| 1. |
- Akujärvi, Ville, et al.
(författare)
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Mapping of magnetic properties for simulations of high-Temperature electromagnetic applications
- 2017
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Ingår i: COMPEL - The International Journal for Computation and Mathematics in Electrical and Electronic Engineering. - 0332-1649. ; 36:2, s. 546-554
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Tidskriftsartikel (refereegranskat)abstract
- Purpose -The purpose of this paper is to investigate the added value of using temperature-dependent electric and magnetic properties in high-Temperature electromagnetic simulations. Design/methodology/approach - In this work, the electromagnetic properties of Domex 420, SSAB, have been characterized as a function of the temperature, from room temperature to 900°C. The measurement of the electric and magnetic properties was performed inside a vacuum furnace at a number of discrete temperature steps, with particularly small intervals around the Curie temperature. A simple transient multi-physics model was used to investigate the impact of the measured properties in three different representations. Findings - In certain intervals, a simplified approximation of the properties produces accurate results, while fully parametric representation is beneficial when heating above the Curie temperature. Originality/value -Temperature-dependent electromagnetic properties are rarely found, especially in an easy-To-use form. Using parameterized temperature-dependent approximation of key properties shows noteworthy differences in the outcome of high-Temperature electromagnetic modeling.
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| 2. |
- Akula, James D., et al.
(författare)
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The scotopic electroretinogram of the sugar glider related to histological features of its retina
- 2011
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Ingår i: Journal of Comparative Physiology A. - : Springer Science and Business Media LLC. - 1432-1351 .- 0340-7594. ; 197:11, s. 1043-1054
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Tidskriftsartikel (refereegranskat)abstract
- The flash electroretinogram (ERG) was used to characterize the scotopic retinal function in a marsupial. Key parameter values of the a- and b-waves of adult male sugar gliders, Petaurus breviceps breviceps, elicited with ganzfeld flashes were determined under dark-and light-adapted conditions. Using standard histological methods, the thicknesses of the major layers of the retina were assessed to provide insight into the nature of the ERG responses. The ERG and histological results were compared to corresponding data for placental C57Bl/6 mice to establish whether the functional retinal specialization that underlies scotopic visual function in a marsupial parallels that of a placental mouse. The sensitivity of the a-wave assessed with the Lamb and Pugh (Invest Ophthalmol Vis Sci 47:5138-5152, 2006) "model" and that of the b-wave assessed with standard methods were lower in the sugar glider compared to the mouse. The thickness of the sugar glider retina was two-third of that of the mouse. The high-intensity flash ERG of the sugar glider substantially differed in shape from that of the mouse reflecting perhaps structural and functional differences between the two species at the level of the inner retina.
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| 3. |
- Akula, Murali K, et al.
(författare)
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Control of the innate immune response by the mevalonate pathway
- 2016
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Ingår i: Nature Immunology. - : Springer Science and Business Media LLC. - 1529-2908 .- 1529-2916. ; 17:8, s. 922-9
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Tidskriftsartikel (refereegranskat)abstract
- Deficiency in mevalonate kinase (MVK) causes systemic inflammation. However, the molecular mechanisms linking the mevalonate pathway to inflammation remain obscure. Geranylgeranyl pyrophosphate, a non-sterol intermediate of the mevalonate pathway, is the substrate for protein geranylgeranylation, a protein post-translational modification that is catalyzed by protein geranylgeranyl transferase I (GGTase I). Pyrin is an innate immune sensor that forms an active inflammasome in response to bacterial toxins. Mutations in MEFV (encoding human PYRIN) result in autoinflammatory familial Mediterranean fever syndrome. We found that protein geranylgeranylation enabled Toll-like receptor (TLR)-induced activation of phosphatidylinositol-3-OH kinase (PI(3)K) by promoting the interaction between the small GTPase Kras and the PI(3)K catalytic subunit p110 delta. Macrophages that were deficient in GGTase I or p110 delta exhibited constitutive release of interleukin 1 beta that was dependent on MEFV but independent of the NLRP3, AIM2 and NLRC4 inflammasomes. In the absence of protein geranylgeranylation, compromised PI(3)K activity allows an unchecked TLR-induced inflammatory responses and constitutive activation of the Pyrin inflammasome.
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| 4. |
- Balatsouka, Dimitra, et al.
