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PROSTAGLANDIN (PG) E2 production was assessed in freely moving rats using the technique of microdialysis in the prefrontal cortex associated with parallel cortical EEG recordings. PGE2 concentrations were 40 higher during wakefulness than during slow wave sleep. PGE2 values varied during wakefulness with a maximal increase in the middle of the stage and a drop towards lower values before the occurrence of slow wave sleep. These variations were similar to those observed previously in the rostromedial hypothalamus, where PGE2 concentration was 2.6 times lower than that in the cortex. These data document a positive correlation between cortical EEG activation and PGE2 levels. Taken together with pharmacological data on the awakening effect of centrally administered PGE2, these observations are in favor of an involvement of PGE2 in the generation of wakefulness.

The very special topography of Greece with the hundreds of mainland and island ports generates vast possibilities for developing routing networks to link the ports to each other while satisfying total demand. An algorithm which minimizes total operating costs (fixed and variable) has been adapted and used to determine an optimal network solution. The total operating costs of this solution is compared to the total operating costs of the existing (1964 data) network and the optimal networks when fixed and variable costs are minimized independently. It is found that the actual network follows the minimal total operating costs solution quite closely.

The aim of this study was to elucidate the role of the neuropil located in the LHA in the acquisition of the association between a taste (conditioned stimulus = saccharin) and a visceral distress (unconditioned stimulus = lithium chloride) leading to long delayed learning of a conditioned taste aversion (CTA). In 82 male rats guide-cannulae were directed bilaterally into the basolateral LHA where bilateral microinjections were made after the conditioned stimulus and before the unconditioned stimulus. We found that: (1) tetrodotoxin, a non-specific blocker of neuronal activity disrupted the acquisition of the CTA; (2) SCH 23390, a specific D1 receptor blocker also disrupted learning of the CTA, while sulpiride, a D2 receptor blocker, did not; (3) neither the specific blockade of D1 nor of D2 receptors could prevent the visceral distress-induced decrease in water intake, showing that the visceral distress was actually experienced; and (4) the sham taste aversion learning (i.e. without visceral distress) revealed that neither the D1 nor the D2 receptors blockade induced by themselves either a taste preference or a taste aversion towards saccharin, indicating that the impaired acquisition of the CTA was not due to a superimposed taste preference that could have been induced by the intra-LHA D1 receptors blockade. It is concluded that the neuropil in the LHA is necessary in the process of the acquisition of long delayed learning and that it uses a D1 receptor specific mechanism.

Rats are able to choose appropriately between two versions of a novel diet, when one is amino-acid devoid and the other corrected. Recognition of the deficiency has been reported to occur within hours and to initiate a strong conditioned aversion. For that purpose the rat can use either oro-sensory cues or another alternative as the conditioned stimulus (CS) with which to associate the unconditioned stimuli (US) of either the adequate diet or the devoid diet. The present investigation was designed to determine whether rats have the ability to use place as a cue in amino-acid preference/aversion. In order to avoid interfering with any other than spatial sensory discrimination between the devoid diet and its corrected version, rats were offered two food cups containing an identical threonine-devoid diet. This was supplemented with an intra-gastric delivery of either threonine or its vehicle, that varied according to the position of the feeder from which the rats had chosen to eat. After three choice sessions, rats chose the food container on the side corresponding to the threonine load. Our results showed that rats use place as a cue for an amino-acid replete nutritional state by learning a conditioned place preference/aversion and that they achieve this type of learning in spite of the long delay elapsing between CS and US.

A method for the preparation of D- and L-glutamyl alpha-chloromethyl ketones (4-amino-6-chloro-5-oxohexanoic acid) is described. These chloromethyl ketones irreversibly inactivated bovine glutamate dehydrogenase, whereas several other related compounds had no adverse effect on the activity of the enzyme. The inactivation process was shown to be due to the modification of lysine-126. The time-courses for the inactivation and the incorporation of radioactivity from tritiated L-glutamyl alpha-chloromethyl ketone into the glutamate dehydrogenase were biphasic. The results were interpreted to suggest the involvement of ‘negative co-operative’ interactions in the reactivity of lysine-126. From the cumulative evidence it is argued that the first subunit of the enzyme, which takes part in catalysis, makes the largest, and the last the smallest, contribution to the overall catalysis. It is emphasized that three of the six subunits of the enzyme may possess as much as 80% of the total activity of bovine glutamate dehydrogenase.

