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| 2. |
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| 3. |
- Farrokhnia, Nasim, et al.
(författare)
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Differential early mitogen-activated protein kinase activation in hyperglycemic ischemic brain injury in the rat
- 2005
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Ingår i: European Journal of Clinical Investigation. - : Wiley. - 0014-2972 .- 1365-2362. ; 35:7, s. 457-463
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Hyperglycemia aggravates brain injury induced by focal ischemia-reperfusion. The mitogen-activated protein kinase (MAPK) members extracellular-signal regulated kinase (Erk) and c-Jun N-terminal kinase (JNK) have been proposed as mediators of ischemic brain injury, and Erk is strongly activated by combined hyperglycemia and transient global ischemia. It is unclear whether similar MAPK activation appears in focal brain ischemia with concomitant hyperglycemia. DESIGN: Hyperglycemia was induced in rats by an intraperitoneal bolus of glucose (2 g kg(-1)). The rats were then subjected to 90 min of transient middle cerebral artery occlusion (MCAO). Erk and JNK activation were investigated with immunofluorescence and Western blot along with infarct size measurement based on tetrazolium staining and neurological score. RESULTS: The hyperglycemic rats showed increased tissue damage and impaired neurological performance after 1 day compared with controls. The hyperglycemia was generally moderate (< 15 mM). Erk activation was increased after 30 min of reperfusion in the ischemic cortex of the hyperglycemic rats, while JNK activation was present on the contralateral side. Phospho-Erk immunofluorescence revealed marked neuronal activation of Erk in the ischemic cortex of hyperglycemic rats compared with controls. CONCLUSION: Besides confirming the detrimental effects of hyperglycemia on focal ischemia-reperfusion, this study shows that hyperglycemia strongly activates the pathogenic mediator Erk in the ischemic brain in the early phase of reperfusion. JNK activation at this stage is present in the nonischemic hemisphere. The functional relevance of these findings needs further investigation.
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| 4. |
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| 5. |
- Farrokhnia, Nasim, et al.
(författare)
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Experimental treatment for focal hyperglycemic ischemic brain injury in the rat
- 2005
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Ingår i: Experimental Brain Research. - : Springer Science and Business Media LLC. - 0014-4819 .- 1432-1106. ; 167:2, s. 310-314
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Tidskriftsartikel (refereegranskat)abstract
- Hyperglycemia aggravates ischemic brain injury, possibly due to the activation of signaling pathways involving reactive oxygen species, Src and mitogen-activated protein kinases. The aim of this study was to investigate the effects of the spin trap agent alpha-phenyl-N-tert-butyl nitrone (PBN), the Src family kinase inhibitor PP2 and the MEK1-inhibitor U0126 on focal hyperglycemic ischemic brain injury. Temporary middle cerebral artery occlusion (90 min) was induced in four groups of rats (PBN, PP2, and U0126 vs. control). Neurological testing and tetrazolium red staining were performed after 1 day. PBN decreased the infarct volume by 70% compared with the control (P<0.05) and a tendency towards reduced infarcts was seen in the PP2 or U0126 groups. Furthermore, neurological testing was consistent with the volumetric analysis. In conclusion, PBN appears to be a potential neuroprotective agent in hyperglycemic, focal ischemic brain injury, while the efficacy of PP2 and U0126 could not be confirmed by the present data.
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| 6. |
- Jonasson, Mats, et al.
(författare)
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Design and evaluation of an active electromechanical wheel suspension system
- 2008
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Ingår i: Mechatronics (Oxford). - : Elsevier BV. - 0957-4158 .- 1873-4006. ; 18:4, s. 218-230
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Tidskriftsartikel (refereegranskat)abstract
- This paper presents an electromechanical wheel suspension, where the upper arm of the suspension has been provided with an electric levelling and a damper actuator, both are allowed to work in a fully active mode. A control structure for the proposed suspension is described. The complex design task involving the control of the electric damper and its machine parameters is tackled by genetic optimisation. During this process, these parameters are optimised to keep the power dissipation of the electric damper as low as possible, while maintaining acceptable comfort and road-holding capabilities. The results of the evaluations carried out demonstrate that the proposed suspension can easily adopt its control parameters to obtain a better compromise of performance than that offered by passive suspensions. If the vehicle is to maintain acceptable performance during severe driving conditions, the damper has to be unrealistically large. However, if the electric damper is combined with a hydraulic damper, the size of the electric damper is significantly reduced. In addition, the design of the electric damper with the suggested control structure, including how it regenerates energy, is discussed.
