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Spikes
Kinds of Spikes Terms modified by Spikes Selected AbstractsMorphological Traits above the Flag Leaf Node as Indicators of Drought Susceptibility Index in Durum WheatJOURNAL OF AGRONOMY AND CROP SCIENCE, Issue 2 2007D. Villegas Abstract Selection criteria for drought tolerance would be helpful tools for wheat breeding programmes. To assess the usefulness of some morphological traits above the flag leaf node as indicators of yield and the susceptibility index (SI) of Fischer and Maurer, 10 durum wheat genotypes were used in experiments conducted under two water regimes at two latitudes in Spain during 3 years. Morphological traits were measured at anthesis, and yield, yield components and quality traits were evaluated at ripening. Principal components analysis showed associations between morphological traits and yield, yield components and quality, most of them caused by differences between environments. Peduncle weight, spike weight and length and awn length were significantly related to SI within environments. Spike and peduncle weight were the traits more related to yield and SI in all the experiments together and in the rainfed sites, while in the irrigated sites spike length was better. The spike weight and length were negatively associated with SI, while peduncle weight was positively associated to SI. Genotype means across all experiments were associated with SI values. These morphological traits could be selection criteria in breeding programmes to obtain varieties with good yield stability. The genetic variability found suggests opportunity for selection. [source] EEG Characteristics Related to Educational Impairments in Children with Benign Childhood Epilepsy with Centrotemporal SpikesEPILEPSIA, Issue 11 2007Joost Nicolai Summary Purpose: Learning and behavioral difficulties often occur in benign childhood epilepsy with centrotemporal spikes (BCECTS). In recent years, several electroencephalogram (EEG) characteristics have been related to the occurrence of learning and behavioral problems. Methods: From 28 children medical, school and psychological reports were present and children were rated according to a 4-point scale for educational and behavioral impairment (Part 1). Thirty 24-h EEG recordings were reanalyzed for spike frequency, the presence of atypical EEG criteria, and the presence of a nondipole spike. EEGs were scored during wakefulness, first hour of sleep and whole night sleep (minus the first hour of sleep) separately (Part 2). Results: The presence of I: an intermittent slow-wave focus during wakefulness, II: a high number of spikes in the first hour of sleep (and during whole night sleep), and III: multiple asynchronous bilateral spike-wave foci in the first hour of sleep correlates significantly with a sum score , 3 which indicates a complicated course with educational or behavioral impairment. It is sufficient to analyze an EEG during wakefulness and a sleep EEG for only the first hour of sleep instead of a whole night recording to demonstrate those EEG criteria. Conclusions: On basis of our reanalysis we can possibly conclude that the aforementioned EEG characteristics correlate with educational impairments, and that analysing an EEG recording during wake and the first hour of sleep is sufficient to look adequately for those EEG criteria in children with BCECTS. [source] Effect of Interictal Spikes on Single-Cell Firing Patterns in the HippocampusEPILEPSIA, Issue 4 2007Jun-Li Zhou Summary:,Purpose: The interictal EEG spike(s) is the hallmark of the epileptic EEG. While focal interictal spike (IS) have been associated with transitory cognitive impairment, with the type of deficit dependent on where in the cortex the IS arises, the mechanism by which IS result in transitory dysfunction is not known. The purpose of this study was to determine the effect of IS on single-cell firing patterns in freely moving rats with a prior history of seizures. Methods: We studied IS in two seizure models; pilocarpine-induced status epilepticus and recurrent flurothyl models. The effect of spontaneous hippocampal spikes on action potentials (APs) of CA1 cells in rats walking in a familiar environment was investigated using 32 extracellular electrodes. We also compared the effect of spikes on two types of hippcampal cells; place cells that discharge rapidly only when the rat's head is in a specific part of the environment, the so-called firing field, and interneurons, which are a main source of inhibition in the hippocampus. Results: IS were associated with a decreased likelihood of AP compared with IS-free portions of the record. Compared to pre-IS baseline, IS were followed by significant decreases in CA1 APs for periods up to 2 s following the IS in both models. When occurring in flurries, IS were associated with a pronounced decrease in APs. The response to IS was cell-dependent; IS resulted in decreases in AP firing after the IS in interneurons but not place cells. Conclusions: This study demonstrates that IS have substantial effects on cellular firing in the hippocampus and that these effects last far longer than the spike and slow wave. Furthermore, the effect of IS on cellular firing was cell specific, affecting interneurons more than place cells. These findings suggest that IS may contribute to seizure-induced cognitive impairment by altering AP firing in a cell-specific manner. [source] Response: Increased Frequency of Rolandic Spikes in ADHD ChildrenEPILEPSIA, Issue 5 2004Martin Holtmann No abstract is available for this article. [source] fMRI Activation in Continuous and Spike-triggered EEG,fMRI Studies of Epileptic SpikesEPILEPSIA, Issue 10 2003Abdulla Al-Asmi Summary:,Purpose: To evaluate functional magnetic resonance imaging (fMRI) with simultaneous EEG for finding metabolic sources of epileptic spikes. To find the localizing value of activated regions and factors influencing fMRI responses. Methods: Patients with focal epilepsy and frequent spikes were subjected to spike-triggered or continuous fMRI with simultaneous EEG. Results were analyzed in terms of fMRI activation, concordance with the location of EEG spiking and anatomic MRI abnormalities, and other EEG and clinical variables. In four patients, results also were compared with those of intracerebral EEG. Results: Forty-eight studies were performed on 38 patients. Seventeen studies were not analyzed, primarily because no spikes occurred during scanning. Activation was obtained in 39% of 31 studies, with an activation volume of 2.55 ± 4.84 cc. Activated regions were concordant with EEG localization in almost all studies and confirmed by intracerebral EEG in four patients. Forty percent of patients without an MRI lesion showed activation; 37.5% of patients with a lesion had an activation; the activation was near or