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EN
Injury to the mature central nervous system (CNS) induces a series of transient changes leading not only to death of neurons, but also to spontaneous rearrangement of the affected network. One of such pro plastic events, detected following injury, is an increased level of neurotrophins. Neurotrophins are a family of proteins involved in survival and outgrowth processes. The other one, more difficult to observe, is a change in the complexity of the dendritic tree, causing arborization or pruning, depending on many circumstances: i.e. lesion etiology. Subsequent therapies like enriched environment or locomotor exercise bring about a functional improvement, which was found to further increase the neurotrophin level and induced additional arborization of dendrites. Another important consequence of damage to CNS connections is deafferentation, shown to induce a down regulation of outgrowth inhibitors. Their suppression in turn may facilitate dendritic plasticity. Taken together, these factors may contribute to enhanced plasticity in the injured mature CNS. Thus the proper use of endogenously increased plastic potential seems to be important for design and optimizing therapeutic strategies. Further investigation of mechanisms involved in switching on plasticity may help to improve on existing therapies and find new ways to obtain better recovery following injury.
EN
The aim of this paper is to introduce a matrix approach for approximate solving of non-commensurate fractional variable order linear control systems in state-space form. The approach is based on switching schemes that realize variable order derivatives. The obtained numerical solution is compared with simulation and analog model results.
EN
Introduction: Mammalian target of rapamycin (mTOR) is a protein kinase that regulates cellular metabolism. Adequate mTOR activity is needed for development as well as proper physiology of mature neurons. Changes in mTOR activity are often observed in neuropathology. Several groups reported that seizures increase mTOR activity, and mTOR contributes to spontaneous seizures. However, the current knowledge about 1) the spatiotemporal and 2) the subcellular pattern of mTOR activation as well as 3) mTOR downstream effectorsin epilepsy is limited. Effects of mTOR insufficiency in seizures also remain under investigated. Aim: The aim of my team is to understand regulation and contribution of mTOR to epilepsy and pinpointing cellular mechanisms downstream mTOR. Methods: To study a role of mTOR in epilepsy we used models of pharmacological treatment with kainic acid (KA). We performed analysis of status epilepticus (SE) severity and progression. We analyzed with quantitative Western-blot and microarrays changes in signaling pathways and gene expression. Subcellular distribution of mTOR and its activity was analyzed by live microscopy. Results: We showed that SE induces mTOR first in neurons and next in astrocytes. At early times post seizures mTOR translocates to the nucleus, where its activity increases gradually. We showed that mTOR is involved in KA-dependent gene expression and genes regulated by mTOR regulate cytoskeleton. One of them, Elmo-1 regulates axonal growth and dendritic spine changes. Our research shows also that insufficient mTOR activity lead to increased sensitivity to KA. Conclusions: mTOR is an important player in epilepsy. One of the processes likely controlled by mTOR in epilepsy is transcription of genes responsible for cytoskeleton rearrangement. On the other hand, insufficient mTOR activity decreases threshold for epileptic-like neuronal activity. FINANCIAL SUPPORT: The research was supported by Polish National Science Centre (grants no. 2012/05/B/ NZ3/00429; 2012/07/E/NZ3/00503), 7FP grant (no. 602391, “EPISTOP”) and the Polish Ministerial funds for science (years 2014–2018) for the implementation of international co‑financed project. JJ is a recipient of the Foundation for Polish Science “Mistrz” Professorial Subsidy.
EN
The common effects of epileptic seizures are aberrant plastic changes in synaptic connectivity and morphological rearrangements in hippocampal mossy fi bers. This phenomenon is believed to be a basis of facilitation of further epileptic episodes, however its molecular mechanism remains elusive. mTOR kinase is crucial for rearrangements of neuronal morphology and for long term synaptic plasticity. Overactivation of mTOR was reported in brain pathologies associated with seizures (tuberous sclerosis, cortical dysplasia). Experimental evidence supports causative role of mTOR in these forms of epilepsy. So far, however, links of mTOR signaling pathway to other types of epilepsy are unknown. To address this issue we investigated activation of mTOR and its downstream effectors in rat brain after kainic acid (KA) induced epilepsy. Animals were sacrifi ced 2, 6, 12, 24 and 72 hours after KA administration and levels of phosphorylated mTOR and S6 has been examined. Both, biochemical methods and immunohistochemistry proved S6 activation in hippocampus and cerebral cortex at all time points after KA. Immunohistochemical analysis additionally revealed that 2 h after KA, activities of mTOR and S6 are upregulated mainly in neurons while after 6 h there was also enhancement of glial S6 immunoreactivity. Our data suggest that KA induced seizures activate mTOR signaling in various cell types with specifi c spatio-temporal pattern. This work has been fi nanced by PNRF-96-AI-1/07 grant.