One hundred and twelve fetuses with structural anomalies (n = 84), intrauterine growth retardation (n = 21) or amniotic fluid volume disorders (n = 7) detected by ultrasound underwent blood sampling from the intrahepatic vein for rapid karyotyping. The procedure was successful in 95.5%. 12.5% of the fetuses had an abnormal karyotype. Fetal bradycardia was observed in two fetuses (1.8%) and intraperitoneal bleeding in three (2.7%). There were three procedure-related losses but these were not due to the intrahepatic vein sampling itself. Fetal blood sampling is the method of choice for rapid karyotyping in the second and third trimesters, and the intrahepatic vein is an alternate site when access is difficult or failure to sample occurs at the placental cord insertion. Additional advantages of fetal blood sampling at the intrahepatic vein include absence of cord complications, reduced risk of fetal blood loss and fetomaternal haemorrhage, and the lack of need to confirm the fetal origin of the sample.

Fetal plasma ferritin concentrations were measured in 43 normal fetuses at 18-36 weeks and in 78 blood samples collected before transfusion from 23 fetuses with Rh alloimmunization. Among controls, there was a significant correlation between fetal serum ferritin and gestational age (r0.39, P.009), consistent with an increase in fetal storage of iron during normal pregnancy. In Rh-alloimmunized fetuses, the ferritin concentration was above the reference range in 63 of the samples. Before the first transfusion, the fetal ferritin concentration was increased compared with controls (mean multiples of the mean2.6, range 1-26) and showed a negative correlation with fetal hematocrit (r-0.43, P<.05), suggesting that the worse the fetal anemia, the higher the iron store. Serial transfusions were associated with further increase in serum ferritin, which correlated primarily with the total volume of blood transfused. Three fetuses had plasma serum ferritin concentrations above 1 mgL, a level compatible with a diagnosis of iron overload in children. These observations suggest that there is a potential risk of iron overload in Rh-alloimmunized fetuses undergoing intrauterine blood transfusion.

This paper deals with the design of a microprocessor dedicated to safety applications and more particularly to Automatic Train Control. This microprocessor is self-checking i.e. able to detect its own errors. Its name is COBRA for Controller with Built in self-checking for RealTime Applications.

Self-checking integrated circuits, i.e. able to detect its own errors, are not adequate to control the actuators of critical systems used in railway transportation, space, chemical and nuclear industries. Only the conventional fail-safe circuits can apply these needs, unfortunately they cannot be implemented in integrated circuits technologies and thus they cannot be used to realise complex systems.

Recent travel demand models and particularly mode-choice models have used a probabilistic disaggregate approach. That is, such models determine choice probabilities at the individual level. It is in this framework that one might be able to include qualitative measures affecting the individual's choice of a travel mode.

The technique of electropalatography (EPG) provides detailed spatio-temporal information on tongue contacts with the hard palate during continuous speech. In most available versions of the technique the contact data are obtained at a sampling rate of 100–200 Hz from a number of electrodes (usually more than 60) mounted on the surface of an artificial palate. Detailed qualitative information is available from appropriate computer processing, but for many purposes, e.g. for statistical analysis, quantitative data are required. This paper reviews some recent methods of EPG data reduction including numerical indices of contact patterns.

