| 1. |
- Aidemark, Mari, et al.
(författare)
-
Trichoderma viride cellulase induces resistance to the antibiotic pore-forming peptide alamethicin associated with changes in the plasma membrane lipid composition of tobacco BY-2 cells
- 2010
-
Ingår i: Bmc Plant Biology. - : Springer Science and Business Media LLC. - 1471-2229. ; 10
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Alamethicin is a membrane-active peptide isolated from the beneficial root-colonising fungus Trichoderma viride. This peptide can insert into membranes to form voltage-dependent pores. We have previously shown that alamethicin efficiently permeabilises the plasma membrane, mitochondria and plastids of cultured plant cells. In the present investigation, tobacco cells (Nicotiana tabacum L. cv Bright Yellow-2) were pre-treated with elicitors of defence responses to study whether this would affect permeabilisation. Results: Oxygen consumption experiments showed that added cellulase, already upon a limited cell wall digestion, induced a cellular resistance to alamethicin permeabilisation. This effect could not be elicited by xylanase or bacterial elicitors such as flg22 or elf18. The induction of alamethicin resistance was independent of novel protein synthesis. Also, the permeabilisation was unaffected by the membrane-depolarising agent FCCP. As judged by lipid analyses, isolated plasma membranes from cellulase-pretreated tobacco cells contained less negatively charged phospholipids ( PS and PI), yet higher ratios of membrane lipid fatty acid to sterol and to protein, as compared to control membranes. Conclusion: We suggest that altered membrane lipid composition as induced by cellulase activity may render the cells resistant to alamethicin. This induced resistance could reflect a natural process where the plant cells alter their sensitivity to membrane pore-forming agents secreted by Trichoderma spp. to attack other microorganisms, and thus adding to the beneficial effect that Trichoderma has for plant root growth. Furthermore, our data extends previous reports on artificial membranes on the importance of lipid packing and charge for alamethicin permeabilisation to in vivo conditions.
|
|
| 2. |
- Andreasson, Martin, et al.
(författare)
-
Correlated Failures of Power Systems : Analysis of the Nordic Grid
- 2011
-
Ingår i: Preprints of Workshop on Foundations of Dependable and Secure Cyber-Physical Systems.
-
Konferensbidrag (refereegranskat)abstract
- In this work we have analyzed the effectsof correlated failures of power lines on the total systemload shed. The total system load shed is determined bysolving the optimal load shedding problem, which is thesystem operator’s best response to a system failure.We haveintroduced a Monte Carlo based simulation framework forestimating the statistics of the system load shed as a functionof stochastic network parameters, and provide explicitguarantees on the sampling accuracy. This framework hasbeen applied to a 470 bus model of the Nordic power systemand a correlated Bernoulli failure model. It has been foundthat increased correlations between Bernoulli failures ofpower lines can dramatically increase the expected valueas well as the variance of the system load shed.
|
|
| 3. |
- Andreasson, Martin, et al.
(författare)
-
Distributed Control of Networked Dynamical Systems : Static Feedback, Integral Action and Consensus
- 2014
-
Ingår i: IEEE Transactions on Automatic Control. - 0018-9286 .- 1558-2523. ; 59:7, s. 1750-1764
-
Tidskriftsartikel (refereegranskat)abstract
- This paper analyzes distributed control protocols for first- and second-order networked dynamical systems. We propose a class of nonlinear consensus controllers where the input of each agent can be written as a product of a nonlinear gain, and a sum of nonlinear interaction functions. By using integral Lyapunov functions, we prove the stability of the proposed control protocols, and explicitly characterize the equilibrium set. We also propose a distributed proportional-integral (PI) controller for networked dynamical systems. The PI controllers successfully attenuate constant disturbances in the network. We prove that agents with single-integrator dynamics are stable for any integral gain, and give an explicit tight upper bound on the integral gain for when the system is stable for agents with double-integrator dynamics. Throughout the paper we highlight some possible applications of the proposed controllers by realistic simulations of autonomous satellites, power systems and building temperature control.
|
|
| 4. |
- Andreasson, Martin, et al.
(författare)
-
Distributed integral action : stability analysis and frequency control of power systems
- 2012
-
Ingår i: 2012 IEEE 51st Annual Conference on Decision and Control (CDC). - : IEEE. - 9781467320665 ; , s. 2077-2083
-
Konferensbidrag (refereegranskat)abstract
- This paper analyzes distributed proportional-integral controllers. We prove that integral action can be successfully applied to consensus algorithms, where attenuation of static disturbances is achieved. These control algorithms are applied to decentralized frequency control of electrical power systems. We show that the proposed algorithm can attenuate step disturbances of power loads. We provide simulations of the proposed control algorithm on the IEEE 30 bus test system that demonstrate its efficiency.
|
|
| 5. |
- Bjerke, Maria, 1977, et al.
(författare)
-
Confounding factors influencing amyloid Beta concentration in cerebrospinal fluid.
- 2010
-
Ingår i: International journal of Alzheimer's disease. - : Hindawi Limited. - 2090-0252. ; 2010
-
Tidskriftsartikel (refereegranskat)abstract
- Background. Patients afflicted with Alzheimer's disease (AD) exhibit a decrease in the cerebrospinal fluid (CSF) concentration of the 42 amino acid form of beta-amyloid (Abeta(42)). However, a high discrepancy between different centers in measured Abeta(42) levels reduces the utility of this biomarker as a diagnostic tool and in monitoring the effect of disease modifying drugs. Preanalytical and analytical confounding factors were examined with respect to their effect on the measured Abeta(42) level. Methods. Aliquots of CSF samples were either treated differently prior to Abeta(42) measurement or analyzed using different commercially available xMAP or ELISA assays. Results. Confounding factors affecting CSF Abeta(42) levels were storage in different types of test tubes, dilution with detergent-containing buffer, plasma contamination, heat treatment, and the origin of the immunoassays used for quantification. Conclusion. In order to conduct multicenter studies, a standardized protocol to minimize preanalytical and analytical confounding factors is warranted.
|
|
| 6. |
- Constantinescu, Radu, 1966, et al.
(författare)
-
Proteomic profiling of cerebrospinal fluid in parkinsonian disorders.
- 2010
-
Ingår i: Parkinsonism & related disorders. - : Elsevier BV. - 1873-5126 .- 1353-8020. ; :16, s. 545-49
-
Tidskriftsartikel (refereegranskat)abstract
- Parkinson's disease (PD) and atypical parkinsonian disorders (APD), including multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD), are a group of neurodegenerative diseases sharing many similar signs and symptoms but distinguished by their particular clinical features, treatment response, prognosis and mortality. The differential diagnosis may be challenging, especially in early disease stages. Considering the importance of an accurate diagnosis both for clinical management and for research, new diagnostic tools are needed. In this study, we investigated 56 PD, 42 MSA, 39 PSP, 9 CBD patients, and 24 healthy controls. After screening the cerebrospinal fluid (CSF) proteome using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS), we identified 4 proteins (ubiquitin [mass-to-charge ratio (m/z) 8590], beta2-microglobulin [m/z 11730], and 2 secretogranin 1 [chromogranin B] fragments [m/z 7260 and m/z 6250]) that differentiated healthy controls and PD patients from patients with APD. However, they could not differentiate PD patients from controls. As none of these changes were APD subgroup-specific, they most likely reflect the intensity and/or extent of the neurodegenerative process in general.
|
|
| 7. |
- Hesse, Camilla, et al.