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Content available remote Accurate CPC power analysis under extreme EAF’s distortion conditions
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EN
Electric Arc Furnaces (EAF) are huge energy consumer. However due a limited power calculation the maximum electrical efficiency is not obtained. Most of the applications in market report the usage of inaccurate power quantities in EAF power control system. Because the extreme distortion conditions of power phenomena produced by the nonlinearity of the load in the EAF, the implementation of Current’s Physical Components (CPC) power theory has the potential of describing more appropriate than traditional power theories the physical load conditions and the electric power phenomenon during the Heat Process. Each one of the current components proposed by CPC offer useful information of the load condition, and give indicators which can be useful as stability indicators of the process for a better identification of the EAF stage.
PL
Piece łukowe rzadko osiągają maksymalną skuteczność. Zastosowanie metody Current Physical Component pozwala bardziej dokładnie analizować warunki obciążenia podczas wyładowania i tym samym osiągać mniejsze zniekształcenia i lepszą skuteczność.
10
Content available remote CPC power theory for analysis of arc furnaces
51%
EN
Electric Arc Furnaces (EAFs) are facilities with an intensive use of energy where small improvements in their control imply significant electrical energy savings. The electric arcs are highly nonlinear and chaotic; a power theory for non-sinusoidal voltages and currents is needed for the analysis of the EAFs. The Current´s Physicals Components (CPC) power theory allows an advanced engineering analysis of the energy transfer at arc furnaces since each one of the current components can be used as performance indicators to improve EAFs power control.
PL
Piece łukowe są bardzo nieliniowe i chaotyczne dlatego są bardzo trudne do analizy. Wykorzystanie teorii CPC (Current Physical Components) umożliwia bardziej dokładną analizę przenoszenia energii i poprawę sterowania mocą.
EN
INTRODUCTION: The mechanistic target of rapamycin (mTOR) is a protein kinase, which integrates eukaryotic cell growth, metabolism and external stimuli. Most research link mTOR with control of protein translation but recent studies revealed additional mTOR function in cell nucleus. Previously, we showed that phosphorylation of mTOR (Ser2448; P-mTOR) is upregulated in neuronal nucleus upon kainate (KA) induced status epilepticus. Whether other stimuli have the same effect on nuclear mTOR phosphorylation and if increased nuclear import of mTOR contributes to this phenomenon remained unknown. Also it was not known if nuclear transport of other proteins affects mTOR signaling. AIM(S): To analyze effects of neuronal activity on nuclear translocation of mTOR and its nuclear activity. To analyze importance of nuclear transport for mTOR signaling. METHOD(S): Cultured hippocampal neurons were treated with: KA, BDNF; NMDA and chemical LTP (cLTP) protocol or TTX. mTOR activity was measured with FRET method. mTOR nuclear translocation was assessed using FRAP. Nuclear import was blocked with importazole. Immunofluorescence of P-S6 protein was used as a marker of mTOR activity. RESULTS: We found that KA, BDNF, NMDA and cLTP caused nuclear upregulation of P-mTOR. However, TTX or cLTD had no effect. FRAP and FRET revealed that mTOR activity due to KA treatment is first observed in cytosol and then in nucleus, where mTOR is translocated upon treatment. Blocking nuclear import silenced mTOR activity in response to KA and inhibited P-mTOR upregulation in the nucleus. CONCLUSIONS: Our experiments showed that increased neuronal activity upregulates nuclear P-mTOR and increases nuclear activity of mTOR due to nuclear translocation of the kinase. FINANCIAL SUPPORT: The research was supported by PNSC grants no. 2012/05/B/NZ3/00429 and 2012/07/E/ NZ3/00503.
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