| 1. |
- Adori, Csaba, et al.
(författare)
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Critical role of somatostatin receptor 2 in the vulnerability of the central noradrenergic system : new aspects on Alzheimer's disease
- 2015
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Ingår i: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 129:4, s. 541-563
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer's disease and other age-related neurodegenerative disorders are associated with deterioration of the noradrenergic locus coeruleus (LC), a probable trigger for mood and memory dysfunction. LC noradrenergic neurons exhibit particularly high levels of somatostatin binding sites. This is noteworthy since cortical and hypothalamic somatostatin content is reduced in neurodegenerative pathologies. Yet a possible role of a somatostatin signal deficit in the maintenance of noradrenergic projections remains unknown. Here, we deployed tissue microarrays, immunohistochemistry, quantitative morphometry and mRNA profiling in a cohort of Alzheimer's and age-matched control brains in combination with genetic models of somatostatin receptor deficiency to establish causality between defunct somatostatin signalling and noradrenergic neurodegeneration. In Alzheimer's disease, we found significantly reduced somatostatin protein expression in the temporal cortex, with aberrant clustering and bulging of tyrosine hydroxylase-immunoreactive afferents. As such, somatostatin receptor 2 (SSTR2) mRNA was highly expressed in the human LC, with its levels significantly decreasing from Braak stages III/IV and onwards, i.e., a process preceding advanced Alzheimer's pathology. The loss of SSTR2 transcripts in the LC neurons appeared selective, since tyrosine hydroxylase, dopamine beta-hydroxylase, galanin or galanin receptor 3 mRNAs remained unchanged. We modeled these pathogenic changes in Sstr2 (-/-) mice and, unlike in Sstr1 (-/-) or Sstr4 (-/-) genotypes, they showed selective, global and progressive degeneration of their central noradrenergic projections. However, neuronal perikarya in the LC were found intact until late adulthood (< 8 months) in Sstr2 (-/-) mice. In contrast, the noradrenergic neurons in the superior cervical ganglion lacked SSTR2 and, as expected, the sympathetic innervation of the head region did not show any signs of degeneration. Our results indicate that SSTR2-mediated signaling is integral to the maintenance of central noradrenergic projections at the system level, and that early loss of somatostatin receptor 2 function may be associated with the selective vulnerability of the noradrenergic system in Alzheimer's disease.
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| 2. |
- Enfors, Sven-Olof, et al.
(författare)
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Physiological responses to mixing in large scale bioreactors
- 2001
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Ingår i: Journal of Biotechnology. - 0168-1656 .- 1873-4863. ; 85:2, s. 175-185
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Tidskriftsartikel (refereegranskat)abstract
- Escherichia coli fed-batch cultivations at 22 m(3) scale were compared to corresponding laboratory scale processes and cultivations using a scale-down reactor furnished with a high-glucose concentration zone to mimic the conditions in a feed zone of the large bioreactor. Formate accumulated in the large reactor, indicating the existence of oxygen limitation zones. It is suggested that the reduced biomass yield at large scale partly is due to repeated production/reassimilation of acetate from overflow metabolism and mixed acid fermentation products due to local moving zones with oxygen limitation. The conditions that generated mixed-acid fermentation in the scale-down reactor also induced a number of stress responses, monitored by analysis of mRNA of selected stress induced genes. The stress responses were relaxed when the cells returned to the substrate limited and oxygen sufficient compartment of the reactor. Corresponding analysis in the large reactor showed that the concentration of mRNA of four stress induced genes was lowest at the sampling port most distant from the feed zone. It is assumed that repeated induction/relaxation of stress responses in a large bioreactor may contribute to altered physiological properties of the cells grown in large-scale bioreactor. Flow cytometric analysis revealed reduced damage with respect to cytoplasmic membrane potential and integrity in cells grown in the dynamic environments of the large scale reactor and the scale-down reactor.
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| 3. |
- Kovacs, T., et al.
(författare)
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Flow and turbulence in the discharge of radial pumping turbines : Influence of the turbine type
- 2001
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Ingår i: Chemical Engineering & Technology. - 0930-7516 .- 1521-4125. ; 24:10, s. 1035-1044
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Tidskriftsartikel (refereegranskat)abstract
- Velocity measurements were made in the impeller discharge of 6SRGT- and Rushton-type impellers in a 0.6 m(3) tank using, constant temperature anemometry with a direction sensitive split-film probe. The reproducibility error of the measurement system was found to be greater than 5 % for all measured properties. The main flow and turbulent parameters measured at three agitation rates in the impeller discharge are compared for the two turbines with respect to both agitation rate and the measured power input. For comparison of the flow properties in the centerline of the two turbines having different diameter and blade height, a uniform representation was used treating the impeller stream as a special kind of free jet. Using this representation, we obtained similar results for both turbines on all measured parameters. The profile measurements showed a similar main flow field for both turbines, but significant differences were found in the axial distribution of turbulent kinetic energy and the energy dissipation rate.
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| 4. |
- Kovacs, T., et al.
(författare)
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Fourier spectrum to recover deterministic and stochastic behavior in stirred tanks
- 2001
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Ingår i: AIChE Journal. - : Wiley. - 0001-1541 .- 1547-5905. ; 47:10, s. 2167-2176
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Tidskriftsartikel (refereegranskat)abstract
- Velocity data from the impeller region of Rushton and 6SRGT pilot-scale impellers were analyzed both in the frequency domain and with respect to periodicity. The four characteristic frequencies and their combination were detected from the Fourier spectrum, and the deterministic part of the signal was recovered by making the amplitude of the other frequencies zero. The deterministic part was then analyzed with tools from nonlinear theories. For the two turbine-types, the dynamics of the deterministic velocity parts were almost identical. The turbulent part of the signal could also be estimated in a similar manner.
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| 5. |
- Revstedt, J., et al.
(författare)
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Influence of impeller type on the flow structure in a stirred reactor
- 2000
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Ingår i: AIChE Journal. - : Wiley. - 0001-1541 .- 1547-5905. ; 46:12, s. 2373-2382
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Tidskriftsartikel (refereegranskat)abstract
- Large eddy simulations (LES) of a stirred reactor with a liquid volume of 0.64 m(3) were performed. The tank was stirred by either two standard Rushton impellers or two Scaba 6SRGT impellers. The LES can provide details of the flow field that cannot be obtained with so-called Reynolds-averaged equations and the corresponding models. The unsteady spatially filtered incompressible Navier-Stokes equations were solved together with a transport equation for the concentration of an inert additive using a multigrid finite difference code with a staggered grid. The unresolved turbulent scales were modeled using a scale similarity model. The aim of this investigation has been to study the influence of impeller type on the flow structure and scalar transport. The results show that, compared at equal power input, the center plane velocities and the volume flow in the impeller stream do not differ much for the impeller types. Also, for the 6SRGT the periodic fluctuations associated with the blade passing is less pronounced.
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