Modelling geomagnetically induced currents in midlatitude Central Europe using a thin-sheet approach

Geomagnetically induced currents (GICs) in power systems, which can lead to transformer damage over the short and the long term, are a result of space weather events and geomagnetic variations. For a long time, only high-latitude areas were considered to be at risk from these currents, but recent studies show that considerable GICs also appear in midlatitude and equatorial countries. In this paper, we present initial results from a GIC model using a thin-sheet approach with detailed surface and subsurface conductivity models to compute the induced geoelectric field. The results are compared to measurements of direct currents in a transformer neutral and show very good agreement for short-period variations such as geomagnetic storms. Long-period signals such as quiet-day diurnal variations are not represented accurately, and we examine the cause of this misfit. The modelling of GICs from regionally varying geoelectric fields is discussed and shown to be an important factor contributing to overall model accuracy. We demonstrate that the Austrian power grid is susceptible to large GICs in the range of tens of amperes, particularly from strong geomagnetic variations in the east–west direction

J Neurosci

The endogenous dynorphin-kappa opioid receptor (KOR) system encodes the dysphoric component of the stress response and controls the risk of depression-like and addiction behaviors; however, the molecular and neural circuit mechanisms are not understood. In this study, we report that KOR activation of p38alpha MAPK in ventral tegmental (VTA) dopaminergic neurons was required for conditioned place aversion (CPA) in mice. Conditional genetic deletion of floxed KOR or floxed p38alpha MAPK by Cre recombinase expression in dopaminergic neurons blocked place aversion to the KOR agonist U50,488. Selective viral rescue by wild-type KOR expression in dopaminergic neurons of KOR(-/-) mice restored U50,488-CPA, whereas expression of a mutated form of KOR that could not initiate p38alpha MAPK activation did not. Surprisingly, while p38alpha MAPK inactivation blocked U50,488-CPA, p38alpha MAPK was not required for KOR inhibition of evoked dopamine release measured by fast scan cyclic voltammetry in the nucleus accumbens. In contrast, KOR activation acutely inhibited VTA dopaminergic neuron firing, and repeated exposure attenuated the opioid response. This adaptation to repeated exposure was blocked by conditional deletion of p38alpha MAPK, which also blocked KOR-induced tyrosine phosphorylation of the inwardly rectifying potassium channel (GIRK) subunit Kir3.1 in VTA dopaminergic neurons. Consistent with the reduced response, GIRK phosphorylation at this amino terminal tyrosine residue (Y12) enhances channel deactivation. Thus, contrary to prevailing expectations, these results suggest that kappa opioid-induced aversion requires regulation of VTA dopaminergic neuron somatic excitability through a p38alpha MAPK effect on GIRK deactivation kinetics rather than by presynaptically inhibiting dopamine release. SIGNIFICANCE STATEMENT: Kappa opioid receptor (KOR) agonists have the potential to be effective, nonaddictive analgesics, but their therapeutic utility is greatly limited by adverse effects on mood. Understanding how KOR activation produces dysphoria is key to the development of better analgesics and to defining how the endogenous dynorphin opioids produce their depression-like effects. Results in this study show that the aversive effects of kappa receptor activation required arrestin-dependent p38alpha MAPK activation in dopamine neurons but did not require inhibition of dopamine release in the nucleus accumbens. Thus, contrary to the prevailing view, inhibition of mesolimbic dopamine release does not mediate the aversive effects of KOR activation and functionally selective kappa opioids that do not activate arrestin signaling may be effective analgesics lacking dysphoric effects

Human native kappa opioid receptor functions not predicted by recombinant receptors: Implications for drug design

International audienc

Traenkverfahren und Vorrichtung zur Ueberwachung der Durchtraenkung eines Traegermaterials

DE 19745404 A UPAB: 19990603 NOVELTY - For the impregnation of a carrier material, by immersion, the dielectric constant of the material changes during impregnation. A value (C) is measured, related to the dielectric constant, which gives the impregnating penetration (D) of the carrier material. DETAILED DESCRIPTION - In an INDEPENDENT CLAIM the monitoring system has a conductor (3) so that the carrier material acts as a dielectric to affect the electrical capacity of the conductor (3), which is measured. The conductor can be an electrically conductive strip, around the carrier material, with the electrical lead of the conductor rod. To measure the value (C), the electrical capacity is used of an electrical conductor, with the carrier material acting as a dielectric. The timed run (C(t)) of the measurement gives the timed run (D(t)) of the impregnation. A functional relationship (DR(C)) between a reference impregnation (DR) and the measured value gives the functional relationship of the impregnation. The timed run (D(t)) of the impregnation (D) is expressed as D(t)=DR(C(t)), where D is the impregnation, DR the reference impregnation, C the measured value and especially capacity, and t is the time. The amount of impregnation is defined as the ratio of impregnated and non-impregnated vols. of the carrier material. To determine the stages of impregnation, according to given parameters, each stage has a reference impregnation provided by a simulation model with a spaced distribution in the carrier material with at least one zone which is not impregnated and one zone which is impregnated. At least one dry zone (4) has an initial dielectric constant and at least one damp zone (5) has another dielectric constant. Each reference impregnation (DR), together with the dielectric constants, is associated with a measured value (C) to give the required functional relationship (CD(C)). Using a porous carrier material, the spaced distribution of the reference impregnation (DR) uses the Darcy law for a current of a Newton impregnation medium or by using a suitable modification of the Darcy law for a non-Newton impregnation medium. From the impregnation (D), the penetration depth is derived of the impregnation medium in the carrier material, in a timed run of the penetration and at least one factor of the filtration coefficient, flow resistance, permeability and relative porosity, which also gives the viscosity of the impregnating medium. The material can be the fibers, to be impregnated and form the compound material, or the carrier material is an electrical insulation. USE - The system is for the impregnation of a carrier for use in resin transfer molding, using a compound material of fibers impregnated with a resin. It can be used for applications such as for the insulation of a conductor rod at the stator of a generator and especially a turbo generator, or the impregnation of the coil of the stator of a generator, and especially a turbo generator, in a total immersion impregnation, and the impregnation indicates if there is an impregnation fault. ADVANTAGE - The system gives an effective impregnation of the carrier material, with positive indications of a fault in the process