(författare)
-
The N-terminal domain of α-dystroglycan is released as a 38kDa protein and is increased in cerebrospinal fluid in patients with Lyme neuroborreliosis.
- 2011
-
Ingår i: Biochemical and biophysical research communications. - : Elsevier BV. - 1090-2104 .- 0006-291X. ; 412:3, s. 494-499
-
Tidskriftsartikel (refereegranskat)abstract
- α-Dystroglycan is an extracellular adhesion protein that is known to interact with different ligands. The interaction is thought to stabilize the integrity of the plasma membrane. The N-terminal part of α-dystroglycan may be proteolytically processed to generate a small 38kDa protein (α-DG-N). The physiological significance of α-DG-N is unclear but has been suggested to be involved in nerve regeneration and myelination and to function as a potential biomarker for neurodegenerative and neuromuscular diseases. In this report we show that α-DG-N is released into different body fluids, such as lachrimal fluid, cerebrospinal fluid (CSF), urine and plasma. To investigate the significance of α-DG-N in CSF we examined the levels of α-DG-N and known neurodegenerative markers in CSF from patients diagnosed with Lyme neuroborreliosis (LNB) and healthy controls. In untreated acute phase LNB patients, 67% showed a significant increase of CSF α-DG-N compared to healthy controls. After treatment with antibiotics the CSF α-DG-N levels were normalized in the LNB patients.
|
|
| 8. |
- Parnetti, L, et al.
(författare)
-
Changes in CSF acetyl- and butyrylcholinesterase activity after long-term treatment with AChE inhibitors in Alzheimer's disease.
- 2011
-
Ingår i: Acta neurologica Scandinavica. - : Hindawi Limited. - 1600-0404 .- 0001-6314. ; 124:2, s. 122-129
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives - To measure cerebrospinal fluid (CSF) activity of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in patients with Alzheimer's disease (AD) participating in randomized clinical trials from three European centers, before and after long-term treatment with different AChE inhibitors (AChEIs). Materials and methods - Of the 144 patients included in the study, 104 were treated with donepezil, 15 with galantamine, 16 with rivastigmine, and nine with placebo. CSF AChE and BChE activities were measured at baseline and after 1-year treatment. Results - Donepezil and galantamine groups showed a significant increase in CSF AChE activity at follow-up, while no changes for BChE activity were observed; in donepezil group, a positive correlation between plasma concentration and AChE activity was documented. Conversely, in rivastigmine group, a decrease in CSF activity of both enzymes was observed. CSF AChE and BChE activities were not correlated with the clinical outcome in any group considered. CSF biomarkers did not show any change after treatment. Conclusions - AChEIs differently influence the activity of target enzymes in CSF independent of their pharmacodynamic effects.
|
|
| 9. |
- Rosén, Christoffer, 1986, et al.
(författare)
-
Increased Levels of Chitotriosidase and YKL-40 in Cerebrospinal Fluid from Patients with Alzheimer's Disease.
- 2014
-
Ingår i: Dementia and geriatric cognitive disorders extra. - : S. Karger AG. - 1664-5464. ; 4:2, s. 297-304
-
Tidskriftsartikel (refereegranskat)abstract
- The cerebrospinal fluid (CSF) biomarkers total tau, abnormally phosphorylated tau and amyloid β 1-42 are strongly associated with Alzheimer's disease (AD). Apart from the pathologic hallmarks that these biomarkers represent, other processes such as inflammation and microglial activation are present in the brains of patients with AD. New biomarkers related to these processes could be valuable for the diagnosis and follow-up of AD patients and for the evaluation of inflammation-related pathologies.
|
|
| 10. |
- Alves, Guido, et al.
(författare)
-
Cerebrospinal fluid amyloid-β and phenotypic heterogeneity in de novo Parkinson's disease.
- 2013
-
Ingår i: Journal of neurology, neurosurgery, and psychiatry. - : BMJ. - 1468-330X .- 0022-3050. ; 84:5, s. 537-43
-
Tidskriftsartikel (refereegranskat)abstract
- In Parkinson's disease (PD), the motor presentation characterised by postural instability/gait difficulties (PIGD) heralds accelerated motor, functional and cognitive decline, as compared with the more benign tremor-dominant (TD) variant. This makes the PIGD complex an attractive target for the discovery of prognostic biomarkers in PD.
|
|
| 11. |
- Alves, G., et al.
(författare)
-
CSF A beta(42) predicts early-onset dementia in Parkinson disease
- 2014
-
Ingår i: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 82:20, s. 1784-1790
-
Tidskriftsartikel (refereegranskat)abstract
- Objective:To test in vivo the proposal from clinicopathologic studies that -amyloid (A) pathology shortens the time to dementia in Parkinson disease (PD), and to explore the utility of CSF A and related measures as early prognostic biomarkers of dementia in an incident PD cohort.Methods:We assessed a population-based incident cohort of 104 patients with PD who underwent lumbar puncture at diagnosis. We analyzed CSF concentrations of A42, A40, and A38 using a multiplexed immunoassay with electrochemiluminescence (ECL) detection and levels of A42, total tau, and phosphorylated tau using ELISA. Patients were followed prospectively for 5 years. Dementia was diagnosed according to published criteria.Results:CSF levels of A42 were significantly decreased in patients who developed dementia (n = 20, 19.2%) compared to those who did not (n = 84, 80.8%), as measured by ECL (-33%, p = 0.006) as well as ELISA (-36%, p < 0.001). No differences were observed for other markers. Low A42 values predicted a substantially increased risk for subsequent dementia at high sensitivity (85%), with hazard ratios of 9.9 (95% confidence interval 2.3-43.5, p = 0.002) for A42(ECL) <376 pg/mL and 7.6 (2.2-26.4, p = 0.001) for A42(ELISA) <443 pg/mL, after adjustment for baseline age and PD-mild cognitive impairment (MCI) status. A42 reductions tended to precede the onset of PD-MCI that progressed to dementia.Conclusions:These in vivo data support the role of A pathology in the etiology and highlight the potential utility of CSF A42 as an early prognostic biomarker of dementia associated with PD.
|
|
| 12. |
- Alves, Guido, et al.
(författare)
-
CSF amyloid-β and tau proteins, and cognitive performance, in early and untreated Parkinson's Disease: the Norwegian ParkWest study
- 2010
-
Ingår i: Journal of neurology, neurosurgery, and psychiatry. - : BMJ. - 1468-330X .- 0022-3050. ; 81:10, s. 1080-1086
-
Tidskriftsartikel (refereegranskat)abstract
- Background Alzheimer's disease (AD) pathology is found in a considerable portion of patients with Parkinson's disease (PD), particularly those with early dementia (PDD). Altered cerebrospinal fluid (CSF) levels of amyloid-beta (Abeta) and tau proteins have been found in PDD, with intermediate changes for Abeta42 in non-demented PD. The authors investigated whether AD-related CSF protein levels are altered and relate to neuropsychological performance in early, untreated PD. Methods CSF concentrations of Abeta42, Abeta40 and Abeta38 were measured by electrochemiluminiscene and levels of total tau (T-tau) and phosphorylated tau (P-tau) by ELISA in 109 newly diagnosed, unmedicated, non-demented, community-based PD patients who had undergone comprehensive neuropsychological testing, and were compared with those of 36 age-matched normal controls and 20 subjects with mild AD. Results PD patients displayed significant reductions in Abeta42 (19%; p=0.009), Abeta40 (15.5%; p=0.008) and Abeta38 (23%; p=0.004) but not T-tau (p=0.816) or P-tau (p=0.531) compared with controls. CSF Abeta42 reductions in PD were less marked than in AD (53%; p=0.002). Sequential regression analyses demonstrated significant associations between CSF levels of Abeta42 (beta=0.205; p=0.019), Abeta40 (beta=0.378; p<0.001) and Abeta38 (beta=0.288; p=0.001) and memory impairment, but not executive-attentional or visuospatial dysfunction. Tau protein levels did not correlate with cognitive measures. Conclusion CSF Abeta levels are altered in a subset of patients with early PD and relate to memory impairment. Our study suggests that alterations in Abeta protein metabolism may contribute to the heterogeneity in pattern and course of cognitive decline associated with PD. Longitudinal studies are needed to clarify the clinical significance of CSF Abeta peptides as prognostic biomarkers in PD.
