| 1. |
- Apweiler, Rolf, et al.
(författare)
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Approaching clinical proteomics : current state and future fields of application in cellular proteomics
- 2009
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Ingår i: Cytometry. Part A : the journal of the International Society for Analytical Cytology. - : Wiley. - 1552-4922. ; 75A:10, s. 816-832
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Forskningsöversikt (refereegranskat)abstract
- Recent developments in proteomics technology offer new opportunities for clinical applications in hospital or specialized laboratories including the identification of novel biomarkers, monitoring of disease, detecting adverse effects of drugs, and environmental hazards. Advanced spectrometry technologies and the development of new protein array formats have brought these analyses to a standard, which now has the potential to be used in clinical diagnostics. Besides standardization of methodologies and distribution of proteomic data into public databases, the nature of the human body fluid proteome with its high dynamic range in protein concentrations, its quantitation problems, and its extreme complexity present enormous challenges. Molecular cell biology (cytomics) with its link to proteomics is a new fast moving scientific field, which addresses functional cell analysis and bioinformatic approaches to search for novel cellular proteomic biomarkers or their release products into body fluids that provide better insight into the enormous biocomplexity of disease processes and are suitable for patient stratification, therapeutic monitoring, and prediction of prognosis. Experience from studies of in vitro diagnostics and especially in clinical chemistry showed that the majority of errors occurs in the preanalytical phase and the setup of the diagnostic strategy. This is also true for clinical proteomics where similar preanalytical variables such as inter- and intra-assay variability due to biological variations or proteolytical activities in the sample will most likely also influence the results of proteomics studies. However, before complex proteomic analysis can be introduced at a broader level into the clinic, standardization of the preanalytical phase including patient preparation, sample collection, sample preparation, sample storage, measurement, and data analysis is another issue which has to be improved. In this report, we discuss the recent advances and applications that fulfill the criteria for clinical proteomics with the focus on cellular proteomics (cytoproteomics) as related to preanalytical and analytical standardization and to quality control measures required for effective implementation of these technologies and analytes into routine laboratory testing to generate novel actionable health information. It will then be crucial to design and carry out clinical studies that can eventually identify novel clinical diagnostic strategies based on these techniques and validate their impact on clinical decision making.
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| 2. |
- Apweiler, Rolf, et al.
(författare)
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Approaching clinical proteomics : current state and future fields of application in fluid proteomics
- 2009
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Ingår i: Clinical Chemistry and Laboratory Medicine. - 1434-6621 .- 1437-4331. ; 47:6, s. 724-744
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Forskningsöversikt (refereegranskat)abstract
- The field of clinical proteomics offers opportunities to identify new disease biomarkers in body fluids, cells and tissues. These biomarkers can be used in clinical applications for diagnosis, stratification of patients for specific treatment, or therapy monitoring. New protein array formats and improved spectrometry technologies have brought these analyses to a level with potential for use in clinical diagnostics. The nature of the human body fluid proteome with its large dynamic range of protein concentrations presents problems with quantitation. The extreme complexity of the proteome in body fluids presents enormous challenges and requires the establishment of standard operating procedures for handling of specimens, increasing sensitivity for detection and bioinformatical tools for distribution of proteomic data into the public domain. From studies of in vitro diagnostics, especially in clinical chemistry, it is evident that most errors occur in the preanalytical phase and during implementation of the diagnostic strategy. This is also true for clinical proteomics, and especially for fluid proteomics because of the multiple pretreatment processes. These processes include depletion of high-abundance proteins from plasma or enrichment processes for urine where biological variation or differences in proteolytic activities in the sample along with preanalytical variables such as inter- and intra-assay variability will likely influence the results of proteomics studies. However, before proteomic analysis can be introduced at a broader level into the clinical setting, standardization of the preanalytical phase including patient preparation, sample collection, sample preparation, sample storage, measurement and data analysis needs to be improved. In this review, we discuss the recent technological advances and applications that fulfil the criteria for clinical proteomics, with the focus on fluid proteomics. These advances relate to preanalytical factors, analytical standardization and quality-control measures required for effective implementation into routine laboratory testing in order to generate clinically useful information. With new disease biomarker candidates, it will be crucial to design and perform clinical studies that can identify novel diagnostic strategies based on these techniques, and to validate their impact on clinical decision-making.
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| 3. |
- Brinkfeldt, Klas, et al.
