational model provide added value from a sustainability point of view, since the use of existing resources is maximized during the retirement process, through the process of reclaiming units and the applicable maintenance termination alternatives. The implementation of the proposed computational model in a PBSP programme provides a detailed and situation-based overview of the stock level dynamics, and contributes to the spares provisioning process by providing solutions to issues such as obsolescence, last-time buys and cannibalization.
|
|
| 14. |
- Block, Jan, 1973, et al.
(author)
-
Ultrathin Pd and Pt Films on W(211)
- 2003
-
In: Thin Solid Films. ; 428, s. 47-
-
Journal article (peer-reviewed)abstract
- The transition metals Pd and Pt have, in bulk, approximately the samenearest neighbor distance as tungsten, so that ultrathin Pd or Pt filmscan be grown on W substrates without creating significant strain.In the present work we studyultrathin Pd and Pt films on the atomically rough W(211) surface byfirst-principles density-functional theory (DFT) methods.Previous experiments, summarized here, have shown that in filmsthicker than 1 physical monolayer (PML), tungsten atoms of the substratediffuse into the film to create alloys. Both toconfirm the alloy formation from theory and to help characterize the alloyswe present studies of Pd and Pt films with included W atoms. The DFT resultsallow us to indicate the energetically preferred alloy structures.
|
|
| 15. |
- Block, Jan, et al.
(author)
-
Using Monte Carlo simulation as support for decision making while negotiating a PBL contract
- 2014
-
In: IEEE Aerospace Conference. Proceedings. - 1095-323X.
-
Journal article (peer-reviewed)abstract
- In connection with performance-based logistics (PBL) contracts for aircraft fleets it is very important to carefully analyse both operations and maintenance before and during the contract negotiation phase. Monte Carlo Simulation is a valuable methodology in this context since it allows delimiting and exploring a complex parameter space in a transparent and relatively easily visualized manner. With timely analyses it is possible to identify both technical and economic risks and minimize the possible consequences, a process that benefits both parties in the negotiation process. This paper describes a part of this process in connection with the negotiation of a PBL contract for the Swedish Air Force SAAB 105 (SK 60) trainer fleet between Saab AB and the Swedish Defence Materiel Administration (FMV). The information used in the simulations was largely empirical data derived from previous operations of the aircraft system. The main factors that were simulated were operational requirements, fleet size, spares inventories, turn-around times, failure rates and influence of extraneous factors (e. g. weather). The simulations resulted in considerable savings due to reduction of the active fleet size, and increased reclamation of surplus spares and units from retired aircraft.
|
|
| 16. |
- Block, Linda, et al.
(author)
-
Ultralow Dose of Naloxone as an Adjuvant to Intrathecal Morphine Infusion Improves Perceived Quality of Sleep but Fails to alter Persistent Pain: A Randomized, Double-blind, Controlled Study.
- 2015
-
In: The Clinical journal of pain. - 1536-5409. ; 31:11, s. 968-975
-
Journal article (peer-reviewed)abstract
- This randomized, cross-over, double-blind, controlled study of continuous intrathecal morphine administration in patients with severe, long-term pain addresses whether the supplementation of low doses of naloxone in this setting is associated with beneficial clinical effects. All of the study subjects (n=11) provided informed consent and were recruited from a subset of patients who were already undergoing long-term treatment with continuous intrathecal morphine because of difficult-to-treat pain. The patients were (in a randomized order) also given intrathecal naloxone (40 ng/24 h or 400 ng/24 h). As control, the patients' ordinary dose of morphine without any additions was used. The pain (Numeric Rating Scale, NRS) during activity, perceived quality of sleep, level of activity and quality of life as well as the levels of several pro- and anti-inflammatory cytokines in the blood were assessed. The pre-study pain (NRS during activity) in the study group ranged from 3 to 10. 64% of the subjects reported improved quality of sleep during treatment with naloxone at a dose of 40 ng/24 hours compared with 9% with sham treatment (P=0.024). Although not statistically significant, pain was reduced by 2 NRS steps or more during supplemental treatment with naloxone in 36% of subjects when using the 40 ng/24 hours dose and in 18% of the subjects when using a naloxone 400 ng/24 hours dose. The corresponding percentage among patients receiving unaltered treatment was 27%. To conclude, the addition of an ultralow dose of intrathecal naloxone (40 ng/24 h) to intrathecal morphine infusion in patients with severe, persistent pain improves perceived quality of sleep. We were not able to show any statistically significant effects of naloxone on pain relief, level of activity or quality of life.This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivitives 3.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially. http://creativecommons.org/licenses/by-nc-nd/3.0.
|
|
| 17. |
- Garmabaki, Amir, et al.
