The usage of remote signals obtained from a wide-area measurement system (WAMS) introduces time delays to a wide-area damping controller (WADC), which would degrade system damping and even cause ...system instability. The time-delay margin is defined as the maximum time delay under which a closed-loop system can remain stable. In this paper, the delay margin is introduced as an additional performance index for the synthesis of classical WADCs for flexible ac transmission systems (FACTS) devices to damp inter-area oscillations. The proposed approach includes three parts: a geometric measure approach for selecting feedback remote signals, a residue method for designing phase-compensation parameters, and a Lyapunov stability criterion and linear matrix inequalities (LMI) for calculating the delay margin and determining the gain of the WADC based on a tradeoff between damping performance and delay margin. Three case studies are undertaken based on a four-machine two-area power system for demonstrating the design principle of the proposed approach, a New England ten-machine 39-bus power system and a 16-machine 68-bus power system for verifying the feasibility on larger and more complex power systems. The simulation results verify the effectiveness of the proposed approach on providing a balance between the delay margin and the damping performance.
•The neosynthesis of xanthurenic acid (XA) from 3-hydroxykynurenine (3-HK) was examined in mice, rats and humans.•In all 3 species, XA formation from 3-HK was traced to a major role of kynurenine ...aminotransferase II (KAT II).•In slices from rat hippocampus, both 3-HK and XA reduced the slopes of dentate gyrus field EPSPs.•Endogenous XA, newly formed from 3-HK, may play a physiological role in attentional and cognitive processes.
Xanthurenic acid (XA), formed from 3-hydroxykynurenine (3-HK) in the kynurenine pathway of tryptophan degradation, may modulate glutamatergic neurotransmission by inhibiting the vesicular glutamate transporter and/or activating Group II metabotropic glutamate receptors. Here we examined the molecular and cellular mechanisms by which 3-HK controls the neosynthesis of XA in rat, mouse and human brain, and compared the physiological actions of 3-HK and XA in the rat brain. In tissue homogenates, XA formation from 3-HK was observed in all three species and traced to a major role of kynurenine aminotransferase II (KAT II). Transamination of 3-HK to XA was also demonstrated using human recombinant KAT II. Neosynthesis of XA was significantly increased in the quinolinate-lesioned rat striatum, indicating a non-neuronal localization of the process. Studies using rat cortical slices revealed that newly produced XA is rapidly released into the extracellular compartment, and that XA biosynthesis can be manipulated experimentally in the same way as the production of kynurenic acid from kynurenine (omission of Na+ or glucose, depolarizing conditions, or addition of 2-oxoacids). The synthesis of XA from 3-HK was confirmed in vivo by striatal microdialysis. In slices from the rat hippocampus, both 3-HK and XA reduced the slopes of dentate gyrus field EPSPs. The effect of 3-HK was reduced in the presence of the KAT inhibitor aminooxyacetic acid. Finally, both 3-HK and XA reduced the power of gamma-oscillatory activity recorded from the hippocampal CA3 region. Endogenous XA, newly formed from 3-HK, may therefore play a physiological role in attentional and cognitive processes.
Cognitive deficits represent core symptoms in schizophrenia (SZ) and predict patient outcome; however, they remain poorly treated by current antipsychotic drugs. Elevated levels of the endogenous ...alpha7 nicotinic receptor negative allosteric modulator and NMDA receptor antagonist, kynurenic acid (KYNA), are commonly seen in post-mortem tissue and cerebrospinal fluid of patients with SZ. When acutely or chronically elevated in rodents, KYNA produces cognitive deficits similar to those seen in the disease, making down-regulation of KYNA, via inhibition of kynurenine aminotransferase II (KAT II), a potential treatment strategy. We determined, in adult Wistar rats, if the orally available KAT II inhibitor BFF816 a) prevents KYNA elevations in prefrontal cortex (PFC) after a systemic kynurenine injection and b) reverses the kynurenine-induced attenuation of evoked prefrontal glutamate release caused by stimulation of the nucleus accumbens shell (NAcSh). Systemic injection of kynurenine (25 or 100 mg/kg, i.p.) increased KYNA levels in PFC (532% and 1104% of baseline, respectively). NMDA infusions (0.15 μg/0.5 μL) into NAcSh raised prefrontal glutamate levels more than 30-fold above baseline. The two doses of kynurenine reduced evoked glutamate release in PFC (by 43% and 94%, respectively, compared to NMDA alone). Co-administration of BFF816 (30 or 100 mg/kg, p.o.) with kynurenine (25 mg/kg, i.p.) attenuated the neosynthesis of KYNA and dose-dependently restored NMDA-stimulated glutamate release in the PFC (16% and 69%, respectively). The ability to prevent KYNA neosynthesis and to normalize evoked glutamate release in PFC justifies further development of KAT II inhibitors for the treatment of cognitive deficits in SZ.
