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- Cenci Nilsson, Angela
(författare)
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Transcription factors involved in the pathogenesis of L-DOPA-induced dyskinesia in a rat model of Parkinson's disease.
- 2002
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Ingår i: Amino Acids. - : Springer Science and Business Media LLC. - 0939-4451 .- 1438-2199. ; 23:1-3, s. 105-109
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Tidskriftsartikel (refereegranskat)abstract
- L-DOPA-induced dyskinesia (abnormal involuntary movements) is one of the most debilitating complications of chron-ic L-DOPA pharmacotherapy in Parkinson's disease. It is generally agreed that dyskinesia arises as a consequence of pulsatile dopamine-receptor stimulation in the brain, causing downstream changes in genes and proteins. Advance in our understanding of such changes is critically dependent on the availability of suitable animal models. We have introduced a new method to classify and rate L-DOPA-induced abnormal involuntary movements (AIMs) in 6-hydroxydopamine (6-OHDA) lesioned rats. This method allows us to dissect the molecular correlates of a dyskinetic motor response to L-DOPA in this species. One of the most prominent molecular changes underlying the development of dyskinesia in the rat consists in the striatal induction of prodynorphin gene expression by L-DOPA. This effect is mediated by FosB-related transcription factors of 32-37 kDa, which are co-induced with prodynophin in striatal neurons of the "direct pathway". Both AIM development and the associated upregulation of prodynorphin mRNA by L-DOPA are significantly inhibited by the intrastriatal infusion of fosB antisense. Antisense-mediated knockdown of CREB (cyclic AMP response-element binding proteins) has however no effect. Our results identify fosB as a potential target for adjunctive antiparkinsonian therapies.
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| 6. |
- Sharma, HS, et al.
(författare)
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Nitric oxide synthase inhibitors influence dynorphin A (1-17) immunoreactivity in the rat brain following hyperthermia
- 2002
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Ingår i: Amino Acids. - : Springer Science and Business Media LLC. - 0939-4451 .- 1438-2199. ; 23:1-3, s. 247-259
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Tidskriftsartikel (refereegranskat)abstract
- The possibility that nitric oxide synthase (NOS) inhibitors influence dynorphin immunoreactivity following hyperthermia was examined in a rat model using a pharmacological approach. Previous reports from our laboratory show that hyperthermia induces an upregulation of NOS in several brain regions that seems to be instrumental in causing cell injury. Recent reports suggest that nitric oxide (NO) can influence dynorphin neurotransmission in the normal brain as well as in several pathological states. Since dynorphin is neurotoxic in different animal models of brain or spinal cord injury, it may be that the peptide will contribute to the cell injury in hyperthermia. The present investigation was carried out to determine whether hyperthermia can influence dynorphin immunoreactivity in the brain, and if so, whether inhibition of NOS will influence the peptide distribution in the brain following heat stress. Rats subjected to hyperthermia at 38degreesC for 4 h in a biological oxygen demand incubator (BOD) resulted in a marked upregulation of dynorphin immunoreactivity in several brain regions e.g., cerebral cortex, hippocampus, cerebellum and brain stem. Pretreatment of rats with two potent NOS inhibitors, L-NAME (30 mg/kg/day, i.p. for 7 days) or L-NMMA (35 mg/kg/day, i.p. for 7 days) significantly attenuated the dynorphin immunoreactivity in the brain. These drugs were also able to reduce hyperthermia induced blood-brain barrier (BBB) permeability, brain edema formation and cell injury. Taken together, our results suggest that (i) hyperthermia has the capacity to upregulate dynorphin immunoreactivity in the brain, (ii) inhibition of NOS considerably attenuates the dynorphin immunoreaction following heat stress and (iii) upregulation of dynorphin is somehow contributing to hyperthermia induced brain damage, not reported earlier.
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| 7. |
- Afshar, Sara, et al.