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| 7. |
- Kepka, Cecilia, et al.
(författare)
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Two-step recovery process for tryptophan tagged cutinase : Interfacing aqueous two-phase extraction and hydrophobic interaction chromatography
- 2005
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Ingår i: Journal of Chromatography A. - : Elsevier BV. - 0021-9673 .- 1873-3778. ; 1075:02-jan, s. 33-41
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Tidskriftsartikel (refereegranskat)abstract
- In this work, the interfacing of a poly(ethylene glycol) (PEG)-phosphate aqueous two-phase system with hydrophobic interaction chromatography (HIC) for primary recovery of an intracellular protein was evaluated. As a model protein, a recombinant cutinase furnished with a tryptophan-proline (WP) peptide tag was used and produced intracellularly in Escherichia coli (E. coli). E. coli cell homogenate was partitioned in a two-phase system and the top phase yield, concentration and purity of the tagged ZZ-cutinase-(WP)(4) was evaluated as function of polymer sizes, system pH and phase volume ratio. The partition behaviour of cell debris, total protein and endotoxin was also monitored. In the HIC part, the chromatographic yield and purity was investigated with respect to ligand hydrophobicity, dilution of loaded top phase and elution conditions. Based on the results, a recovery process was demonstrated where a PEG 1500-K-Na phosphate salt aqueous two-phase system was interfaced with a HIC column. The interfacing was facilitated by the Trp-tagged peptide. The tagged ZZ-cutinase-(WP)4 was obtained in a PEG-free phase and purified to > 95% purity according to silver stained sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) gels with a total yield of 83% during the two-step recovery process. © 2005 Elsevier B.V. All rights reserved.
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| 8. |
- Nordfjäll, Katarina, et al.
(författare)
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The individual blood cell telomere attrition rate is telomere length dependent.
- 2009
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Ingår i: PLoS genetics. - : Public Library of Science. - 1553-7404. ; 5:2, s. e1000375-
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Tidskriftsartikel (refereegranskat)abstract
- Age-associated telomere shortening is a well documented feature of peripheral blood cells in human population studies, but it is not known to what extent these data can be transferred to the individual level. Telomere length (TL) in two blood samples taken at approximately 10 years interval from 959 individuals was investigated using real-time PCR. TL was also measured in 13 families from a multigenerational cohort. As expected, we found an age-related decline in TL over time (r = -0.164, P<0.001, n = 959). However, approximately one-third of the individuals exhibited a stable or increased TL over a decade. The individual telomere attrition rate was inversely correlated with initial TL at a highly significant level (r = -0.752, P<0.001), indicating that the attrition rate was most pronounced in individuals with long telomeres at baseline. In accordance, the age-associated telomere attrition rate was more prominent in families with members displaying longer telomeres at a young age (r = -0.691, P<0.001). Abnormal blood TL has been reported at diagnosis of various malignancies, but in the present study there was no association between individual telomere attrition rate or prediagnostic TL and later tumor development. The collected data strongly suggest a TL maintenance mechanism acting in vivo, providing protection of short telomeres as previously demonstrated in vitro. Our findings might challenge the hypothesis that individual TL can predict possible life span or later tumor development.
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| 9. |
- Orho-Melander, Marju, et al.