|
|
| 13. |
- Alves, Guido, et al.
(författare)
-
CSF Aβ42 predicts early-onset dementia in Parkinson disease.
- 2014
-
Ingår i: Neurology. - 1526-632X. ; 82:20, s. 1784-90
-
Tidskriftsartikel (refereegranskat)abstract
- To test in vivo the proposal from clinicopathologic studies that β-amyloid (Aβ) pathology shortens the time to dementia in Parkinson disease (PD), and to explore the utility of CSF Aβ and related measures as early prognostic biomarkers of dementia in an incident PD cohort.
|
|
| 14. |
- Andreasson, Eskil, et al.
(författare)
-
Integrating Moldflow and Abaqus in the Package Simulation Workflow
- 2013
-
Konferensbidrag (refereegranskat)abstract
- Tetra Pak has used numerical simulation tools for plastic injection molding (Moldflow) and structural analysis (Abaqus/Implicit and Abaqus/Explicit) for many years. Today these two simulation tools are used independently of each other without any coupling. How these two disciplines can be combined to better predict the mechanical response of a polymer component is presented in this work. The manufacturing process, in this case injection molding, creates the mechanical properties of the produced polymer part. Process settings, material selection and molding tool geometry affect the polymer flow, material orientation and rate of crystallinity. A method to build a layered finite element model in Abaqus using results from Moldflow simulations regarding crystallinity growth and molecular orientation is proposed. Relatively simple material models were utilized and assigned for each individual material layer through the thickness in the polymer part. These constitutive models were derived phenomenologically from experimental test results and could adequately capture both the microscopic and the macroscopic behavior in a more realistic way. The numerical results showed a good agreement with the experimental results, both regarding visual appearance and force/displacement response.
|
|
| 15. |
- Andreasson, Henrik, 1977-, et al.
(författare)
-
6D scan registration using depth-interpolated local image features
- 2010
-
Ingår i: Robotics and Autonomous Systems. - Amsterdam, Netherlands : Elsevier. - 0921-8890 .- 1872-793X. ; 58:2, s. 157-165
-
Tidskriftsartikel (refereegranskat)abstract
- This paper describes a novel registration approach that is based on a combination of visual and 3D range information.To identify correspondences, local visual features obtained from images of a standard color camera are compared and the depth of matching features (and their position covariance) is determined from the range measurements of a 3D laserscanner. The matched depth-interpolated image features allows to apply registration with known correspondences.We compare several ICP variants in this paper and suggest an extension that considers the spatial distance betweenmatching features to eliminate false correspondences. Experimental results are presented in both outdoor and indoor environments. In addition to pair-wise registration, we also propose a global registration method that registers allscan poses simultaneously.
|
|
| 16. |
- Andreasson, Henrik, 1977-, et al.
(författare)
-
Drive the Drive : From Discrete Motion Plans to Smooth Drivable Trajectories
- 2014
-
Ingår i: Robotics. - Basel, Switzerland : M D P I AG. - 2218-6581. ; 3:4, s. 400-416
-
Tidskriftsartikel (refereegranskat)abstract
- Autonomous navigation in real-world industrial environments is a challenging task in many respects. One of the key open challenges is fast planning and execution of trajectories to reach arbitrary target positions and orientations with high accuracy and precision, while taking into account non-holonomic vehicle constraints. In recent years, lattice-based motion planners have been successfully used to generate kinematically and kinodynamically feasible motions for non-holonomic vehicles. However, the discretized nature of these algorithms induces discontinuities in both state and control space of the obtained trajectories, resulting in a mismatch between the achieved and the target end pose of the vehicle. As endpose accuracy is critical for the successful loading and unloading of cargo in typical industrial applications, automatically planned paths have not been widely adopted in commercial AGV systems. The main contribution of this paper is a path smoothing approach, which builds on the output of a lattice-based motion planner to generate smooth drivable trajectories for non-holonomic industrial vehicles. The proposed approach is evaluated in several industrially relevant scenarios and found to be both fast (less than 2 s per vehicle trajectory) and accurate (end-point pose errors below 0.01 m in translation and 0.005 radians in orientation).
|
|
| 17. |
- Andreasson, Henrik, 1977-, et al.
(författare)
-
Gold-fish SLAM : An application of SLAM to localize AGVs
- 2014
-
Ingår i: Field and Service Robotics. - Heidelberg : Springer. - 9783642406850 - 9783642406867 ; , s. 585-598
-
Konferensbidrag (refereegranskat)abstract
- The main focus of this paper is to present a case study of a SLAM solution for Automated Guided Vehicles (AGVs) operating in real-world industrial environments. The studied solution, called Gold-fish SLAM, was implemented to provide localization estimates in dynamic industrial environments, where there are static landmarks that are only rarely perceived by the AGVs. The main idea of Gold-fish SLAM is to consider the goods that enter and leave the environment as temporary landmarks that can be used in combination with the rarely seen static landmarks to compute online estimates of AGV poses. The solution is tested and verified in a factory of paper using an eight ton diesel-truck retrofitted with an AGV control system running at speeds up to 3m/s. The paper includes also a general discussion on how SLAM can be used in industrial applications with AGVs. © Springer-Verlag Berlin Heidelberg 2014.
|
|
| 18. |
- Andreasson, Henrik, 1977-, et al.
(författare)
-
Gold-fish SLAM : an application of SLAM to localize AGVs
- 2012
-
Ingår i: Proceedings of the International Conference on Field and Service Robotics (FSR), July 2012..
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The main focus of this paper is to present a case study of a SLAM solution for Automated Guided Vehicles (AGVs) operating in real-world industrial environ- ments. The studied solution, called Gold-fish SLAM, was implemented to provide localization estimates in dynamic industrial environments, where there are static landmarks that are only rarely perceived by the AGVs. The main idea of Gold-fish SLAM is to consider the goods that enter and leave the environment as temporary landmarks that can be used in combination with the rarely seen static landmarks to compute online estimates of AGV poses. The solution is tested and verified in a factory of paper using an eight ton diesel-truck retrofitted with an AGV control sys- tem running at speeds up to 3 meters per second. The paper includes also a general discussion on how SLAM can be used in industrial applications with AGVs.
|
|
| 19. |
- Andreasson, Helena, et al.