(författare)
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The impact of nicotine on osseointegration. An experimental study in the femur and tibia of rabbits.
- 2005
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Ingår i: Clinical oral implants research. - : Wiley. - 0905-7161 .- 1600-0501. ; 16:4, s. 389-95
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The aim of the present study was to analyze the effect of an enhanced systematic dose of nicotine on osseointegration of titanium implants. MATERIAL AND METHODS: Sixteen female rabbits received either nicotine (n=8) or saline (n=8) administered subcutaneously via mini-osmotic pumps for 2 months. The pump delivered 6 mug/kg/min of nicotine for the animals in the test group. Blood was withdrawn and plasma cotinine levels were measured weekly. Thirty-two titanium implants were inserted into the femur and tibia of all rabbits after 4 weeks and after 6 weeks of nicotine/placebo exposure. Thus, 2- and 4-week healing groups were created. Biomechanical evaluation by (i) resonance frequency analysis test (RFA) on all implants after insertion and before sacrifice and (ii) removal torque test (RMT) on tibial implants before sacrifice was performed. All implants placed in the femur were processed to undecalcified ground sections. The percentage of bone-to-implant contact (BIC) and of bone area within the threads (BD-i) were measured. RESULTS: No significant difference in RMT and RFA values was found between the test and the control group. Histomorphometric measurements of the BIC and the peri-implant BD-i showed no significant differences between the test and the control group after 2 or after 4 weeks. CONCLUSION: Nicotine exposure for a short period of time even in a high dose did not have a significant impact on implant osseointegration in rabbits.
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| 5. |
- Bandaru, Sunith, 1984-, et al.
(författare)
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A parameterless performance metric for reference-point based multi-objective evolutionary algorithms
- 2019
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Ingår i: GECCO '19. - New York, NY, USA : ACM Digital Library. - 9781450361118 ; , s. 499-506
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Konferensbidrag (refereegranskat)abstract
- Most preference-based multi-objective evolutionary algorithms use reference points to articulate the decision maker's preferences. Since these algorithms typically converge to a sub-region of the Pareto-optimal front, the use of conventional performance measures (such as hypervolume and inverted generational distance) may lead to misleading results. Therefore, experimental studies in preference-based optimization often resort to using graphical methods to compare various algorithms. Though a few ad-hoc measures have been proposed in the literature, they either fail to generalize or involve parameters that are non-intuitive for a decision maker. In this paper, we propose a performance metric that is simple to implement, inexpensive to compute, and most importantly, does not involve any parameters. The so called expanding hypercube metric has been designed to extend the concepts of convergence and diversity to preference optimization. We demonstrate its effectiveness through constructed preference solution sets in two and three objectives. The proposed metric is then used to compare two popular reference-point based evolutionary algorithms on benchmark optimization problems up to 20 objectives.
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| 6. |
- Bandaru, Sashidar
(författare)
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Filamin A in Cardiovascular Remodeling
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Filamin A (FLNA) is a large actin-binding cytoskeletal protein that stabilizes actin networks and integrates them with cell membranes. FLNA is therefore important for cell motility and organ development. We recently discovered that a C-terminal fragment of FLNA (FLNACT) can be cleaved off by calpain and stimulate angiogenesis by transporting transcription factors into the nucleus. However, little is known about the role of FLNA in cell types that participate in the pathogenesis of vascular diseases where angiogenesis typically plays an important role. In this thesis, we defined the impact of inactivating Flna in mouse vascular endothelial cells and macrophages on the pathogenesis of myocardial infarction (MI) and atherosclerosis, respectively—and made several exciting discoveries. In Study I, we induced MI by ligating the left descending coronary artery in wt control mice and mice lacking FLNA in endothelial cells. The Flna-knockout mice developed larger MI lesions than controls, and exhibited larger and thinner left ventricles, impaired cardiac function, elevated plasma levels of the cardiac damage biomarker NT-proBNP, and reduced plasma levels of the angiogenesis-promoting factor VEGF-A. Hearts from the Flna-knockout mice exhibited reduced capillary structures within infarcted regions; and cultured Flna-deficient endothelial cells showed impaired migration and tubular formation, along with reduced levels of the signaling molecules p-ERK and p-AKT and the small GTPase RAC1. In Study II, we first discovered that FLNA expression was higher in human carotid arteries with advanced atherosclerotic plaques than with intermediate plaques. We generated mice lacking FLNA in macrophages and found that their macrophages proliferated and migrated less compared with littermate controls. Moreover, Flna-deficient macrophages exhibited reduced levels of p-ERK and p-AKT, and reduced lipid uptake and increased cholesterol efflux. In two different mouse atherosclerosis models, the knockout of FLNA in macrophages markedly reduced lesion size and number of CD68-positive lesional macrophages. Interestingly, the calpain-cleaved FLNACT fragment interacted strongly with STAT3 in wt macrophages. Inhibiting FLNA cleavage with the calpain inhibitor calpeptin reduced nuclear p-STAT3 levels and subsequent IL-6 secretion in vitro; and reduced atherosclerotic lesions in vivo. We conclude that FLNA interacts with transcription factors and thereby regulates angiogenesis and inflammatory responses which are important events in the progression of MI and atherosclerosis. These findings identify FLNA as an important new mediator of cardiovascular remodeling and as a potential target for therapy.