(author)
-
A Reliability Decision Framework for Multiple Repairable Units
- 2016
-
In: Reliability Engineering & System Safety. - : Elsevier BV. - 0951-8320 .- 1879-0836. ; 150, s. 78-88
-
Journal article (peer-reviewed)abstract
- In practice, the analyst is often dealing with multiple repairable units, installed in different positions or functioning under different operating conditions, and maintained by different disciplines. This paper presents a decision framework to identify an appropriate reliability model for massive multiple repairable units. It splits non-homogeneous failure data into homogeneous groups and classifies them based on their failure trends using statistical tests. The framework discusses different scenarios for analysing multiple repairable units, according to trend, intensity, and dependency of the units’ failure data. The proposed framework has been verified in a fleet of aircraft and in two simulated data sets. The results show a reliability model of multiple repairable units may contain a mixture of different stochastic models. Considering single reliability models for such populations may cause erroneous calculation of the time to failure of a particular unit, which can, in turn, lead to faulty conclusions and decisions. When dealing with massive and non-homogeneous multiple repairable units, the application of the proposed framework can facilitate the selection of an appropriate reliability model.
|
|
| 18. |
- Garmabaki, Amir Soleimani, et al.
(author)
-
Fleet-level reliability estimation of repairable units
- 2015
-
In: Safety and Reliability. - London : CRC Press. - 9781138026810 ; , s. 1977-1982
-
Conference paper (peer-reviewed)abstract
- This paper investigates reliability analysis of a repairable unit at fleet level. In fleet, multiple similar systems are running in different operating environments. In fact, due to the highly censored data as well as high variations in failure rate within the fleet, merging the datasets becomes a challenge. The non-parametric analysis is used to capture the failure trend of repairable units at fleet level. Consequently, fleet data have been aggregated and the actual number of failure has been compared with the expected total number of failures. In addition, parametric models are used to model the reliability trend obtained through a non-parametric approach to identify the reliability parameters at fleet level. Real data are used to demonstrate the applicability and validity of the proposed method. Results shows the accuracy of log-linear process is reasonably acceptable.
|
|
| 19. |
- Rupert, Deborah, 1986, et al.
(author)
-
Determination of exosome concentration in solution using surface plasmon resonance spectroscopy.
- 2014
-
In: Analytical Chemistry. - : American Chemical Society (ACS). - 0003-2700 .- 1520-6882. ; 86:12, s. 5929-5936
-
Journal article (peer-reviewed)abstract
- Exosomes are cell-secreted nanometer-sized extracellular vesicles that have been reported to play an important role in intercellular communication. They are also considered potential diagnostic markers for various health disorders, and intense investigations are presently directed towards their use as carriers in drug-delivery and gene-therapy applications. This has generated a growing need for sensitive methods capable of accurately and specifically determining the concentration of exosomes in complex biological fluids. Here, we explore the use of label-free surface-based sensing with surface plasmon resonance (SPR) read-out to determine the concentration of exosomes in solution. Human mast cell secreted exosomes carrying the tetraspanin membrane protein CD63 were analyzed by measuring their diffusion-limited binding rate to an SPR sensor surface functionalized with anti-CD63 antibodies. The concentration of suspended exosomes was determined by first converting the SPR response into surface-bound mass. The increase in mass uptake over time was then related to the exosome concentration in solution using a formalism describing diffusion-limited binding under controlled flow conditions. The proposed quantification method is based on a calibration and control measurements performed with proteins and synthetic lipid vesicles and takes into account i) the influence of the broad size distribution of the exosomes on the surface coverage, ii) the fact that their size is comparable to the ~150 nm probing depth of SPR, and iii) possible deformation of exosomes upon adsorption. Under those considerations, the accuracy of the concentration determination was estimated to be better than ±50% and significantly better if exosome deformation is negligible.
|
|
| 20. |
- Rupert, Deborah, 1986, et al.
(author)
-
Dual-Wavelength Surface Plasmon Resonance for Determining the Size and Concentration of Sub-Populations of Extracellular Vesicles
- 2016
-
In: Analytical Chemistry. - : American Chemical Society (ACS). - 0003-2700 .- 1520-6882. ; 88:20, s. 9980-9988
-
Journal article (peer-reviewed)abstract
- Accurate concentration determination of subpopulations of extracellular vesicles (EVs), such as exosomes, is of importance both in the context of understanding their fundamental biological role and of potentially using them as disease biomarkers. In principle, this can be achieved by measuring the rate of diffusion-limited mass uptake to a sensor surface modified with a receptor designed to only bind the subpopulation of interest. However, a significant error is introduced if the targeted EV subpopulation has a size, and thus hydrodynamic diffusion coefficient, that differs from the mean size and diffusion coefficient of the whole EV population and/or if the EVs become deformed upon binding to the surface. We here demonstrate a new approach to determine the mean size (or effective film thickness) of bound nanoparticles, in general, and EV subpopulation carrying a marker of interest, in particular. The method is based on operating surface plasmon resonance simultaneously at two wavelengths with different sensing depths and using the ratio of the corresponding responses to extract the particle size on the surface. By estimating in this way the degree of deformation of adsorbed EVs, we markedly improved their bulk concentration determination and showed that EVs carrying the exosomal marker CD63 correspond to not more than around 10% of the EV sample.
|
|
| 21. |
- Rupert, Deborah, 1986, et al.