(författare)
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Common Missense Variant in the Glucokinase Regulatory Protein Gene Is Associated With Increased Plasma Triglyceride and C-Reactive Protein but Lower Fasting Glucose Concentrations
- 2008
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Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 57:11, s. 3112-3121
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE-Using the genome-wide association approach, we recently identified the glucokinase regulatory protein gene (GCKR, rs780094) region as a novel quantitative trait locus for plasma triglyceride concentration in Europeans. Here, we sought to study the association of GCKR variants with metabolic phenotypes, including measures of glucose homeostasis, to evaluate the GCYR locus in samples of non-European ancestry and to fine-map across the associated genomic interval. RESEARCH DESIGN AND METHODS-We performed association studies in 12 independent cohorts comprising >45,000 individuals representing several ancestral groups (whites from Northern and Southern Europe, whites from the U.S., African Americans from the U.S., Hispanics of Caribbean origin, and Chinese, Malays, and Asian Indians from Singapore). We conducted genetic fine-mapping across the similar to 417-kb region of linkage disequilibrium. spanning GCKR and 16 other genes on chromosome 2p23 by imputing untyped HapMap single nucleotide polymorphisms (SNPs) and genotyping 104 SNPs across the associated genomic interval. RESULTS-We provide comprehensive evidence that GCYR rs780094 is associated with opposite effects on fasting plasma triglyceride (P-meta = 3 x 10(-56)) and glucose (P-meta = 1 x 10(-13)) concentrations. In addition, we confirmed recent reports that the same SNP is associated with C-reactive protein (CRP) level (P = 5 x 10(-5)). Both fine-mapping approaches revealed a common missense GCKR variant (rs1260326, Pro446Leu, 34% frequency, r(2) = 0.93 with rs780094) as the strongest association signal in the region. CONCLUSIONS-These findings point to a molecular mechanism in humans by which higher triglycerides and CRP can be coupled with lower plasma glucose concentrations and position GCKR in central pathways regulating both hepatic triglyceride and glucose metabolism. Diabetes 57:3112-3121, 2008
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| 10. |
- Palmqvist, Richard, et al.
(författare)
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hTERT gene copy number is not associated with hTERT RNA expression or telomerase activity in colorectal cancer
- 2005
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Ingår i: International Journal of Cancer. - Geneve : International union against cancer. - 0020-7136 .- 1097-0215. ; 116:3, s. 395-400
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Tidskriftsartikel (refereegranskat)abstract
- In a majority of malignant human tumors telomerase activity can be detected, suggesting an immortal phenotype. Expression of the reverse transcriptase subunit, hTERT, in the human telomerase complex is required for telomerase activity. The regulation of hTERT, from gene level to a fully functional protein, is still a poorly understood process. Increased copy number of the hTERT gene has been demonstrated in a significant portion of established cell lines and tumors of different origin but its relevance for telomerase activity levels is unclear. In the present study, we examined the hTERT gene copy number using fluorescence in situ hybridization (FISH) in samples from 64 colorectal carcinomas and an increased copy number (≥ 3 hTERT gene copies/nucleus) was observed in 31 cases (48%). No statistical association existed between hTERT gene copy number and hTERT RNA expression or telomerase activity. However, a significant relationship was found between an increase in hTERT gene copy number and p53 protein accumulation (p = 0.002) and aneuploidy (p = 0.036). Only 4 tumors showed microsatellite instability, 3 of which had a normal hTERT gene copy number. The data indicated that the increased copy number of the hTERT gene in colorectal carcinoma was a result of genomic instability with no obvious consequence for telomerase activity levels.