(författare)
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Design and Fabrication of a SiC-Based Power Module with Double-Sided Cooling for Automotive Applications
- 2016
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Ingår i: Lecture Notes in Mobility. - Cham : Springer International Publishing. - 2196-5544 .- 2196-5552. ; , s. 157-171, s. 157-172
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- The electrification of drive trains combined with special requirements of the automotive and heavy construction equipment applications drives the development of small, highly integrated and reliable power inverters. To minimize the volume and increase the reliability of the power switching devices a module consisting of SiC devices with double sided cooling capability has been developed. There are several benefits related to cooling the power devices on both sides. The major improvement is the ability to increase the power density, and thereby reduce the number of active switching devices required which in turn reduces costs. Other expected benefits of more efficient cooling are reductions in volume and mass per power ratio. Alternatively, improved reliability margins due to lower temperature swings during operation are can be expected. Removing the wire bonds on the top side of the devices is expected to improve the reliability regardless, since wire bonds are known to be one of the main limitations in power switching devices. In addition, it is possible to design the package with substantially lower inductance, which can allow faster switching of the devices. In this paper the design, simulations and fabrication process of a double sided SiC-based power module are presented.
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| 4. |
- Brinkfeldt, Klas, et al.
(författare)
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Model verification of heat exchangers in a flow test rig
- 2015
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Ingår i: 2015 16th International Conference on Thermal, Mechanical and Multi-Physics Simulation and Experiments in Microelectronics and Microsystems, EuroSimE 2015. - : Institute of Electrical and Electronics Engineers Inc.. - 9781479999507 ; , s. 7103135-
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Konferensbidrag (refereegranskat)abstract
- In power electronics, more efficient removal of heat from the junction of power devices leads to a higher power rating per die, which in turn leads to fewer die and reduced system volume. Since temperature is a main driver in expected failure modes an increase in cooling capability can also enhance margins of the device reliability. Previously, CFD simulations of two novel heat exchanger designs that will be used in a power module with double sided cooling have been reported on. The heat exchangers are fabricated by direct 3D manufacturing of copper structures, which allows almost complete freedom in geometric design. Two novel geometries of heat exchanger cooling structures have previously been modeled in terms of thermal performance and expected pressure drop. A flow rig has been designed and calibrated to measure thermal performance and pressure drops of these heat sinks. For calibration purposes, measurements of the thermal response of wave structured and unstructured heat sinks are reported here. The results show that, as expected, the heat sink temperatures are lower for all flow rates in the wavestructured geometry. A thermal CFO model accurately predicts the behavior of the temperature difference between inlet and outlet versus flow rate, but predicts higher absolute temperature values. It was also found that the model underestimates the pressure drop over the tested heat sillies. The pressure drop across a novel pine cone geometry heat sink fabricated by additive manufacturing methods was also measured. Comparisons to a reduced model, which neglects everything before the inlet and after the outlet of the tested device, showed that the behavior of this pine structured heat sink was not predicted correctly. The pressure drop increased more rapidly with flow rates in the model than in the measurements. The main source of error in the measurements and simulations comes from a lack of thermal loading. Future work to improve the flow rig includes possibilities to increase the temperature loading at the bottom of the heat sink under test.
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| 5. |
- Brinkfeldt, Klas, et al.
(författare)
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Modeling of SiC power modules with double sided cooling
- 2014
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Ingår i: 2014 15th International Conference on Thermal, Mechanical and Multi-Physics Simulation and Experiments in Microelectronics and Microsystems, EuroSimE 2014. - : IEEE Computer Society. - 9781479947904
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Konferensbidrag (refereegranskat)abstract
- Silicon Carbide (SiC) based transistor devices have demonstrated higher efficiency switching operation compared to silicon-based, state-of-the-art solutions due to the superior electrical and thermal properties of the SiC material. The improved current density and thermal conductivity allows SiC-based power modules to be smaller than their silicon counterparts for comparable current densities. The active chip area can be reduced further by effectively cooling the devices. In this work, a new power module including SiC bipolar junction transistors (BJT) and diodes and integrated double sided cooling will be introduced. The target application of these modules is a new drive-train system for commercial electric vehicles.
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| 6. |
- Brinkfeldt, Klas, et al.
(författare)
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Thermo-Mechanical Simulations of SiC Power Modules with Single and Double Sided Cooling
- 2015
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Ingår i: 16th International Conference on Thermal, Mechanical and Multi-Physics Simulation and Experiments in Microelectronics and Microsystems (EuroSimE), 2015. - : Institute of Electrical and Electronics Engineers Inc.. - 9781479999491 - 9781479999507 ; , s. 1 - 7
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Konferensbidrag (refereegranskat)abstract
- Effectively removing dissipated heat from the switching devices enables a higher current carrying capability per chip area ratio, thus leading to smaller or fewer devices for a given power requirement specification. Further, the use of SiC based devices has proven to increase the efficiency of the system thereby reducing the dissipated heat. Thermal models have been used to compare SiC power modules. Single and double sided cooling have been simulated. The simulated maximum temperatures were 141 °C for the single sided version and 119.7 °C for the double sided version. In addition, the reliability of a single sided module and thermally induced plastic strains of a double sided module have been investigated. A local model of the wire bond interface to the transistor metallization shows a 30/00 maximum increase in plastic strain during the power cycle. Simulations of the creep strain rates in the die attach solder layer for a power cycling loads also shows a 30/00 increase in creep strain per cycle.