(författare)
-
Predictors of length of stay in forensic psychiatry: The influence of perceived risk of violence
- 2014
-
Ingår i: International Journal of Law and Psychiatry. - : Elsevier BV. - 0160-2527. ; 37:6, s. 635-642
-
Tidskriftsartikel (refereegranskat)abstract
- This study describes the prevalence of adverse events and length of stay in forensic psychiatric patients with and without a restriction order. Detailed clinical and administrative information from medical records and written court decisions was gathered retrospectively from admission until discharge for a Swedish population-based, consecutive cohort of forensic psychiatric patients (n = 125). The median length of stay for the whole cohort was 951 days, but patients with a restriction order stayed in hospital almost five times as long as patients without. Restriction orders were related to convictions for violent crime, but not for any other differences in demographic or clinical variables. The majority of the patients (60%) were involved in adverse events (violence, threats, substance abuse, or absconding) at some time during their treatment. Patients with restriction orders were overrepresented in violent and threat events. Previous contact with child and adolescence psychiatric services, current violent index crime, psychotic disorders, a history of substance, and absconding during treatment predicted longer length of stay. Being a parent, high current Global Assessment of Functioning scores, and mood disorders were all significantly related to earlier discharge. In a stepwise Cox regression analysis current violent index crime and absconding remained risk factors for a longer hospital stay, while a diagnosis of mood disorder was significantly related to a shorter length of stay.
|
|
| 20. |
- Andreasson, Henrik, 1977-, et al.
(författare)
-
Real time registration of RGB-D data using local visual features and 3D-NDT registration
- 2012
-
Ingår i: Proc. of International Conference on Robotics and Automation (ICRA) Workshop on Semantic Perception, Mapping and Exploration (SPME). - : IEEE. - 9781467314039
-
Konferensbidrag (refereegranskat)abstract
- Recent increased popularity of RGB-D capable sensors in robotics has resulted in a surge of related RGBD registration methods. This paper presents several RGB-D registration algorithms based on combinations between local visual feature and geometric registration. Fast and accurate transformation refinement is obtained by using a recently proposed geometric registration algorithm, based on the Three-Dimensional Normal Distributions Transform (3D-NDT). Results obtained on standard data sets have demonstrated mean translational errors on the order of 1 cm and rotational errors bellow 1 degree, at frame processing rates of about 15 Hz.
|
|
| 21. |
- Andreasson, Martin, 1987-, et al.
(författare)
-
Control of MTDC Transmission Systems under Local Information
- 2014
-
Ingår i: Decision and Control (CDC), 2014 IEEE 53rd Annual Conference on. - : IEEE conference proceedings. - 9781479977468 ; , s. 1335-1340
-
Konferensbidrag (refereegranskat)abstract
- High-voltage direct current (HVDC) is a commonly used technology for long-distance electric power transmission, mainly due to its low resistive losses. In this paper a distributed controller for multi-terminal high-voltage direct current (MTDC) transmission systems is considered. Sufficient conditions for when the proposed controller renders the closed-loop system asymptotically stable are provided. Provided that the closed loop system is asymptotically stable, it is shown that in steady-state a weighted average of the deviations from the nominal voltages is zero. Furthermore, a quadratic cost of the current injections is minimized asymptotically.
|
|
| 22. |
- Andreasson, Martin, et al.
(författare)
-
Distributed PI-Control with Applications to Power Systems Frequency Control
- 2014
-
Ingår i: American Control Conference (ACC), 2014. - : IEEE conference proceedings. - 9781479932740 ; , s. 3183-3188
-
Konferensbidrag (refereegranskat)abstract
- This paper considers a distributed PI-controller for networked dynamical systems. Sufficient conditions for when the controller is able to stabilize a general linear system and eliminate static control errors are presented. The proposed controller is applied to frequency control of power transmission systems. Sufficient stability criteria are derived, and it is shown that the controller parameters can always be chosen so that the frequencies in the closed loop converge to nominal operational frequency. We show that the load sharing property of the generators is maintained, i.e., the input power of the generators is proportional to a controller parameter. The controller is evaluated by simulation on the IEEE 30 bus test network, where its effectiveness is demonstrated.
|
|
| 23. |
- Andreasson, Martin, 1987-, et al.
(författare)
-
Distributed Voltage and Current Control of Multi-Terminal High-Voltage Direct Current Transmission Systems
- 2014
-
Ingår i: Proceedings of the 19th IFAC World Congress, 2014. - : IFAC Papers Online. ; , s. 11910-11916
-
Konferensbidrag (refereegranskat)abstract
- High-voltage direct current (HVDC) is a commonly used technology for long-distance power transmission, due to its low resistive losses and low costs. In this paper, a novel distributed controller for multi-terminal HVDC (MTDC) systems is proposed. Under certain conditions on the controller gains, it is shown to stabilize the MTDC system. The controller is shown to always keep the voltages close to the nominal voltage, while assuring that the injected power is shared fairly among the converters. The theoretical results are validated by simulations, where the affect of communication time-delays is also studied.
|
|
| 24. |
- Andreasson, Martin, 1987-, et al.
(författare)
-
Distributed vs. centralized power systems frequency control
- 2013
-
Ingår i: 2013 European Control Conference, ECC 2013. - : IEEE. - 9783033039629 ; , s. 3524-3529
-
Konferensbidrag (refereegranskat)abstract
- This paper considers a distributed control algorithm for frequency control of electrical power systems. We propose a distributed controller which retains the reference frequency of the buses under unknown load changes, while asymptotically minimizing a quadratic cost of power generation. For comparison, we also propose a centralized controller which also retains the reference frequency while minimizing the same cost of power generation. We derive sufficient stability criteria for the parameters of both controllers. The controllers are evaluated by simulation on the IEEE 30 bus test network, where their performance is compared.
|
|
| 25. |
- Andreasson, Ulf, 1968, et al.
(författare)
-
Analytical aspects of molecular Alzheimer's disease biomarkers
- 2012
-
Ingår i: Biomarkers in Medicine. - : Future Medicine Ltd. - 1752-0363 .- 1752-0371. ; 6:4, s. 377-389
-
Forskningsöversikt (refereegranskat)abstract
- In general, a biomarker has multiple uses such as a diagnostic tool and a method to monitor therapy. The quality of a biomarker depends on how big the difference is between, for example, patients and healthy controls, but also on the capacity of the method used to measure it (the uncertainty in the method should be much less than the difference between the groups). A good biomarker should also be specific towards a disease, allowing for differentiation between clinically related syndromes. In addition, it is of importance that the stability of the methods used is high enough to establish cut-off levels both in individual laboratories and on a global scale. In the field of Alzheimer's disease, there are currently three cerebrospinal fluid markers that have been verified in multiple studies and the analytical aspects of measuring them will be discussed.
|
|
| 26. |
|
|
| 27. |
- Andreasson, Ulf, 1968, et al.
(författare)
-
Multiplexing and multivariate analysis in neurodegeneration.
- 2012
-
Ingår i: Methods (San Diego, Calif.). - : Elsevier BV. - 1095-9130 .- 1046-2023. ; 56:4, s. 464-70
-
Tidskriftsartikel (refereegranskat)abstract
- Limited sample volume is often an obstacle in clinical research and one way to circumvent this is to use multiplex techniques where several different analytes are simultaneously measured. There is a multitude of different platforms that can be used for multiplexing and their uniqueness and similarities will be described. Multivariate analysis is a powerful tool for extracting information from multiplex data. An introduction to one such algorithm is presented followed by examples from the literature, in the field of neurodegeneration, where multiplex and multivariate methods have been used.
|
|
| 28. |
- Augutis, Kristin, et al.