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| 11. |
- Roos, Fredrik
(författare)
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Electricity Supply Reliability: Evaluation of Improvement Solutions for Existing Electricity Networks
- 2005
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Regulation of the electricity network business is continuously under development in many countries. This is a reaction of an increasingly electricity dependent society, which demands electricity supplies at acceptable quality levels and at reasonable tariffs. Thus, electric network companies are facing new requirements that change the conditions for exercising network activities. Generally, incentives are given to the network companies to maintain the present level of reliability in a cost-efficient way. In Norway, however, incentives are given to the network companies to plan, operate and maintain the networks in a socio-economically optimal way, taking into account the supply-interruption cost to the customers. Therefore, in Norway, electricity network companies strive to identify and implement the most cost-efficient reliability improvement projects, i.e., the projects that yield the greatest overall reduction in supply-interruption cost to the customers for the invested money. In this thesis, implementations of reliability improvement solutions on a test system have been evaluated from a socio-economical point of view. For each of the alternative solutions implemented on the test system, the average annual supply-interruption cost to the customers supplied from the test system has been estimated. Furthermore, the maximum annual capital cost associated with the implementation of each solution has been estimated. Then, a reliability improvement solution is considered justified socioeconomically if the capital cost associated with its implementation is less than the resulting reduction in the interruption cost to the customers. The general conclusion from this thesis work is that the supply-interruption cost to the customers supplied from a test system can be reduced significantly by implementing reliability improvement solutions that are justified socioeconomically. Even if the uncertainty of the input data is taken into account, it is obvious from the results that the interruption cost to the test system customers can be reduced to at least half the initial value.
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| 12. |
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| 13. |
- Roos, Fredrik, 1976-
(författare)
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On design methods for mechatronics : servo motor and gearhead
- 2005
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The number of electric powered sub-systems in road-vehicles is increasing fast. This development is primarily driven by the new and improved functionality that can be implemented with electro-mechanical sub-systems, but it is also necessary for the transition to electric and hybrid-electric drive trains. An electromechanical sub-system can be implemented as a physically integrated mechatronic module: controller, power electronics, electric motor, transmission and sensors, all integrated into one component. A mechatronic module, spans, as all mechatronic systems, over several closely coupled engineering disciplines: mechanics, electronics, electro-mechanics, control theory and computer science. In order to design and optimize a mechatronic system it is therefore desirable to design the system within all domains concurrently. Optimizing each domain or component separately will not result in the optimal system design. Furthermore, the very large production volumes of automotive sub-systems increase the freedom in the mechatronics design process. Instead of being limited to the selection from off-the shelf components, application specific components may be designed. The research presented in this thesis aims at development of an integrated design and optimization methodology for mechatronic modules. The target of the methodology is the conceptual design phase, where the number of design parameters is relatively small. So far, the focus has been on design methods for the electric motor and gearhead, two of the most important components in an actuation module. The thesis presents two methods for design and optimization of motor and gearhead in mechatronic applications. One discrete method, intended for the selection of off-the-shelf components, and one method mainly intended for high volume applications where new application specific components may be designed. Both methods can handle any type of load combination, which is important in mechatronic systems, where the load seldom can be classified as pure inertial or constant speed. Furthermore, design models relating spur gear weight, size and inertia to output torque and gear ratio are presented. It is shown that a gearhead has significantly lower inertia and weight than a motor. The results indicate that it almost always is favorable from a weight and size perspective to use a gearhead. A direct drive configuration may only be lighter for very high speed applications. The main contribution of this thesis is however the motor/gear ratio sizing methods that can be applied to any electromechanical actuation system that requires rotational motion.
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| 14. |
- Roos, Fredrik, et al.
(författare)
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Optimal Selection of motor and gearhead in mechatronic applications
- 2006
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Ingår i: Mechatronics (Oxford). - : Elsevier BV. - 0957-4158 .- 1873-4006. ; 16:1, s. 63-72
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Tidskriftsartikel (refereegranskat)abstract
- A method for the selection of motor and gearhead in mechatronic applications is proposed. The method is applicable to any kind of load and helps to find the optimal motor gearhead combination with respect to output torque, peak power, mass/size and/or cost. The input to the method is the load cycle and component data on candidate motors and gearheads. Output is a set of graphs of all motor/gear ratio combinations that can drive the given load. From these graphs it is easy to read out the peak power, motor torque and energy efficiency for all feasible motor/gear ratio combinations.
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| 15. |
- Roos, Fredrik, et al.