inside the lesion. Bursts of spikes were more likely to generate an fMRI response than were isolated spikes (76 vs. 11%; p < 0.05). Conclusions: Combining EEG and fMRI in focal epilepsy yields regions of activation that are presumably the source of spiking activity. These regions are highly linked with epileptic foci and epileptogenic lesions in a significant number of patients. Activation also is found in patients with no visible MRI lesion. Intracerebral recordings largely confirm that these activation regions represent epileptogenic areas. It is still unclear why many patients show no activation. [source] A Sheep Model for the Study of Focal Epilepsy with Concurrent Intracranial EEG and Functional MRIEPILEPSIA, Issue 8 2002Helen I. Opdam Summary: ,Purpose: We describe a sheep model of penicillin-induced seizure activity using electroencephalography (EEG) and functional MRI (fMRI). Methods: Ten adult sheep were used. Spikes and seizures were generated by instillation of 8,000,10,000 IU of penicillin into the right prefrontal cortex via a specially designed port. Bilateral intracranial EEG was acquired by using carbon fiber electrodes. Animals had behavioral characterization of their seizures and were then anesthetized for fMRI studies. Functional MRI was performed at 1.5 and 3 Tesla by measuring blood oxygen level,dependent (BOLD) weighted signal intensity at different times during the evolution of seizures. Results: Behavioral seizures were associated with electrographic seizures. Intracranial EEG obtained in the MR scanner was of high quality. Focal spiking and seizures were seen in all animals and developed 11.3 ± 11.2 s and 17.3 ± 12.1 min after penicillin administration, respectively. An average of 13 ± 4.8 seizures were seen per animal, each lasting 27.3 ± 12.3 s. Functional MR images with little parenchymal artefact were obtained. Regional BOLD signal-intensity changes were observed during seizures at the seizure focus and ipsilateral amygdala. Conclusions: We have developed an animal model of partial epilepsy in which seizures can be reliably elicited with concurrent fMRI and intracranial EEG. During unilateral electrographic seizures, focal BOLD signal changes occurred at the seizure focus and ipsilateral amygdala, suggesting the presence of a cortico,subcortical loop. This observation illustrates the potential of the model for understanding seizure generation, spread, and possibly the consequences of repeated seizures on the brain. [source] VIQ-PIQ Discrepancies in Partial Epilepsy: On the Relation to Lat- eralities of Focal MRI Lesions, P3 Peaks, and Focal Spikes.EPILEPSIA, Issue 2000Osamu Kanazawa Purpose: A number of previous ncurophysiological studies have indicated that the glutamatergic system is important in the induction of epileptiform activity and the dcvelopment of epileptogenesis. Clutamate transport is the primary mechanism of inactivation of syiiaptically released glutamate. GLAST is classified BS an astrocytic transporter and occurs in high concentrations in the ccrebcllum. The pathophysiologic rolc of GLAST in epilepsy is not known in detail. To investigate the role of thc astroglial glutamatc transporter GLAST in epileptogenesis, we compared amygdalu-kindling and pentylenctetrazolc (PTZ) induced seizures in GLAST-deficient mice (GLAST(-/-)) wild-type mice (GLAST(+/+)), and maternal C57Black6/J mice (C57). Purpose: Subtest IQ such as verbal IQ (VIQ) and performance IQ (PIQ) in WAIS or WISC are thought to represent neuropsychological functions of the left and right hemispheres, respectively. The P300 (P3) event-related potential reflects cognitive processes. We do not ye1 know the brain site of P3 origin or how epileptogenic foci (EF) influ- ence P3 potentials. To examine neuropsychological influence by partial epilepsy (PE), we studied VIQ-PIQ discrepancies in PE in relation to lateralities of focal MRI lesions, P3 peaks, and EF. Methods: Thirteen patients showed VIQ-PIQ discrepancies significant at the p7lt;O.O5 level, represented by a>l2-point spread for the WAIS in adults, and a 15-point spread in the WISC in children. We evoked P3 potentials in the individuals with discrepant IQ differences by asking them to keep a mental count of rare tones, including introduction of oddbail tones. EEGs were recorded by the international 10,20 system and P3 peaks were shown in a topographical view by offline analysis. Patients were divided into normal and abnormal groups according to MRI findings, and were examined for the laterali- ties of the dominant side in subtest IQ (conventionally, we regarded higher VIQ as left hemisphere dominant and higher PIQ as right hemisphere dominant), P3 peaks, and EF. We did not correlate results with lert or right handedness. Results: Five patients (38.5%) were in the normal group and 8 patients (61.5%) were in the abnormal group. Concordance of the lateralities in P3 peaks and dominant side in subtest IQ was shown in 1 patient (20%) in the normal group and 5 patients (62.5%) in the abnormal group. In the normal group, all patients showed contralateral P3 peak shift to EF, and all except I patient showed contralateral P3 peak shift to the dominant side in subtest IQ. The other 3 patients in the abnormal group showed unilateral focal cortical dysplasias (FCD), ipsilateral P3 shift, and contralateral dominant side in subtest IQ to the focal MRI lesions. Conclusion: In our partial epilepsy series with VIQ-PIQ discrepancies, concordance of the lateralities in P3 peaks and dominant side in subtest IQ was shown in < half of the patients. Epileptogenic foci seem to have 3 different grades of influence on P3 peak shift and dominant side in subtest IQ according to the severities of accompanying focal MRI lesions: 1. Without MRI lesions, EF can make P3 peak shift contralaterally, but the dominant side in the subtest IQ shift ipsilaterally; 2. With less severe focal MRI lesions such as hippocampal atrophy etc., EF can make not only P3 peaks but also the dominant side in the subtest IQ shift contralaterally; 3. With severe focal MRI lesions such as FCD, EF can make the dominant side in the subtest IQ shift contralaterally, but the P3 peak may shift ipsilaterally. Epileptogenic foci without MRI lesions seem to control ipsilateral P3 potentials. MRI lesions render a hemisphere unlikely to become dominant, but epileptogenic foci can coexist with apparently normal neuropsychological function. [source] Characterization in vivo of bilaterally branching pontocerebellar mossy fibre to Golgi cell inputs in the rat cerebellumEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2009Tahl Holtzman Abstract Golgi cells regulate the flow of information from mossy fibres to the cerebellar cortex, through a mix of feedback and feedforward inhibitory actions on granule cells. The aim of the current study was to examine mossy fibre