A method for the analysis and control of mica tape impregnation processes

The impregnation of mica tape insulations usually is monitored with dielectric capacitance measurements. In this work, a method is developed that translates measured capacitance and loss into an average drag coefficient that characterizes flow resistance, which is the critical parameter of the process. In a first step, the impregnation depth is determined based on an appropriate model of the dielectric measurement. The impregnation depth curve and its derivative are then used to compute the average drag coefficient, which is defined in the framework of a standard porous media flow model. The method has been developed and tested for cylindrical insulators. Appropriate extensions to rectangular insulators are indicated

Release of endogenous dynorphin opioids in the prefrontal cortex disrupts cognition

Following repeated opioid use, some dependent individuals experience persistent cognitive deficits that contribute to relapse of drug-taking behaviors, and one component of this response may be mediated by the endogenous dynorphin/kappa opioid system in neocortex. In C57BL/6 male mice, we find that acute morphine withdrawal evokes dynorphin release in the medial prefrontal cortex (PFC) and disrupts cognitive function by activation of local kappa opioid receptors (KORs). Immunohistochemical analyses using a phospho-KOR antibody confirmed that both withdrawal-induced and optically evoked dynorphin release activated KOR in PFC. Using a genetically encoded sensor based on inert KOR (kLight1.2a), we revealed the in vivo dynamics of endogenous dynorphin release in the PFC. Local activation of KOR in PFC produced multi-phasic disruptions of memory processing in an operant-delayed alternation behavioral task, which manifest as reductions in response number and accuracy during early and late phases of an operant session. Local pretreatment in PFC with the selective KOR antagonist norbinaltorphimine (norBNI) blocked the disruptive effect of systemic KOR activation during both early and late phases of the session. The early, but not late phase disruption was blocked by viral excision of PFC KORs, suggesting an anatomically dissociable contribution of pre- and postsynaptic KORs. Naloxone-precipitated withdrawal in morphine-dependent mice or optical stimulation of pdynCre neurons using Channelrhodopsin-2 disrupted delayed alternation performance, and the dynorphin-induced effect was blocked by local norBNI. Our findings describe a mechanism for control of cortical function during opioid dependence and suggest that KOR antagonism could promote abstinence

Activation of the kappa opioid receptor in the dorsal raphe nucleus mediates the aversive effects of stress and reinstates drug seeking

Although stress has profound effects on motivated behavior, the underlying mechanisms responsible are incompletely understood. In this study we elucidate a functional pathway in mouse brain that encodes the aversive effects of stress and mediates stress-induced reinstatement of cocaine place preference (CPP). Activation of the dynorphin/kappa opioid receptor (KOR) system by either repeated stress or agonist produces conditioned place aversion (CPA). Because KOR inhibition of dopamine release in the mesolimbic pathway has been proposed to mediate the dysphoria underlying this response, we tested dopamine-deficient mice in this study and found that KOR agonist in these mice still produced CPA. However, inactivation of serotonergic KORs by injection of the KOR antagonist norBNI into the dorsal raphe nucleus (DRN), blocked aversive responses to the KOR agonist U50,488 and blocked stress-induced reinstatement of CPP. KOR knockout (KO) mice did not develop CPA to U50,488; however, lentiviral re-expression of KOR in the DRN of KOR KO mice restored place aversion. In contrast, lentiviral expression in DRN of a mutated form of KOR that fails to activate p38 MAPK required for KOR-dependent aversion, did not restore place aversion. DRN serotonergic neurons project broadly throughout the brain, but the inactivation of KOR in the nucleus accumbens (NAc) coupled with viral re-expression in the DRN of KOR KO mice demonstrated that aversion was encoded by a DRN to NAc projection. These results suggest that the adverse effects of stress may converge on the serotonergic system and offers an approach to controlling stress-induced dysphoria and relapse