(författare)
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Relations between size and gear ratio in spur and planetary gear trains
- 2005
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- In this report equations for the minimum gear sizes necessary to drive a given load are derived. The equations are based on the Swedish standards for spur gear dimensioning:SS 1863 and SS1871. Minimum size equations for both spur gear pairs and three-wheel planetary gears are presented. Furthermore, expressions for the gear weight and inertiaas function of gear ratio, load torque and gear shape are derived.For a given load torque and gear material, it is possible to retrieve the necessary gearsize, weight and inertia as function of gear ratio. This is useful for gear optimization,but also for optimization of a complete drive system, where the gear size, inertia and weight may affect the requirements on the other parts of the drive system.The results indicate that the Hertzian flank pressure limits the gear size in most cases.The teeth root bending stress is only limiting for very hard steels. Furthermore, then ecessary sizes, weights and inertias are shown to be smaller for planetary gears than for the equivalent pinion and gear configuration. Both these results are consistent with state of practice; planetary gears are commonly known to be compact and to have low inertia.
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| 16. |
- Roos, Fredrik, et al.
(författare)
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The influence of gear ratio on performance of electro-mechanical servo systems
- 2006
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Ingår i: Proceedings of the 4th IFAC Symposium on Mechatronic Systems. - : Elsevier BV. - 9783902661173 ; , s. 884-889
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Konferensbidrag (refereegranskat)abstract
- The gear ratio's influence on the performance of electromechanical servo systems is analyzed. Even though a gear primarily is used to reduce the actuator size and weight it is important to understand how the gear ratio affects the dynamics of the system. A good choice of gear ratio may improve the control performance while reducing the physical size of the system. It is concluded that for low gear ratios the plant bandwidth is increased with gear ratio. The torque margin of the motor is also shown to increase with gear ratio. Thus, from a control perspective, high gear ratios appear to be better than low.
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| 17. |
- Roos, Fredrik, 1976-
(författare)
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Towards a methodology for integrated design of mechatronic servo systems
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Traditional methods for mechatronics design are often based on a sequential approach, where the mechanical structure is designed first, and then fitted with off-the-shelf electric motors, drive electronics, gearheads and sensors. Finally a control system is designed and optimized for the already existing physical system. Such a design method, that doesn’t consider aspects from a control point of view during the design of the physical system, is unlikely to result in a system with optimal control performance. Furthermore, to separately design and optimize each of the physical components will, from a global perspective, generally not result in a system that is optimal from a weight, size or cost perspective. In order to reach the optimal design of an integrated mechatronic system (mechatronic module) it is necessary to treat the system as a whole, considering aspects from all involved engineering domains concurrently. In this thesis such an approach to integrated design of mechatronic servo systems is presented. A design methodology that considers the simultaneous design of the electric machine, gearhead, machine driver and control system, and therefore enables global optimization, has been developed. The target of the design methodology is conceptual design and evaluation. It is assumed that the load to be driven by the servo system is known and well defined, a load profile describing the wanted load motion and the corresponding torque, is required as input. The methodology can then be used to derive the lightest or smallest possible system that can drive the specified load. Furthermore, the control performance is evaluated and optimized, such that the physical system design and the controller design are integrated. The methodology is based on modelling and simulation. Two types of component models have been developed, static and dynamic models. The static models describe relations between the parameters of the physical components, for example a component’s torque rating as function of its size. The static models are based on traditional design rules and are used to optimize the physical parts of the system. The dynamic models describe the behaviour of the components and are used for control system design and performance optimization. The gear ratio is identified to be the most central design variable when designing and optimizing electromechanical servo systems. The gear ratio directly affects the required size of the gearhead, electric machine and the machine driver. But it has also large influences on the system’s control performance. It is concluded that high gear ratios generally are better from a control point of view than low ratios. A consequence of this is that it is possible, without compromising the control performance, to use less expensive (less accurate) sensors and microprocessors in high gear ratio servo systems, while low gear ratio systems require more expensive hardware. It is also concluded that it is essential to include all performance limiting phenomena, linear as well as non-linear, in this type of integrated analysis. Using for example a linearized system description for controller design, means that many of the most important couplings between control system and physical system design are overlooked.
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