(author)
-
Effective Refractive Index and Lipid Content of Extracellular Vesicles Revealed Using Optical Waveguide Scattering and Fluorescence Microscopy
- 2018
-
In: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 34:29, s. 8522-8531
-
Journal article (peer-reviewed)abstract
- Extracellular vesicles (EVs) are generating a growing interest because of the key roles they play in various biological processes and because of their potential use as biomarkers in clinical diagnostics and as efficient carriers in drug-delivery and gene-therapy applications. Their full exploitation, however, depends critically on the possibility to classify them into different subpopulations, a task that in turn relies on efficient means to identify their unique biomolecular and physical signatures. Because of the large heterogeneity of EV samples, such information remains rather elusive, and there is accordingly a need for new and complementary characterization schemes that can help expand the library of distinct EV features. In this work, we used surface-sensitive waveguide scattering microscopy with single EV resolution to characterize two subsets of similarly sized EVs that were preseparated based on their difference in buoyant density. Unexpectedly, the scattering intensity distribution revealed that the scattering intensity of the high-density (HD) population was on an average a factor of three lower than that of the low-density (LD) population. By further labeling the EV samples with a self-inserting lipid-membrane dye, the scattering and fluorescence intensities from EVs could be simultaneously measured and correlated at the single-particle level. The labeled HD sample exhibited not only lower fluorescence and scattering intensities but also lower effective refractive index (n approximate to 1.35) compared with the LD EVs (n approximate to 1.38), indicating that both the lipid and protein contents were indeed lower in the HD EVs. Although separation in density gradients of similarly sized EVs is usually linked to differences in biomolecular content, we suggest based on these observations that the separation rather reflects the ability of the solute of the gradient to penetrate the lipid membrane enclosing the EVs, that is, the two gradient bands are more likely because of the differences in membrane permeability than to differences in biomolecular content of the EVs.
|
|
| 22. |
- Shrestha, Sarita, 1991-, et al.
(author)
-
The use of ICD codes to identify IBD subtypes and phenotypes of the Montreal classification in the Swedish National Patient Register
- 2020
-
In: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 55:4, s. 430-435
-
Journal article (peer-reviewed)abstract
- Introduction: Whether data on International Classification of Diseases (ICD)-codes from the Swedish National Patient Register (NPR) correctly correspond to subtypes of inflammatory bowel disease (IBD) and phenotypes of the Montreal classification scheme among patients with prevalent disease is unknown. Materials and methods: We obtained information on IBD subtypes and phenotypes from the medical records of 1403 patients with known IBD who underwent biological treatment at ten Swedish hospitals and retrieved information on their IBD-associated diagnostic codes from the NPR. We used previously described algorithms to define IBD subtypes and phenotypes. Finally, we compared these register-generated subtypes and phenotypes with the corresponding information from the medical records and calculated positive predictive values (PPV) with 95% confidence intervals. Results: Among patients with clinically confirmed disease and diagnostic listings of IBD in the NPR (N = 1401), the PPV was 97 (96-99)% for Crohn's disease, 98 (97-100)% for ulcerative colitis, and 8 (4-11)% for IBD-unclassified. The overall accuracy for age at diagnosis was 95% (when defined as A1, A2, or A3). Examining the validity of codes representing disease phenotype, the PPV was 36 (32-40)% for colonic Crohn's disease (L2), 61 (56-65)% for non-stricturing/non-penetrating Crohn's disease behaviour (B1) and 83 (78-87)% for perianal disease. Correspondingly, the PPV was 80 (71-89)% for proctitis (E1)/left-sided colitis (E2) in ulcerative colitis. Conclusions: Among people with known IBD, the NPR is a reliable source of data to classify most subtypes of prevalent IBD, even though misclassification commonly occurred in Crohn's disease location and behaviour and also among IBD-unclassified patients.
|
|
| 23. |
- Wijk, Olle, et al.
(author)
-
Phase-out maintenance optimization for an aircraft fleet
- 2017
-
In: International Journal of Production Economics. - : Elsevier. - 0925-5273 .- 1873-7579. ; 188, s. 105-115
-
Journal article (peer-reviewed)abstract
- This paper presents a novel approach for cost-effective optimization of stop-maintenance strategies for a set of repairable items (rotables). The optimization method has two steps. First, the novel concept of matrix simulations is introduced to locate the solution space of the optimization problem in question. Second, a genetic algorithm is applied to find the minimum cost solution. The combination of matrix simulations and genetic algorithm is shown to constitute a powerful method for solving the optimization problem in a fast manner. To demonstrate the efficacy of the proposed method, it is compared with a crude search, and a steepest descent algorithm. Our proposed method is faster than the crude search and also locates the optimum more often than the steepest descent search. The method is illustrated by applying it to a phase-out scenario of an aircraft fleet, where the optimal stop-maintenance strategy is determined for a set of rotables.
|
|