(författare)
-
Cerebrospinal fluid biomarkers of β-amyloid metabolism in multiple sclerosis.
- 2013
-
Ingår i: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1477-0970 .- 1352-4585. ; 19:5, s. 543-52
-
Tidskriftsartikel (refereegranskat)abstract
- Amyloid precursor protein (APP) and amyloid β (Aβ) peptides are intensely studied in neuroscience and their cerebrospinal fluid (CSF) measurements may be used to track the metabolic pathways of APP in vivo. Reduced CSF levels of Aβ and soluble APP (sAPP) fragments are reported in inflammatory diseases, including multiple sclerosis (MS); but in MS, the precise pathway of APP metabolism and whether it can be affected by disease-modifying treatments remains unclear.
|
|
| 29. |
- Bjerke, Maria, 1977, et al.
(författare)
-
Cerebrospinal Fluid Matrix Metalloproteinases and Tissue Inhibitor of Metalloproteinases in Combination with Subcortical and Cortical Biomarkers in Vascular Dementia and Alzheimer's Disease.
- 2011
-
Ingår i: Journal of Alzheimer's disease : JAD. - 1387-2877. ; 27:3, s. 665-676
-
Tidskriftsartikel (refereegranskat)abstract
- Alzheimer's disease (AD) and vascular dementia (VaD) are intertwined by mixed dementia (MD) harboring varying degrees of AD pathology in combination with cerebrovascular disease. The aim was to assess whether there is a difference in the cerebrospinal fluid (CSF) profile, of selected proteins, between patients with VaD and MD with subcortical vascular disease (SVD), AD, and healthy controls that could contribute in the separation of the groups. The study included 30 controls, 26 SVD patients (9 VaD and 17 MD) and 30 AD patients. The protein panel included total tau (T-tau), hyperphosphorylated tau 181 (P-tau181), amyloid β 1-42 (Aβ1-42), neurofilament light (NF-L), myelin basic protein (MBP), heart fatty acid binding protein (H-FABP), matrix metalloproteinases (MMP-1, -2, -3, -9, and -10), and tissue inhibitors of metalloproteinases (TIMP-1 and -2). Immunochemical methods were utilized for quantification of the proteins in CSF and data analysis was performed with a multivariate discriminant algorithm. The concentrations of MBP, TIMP-1, P-tau181, NF-L, T-tau, MMP-9, Aβ1-42, and MMP-2 contributed the most to the separation between SVD and AD, with a sensitivity of 89% and a specificity of 90% (AUC = 0.92). MBP and NF-L performed the best in discriminating SVD from controls, while T-tau and Aβ1-42 contributed the most in segregating AD from controls. The CSF biomarkers reflecting AD pathology (T-tau, P-tau181, and Aβ1-42), white matter lesions (NF-L and MBP) and matrix remodeling (MMP-9 and TIMP-1) perform well in differentiating between SVD and AD patients.
|
|
| 30. |
- Bremell, Daniel, 1978, et al.
(författare)
-
Cerebrospinal fluid CXCL13 in Lyme neuroborreliosis and asymptomatic HIV infection.
- 2013
-
Ingår i: BMC neurology. - : Springer Science and Business Media LLC. - 1471-2377. ; 13
-
Tidskriftsartikel (refereegranskat)abstract
- Background It has been suggested that cerebrospinal fluid (CSF) CXCL13 is a diagnostic marker of Lyme neuroborreliosis (LNB), as its levels have been shown to be significantly higher in LNB than in several other CNS infections. Levels have also been shown to decline after treatment with intravenous ceftriaxone, but levels after treatment with oral doxycycline have previously not been studied. Like Borrelia burgdorferi, HIV also has neurotropic properties. Elevated serum CXCL13 concentrations have been reported in HIV patients, but data on CSF levels are limited. Methods We longitudinally analysed CSF CXCL13 concentrations in 25 LNB patients before and after oral doxycycline treatment. Furthermore, we analysed CSF CXCL13 concentrations in 16 untreated LNB patients, 27 asymptomatic untreated HIV-1 infected patients and 39 controls with no signs of infectious or inflammatory disease. Results In the longitudinal LNB study, initially high CSF CXCL13 levels declined significantly after doxycycline treatment, which correlated to a decreased CSF mononuclear cell count. In the cross-sectional study, all the LNB patients had CSF CXCL13 levels elevated above the lowest standard point of the assay (7.8 pg/mL), with a median concentration of 500 pg/mL (range 34–11,678). Of the HIV patients, 52% had elevated CSF CXCL13 levels (median 10 pg/mL, range 0–498). There was a clear overlap in CSF CXCL13 concentrations between LNB patients and asymptomatic HIV patients. All but one of the 39 controls had CSF CXCL13 levels below 7.8 pg/mL. Conclusions We confirm previous reports of highly elevated CSF CXCL13 levels in LNB patients and that these levels decline after oral doxycycline treatment. The same pattern is seen for CSF mononuclear cells. CSF CXCL13 levels are elevated in neurologically asymptomatic HIV patients and the levels overlap those of LNB patients. The diagnostic value of CSF CXCL13 in LNB remains to be established.
|
|
| 31. |
- Brinkmalm, Gunnar, et al.
(författare)
-
Soluble amyloid precursor protein alpha and beta in CSF in Alzheimer's disease
- 2013
-
Ingår i: Brain Research. - : Elsevier BV. - 1872-6240 .- 0006-8993. ; 1513, s. 117-126
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: Cerebral accumulation of amyloid beta (A beta) is a pathological hallmark of Alzheimer's disease (AD). Proteolytic processing of amyloid precursor protein (APP) by alpha- or beta-secretase results in two soluble metabolites, sAPP alpha and sAPP beta, respectively. However, previous data have shown that both alpha- and beta-secretase have multiple cleavage sites. The aim of this study was to characterize the C-termini of sAPP alpha and sAPP beta in cerebrospinal fluid (CSF) by mass spectrometry (MS) and to evaluate whether different combinations of these fragments better separate between AD patients and controls by comparing two different sAPP immunoassays. Methods: Using immunoprecipitation and high resolution MS, the APP species present in CSF were investigated. CSF levels of sAPP alpha and sAPP beta from patients with AD (n=43) and from non-demented controls (n=44) were measured using AlphaLISA and MSD immunoassays that employ different antibodies for C-terminal recognition of sAPP alpha. Results: Four different C-terminal forms of sAPP were identified, sAPP beta-M671, sAPP beta-Y681, sAPP alpha-Q686, and 5APP alpha-K687 (APP770 numbering). Neither immunoassay for the sAPP species could separate the two patient groups. The correlation (R-2) between the two immunoassays was 0.41 for sAPP alpha and 0.45 for sAPP beta. Conclusion: Using high resolution MS, we show here for the first time that sAPP alpha in CSF ends at Q686 and K687. The findings also support the conclusion from several previous studies that sAPP alpha and sAPP beta levels are unaltered in AD. (C) 2013 Elsevier B.V. All rights reserved.
|
|
| 32. |
- Brinkmalm, Gunnar, et al.