•Kynurenine increases KYNA and attenuates evoked glutamate release in PFC.•BFF816 decreases basal and elevated KYNA in PFC.•BFF816 rescues kynurenine-induced reductions in evoked glutamate in PFC.•Control of KYNA levels justifies the use of KAT II inhibitors for treatment in SZ.
The forecasting of electricity demand has become one of the major research fields in electrical engineering. Accurately estimated forecasts are essential part of an efficient power system planning ...and operation. In this paper, a modified version of the support vector regression (SVR) is presented to solve the load forecasting problem. The proposed model is derived by modifying the risk function of the SVR algorithm with the use of locally weighted regression (LWR) while keeping the regularization term in its original form. In addition, the weighted distance algorithm based on the Mahalanobis distance for optimizing the weighting function's bandwidth is proposed to improve the accuracy of the algorithm. The performance of the new model is evaluated with two real-world datasets, and compared with the local SVR and some published models using the same datasets. The results show that the proposed model exhibits superior performance compare to that of LWR, local SVR, and other published models.
Abstract Fluctuations in the endogenous levels of kynurenic acid (KYNA), a potent α7 nicotinic and NMDA receptor antagonist, affect extracellular dopamine (DA) concentrations in the rat brain. ...Moreover, reductions in KYNA levels increase the vulnerability of striatal neurons to NMDA receptor-mediated excitotoxic insults. We now assessed the role of a key KYNA-synthesizing enzyme, kynurenine aminotransferase II (KAT II), in these processes in the rodent striatum, using KAT II KO mice—which have reduced KYNA levels—and the selective KAT II inhibitor ( S )-4-(ethylsulfonyl)benzoylalanine ( S -ESBA) as tools. S -ESBA (applied by reverse dialysis) raised extracellular DA levels in the striatum of KYNA-deficient mice threefold and caused a much larger, 15-fold increase in wild-type mice. In the rat striatum, S -ESBA produced a 35% reduction in extracellular KYNA, which was accompanied by a 270% increase in extracellular DA. The latter effect was abolished by co-infusion of 100 nM KYNA. Intrastriatal S -ESBA pre-treatment augmented the size of a striatal quinolinate lesion by 370%, and this potentiation was prevented by co-infusion of KYNA. In separate animals, acute inhibition of KAT II reduced the de novo synthesis of KYNA during an early excitotoxic insult without enhancing the formation of the related neurotoxic metabolites 3-hydroxykynurenine and quinolinate. Taken together, these results provide further support for the concept that KAT II is a critical determinant of functionally relevant KYNA fluctuations in the rodent striatum.
This paper investigates the delay-dependent stability of a power system equipped with a wide-area damping controller (WADC) using a new method which consists of a delay-dependent criterion based on ...Lyapunov theory and model reduction technique. The delay margin, the maximal delay which allows the closed-loop power system to retain stable, is calculated based on the reduced order model and linear matrix inequality (LMI) technique. Both constant and time-varying delays introduced by the transmission of the remote signals are investigated. Cases studies are carried out based on a two-area four-machine power system controlled by a conventional lead-lag WADC and a robust WADC. The relationship between the parameters of WADC and the delay margin has been investigated and is used to guide the design of WADC and achieve a trade-off between the damping performance and delay margin. The effectiveness of the proposed method is verified by simulation studies.
Highlights ► A novel neurodevelopmental animal model of schizophrenia is presented. ► Developmental kynurenine treatment results in elevated KYNA levels into adulthood. ► Adults with elevated KYNA ...levels during development exhibit deficits in cognitive flexibility. ► These cognitive deficits are ameliorated by acute treatment with galantamine.