input to Golgi cells, in order to assess their impact on switching Golgi cells into feedforward behaviour. In urethane-anaesthetized rats, extracellular recordings were made from Golgi cells in Crus II (n = 18). Spikes were evoked in all Golgi cells by microstimulation within the contralateral hemispheral cortex, via branches of mossy fibres that terminate in both cerebellar hemispheres. The latencies of these responses were very short, consistent with a monosynaptic mossy fibre contact [average onset latency 2.3 ± 0.1 ms (SEM)]. The same stimuli had no measurable effect on spike responses of nearby Purkinje cells (n = 12). Systematic mapping in the contralateral cerebellar hemisphere (Crus Ib, IIa, IIb and the paramedian lobule) usually revealed one low-intensity stimulus ,hotspot' (12,35 ,A) from which short-latency spikes could be evoked in an individual Golgi cell. Microinjections of red and green retrograde tracers (latex beads, ,50,150 nL injection volume) made at the recording site and the stimulation hotspot resulted in double-labelled neurons within the pontine nuclei. Overall, this suggests that subsets of pontine neurons supply mossy fibres that branch to both hemispheres, some of which directly target Golgi cells. Such an arrangement may provide a common feedforward inhibitory link to temporally couple activity on both sides of the cerebellum during behaviour. [source] Ultrastructural and Cytochemical Studies on Cellulose, Xylan and Pectin Degradation in Wheat Spikes Infected by Fusarium culmorumJOURNAL OF PHYTOPATHOLOGY, Issue 5 2000Z. Kang The cell wall components cellulose, xylan and pectin in different tissues of noninoculated healthy and Fusarium culmorum (W. G. Smith) Sacc-infected wheat spikes were localized by means of enzyme-gold and immuno-gold labelling techniques. The cell walls in the ovary, lemma and rachis of the healthy wheat spike showed labellings in different patterns and densities with cellulase-gold and xylanase-gold probes, as well as with the antipectin monoclonal antibody JIM7. The inter- and intracellular growth of the pathogen in the ovary, lemma and rachis of the infected wheat spike, not only caused pronounced alterations of cell walls and middle lamella matrices, but also led to marked modifications of cell wall components. The enzyme-gold and immuno-gold labellings in the infected host tissues revealed that the labelling densities for cellulose, xylan and pectin were significantly reduced in the cell walls of infected ovary, lemma and rachis as compared with corresponding healthy host tissues. The host cell walls in contact with or close to hyphae of the pathogen showed more marked morphological changes and much greater reduction of the labelling density than those in distance from the hyphae. These results provide evidence that F. culmorum may produce cell-wall-degrading enzymes such as cellulases, xylanases and pectinases during infection and colonization of wheat spikes tissues. Furthermore, at the early stage of infection (e.g. 3 days after inoculation), the degradation of pectin was greater than that of cellulose and xylan in the cell walls of the same infected host tissues, indirectly suggesting that the pectinases may be secreted earlier or exert higher activities than cellulases and xylanases. Zusammenfassung Die Zellwandkomponenten Zellulose, Xylan und Pektin in verschiedenen Geweben von nicht inokulierten gesunden und Fusarium culmorum (W. G. Smith) Sacc. infizierten Weizenähren wurden mit Hilfe von Enzym-Gold- und Immun-Gold-Markierungstechniken nachgewiesen. Die Zellwände des Fruchtknotens der gesunden Ähre wiesen unterschiedliche Markierungsmuster und -dichten mit Zellulase-Gold- und Xylanase-Gold-Proben sowie mit dem monoklonalen Anti-Pektin Antikörper JIM7 auf. Das inter-und intrazelluläre Wachstum des Pathogens im Fruchtknoten, in der Deckspelze und Spindel der infizierten Ähre verursachte nicht nur ausgeprägte Veränderungen der Zellwände und der Matrix der Mittellamelle sondern führte auch zu deutlichen Modifikationen der Zellwandkomponenten. Die Enzym-Gold- und die Immun-Gold-Markierungen in den infizierten Wirtsgeweben ergaben deutlich verminderte Markierungsdichten für Zellulose, Xylan und Pektin in den Zellwänden des infizierten Fruchtknotens, der Deckspelze und Spindel im Vergleich zum entsprechenden gesunden Wirtsgewebe. Wirtszellwände, die sich in Kontakt mit den Hyphen oder in der Nähe der Hyphen des Pathogens befanden, zeigten deutlichere morphologische Veränderungen und stärkere Reduktionen der Markierungsdichten als die, die entfernt von Hyphen waren. Diese Ergebnisse weisen darauf hin, da,F. culmorum zellwandabbauende Enzyme wie Zellulasen, Xylanasen und Pektinasen während der Infektion und Besiedlung der Gewebe von Weizenähren ausscheidet. Au,ierdem war im frühen Infektionsstadium (z. B. 3 Tage nach Inokulation) der Abbau von Pektin stärker als der von Zellulose und Xylan in den Zellwänden infizierter Wirtsgewebe. Dies deutet darauf hin, da, Pektinasen früher ausgeschieden werden oder stärkere Aktivität als Zellulasen und Xylanasen besitzen. [source] Isotopic climate record in a Holocene stalagmite from Ursilor Cave (Romania)JOURNAL OF QUATERNARY SCIENCE, Issue 4 2002Bogdan Petroniu Onac Abstract The PU-2 stalagmite from Ursilor Cave provides the first dated Romanian isotope record for the Holocene. The overall growth rate of the speleothem was 3.5 cm kyr,1, corresponding to a temporal resolution of 142 y between each isotope analysis. The ,Hendy' tests indicate that isotopic equilibrium conditions occurred during the formation of PU-2, and hence that it is suitable for palaeoclimatic studies. The relationship between ,18O and temperature was found to be positive. This can be interpreted either as rain-out with distance from the west-northwest ocean source of evaporation or shifts in air mass source with changing North Atlantic Oscillation indices. Applying five U,Th thermal ionisation mass spectrometric (TIMS) dates to a 17.5 cm isotope profile (,18O and ,13C) along the stalagmite growth axis enabled a tentative interpretation of the palaeoclimate signal over the past 7.1 kyr. Spikes of depleted isotopic ,18O values are centred near ca. 7, ca. 5.2 and ca. 4 ka, reflecting cool conditions. The record shows two warm intervals between ca. 3.8 and ca. 3.2 ka (the maximum warmth) and from ca. 2 to ca. 1.4 ka, when the ,18O values were less negative than present. The ,Holocene Climate Optimum' spanning the time interval from ca. 6.8 to ca. 4.4 ka is not well expressed in the PU-2 stalagmite. Individual spikes of lighter ,13C are interpreted as indicative of periods of heavy rainfall, at ca. 7, ca. 5.5, and ca. 3.5 ka. The overall trend to lighter ,13C in the PU-2 stalagmite may reflect a gradual decrease in water,rock interaction. The results demonstrate that the effect of North Atlantic