(författare)
-
Soluble amyloid precursor protein α and β in CSF in Alzheimer's disease.
- 2013
-
Ingår i: Brain research. - : Elsevier BV. - 1872-6240 .- 0006-8993. ; 1513, s. 117-26
-
Tidskriftsartikel (refereegranskat)abstract
- Cerebral accumulation of amyloid β (Aβ) is a pathological hallmark of Alzheimer's disease (AD). Proteolytic processing of amyloid precursor protein (APP) by α- or β-secretase results in two soluble metabolites, sAPPα and sAPPβ, respectively. However, previous data have shown that both α- and β-secretase have multiple cleavage sites. The aim of this study was to characterize the C-termini of sAPPα and sAPPβ in cerebrospinal fluid (CSF) by mass spectrometry (MS) and to evaluate whether different combinations of these fragments better separate between AD patients and controls by comparing two different sAPP immunoassays. Methods: Using immunoprecipitation and high resolution MS, the APP species present in CSF were investigated. CSF levels of sAPPα and sAPPβ from patients with AD (n=43) and from non-demented controls (n=44) were measured using AlphaLISA and MSD immunoassays that employ different antibodies for C-terminal recognition of sAPPα. Results: Four different C-terminal forms of sAPP were identified, sAPPβ-M671, sAPPβ-Y681, sAPPα-Q686, and sAPPα-K687 (APP770 numbering). Neither immunoassay for the sAPP species could separate the two patient groups. The correlation (R(2)) between the two immunoassays was 0.41 for sAPPα and 0.45 for sAPPβ. Conclusion: Using high resolution MS, we show here for the first time that sAPPα in CSF ends at Q686 and K687. The findings also support the conclusion from several previous studies that sAPPα and sAPPβ levels are unaltered in AD.
|
|
| 33. |
- Chiasserini, Davide, et al.
(författare)
-
CSF Levels of Heart Fatty Acid Binding Protein are Altered During Early Phases of Alzheimer's Disease.
- 2010
-
Ingår i: Journal of Alzheimer's disease : JAD. - 1875-8908. ; 22:4, s. 1281-8
-
Tidskriftsartikel (refereegranskat)abstract
- Heart fatty acid binding protein (HFABP) has been proposed as a putative marker for dementia disorders. To evaluate the value of this protein as an early marker of Alzheimer's disease (AD), we analyzed HFABP level and the classical biomarkers amyloid-β (Aβ)1-42, total tau (t-tau), and phosphorylated tau (p-tau) in cerebrospinal fluid (CSF) of patients with mild cognitive impairment (MCI) followed up for four years (n=41), AD (n=32), and subjects with other neurological diseases without dementia (OND, n=25). HFABP levels were higher in AD patients and in MCI converting to AD (MCI-AD) with respect to OND and to cognitively stable MCI patients (MCI-MCI). The receiver operator characteristics analysis for HFABP alone showed a sensitivity of 87% and a specificity of 81% for AD versus OND (area under the curve, AUC=0.83); sensitivity and specificity were 46% and 94%, respectively, when comparing MCI-MCI versus MCI-AD. CSF HFABP levels showed a strong positive correlation with both t-tau and p-tau. Interestingly, the ratio between HFABP and Aβ1-42 improved the performance in distinguishing AD from OND (sensitivity: 90%; specificity 82%, AUC=0.89), and gave the best accuracy in discriminating MCI-AD from MCI-MCI (sensitivity: 80%; specificity 100%, AUC=0.90). Survival analysis by means of Kaplan-Meier curve showed a significantly higher proportion of MCI patients converting to AD in the group with higher values of HFABP/Aβ1-42 ratio (cut-off=0.7). A significant correlation between HFABP/Aβ1-42 ratio and MMSE annual decrease rate was also documented (p< 0.0001). HFABP /Aβ1-42 ratio might be a useful predictor of conversion in MCI patients.
|
|
| 34. |
- Cirillo, Marcello, 1978-, et al.
(författare)
-
Integrated Motion Planning and Coordination for Industrial Vehicles
- 2014
-
Ingår i: Proceedings of the 24th International Conference on Automated Planning and Scheduling. - : AAAI Press. - 9781577356608
-
Konferensbidrag (refereegranskat)abstract
- A growing interest in the industrial sector for autonomous ground vehicles has prompted significant investment in fleet management systems. Such systems need to accommodate on-line externally imposed temporal and spatial requirements, and to adhere to them even in the presence of contingencies. Moreover, a fleet management system should ensure correctness, i.e., refuse to commit to requirements that cannot be satisfied. We present an approach to obtain sets of alternative execution patterns (called trajectory envelopes) which provide these guarantees. The approach relies on a constraint-based representation shared among multiple solvers, each of which progressively refines trajectory envelopes following a least commitment principle.
|
|
| 35. |
- Constantinescu, Radu, 1966, et al.
(författare)
-
Serum and cerebrospinal fluid urate levels in synucleinopathies versus tauopathies
- 2013
-
Ingår i: Acta Neurologica Scandinavica. - : Hindawi Limited. - 0001-6314. ; 127:2
-
Tidskriftsartikel (refereegranskat)abstract
- Background Low levels of serum urate are associated with a higher risk of Parkinson's disease (PD). Higher serum and cerebrospinal fluid (CSF) urate levels are associated with slower rates of clinical decline in PD and in multiple system atrophy (MSA). Aims To compare CSF and blood urate levels in healthy controls, patients with synucleinopathies and with tauopathies. Methods We investigated urate levels in serum and CSF from 18 healthy controls, 19 patients with synucleinopathies (six patients with PD and 13 with MSA), and 24 patients with tauopathies (18 with progressive supranuclear palsy and six with corticobasal degeneration). None of the patients were treated with dopaminergic medications. Results No significant differences were seen when comparing serum and CSF urate levels from controls across the parkinsonian diagnostic groups. However, in men, serum urate levels were significantly lower in the synucleinopathy group compared with the tauopathy group (P = 0.046), although with a broad overlap. Conclusion Our study suggests that urate levels might provide new insights into the potential pathophysiological mechanisms underlying Parkinsonism and thereby contribute to the future management of these disorders.
|
|
| 36. |
- Daborg, Jonny, et al.
(författare)
-
Cerebrospinal fluid levels of complement proteins C3, C4 and CR1 in Alzheimer's disease.
- 2012
-
Ingår i: Journal of neural transmission (Vienna, Austria : 1996). - : Springer Science and Business Media LLC. - 1435-1463 .- 0300-9564. ; 119:7, s. 789-97
-
Tidskriftsartikel (refereegranskat)abstract
- Alzheimer's disease (AD) is strongly associated with loss of synapses. The complement system has been shown to be involved in synaptic elimination. Several studies point to an association between AD and the complement system. The purpose of this study was to examine the association of cerebrospinal fluid (CSF) levels of complement components 3 and 4 (C3 and C4, respectively), and complement receptor 1 (CR1) with AD in 43 patients with AD plus dementia, 42 patients with mild cognitive impairment (MCI) who progressed to AD during follow-up (MCI-AD), 42 patients with stable MCI and 44 controls. Complement levels were also applied in a multivariate model to determine if they provided any added value to the core AD biomarkers Aβ42, T-tau and P-tau. We found elevated CSF levels of C3 and C4 in AD compared with MCI without progression to AD, and elevated CSF levels of CR1 in MCI-AD and AD when these groups were merged. These results provide support for aberrant complement regulation as a part in the AD process, but the changes are not diagnostically useful.
|
|
| 37. |
- Daborg, Jonny, et al.