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| 7. |
- Ibrahim, Eman I. K., et al.
(författare)
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Bridging responses to a human telomerase reverse transcriptase-based peptide cancer vaccine candidate in a mechanism-based model
- 2024
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Ingår i: International Immunopharmacology. - : Elsevier. - 1567-5769 .- 1878-1705. ; 126
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Tidskriftsartikel (refereegranskat)abstract
- Therapeutic cancer vaccines are novel immuno-therapeutics, aiming to improve clinical outcomes with other immunotherapies. However, obstacles to their successful clinical development remain, which model-informed drug development approaches may address. UV1 is a telomerase based therapeutic cancer vaccine candidate being investigated in phase I clinical trials for multiple indications. We developed a mechanism-based model structure, using a nonlinear mixed‐effects modeling techniques, based on longitudinal tumor sizes (sum of the longest diameters, SLD), UV1-specific immunological assessment (stimulation index, SI) and overall survival (OS) data obtained from a UV1 phase I trial including non-small cell lung cancer (NSCLC) patients and a phase I/IIa trial including malignant melanoma (MM) patients. The final structure comprised a mechanistic tumor growth dynamics (TGD) model, a model describing the probability of observing a UV1-specific immune response (SI ≥ 3) and a time-to-event model for OS. The mechanistic TGD model accounted for the interplay between the vaccine peptides, immune system and tumor. The model-predicted UV1-specific effector CD4+ T cells induced tumor shrinkage with half-lives of 103 and 154 days in NSCLC and MM patients, respectively. The probability of observing a UV1-specific immune response was mainly driven by the model-predicted UV1-specific effector and memory CD4+ T cells. A high baseline SLD and a high relative increase from nadir were identified as main predictors for a reduced OS in NSCLC and MM patients, respectively. Our model predictions highlighted that additional maintenance doses, i.e. UV1 administration for longer periods, may result in more sustained tumor size shrinkage.
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| 8. |
- Karlsson, Charlie, 1945-
(författare)
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ICT, Functional Urban Regions, and the New Economic Geography
- 2004
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Ingår i: Engineering Economics. - : KTH Royal Institute of Technology. - 1392-2785 .- 2029-5839. ; 40:14, s. 57-68
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Tidskriftsartikel (refereegranskat)abstract
- The rapid developments in information and communication technologies (ICT) and the increased use of ICT motivate the vision of an evolving digital economy. During the last decade this evolving digital economy has been the pre-eminent driver of structural change and economic growth at both the national and the regional level in the developed, industrialised economies. The reason is, of course, that ICT functions as a new generic technology, which impacts society both broadly and deeply. ICT has, in essence, destabilised the near equilibrium conditions of an earlier time and contributed to conditions of greater disequilibrium. Thus, one major implication of ICT is that it has created prime conditions for entrepreneurial discovery and action. This implies that there are strong motives to study various aspects of the digital economy, since ICT continues to penetrate the developed economies also after the burst of the ICT stimulated stock market bubble. In this paper we analyse one aspect of the digital economy, namely its effect of the system of functional urban regions. The motivation for this focus is that ICT offers new tools to organise information and enables major reductions in geographical transaction costs, the full implications of which is not yet well understood.
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