oceanic changes extended to the investigated area. Nevertheless, some differences in temporal correlation and intensity of stable isotopic response to these climatic events have been found, but the exact nature of these differences and the underlying mechanism is yet to be determined. Copyright © 2002 John Wiley & Sons, Ltd. [source] Modelling Spikes in Electricity Prices,THE ECONOMIC RECORD, Issue 263 2007RALF BECKER During periods of market stress, electricity prices can rise dramatically. Electricity retailers cannot pass these extreme prices on to customers because of retail price regulation. Improved prediction of these price spikes therefore is important for risk management. This paper builds a time-varying-probability Markov-switching model of Queensland electricity prices, aimed particularly at forecasting price spikes. Variables capturing demand and weather patterns are used to drive the transition probabilities. Unlike traditional Markov-switching models that assume normality of the prices in each state, the model presented here uses a generalised beta distribution to allow for the skewness in the distribution of electricity prices during high-price episodes. [source] Spike-monitoring of anaesthesia for corpus callosotomy using bilateral bispectral indexANAESTHESIA, Issue 7 2009S. Ogawa Summary During corpus callosotomy for intractable epilepsy, the electrocorticogram is commonly recorded from electrodes placed on the brain surface to monitor of epileptic activity and assess the synchronisation of epileptic signals between the left and the right hemispheres. We evaluated the usefulness of bilateral bispectral index monitoring using two monitors and two sensors placed above the frontal region. Spikes were readily detected on the electroencephalogram on the bispectral index monitor, and the frequency of their occurrence increased or decreased in response to adjustment of the sevoflurane concentration. The disappearance of synchronisation between the left and the right hemispheres was observed with use of the bispectral index , in concordance with the electrocorticogram. Thus, ,spike-monitoring anaesthesia' using bilateral bispectral index was useful in assessing both the effect of anaesthetics on the electroencephalogram signals and the surgical therapeutic effect. [source] Di- and Trinuclear [70]Fullerene Complexes: Syntheses and Metal,Metal Electronic Interactions,ANGEWANDTE CHEMIE, Issue 34 2009Yutaka Matsuo Prof. Buckyballs mit Spikes: [70]Fulleren wurde in die Zwei- und Dreikernkomplexe [M2(C70Ar6)Cp2], [M2(C70Ar7H)Cp2] und [M3(C70Ar7)Cp3] überführt (M=Fe, Ru; Ar=Aryl; Cp=C5H5; siehe Bild: M,violett, C,rosa, blau, grau), in denen die Metallatome über das ,-konjugierte System des Fullerens elektronisch wechselwirken. Die Komplexe sollten sich wegen ihrer Strukturen und elektrochemischen Eigenschaften für den Einsatz in der molekularen Elektronik eignen. [source] Heterosis for yield and other agronomic traits of winter triticale F1 and F2 hybridsPLANT BREEDING, Issue 4 2001G. Oettler Abstract Triticale is generally treated as a self-pollinating crop and line breeding is practised. Hybrid breeding has been discussed for some time, but there is little information for winter triticale. This study investigated heterosis for eight agronomic traits in F1 and F2 hybrids grown together with their parents as drilled plots in three environments. On average, grain yield heterosis was 12.5 dt/ha (a relative 10.5%) compared with the mid-parent value for F1 hybrids, and 6.2 dt/ha (5.0%) for F2 hybrids and withawide range of 4.4,17.1 dt/ha for F1 hybrids. A positive contribution to the heterosis of yield was made by kernels/spike and 1000-kernel weight, whereas spikes/m2 showed negative heterosis. Hybrid plants in F1 and F2 were taller than mid-parents (8.3 cm and 5.3 cm, respectively), with a tendency to earlier heading. The negative heterosis for falling number in F1 and F2 hybrids could be a problem for commercial production of triticale hybrids. By selecting parents for combining ability and the identification of heterotic patterns, grain yield heterosis of 20% appears feasible. [source] Treatment of Recurrent Ingrown Great Toenail Associated with Granulation Tissue by Partial Nail Avulsion Followed by Matricectomy with Sharpulse Carbon Dioxide LaserDERMATOLOGIC SURGERY, Issue 5 2002Kuo-chia Yang MD background. The effectiveness of partial nail avulsion followed by matricectomy with carbon dioxide (CO2) laser for the treatment of ingrown great toenails remains unclear. objective. This study sought to determine the effectiveness of partial nail avulsion followed by matricectomy with sharpulse CO2 laser in the treatment of recurrent ingrown great toenails associated with granulation tissue. materials and methods. Fourteen patients with a total of 18 recurrent ingrown great toenails were randomly selected for participation in this study. Partial nail avulsions followed by matricectomy with sharpulse CO2 laser were performed on the involved nails. After at least 6 months, we evaluated the recurrence of ingrown toenails, regrowth of the nail spike, duration of post-treatment pain and post-treatment infection. results. Partial nail avulsion followed by matricectomy with sharpulse CO2 laser in the treatment of ingrown toenails resulted in a high cure rate, short postoperative pain duration and low risk of postoperative infection. conclusion. This method we advocate is convenient and effective for the treatment of recurrent ingrown great toenail associated with granulation tissue. [source] Effects of activation of hedgehog signaling on patterning, growth, and differentiation in Xenopus froglet limb regenerationDEVELOPMENTAL DYNAMICS, Issue 8 2009Nayuta Yakushiji Abstract Regenerating limbs of urodele amphibians and Xenopus tadpole are reconstructed along proximal,distal, anterior,posterior (AP), and dorsal,ventral axes. In contrast, a regenerated limb of the Xenopus froglet does not have digits, and only a simple cartilaginous structure referred to as a "spike" is formed. This suggests that repatterning along the AP axis is absent in the froglet blastema. Previous studies have shown that Shh and its target genes are not expressed in the froglet blastema. In this study, we activated Hedgehog signaling in the froglet blastema and found that target genes of Shh were inducible in the mesenchyme of limb blastema. Furthermore, we found that activation of the signaling had effects on blastema cell proliferation and chondrogenesis and resulted in the formation of multiple cartilaginous structures. These findings indicate that activation of signaling that is absent in the froglet blastema is effective for improvement of limb regeneration ability in the Xenopus froglet. Developmental Dynamics, 2009. © 2009 Wiley-Liss, Inc. [source] A dendrobranchiate, Peisos petrunkevitchi (Decapoda, Sergestidae), with reptant-like sperm: a spermiocladistic assessmentACTA ZOOLOGICA, Issue 2 2004Marcelo A. Scelzo Abstract The spermatozoon of Peisos petrunkevitchi differs significantly from those of any of the investigated dendrobranchiates in the anterior fusiform acrosome, lacking a spike, and embedded in (instead of capping) the nuclear region. In contrast, the position of the acrosome and the internal arrangement of its contents, as well as the apomorphic presence of a pair of centrioles (absent in all known dendrobranchiate spermatozoa) at the base of the acrosomal perforatorium, indicate a close affinity between this sperm plan and that found in reptants, especially anomurans and brachyurans. Based on the present and previous observations on decapod spermatozoal ultrastructure, we review the phylogeny of dendrobranchiate spermatozoa in the perspective of most recent phylogenetic analyses of malacostracan crustaceans. [source] Economic evaluation of demand-side energy storage systems by using a multi-agent-based electricity marketELECTRICAL ENGINEERING IN JAPAN, Issue 3 2009Ken Furusawa Abstract With the wholesale electric power market opened in April 2005, deregulation of the electric power industry in Japan has faced a new competitive environment. In the new environment, Independent Power Producer (IPP), Power Producer and Supplier (PPS), Load Service Entity (LSE), and electric utility can trade electric energy through both bilateral contracts and single-price auction at the electricity market. In general, the market clearing price (MCP) is largely changed by the amount of total load demand in the market. The influence may cause a price spike, and consequently the volatility of MCP will make LSEs and their customers face a risk of higher revenue and cost. DSM is attractive as a means of load leveling, and has an effect on decreasing MCP at peak load period. Introducing Energy Storage systems (ES) is one DSM in order to change demand profile at the customer side. In the case that customers decrease their own demand due to increased MCP, a bidding strategy of generating companies may be changed. As a result, MCP is changed through such complex mechanism. In this paper the authors evaluate MCP by multi-agent. It is considered that customer-side ES has an effect on MCP fluctuation. Through numerical examples, this paper evaluates the influence on MCP by controlling customer-side ES corresponding to variation of MCP. © 2009 Wiley Periodicals, Inc. Electr Eng Jpn, 167(3): 36,45, 2009; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.20658 [source] EEG Characteristics Related to Educational Impairments in Children with Benign Childhood Epilepsy with Centrotemporal SpikesEPILEPSIA, Issue 11 2007Joost Nicolai Summary Purpose: Learning and behavioral difficulties often occur in benign childhood epilepsy with centrotemporal spikes (BCECTS). In recent years, several electroencephalogram (EEG) characteristics have been related to the occurrence of learning and behavioral problems. Methods: From 28 children medical, school and psychological reports were present and children were rated according to a 4-point scale for educational and behavioral impairment (Part 1). Thirty 24-h EEG recordings were reanalyzed for spike frequency, the presence of atypical EEG criteria, and the presence of a nondipole spike. EEGs were scored during wakefulness, first hour of sleep and whole night sleep (minus the first hour of sleep) separately (Part 2). Results: The presence of I: an intermittent slow-wave focus during wakefulness, II: a high number of spikes in the first hour of sleep (and during whole night sleep), and III: multiple asynchronous bilateral spike-wave foci in the first hour of sleep correlates significantly with a sum score , 3 which indicates a complicated course with educational or behavioral impairment. It is sufficient to analyze an EEG during wakefulness and a sleep EEG for only the first hour of sleep instead of a whole night recording to demonstrate those EEG criteria. Conclusions: On basis of our reanalysis we can possibly conclude that the aforementioned EEG characteristics correlate with educational impairments, and that analysing an EEG recording during wake and the first hour of sleep is sufficient to look adequately for those EEG criteria in children with BCECTS. [source] Effect of Interictal Spikes on Single-Cell Firing Patterns in the HippocampusEPILEPSIA, Issue 4 2007Jun-Li Zhou Summary:,Purpose: The interictal EEG spike(s) is the hallmark of the epileptic EEG. While focal interictal spike (IS) have been associated with transitory cognitive impairment, with the type of deficit dependent on where in the cortex the IS arises, the mechanism by which IS result in transitory dysfunction is not known. The purpose of this study was to determine the effect of IS on single-cell firing patterns in freely moving rats with a prior history of seizures. Methods: We studied IS in two seizure models; pilocarpine-induced status epilepticus and recurrent flurothyl models. The effect of spontaneous hippocampal spikes on action potentials (APs) of CA1 cells in rats walking in a familiar environment was investigated using 32 extracellular electrodes. We also compared the effect of spikes on two types of hippcampal cells; place cells that discharge rapidly only when the rat's head is in a specific part of the environment, the so-called firing field, and interneurons, which are a main source of inhibition in the hippocampus. Results: IS were associated with a decreased likelihood of AP compared with IS-free portions of the record. Compared to pre-IS baseline, IS were followed by significant decreases in CA1 APs for periods up to 2 s following the IS in both models. When occurring in flurries, IS were associated with a pronounced decrease in APs. The response to IS was cell-dependent; IS resulted in decreases in AP firing after the IS in interneurons but not place cells. Conclusions: This study demonstrates that IS have substantial effects on cellular firing in the hippocampus and that these effects last far longer than the spike and slow wave. Furthermore, the effect of IS on cellular firing was cell specific, affecting interneurons more than place cells. These findings suggest that IS may contribute to seizure-induced cognitive impairment by altering AP firing in a cell-specific manner. [source] Coexistence of Idiopathic Rolandic Epilepsy and CSWS in Two FamiliesEPILEPSIA, Issue 10 2006Xavier De Tiège Summary:,Purpose: To report two families combining benign childhood epilepsy with centrotemporal spikes (BCECS) and cryptogenic epilepsy with continuous spike,waves during sleep (CSWS) in first-degree relatives. Methods: Clinical, EEG, and cerebral imaging data are described. Results: Family 1: The proband was 3 years old at epilepsy onset. First