(författare)
-
Complement Gene Single Nucleotide Polymorphisms and Biomarker Endophenotypes of Alzheimer's Disease
- 2013
-
Ingår i: Journal of Alzheimer's Disease. - 1387-2877. ; 35:1, s. 51-57
-
Tidskriftsartikel (refereegranskat)abstract
- The complement system has been implicated in both physiological synapse elimination and Alzheimer's disease (AD). Here, we investigated associations between four single nucleotide polymorphisms (SNPs) in complement genes and cerebrospinal fluid (CSF) biomarkers for AD in 452 neurochemically or neuropathologically verified AD cases and 678 cognitively normal controls. None of the SNPs associated with risk of AD but there were potential associations of rs9332739 in the C2 gene and rs4151667 in the complement factor B gene with CSF tau levels (p = 0.023) and Mini-Mental State Examination scores (p = 0.012), both of which may be considered markers of disease intensity/severity.
|
|
| 38. |
- Eckerström, Carl, et al.
(författare)
-
Combination of Hippocampal Volume and Cerebrospinal Fluid Biomarkers Improves Predictive Value in Mild Cognitive Impairment.
- 2010
-
Ingår i: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1421-9824 .- 1420-8008. ; 29:4, s. 294-300
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Mild cognitive impairment (MCI) is a heterogeneous condition, and the prognosis differs within the group. Recent findings suggest that hippocampal volumetry and CSF biomarkers can be used to predict which MCI patients have an underlying neurodegenerative disorder. Objective: To examine the combined predictive value of hippocampal volume and CSF levels of total tau (T-tau) and beta-amyloid(42) (Abeta(42)) in stable and converting MCI patients. The participants (n = 68) included patients with MCI at baseline and who converted to dementia by the time of the 2-year follow-up (n = 21), stable MCI patients (n = 21) and healthy controls (n = 26). Methods: The Göteborg MCI study is a clinically based longitudinal study with biannual clinical assessments. Hippocampal volumetry was performed manually, based on data from the 0.5-tesla MRI investigations at baseline. Baseline CSF levels of T-tau and Abeta(42) were measured using commercially available, enzyme-linked immunosorbent assays. Results: The converting MCI group had significantly smaller left hippocampi, lower CSF Abeta(42) and higher T-tau compared to both the stable MCI group and the healthy controls. Multivariate analysis revealed that a combination of the variables outperformed the prognostic ability of the separate variables. Conclusions: Hippocampal volumes supplement the prognostic accuracy of CSF Abeta(42) and T-tau in MCI.
|
|
| 39. |
|
|
| 40. |
|
|
| 41. |
- Hansson, Oskar, et al.
(författare)
-
Evaluation of plasma Abeta(40) and Abeta(42) as predictors of conversion to Alzheimer's disease in patients with mild cognitive impairment.
- 2010
-
Ingår i: Neurobiology of aging. - : Elsevier BV. - 1558-1497 .- 0197-4580. ; 31:3, s. 357-67
-
Tidskriftsartikel (refereegranskat)abstract
- Numerous studies have shown a marked decrease of beta-amyloid(42) (Abeta(42)) in the cerebrospinal fluid (CSF) of patients with incipient Alzheimer's disease (AD). However, studies on Abeta in plasma are contradictory, and show very marginal differences between patients and controls. Here, we analyzed plasma samples using a new multiplex immunoassay for simultaneous analysis of Abeta(1-40), Abeta(n-40), Abeta(1-42), and Abeta(n-42). The plasma samples were obtained at baseline from two independent cohorts of patients with mild cognitive impairment (MCI) and age-matched controls. In the first cohort, 41% of the 117 MCI cases converted to AD during a clinical follow-up period of 4-7 years. In the second cohort, 14% of the 110 MCI subjects developed AD during a clinical follow-up period of 2-4 years. None of the plasma Abeta isoforms differed between MCI patients that subsequently developed AD and healthy controls or stable MCI patients. The Cox proportional hazards model did not reveal any differences in the probability of progression from MCI to AD related to plasma Abeta levels. In contrast, low levels of Abeta(1-42) in CSF were strongly associated with increased risk of future AD. The absence of a change in plasma Abeta in incipient AD, despite the marked change in CSF, may be explained by the lack of a correlation between the levels of Abeta(1-42) in CSF and plasma. In conclusion, the results show that CSF biomarkers are better predictors of progression to AD than plasma Abeta isoforms.
|
|
| 42. |
- Hölttä, Mikko, et al.
(författare)
-
Evaluating amyloid-β oligomers in cerebrospinal fluid as a biomarker for Alzheimer's disease.
- 2013
-
Ingår i: PloS one. - San Francisco, CA, United States : Public Library of Science (PLoS). - 1932-6203. ; 8:6
-
Tidskriftsartikel (refereegranskat)abstract
- The current study evaluated amyloid-β oligomers (Aβo) in cerebrospinal fluid as a clinical biomarker for Alzheimer's disease (AD). We developed a highly sensitive Aβo ELISA using the same N-terminal monoclonal antibody (82E1) for capture and detection. CSF samples from patients with AD, mild cognitive impairment (MCI), and healthy controls were examined. The assay was specific for oligomerized Aβ with a lower limit of quantification of 200 fg/ml, and the assay signal showed a tight correlation with synthetic Aβo levels. Three clinical materials of well characterized AD patients (n=199) and cognitively healthy controls (n=148) from different clinical centers were included, together with a clinical material of patients with MCI (n=165). Aβo levels were elevated in the all three AD-control comparisons although with a large overlap and a separation from controls that was far from complete. Patients with MCI who later converted to AD had increased Aβo levels on a group level but several samples had undetectable levels. These results indicate that presence of high or measurable Aβo levels in CSF is clearly associated with AD, but the overlap is too large for the test to have any diagnostic potential on its own.
|
|
| 43. |
- Johansson, Per, et al.
(författare)
-
Cerebrospinal Fluid Biomarkers for Alzheimer's Disease: Diagnostic Performance in a Homogeneous Mono-Center Population
- 2011
-
Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 24:3, s. 537-546
-
Tidskriftsartikel (refereegranskat)abstract
- The cerebrospinal fluid (CSF) biomarkers amyloid-beta (A beta)(1-42), T-tau, and P-tau have good diagnostic accuracy for clinically diagnosed Alzheimer's disease (AD). However, in multi-center studies, the predictive values of the CSF biomarkers have been lower, possibly due to differences in procedures for lumbar puncture and CSF handling and storage, and to differences in patient populations, clinical evaluations, and diagnostic procedures. Here we investigate the diagnostic accuracy of CSF biomarkers in a well defined homogeneous mono-center population. We also evaluate an extended panel of amyloid related biomarkers. Sixty consecutive patients admitted for cognitive impairment to a memory clinic were recruited. The participants included patients with AD or mild cognitive impairment (MCI) diagnosed with AD upon follow-up (n = 32), patients with stable MCI (n = 13), patients with other dementias diagnosed at primary evaluation or upon follow-up (n = 15), and healthy controls (n = 20). CSF was analyzed for A beta(1-42), T-tau, P-tau, A beta(X-38), A beta(X-40), A beta(X-42), sA beta PP alpha, and sA beta PP beta. In multivariate analysis, the core biomarkers A beta(1-42), T-tau, and P-tau demonstrated a high ability to diagnose AD versus the combined groups of controls and stable MCI, with an area under the receiver operating characteristic curve (AUROC) of 0.97 (95% CI 0.93-1.00, p < 0.0001). The additional biomarkers only marginally increased AUROC to 0.98 (95% CI 0.95-1.00, p < 0.0001), this increase mainly mediated by A beta(X-42). In conclusion, CSF biomarkers A beta(1-42), T-tau, and P-tau have very high diagnostic accuracy in a well defined cohort of untreated patients, demonstrating the excellent potency of CSF biomarkers to identify pathological processes in AD when a stringent analytical protocol is used.
|
|
| 44. |
|
|
| 45. |
- Jurgilaitis, Andrius, et al.