(författare)
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Per Processor Spin-Lock Priority for Partitioned Multiprocessor Real-Time Systems
- 2017
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Ingår i: Leibniz Transactions on Embedded Systems. - 2199-2002. ; :2
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Two traditional approaches exist for a task that is blocked on a global resource; a task either performs a non-preemptive busy wait, i.e., spins, or suspends and releases the processor. Previously, we have shown that both approaches can be viewed as spinning either at the highest priority HP or at the lowest priority on the processor LP, respectively. Based on this view, previously we have generalized a task's blocking behavioral model, as spinning at any arbitrary priority level. In this paper, we focus on a particular class of spin-lock protocols from the introduced flexible spin-lock model where spinning is performed at a priority equal to or higher than the highest local ceiling of the global resources accessed on a processor referred to as CP spin-lock approach. In this paper, we assume that all tasks of a specific processor are spinning on the same priority level. Given this class and assumption, we show that there exists a spin-lock protocol in this range that dominates the classic spin-lock protocol which tasks spin on highest priority level (HP). However we show that this new approach is incomparable with the CP spin-lock approach. Moreover, we show that there may exist an intermediate spin-lock approach between the priority used by CP spin-lock approach and the new introduced spin-lock approach that can make a task set schedulable when those two cannot. We provide an extensive evaluation results comparing the HP, CP and the new proposed approach.
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| 8. |
- Krüger, Kristin, et al.
(författare)
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Randomization as Mitigation of Directed Timing Inference Based Attacks on Time-Triggered Real-Time Systems with Task Replication
- 2021
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Ingår i: Leibniz Transactions on Embedded Systems. - 2199-2002.
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Tidskriftsartikel (refereegranskat)abstract
- Time-triggered real-time systems achieve deterministic behavior using schedules that are constructed offline, based on scheduling constraints. Their deterministic behavior makes time-triggered systems suitable for usage in safety-critical environments, like avionics. However, this determinism also allows attackers to fine-tune attacks that can be carried out after studying the behavior of the system through side channels, targeting safety-critical victim tasks. Replication -- i.e., the execution of task variants across different cores -- is inherently able to tolerate both accidental and malicious faults (i.e. attacks) as long as these faults are independent of one another. Yet, targeted attacks on the timing behavior of tasks which utilize information gained about the system behavior violate the fault independence assumption fault tolerance is based on. This violation may give attackers the opportunity to compromise all replicas simultaneously, in particular if they can mount the attack from already compromised components. In this paper, we analyze vulnerabilities of time-triggered systems, focusing on safety-certified multicore real-time systems. We introduce two runtime mitigation strategies to withstand directed timing inference based attacks: (i) schedule randomization at slot level, and (ii) randomization within a set of offline constructed schedules. We evaluate these mitigation strategies with synthetic experiments and a real case study to show their effectiveness and practicality.
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- Chatzigiannakou, Maria Angeliki, et al.
(författare)
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Offshore deployments of wave energy converters by Uppsala University, Sweden
- 2019
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Ingår i: Marine Systems and Ocean Technology. - : Springer Science and Business Media LLC. - 1679-396X .- 2199-4749. ; 14:2-3, s. 67-74
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Tidskriftsartikel (refereegranskat)abstract
- Ocean can provide an inexhaustible amount of energy. Many marine energy converters have been developed but most of them have not surpassed the experimental phase due to the high costs in installation, operation, and maintenance. Since 2002 Uppsala University has developed and deployed several units of wave energy converters of various designs. The Uppsala University wave energy converter concept consists of a linear generator directly connected to a point absorber buoy that is mounted on a concrete gravity foundation. Uppsala University deployments have been carried out using different deployment vessels and methods. Three main methods were utilized for these deployments that are discussed in terms of cost, manpower, and time efficiency. Depending on the desired outcome—multiple- or single-device deployment, low budget, etc.—one of the proposed methods can be used for the optimal outcome.
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