seizures were convulsive, with centrotemporal spikes on EEG. At age 5 years, he had complex partial seizures, psychomotor regression, and centrotemporal CSWS. [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) showed left parietal hypermetabolism. After several antiepileptic drug (AED) trials, valproate (VPA) and ethosuximide (ESM) induced seizure remission, CSWS disappearance, and psychomotor improvement. Learning disabilities, however, persisted. Family history was remarkable for BCECS in his father. Family 2: The proband was 2 years old at epilepsy onset. First seizures were convulsive, with centrotemporal CSWS on EEG. Despite several AED trials including corticosteroids, focal negative myoclonia, atypical absences, and psychomotor regression occurred, leading to severe mental retardation. FDG-PET showed bilateral parietal hypermetabolism. Vagus nerve stimulator was implanted. Her family history was remarkable for BCECS in her father and febrile convulsions in infancy in her mother. Conclusions: These data suggest the existence of a common genetic basis between BCECS and cryptogenic epilepsies with CSWS. The higher expression in patients with CSWS could be related to other genetic or acquired factors. These data suggest that these epileptic syndromes constitute edges of a continuum. [source] A Magnetoencephalographic Study of Patients with Panayiotopoulos SyndromeEPILEPSIA, Issue 7 2005Osamu Kanazawa Summary:,Purpose: Panayiotopoulos syndrome (PS) is a newly identified type of benign childhood epilepsy characterized by ictal vomiting and eye deviation. It is usually accompanied by occipital spike discharges; however, its classification as an early-onset benign childhood occipital epilepsy is controversial. To characterize this condition further, we examined the localization of equivalent current dipoles (ECDs) of spike discharges by magnetoencephalography (MEG) in patients with PS. Methods: We studied 13 patients with a mean age at time of examination of 5 years (range, 3,14 years). MEG was measured by using a whole-head 204-channel neuromagnetometer with simultaneous EEG recordings. The estimated locations of ECDs of each peak of the spike discharges were overlaid on magnetic resonance images of the brain. Results: Eleven (84.6%) patients showed clustered ECDs in the areas alongside the parietooccipital sulcus (eight of 13; 61.5%) and/or the calcarine sulcus (four of 13; 30.8%). Despite Fp-O synchronization of the spike discharges in the scalp EEG of five patients, no frontal locations of ECDs were found. All five (38.5%) boys with sylvian seizures, who also showed clustered ECDs in rolandic areas, had an earlier age at onset and higher seizure frequency than did other patients. ECD orientations were regular in all but one patient, who showed irregular and dispersed ECDs alongside bilateral calcarine sulci. Conclusions: Our results demonstrate localized cortical hyperexcitability in the areas alongside major cortical sulci in PS and indicate that PS is closely related to benign childhood epilepsy with centrotemporal spikes. [source] fMRI of Generalized Absence Status Epilepticus in Conscious Marmoset Monkeys Reveals Corticothalamic ActivationEPILEPSIA, Issue 10 2004Jeffrey R. Tenney Summary:,Purpose: A nonhuman primate model of generalized absence status epilepticus was developed for use in functional magnetic resonance imaging (fMRI) experiments to elucidate the brain mechanisms underlying this disorder. Methods: Adult male marmoset monkeys (Callithrix jacchus) were treated with ,-butyrolactone (GBL) to induce prolonged absence seizures, and the resulting spike,wave discharges (SWDs) were analyzed to determine the similarity to the 3-Hz SWDs that characterize the disorder. In addition, blood-oxygenation-level,dependent (BOLD) fMRI was measured at 4.7 Tesla after absence seizure induction with GBL. Results: Electroencephalographic recordings during imaging showed 3-Hz SWDs typical of human absence seizures. This synchronized EEG pattern started within 15 to 20 min of drug administration and persisted for >60 min. In addition, pretreatment with the antiepileptic drug, ethosuximide (ESM), blocked the behavioral and EEG changes caused by GBL. Changes in BOLD signal intensity in the thalamus and sensorimotor cortex correlated with the onset of 3-Hz SWDs. The change in BOLD signal intensity was bilateral but heterogeneous, affecting some brain areas more than others. No significant negative BOLD changes were seen. Conclusions: The BOLD fMRI data obtained in this marmoset monkey model of absence status epilepticus shows activation within the thalamus and cortex. [source] Corticothalamic Modulation during Absence Seizures in Rats: A Functional MRI AssessmentEPILEPSIA, Issue 9 2003Jeffrey R. Tenney Summary:,Purpose: Functional magnetic resonance imaging (fMRI) was used to identify areas of brain activation during absence seizures in an awake animal model. Methods: Blood-oxygenation-level,dependent (BOLD) fMRI in the brain was measured by using T2*-weighted echo planar imaging at 4.7 Tesla. BOLD imaging was performed before, during, and after absence seizure induction by using ,-butyrolactone (GBL; 200 mg/kg, intraperitoneal). Results: The corticothalamic circuitry, critical for spike,wave discharge (SWD) formation in absence seizure, showed robust BOLD signal changes after GBL administration, consistent with EEG recordings in the same animals. Predominantly positive BOLD changes occurred in the thalamus. Sensory and parietal cortices showed mixed positive and negative BOLD changes, whereas temporal and motor cortices showed only negative BOLD changes. Conclusions: With the BOLD fMRI technique, we demonstrated signal changes in brain areas that have been shown, with electrophysiology experiments, to be important for generating and maintaining the SWDs that characterize absence seizures. These results corroborate previous findings from lesion and electrophysiological experiments and show the technical feasibility of noninvasively imaging absence seizures in fully conscious rodents. [source] Mild Generalized Epilepsy and Developmental Disorder Associated with Large Inv Dup(15)EPILEPSIA, Issue 9 2002Rosanna Chifari Summary: ,Purpose: Several studies attempted to clarify the genotype,phenotype correlations in patients with inverted duplication of chromosome 15 [inv dup(15)], which is usually characterized by severe mental retardation and epilepsy in individuals with large duplications including the Prader,Willi/Angelman region. We report two patients with inv dup(15) who, in spite of a large duplication, had a mild phenotype including adult-onset epilepsy. This report may help to define the milder spectrum of the syndrome. Methods: A 25-year-old girl with mild mental retardation had a 6-year history of absence seizures, with occasional head drop. Interictal