(författare)
-
Time-Resolved X-ray Diffraction Investigation of the Modified Phonon Dispersion in InSb Nanowires
- 2014
-
Ingår i: Nano letters (Print). - Washington, DC : American Chemical Society (ACS). - 1530-6984 .- 1530-6992. ; 14:2, s. 541-546
-
Tidskriftsartikel (refereegranskat)abstract
- The modified phonon dispersion is of importance for understanding the origin of the reduced heat conductivity in nanowires. We have measured the phonon dispersion for 50 nm diameter InSb (111) nanowires using time-resolved X-ray diffraction. By comparing the sound speed of the bulk (3880 m/s) and that of a classical thin rod (3600 m/s) to our measurement (2880 m/s), we conclude that the origin of the reduced sound speed and thereby to the reduced heat conductivity is that the C44 elastic constant is reduced by 35% compared to the bulk material. © 2014 American Chemical Society.
|
|
| 46. |
- Lautner, Ronald, et al.
(författare)
-
Apolipoprotein e genotype and the diagnostic accuracy of cerebrospinal fluid biomarkers for Alzheimer disease.
- 2014
-
Ingår i: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 71:10, s. 1183-91
-
Tidskriftsartikel (refereegranskat)abstract
- Several studies suggest that the apolipoprotein E (APOE) ε4 allele modulates cerebrospinal fluid (CSF) levels of β-amyloid 42 (Aβ42). Whether this effect is secondary to the association of the APOE ε4 allele with cortical Aβ deposition or whether APOE ε4 directly influences CSF levels of Aβ42 independently of Aβ pathology remains unknown.
|
|
| 47. |
- Leinenbach, Andreas, et al.
(författare)
-
Mass spectrometry-based candidate reference measurement procedure for quantification of amyloid-β in cerebrospinal fluid.
- 2014
-
Ingår i: Clinical chemistry. - : Oxford University Press (OUP). - 1530-8561 .- 0009-9147. ; 60:7, s. 987-94
-
Tidskriftsartikel (refereegranskat)abstract
- Cerebrospinal fluid (CSF) amyloid-β (Aβ42) is a well-established biomarker for Alzheimer disease. Several immunoassays for Aβ42 exist but differ in absolute concentrations and may suffer from matrix interference, thereby hampering interlaboratory comparisons and the use of general cutoff levels. Together with the IFCC Working Group on CSF Proteins, we developed a candidate reference measurement procedure (RMP) for Aβ42.
|
|
| 48. |
|
|
| 49. |
- Mattsson, Niklas, 1979, et al.
(författare)
-
Amyloid-β metabolism in Niemann-Pick C disease models and patients.
- 2012
-
Ingår i: Metabolic brain disease. - : Springer Science and Business Media LLC. - 1573-7365 .- 0885-7490. ; 27:4, s. 573-85
-
Tidskriftsartikel (refereegranskat)abstract
- Niemann-Pick type C (NPC) is a progressive neurodegenerative lysosomal disease with altered cellular lipid trafficking. The metabolism of amyloid-β (Aβ) - previously mainly studied in Alzheimer's disease - has been suggested to be altered in NPC. Here we aimed to perform a detailed characterization of metabolic products from the amyloid precursor protein (APP) in NPC models and patients. We used multiple analytical technologies, including immunoassays and immunoprecipitation followed by mass spectrometry (IP-MS) to characterize Aβ peptides and soluble APP fragments (sAPP-α/β) in cell media from pharmacologically (U18666A) and genetically (NPC1 ( -/- ) ) induced NPC cell models, and cerebrospinal fluid (CSF) from NPC cats and human patients. The pattern of Aβ peptides and sAPP-α/β fragments in cell media was differently affected by NPC-phenotype induced by U18666A treatment and by NPC1 ( -/- ) genotype. U18666A treatment increased the secreted media levels of sAPP-α, AβX-40 and AβX-42 and reduced the levels of sAPP-β, Aβ1-40 and Aβ1-42, while IP-MS showed increased relative levels of Aβ5-38 and Aβ5-40 in response to treatment. NPC1 ( -/- ) cells had reduced media levels of sAPP-α and Aβ1-16, and increased levels of sAPP-β. NPC cats had altered CSF distribution of Aβ peptides compared with normal cats. Cats treated with the potential disease-modifying compound 2-hydroxypropyl-β-cyclodextrin had increased relative levels of short Aβ peptides including Aβ1-16 compared with untreated cats. NPC patients receiving β-cyclodextrin had reduced levels over time of CSF Aβ1-42, AβX-38, AβX-40, AβX-42 and sAPP-β, as well as reduced levels of the axonal damage markers tau and phosphorylated tau. We conclude that NPC models have altered Aβ metabolism, but with differences across experimental systems, suggesting that NPC1-loss of function, such as in NPC1 ( -/- ) cells, or NPC1-dysfunction, seen in NPC patients and cats as well as in U18666A-treated cells, may cause subtle but different effects on APP degradation pathways. The preliminary findings from NPC cats suggest that treatment with cyclodextrin may have an impact on APP processing pathways. CSF Aβ, sAPP and tau biomarkers were dynamically altered over time in human NPC patients.
|
|
| 50. |
- Mattsson, Niklas, 1979, et al.
(författare)
-
BACE1 inhibition induces a specific cerebrospinal fluid β-amyloid pattern that identifies drug effects in the central nervous system.
- 2012
-
Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 7:2
-
Tidskriftsartikel (refereegranskat)abstract
- BACE1 is a key enzyme for amyloid-β (Aβ) production, and an attractive therapeutic target in Alzheimer's disease (AD). Here we report that BACE1 inhibitors have distinct effects on neuronal Aβ metabolism, inducing a unique pattern of secreted Aβ peptides, analyzed in cell media from amyloid precursor protein (APP) transfected cells and in cerebrospinal fluid (CSF) from dogs by immunoprecipitation-mass spectrometry, using several different BACE1 inhibitors. Besides the expected reductions in Aβ1-40 and Aβ1-42, treatment also changed the relative levels of several other Aβ isoforms. In particular Aβ1-34 decreased, while Aβ5-40 increased, and these changes were more sensitive to BACE1 inhibition than the changes in Aβ1-40 and Aβ1-42. The effects on Aβ5-40 indicate the presence of a BACE1 independent pathway of APP degradation. The described CSF Aβ pattern may be used as a pharmacodynamic fingerprint to detect biochemical effects of BACE1-therapies in clinical trials, which might accelerate development of novel therapies.
|
|