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| 7. |
- Hogan, Aidan, et al.
(författare)
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Knowledge Graphs
- 2021
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Ingår i: ACM Computing Surveys. - : ASSOC COMPUTING MACHINERY. - 0360-0300 .- 1557-7341. ; 54:4
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Tidskriftsartikel (refereegranskat)abstract
- In this article, we provide a comprehensive introduction to knowledge graphs, which have recently garnered significant attention from both industry and academia in scenarios that require exploiting diverse, dynamic, large-scale collections of data. After some opening remarks, we motivate and contrast various graph-based data models, as well as languages used to query and validate knowledge graphs. We explain how knowledge can be represented and extracted using a combination of deductive and inductive techniques. We conclude with high-level future research directions for knowledge graphs.
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| 8. |
- Hogan, Aidan, et al.
(författare)
-
Knowledge Graphs
- 2021
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Bok (övrigt vetenskapligt/konstnärligt)abstract
- This book provides a comprehensive and accessible introduction to knowledge graphs, which have recently garnered notable attention from both industry and academia. Knowledge graphs are founded on the principle of applying a graph-based abstraction to data, and are now broadly deployed in scenarios that require integrating and extracting value from multiple, diverse sources of data at large scale.The book defines knowledge graphs and provides a high-level overview of how they are used. It presents and contrasts popular graph models that are commonly used to represent data as graphs, and the languages by which they can be queried before describing how the resulting data graph can be enhanced with notions of schema, identity, and context. The book discusses how ontologies and rules can be used to encode knowledge as well as how inductive techniques—based on statistics, graph analytics, machine learning, etc.—can be used to encode and extract knowledge. It covers techniques for the creation, enrichment, assessment, and refinement of knowledge graphs and surveys recent open and enterprise knowledge graphs and the industries or applications within which they have been most widely adopted. The book closes by discussing the current limitations and future directions along which knowledge graphs are likely to evolve.This book is aimed at students, researchers, and practitioners who wish to learn more about knowledge graphs and how they facilitate extracting value from diverse data at large scale. To make the book accessible for newcomers, running examples and graphical notation are used throughout. Formal definitions and extensive references are also provided for those who opt to delve more deeply into specific topics.
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| 9. |
- Kranaster, Laura, et al.
(författare)
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The novel seizure quality index for the antidepressant outcome prediction in electroconvulsive therapy: association with biomarkers in the cerebrospinal fluid.
- 2020
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Ingår i: European archives of psychiatry and clinical neuroscience. - : Springer Science and Business Media LLC. - 1433-8491 .- 0940-1334. ; 270:7, s. 911-919
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Tidskriftsartikel (refereegranskat)abstract
- For patients with depression treated with electroconvulsive therapy (ECT), the novel seizure quality index (SQI) can predict the risk of non-response (and non-remission)-as early as after the second ECT session-based the extent of several ictal parameters of the seizure. We aim to test several CSF markers on their ability to predict the degree of seizure quality, measured by the SQI to identify possible factors, that could explain some variability of the seizure quality. Baseline CSF levels of metabolites from the kynurenine pathway, markers of neurodegeneration (tau proteins, β-amyloids and neurogranin), elements of the innate immune system, endocannabinoids, sphingolipids, neurotrophic factors (VEGF) and Klotho were measured before ECT in patients with depression (n=12) to identify possible correlations with the SQI by Pearson's partial correlation. Negative, linear relationships with the SQI for response were observed for CSF levels of T-tau (rpartial=-0.69, p=0.019), phosphatidylcholines (rpartial=-0.52, p=0.038) and IL-8 (rpartial=-0.67, p=0.047). Regarding the SQI for remission, a negative, linear relationship was noted with CSF levels of the endocannabinoid AEA (rpartial=-0.70, p=0.024) and CD163 (rpartial=-0.68, p=0.029). In sum, CSF Markers for the innate immune system, for neurodegeneration and from lipids were found to be associated with the SQI for response and remission after adjusting for age. Consistently, higher CSF levels of the markers were always associated with lower seizure quality. Based on these results, further research regarding the mechanism of seizure quality in ECT is suggested.
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