EEG revealed diffuse spike,wave complexes. Epilepsy was well controlled by a combination of lamotrigine (LTG) and valproate (VPA). The other patient, a 27-year-old man with mild mental retardation, had a 5-year history of rare generalized tonic,clonic seizure during sleep, and frequent episodes of unresponsiveness, which appeared to be atypical absence seizures on video-EEG recordings. A combination of VPA and LTG led to a remarkable improvement, although no complete control. Results: Molecular analysis revealed a large inv dup15 in both patients. Conclusions: The discrepancy between the mild phenotype and the severe chromosomal abnormality detected in these two patients further supports the notion that the site of breakpoint might be contributory to the inv dup(15) phenotype. Inv dup(15) should be considered in atypical cases of generalized epilepsy of adult onset without clear-cut etiology. [source] Abnormal Excitability of Hippocampal CA3 Neurons in Noda Epileptic Rat (NER): Alteration of Seizure with AgingEPILEPSIA, Issue 2000Ryosuke Hanaya Purpose: Noda epileptic rat (NER), a mutant found in thc colony of Crj:Wistar rats, spontaneously shows tonic-clonic convulsions approximately once every 30 hours from 8,16 weeks of age. A long-lasting dcpolarization shift accompanied by repetitivc firings are observed in hippocampal CA3 pyramidal neurons of NER with seizures. Using hippocampal slice preparations of NER, the present electrophysiologi- cal study was performed to elucidate whether this abnormal firing in CA3 neurons developed with age and if abnormality of Ca2+ channel was involved. Methods: Hippocampal slices (40Opm) werc prepared from NER and normal Wistar rats (age; 4,29 weeks). A single rectangular pulse stimulus composed of 0.1-ms duration was delivered to the mossy fibers every 5 seconds though a bipolar electrode placed in the granular cell layer of the dentate gyrus. Intracellular recording was made from the CA3 pyramidal cell using a microelectrode containing 3M KCI intracellular recordings. A Ca2+ spike was elicited by applying a depolarizing pulse (InA, 120ms) in the cell through the recording electrode under a blockadc of Na+ and K+ channels using 1 pM tetrodotoxin and I 0mM tctraethylammonium added to the artificial CSF, respectivcly. Nicardipine (I-IOOnM), a Ca2+ channel blocker, was applicd to the bath. Results: Thirty-seven slices from I9 NER and 6 slices from 4 normal Wishe rats were used. There were no obvious changes in the resting membrane potentials of CA3 neurons between NER and Wistar rats tested. When a single stimulus was delivered to the mossy fibers, a long-lasting depolarization shift accompanied by repetitive firings followed by after-hyperpolarization werc also obtained i n hippocampal CA3 neurons of young NER (4,5 weeks of age) before occurrence of any seizurcs, although the depolarization shift in younger NER was shorter than that in NER aged more than 6 weeks. These abnormal firings werc evokcd in 58% and 30% of all CA3 neurons tested in the younger and mature NER (6,1 5 weeks of age), respectively. Furthermore, abnormal firing was not elicited in NER aged after I6 weeks. Agc-matched Wistar rats showed only single action potentials without any depolarization shift with single mossy fiber stimulation. Bath application of nicardipine (IOnM) inhibited this long-lasting depolarization shift and the accompanying repetitive firing followed by afterhypcrpolarization without affecting the first spike induced by mossy fiber stimulations. Furthermore, nicai-dipine (IOnM) inhibited the Ca2+ spikes elicited by applying a depolarizing pulse in the neurons of NER with seizures, although a higher dose (100nM) did not affect those in Wistar rats. Conclusions: These findings indicate that abnormal excitability of the NER CA3 pyramidal neurons is probably due to abnormality in the Ca2+ channcls. The abnorinal excitability was observed in NER at an age when tonic-clonic convulsions were not detected, suggesting that thc hippocampus may probably scrve as an epileptogenic focus in younger NER and the seizure impulses originating i n this area are transinittcd to the new other seizurc foci in mature NER. [source] Dipole Tracing Examination for the Electric Source of Photoparoxysmal Response Provoked by Half-Field StimulationEPILEPSIA, Issue 2000Kazuhiko Kobayashi Purpose: Dipole tracing (DT) is a computer-aidcd noninvasive method used to estimate the location of epileptic discharges from the scalp EEG. In DT equivalent current dipoles (ECDs), which rcflcct the electric source in the brain, are rcsponsible for the potential distribution on the scalp EEC. Thercfore, the DT method is useful to estimatc the focal paroxysmal discharges. In this study we examined the location of the clectric source of photoparoxysmal response (PPR) using scalpskull-brain dipolc tracing (SSB-DT) after hal[-field stimulation, which produced focal PPR on the scalp EEG. Methods: We studied 4 cases of photoscnsitive epilepsy. Wc performed 20 Hz red flicker and flickcring dot pattern half-ficld stimulation to provoke PPR. In this method, the loci of gcnerators corresponding to the paroxysmal discharges were estimated as ECDs by I - and 2-dipole analyses. Each location of the ECDs was estimated by iterative calculation. Algorithms minimizing the squarcd difference betwccn the electrical potentials recorded from the scalp EEG and those calculated theoretically from the voluntary dipoles were uscd. In the SSB model, the scalp shell was reconstructed from the helmet mcasurements, and the shapc of the skull and brain was 3-dimcnsionally reconstructed from CT images. A dipolarity larger than 98% w the accuracy of the estimation. We recorded thcir 2 I channel monopolar scalp EEG. Each spike was sampled analyzed at 10 points around the peaks of at least 10 spikes in each patient using the SSB-DT method. The ECDs were then supcrimposed on thc MRI of each palient to idcntify the more cxact anatomical region. Results: This study showed the location of cach focus and a dipolarity of greater than 98% in all cases, although the results from the 2-dipole method showed scattered location. We considered that the analyzed signals were generated from single source. PPR was elicitcd cross-lateral to the field stimulated. By red flicker half-field stimulation, EEG revealed eithcr focal spikes and waves in the contralatcral occipital, temporo-occipitel region, or diffuse spikes and wave complex bursts, sccn dominantly at the contralateral hcmisphere. The supcrimposed ESDs on MRI were located at the occipital or inferior temporal lobe. PPR, provoked by flickering dot pattern half-field stimulation, werc focal spikes and waves, mainly in the occipital, parieto-occipital region, or diffuse spikes and wave complcx bursts, seen dominantly at thc contralateral hcmiaphere. The ECDs of their