We tested the hypothesis that fluctuations in the levels of kynurenic acid (KYNA), an endogenous antagonist of the α7 nicotinic acetylcholine (ACh) receptor, modulate extracellular ACh levels in the ...medial prefrontal cortex in rats. Decreases in cortical KYNA levels were achieved by local perfusion of S‐ESBA, a selective inhibitor of the astrocytic enzyme kynurenine aminotransferase II (KAT II), which catalyses the formation of KYNA from its precursor l‐kynurenine. At 5 mm, S‐ESBA caused a 30% reduction in extracellular KYNA levels, which was accompanied by a two‐threefold increase in basal cortical ACh levels. Co‐perfusion of KYNA in the endogenous range (100 nm), which by itself tended to reduce basal ACh levels, blocked the ability of S‐ESBA to raise extracellular ACh levels. KYNA perfusion (100 nm) also prevented the evoked ACh release caused by d‐amphetamine (2.0 mg/kg). This effect was duplicated by the systemic administration of kynurenine (50 mg/kg), which resulted in a significant increase in cortical KYNA formation. Jointly, these data indicate that astrocytes, by producing and releasing KYNA, have the ability to modulate cortical cholinergic neurotransmission under both basal and stimulated conditions. As cortical KYNA levels are elevated in individuals with schizophrenia, and in light of the established role of cortical ACh in executive functions, our findings suggest that drugs capable of attenuating the production of KYNA may be of benefit in the treatment of cognitive deficits in schizophrenia.
Intrastriatal infusion of nanomolar concentrations of kynurenic acid (KYNA), an astrocyte-derived neuroinhibitory tryptophan metabolite, reduces basal extracellular dopamine (DA) levels in the rat ...striatum. This effect is initiated by the inhibition of alpha7 nicotinic acetylcholine receptors (alpha7nAChRs) on glutamatergic afferents. The present study was designed to further investigate this functional link between KYNA and DA using striatal microdialysis in awake animals. In rats, increases in KYNA, caused by intrastriatal infusions of KYNA itself (100 nM) or of KYNA's bioprecursor L-kynurenine (2 microM), were associated with substantial reductions in DA. Co-infusion of KYNA with the alpha7nAChR agonist galantamine (5 microM), but not with the NMDA receptor agonist D-serine (100 nM), prevented this effect. Moreover, KYNA also reduced DA levels in the NMDA-lesioned striatum. Conversely, extracellular DA levels were enhanced when KYNA formation was compromised, either by astrocyte poisoning with fluorocitrate or by perfusion with aminooxyacetic acid (AOAA; 5 mM), a non-specific inhibitor of KYNA synthesis. Notably, this effect of AOAA was prevented by co-perfusion with 100 nM KYNA. In the striatum of 21 day-old mice with a targeted deletion of kynurenine aminotransferase II, extracellular KYNA levels were reduced by 67 +/- 6%, while extracellular DA levels were simultaneously increased by 170 +/- 14%. Taken together, a picture emerges where fluctuations in the astrocytic production of KYNA, possibly through volume transmission, inversely regulate dopaminergic tone. This newly uncovered mechanism may profoundly influence DA function under physiological and pathological conditions.
Seed ageing has an important effect on germination and productivity. During natural ageing, seed vigour decreases rapidly but, to date, the molecular mechanisms underlying this decrease have not been ...fully elucidated. Using omics, some of the details regarding seed vigour decline during natural ageing might be elucidated through integrated analysis.
Safflower seed germination and physio‐biochemical changes during natural ageing (stored for 4, 16 and 28 months) were determined. Proteome and lipidome profiling during natural seed ageing was performed, and the differentially expressed proteins and lipid metabolite species analysed. The surface and internal structures of cotyledons were observed. An integrating analysis of the proteome and lipidome was also carried out.
Natural seed ageing significantly decreased safflower seed germination and vigour. 4,184 proteins and 1,193 lipids were quantified, both of which show huge differences among the different naturally aged seeds. The surface of the cotyledons collapsed and cracked, and the oil bodies become looser during natural ageing. The total content of DAG and PA increased, while the content of TAG and PL (PC, PE, PS, PI and PL) significantly decreased during seeds ageing. Two lipase genes (HH‐026818‐RA and HH‐025320) likely participated in this degradation of lipids.
We conclude that the enzymes that participate in glycerolipid metabolism and fatty acid degradation probably lead to the degradation of oil bodies (TAG) and membrane lipids (PC, PE, PS, PI, PG) and, ultimately, destroy the structure, causing a decline in seed vigour during natural seed ageing.
Enzymes probably led to the degradation of oil bodies and membrane lipids, devastated the seed structure, and caused a decline in seed vigour.
PDF