PPRs were located in the occipital, inferior temporal, or inferior pirietal lobules on MRI. Conclusion: Our findings suggest that the inferior temporal and inferior parictal lobules which are important for the processing sequence of the visual system in addition to the occipital lobc, might he responsible for thc mechanism of PPR by half-ficld stimulation, espccially for electric source expansion. [source] NMDA receptors are essential for the acquisition, but not expression, of conditional fear and associative spike firing in the lateral amygdalaEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2004Ki A. Goosens Abstract We examined the contribution of N -methyl- D -aspartate (NMDA) receptors (NMDARs) to the acquisition and expression of amygdaloid plasticity and Pavlovian fear conditioning using single-unit recording techniques in behaving rats. We demonstrate that NMDARs are essential for the acquisition of both behavioral and neuronal correlates of conditional fear, but play a comparatively limited role in their expression. Administration of the competitive NMDAR antagonist ±-3-(2-carboxypiperazin-4-yl) propyl-1-phosphonic acid (CPP) prior to auditory fear conditioning completely abolished the acquisition of conditional freezing and conditional single-unit activity in the lateral amygdala (LA). In contrast, CPP given prior to extinction testing did not affect the expression of conditional single-unit activity in LA, despite producing deficits in conditional freezing. Administration of CPP also blocked the induction of long-term potentiation in the amygdala. Together, these data suggest that NMDARs are essential for the acquisition of conditioning-related plasticity in the amygdala, and that NMDARs are more critical for regulating synaptic plasticity and learning than routine synaptic transmission in the circuitry supporting fear conditioning. [source] Electrophysiological characterization of laminar synaptic inputs to the olfactory tubercle of the rat studied in vitro: modulation of glutamatergic transmission by cholinergic agents is pathway-specificEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 9 2001G. S. Owen Abstract We have exploited the complementary arrangement of afferents in a coronal slice (300,400 µm) of the rat olfactory tubercle (OT) maintained in vitro to investigate transmission in two separate synaptic pathways. We recorded extracellular responses within the OT dense cell layer in slices and stimulated either the outermost layer to activate primary olfactory fibres or deeper to activate secondary input. Superficial stimulation produced a synaptic potential with superimposed population spike. This interpretation was based on blockade by calcium removal from the bathing medium and the use of the glutamate antagonist DNQX (10 µm); the spike was found to be selectively suppressed by tetrodotoxin applied near the cells. The spike, but not the synaptic wave, was depressed by 12 mm Ca2+ and enhanced by 1 mm Ba2+ in the bathing medium. Deep stimulation to activate association and intrinsic fibres elicited a nerve volley followed by a later response, also blocked by Ca2+ removal or 10 µm DNQX. It was unaffected by high Ca2+ or Ba2+, hence resulting from synaptic and not action current flow. Removal of Mg2+ from the bathing medium revealed an NMDA component of synaptic transmission at both loci that was selectively blocked by D-AP-5. The deep synaptic response, only, was depressed by carbachol IC50 7 µm or muscarine IC50 13 µm. This depression was also induced by AChE inhibitors eserine or tacrine and was antagonized by 1 µm atropine or 5,10 µm clozapine. These results characterize transmission in the OT and demonstrate a role for muscarinic modulation of deeper synapses in the OT that is influenced by psychotherapeutic drugs. [source] Determination of Lithium Contents in Silicates by Isotope Dilution ICP-MS and its Evaluation by Isotope Dilution Thermal Ionisation Mass SpectrometryGEOSTANDARDS & GEOANALYTICAL RESEARCH, Issue 3 2004Takuya Moriguti Lithium; ICP-MS avec dilution isotopique; TIMS; matériaux silicatés de référence; météorites A precise and simple method for the determination of lithium concentrations in small amounts of silicate sample was developed by applying isotope dilution-inductively coupled plasma-mass spectrometry (ID-ICP-MS). Samples plus a Li spike were digested with HF-HClO4, dried and diluted with HNO3, and measured by ICP-MS. No matrix effects were observed for 7Li/6Li in rock solutions with a dilution factor (DF) of 97 at an ICP power of 1.7 kW. By this method, the determination of 0.5 ,g g -1 Li in a silicate sample of 1 mg can be made with a blank correction of < 1%. Lithium contents of ultrabasic to acidic silicate reference materials (JP-1, JB-2, JB-3, JA-1, JA-2, JA-3, JR-1 and JR-2 from the Geological Survey of Japan, and PCC-1 from the US Geological Survey) and chondrites (three different Allende and one Murchison sample) of 8 to 81 mg were determined. The relative standard deviation (RSD) was typically < 1.7%. Lithium contents of these samples were further determined by isotope dilution-thermal ionisation mass spectrometry (ID-TIMS). The relative differences between ID-ICP-MS and ID-TIMS were typically < 2%, indicating the high accuracy of ID-ICP-MS developed in this study. Nous avons développé une méthode simple et précise de détermination des concentrations en lithium dans de très petits échantillons silicatés. Elle est basée sur la méthode de dilution isotopique couplée à l'analyse par spectrométrie de masse avec couplage induit (ID-ICP-MS). Les échantillons auxquels est ajouté le spike de Li, sont mis en solution avec un mélange HF-HclO4, évaporés à sec, puis repris avec HNO3 et analysés à l'ICP-MS. Aucun effet de matrice n'est observé sur les rapports 7Li/6Li dans les solutions quand les facteurs de dilution sont 97 et qu'elles sont analysées avec une puissance du plasma de 1.7 kW. Par cette méthode, la détermination de 0.5 ,g g -1 de Li dans un échantillon silicaté de 1 mg peut être effectuée avec une correction de blanc < 1 %. Les teneurs en lithium des matériaux de référence de composition ultrabasique à acide (JP-1, JB-2, JB-3, JA-1, JA-2, JA-3, JR- 1 et JR-2 du Service Géologique du Japon, et PCC-1 du Service Géologique des USA) et de chondrites (trois échantillons différents d'Allende et un de Murchison), de poids variant entre 8 et 81 mg ont été déterminées. La déviation standard relative typique était < 1.7%. Les teneurs en lithium de ces échantillons ont été ensuite mesurées par dilution isotopique et spectrométrie de masse à thermo-ionisation (ID-TIMS). Les différences entre les résultats obtenus par ID-ICP-MS et ID-TIMS étaient < 2%, démontrant ainsi la grande justesse de la technique ID-ICP-MS développée dans cette étude. [source] | ||||||||||||||||||||||||||||||||||||||||||||||