In homozygous ß-thalassemia, the organ damage is mainly attributed to excessive iron deposition through the formation of oxygen free radicals. Despite appropriate transfusion and chelation therapy and low ferritin levels, patients still develop organ failure, heart failure being the main cause of death. This study was designed to determine whether the decreased antioxidant activity of the apolipoprotein E (APOE) ?4 allele could represent a genetic risk factor for the development of left ventricular failure (LVF) in ß-thalassemia homozygotes. A total of 251 Greek ß-thalassemia homozygotes were studied. Patients were divided in three groups: group A (n = 151) with no cardiac impairment, group C (n = 47) with LVF, and 53 patients with LV dilatation and normal LV systolic function constituted the group B. DNA was obtained from all patients, and the polymerase chain reaction was used to analyze the polymorphism at the APOE locus. The APOE allele frequencies were compared with those of a Greek control sample of 216 healthy blood donors. Patients with no cardiac impairment had an APOE ?4 allele frequency (7.9%) not different from population controls (6.5%, P > .05), while patients with LVF had a significantly higher frequency of APOE ?4 (12.8%) than the controls (P < .05, odds ratio = 2.11, 95% confidence interval 1.03 to 4.32). The APOE ?4 allele may represent an important genetic risk factor for the development of organ damage in homozygous ß-thalassemia. © 1998 by The American Society of Hematology.

This study has determined in rats the ontogenetic schedule of the onset of pituitary prolactin (PRL) synthesis and release as well as of the establishment of the dopamine (DA) inhibitory control of PRL secretion. RIA recognized PRL traces in the pituitary at the 18th embryonic day (E18), although a clearly detectable amount of this hormone was first measured at E20, suggesting the onset of PRL synthesis. The PRL level in the pituitary increased significantly by E22, in females to a higher extent than in males. Decapitation of fetuses did not cause any change in the PRL plasma level in males showing no PRL release from the pituitary until term. Conversely, there was a slight but significant fall of plasma PRL in decapitated females, suggesting PRL release from the pituitary. An inhibition of DA receptors on lactotropes of fetuses resulted in an increased level of plasma PRL at E20, but not at E18, while the pituitary content of PRL remained unchanged. The same treatment at E22 caused a significant increase of the PRL concentration in plasma and a concomitant fall in the pituitary that could be prevented by preliminary encephalectomy. These data show that the tuberoinfundibular DA system begins to inhibit PRL release from lactotropes between E20 and E22, completely arresting PRL release from the pituitary in males but not in females.

In order to plan bus operations, it is necessary for transit planners to understand what factors may influence travelers' choice of buses for travels within a city. The proposed method involves various scenarios of a hypothetical bus operation which was rated by a group of individuals.Analysis of Covariance technique is employed to analyze people's sensitivities to their perceived levels of bus service characteristics. The technique involves: testing for the significant effects of varying levels of service characteristics upon people's intentions to use bus service, and assessing differences among various population segments in their sensitivity patterns towards bus service characteristics.Results from the application of the technique to attitudinal data collected by the Orange County Transit District indicate that bus service characteristics do influence, independently and jointly, respondents' stated intentions to use buses.Sensitivity pattern differed across the five homogeneous segments identified in an earlier research based on socioeconomic characteristics.One segment (an older, predominatly male population segment with higher home ownership level and lower income than the rest of the sample) was relatively insensitive to changes in bus fare and was influenced by changes in headway independent of changes in access distance. Another segment consisting of fewer registered voters with lower education also exhibited similar independent impact of headway and access distance.The technique is especially useful in reducing a large number of proposed alternative bus systems to a smaller set for further planning considerations by specifying the ranges within which variation of service characteristic would cause substantial changes in the intended usage responses.

Energy metabolism and food intake affect each other. Many studies demonstrated that the lateral hypothalamus (LH) participates in the control of both feeding behavior and energy metabolism. We assessed the effect of a bipolar near threshold feeding eliciting electrical stimulation of the LH first on the feeding response and then on the background metabolism (metabolism free from the part due to locomotion) and respitory quotient (RQ), on Wistar male rats, during either the light or the dark phase of the nycthemeron. LH stimulation resulted in a delayed and rather long increase in background metabolism that was more dramatic during the light phase. This metabolic response paralleled the delayed feeding response (more than 10 min) we obtained during behavioral tests. The increase in energy production was sustained by release of energy substrates from the endogenous stores, and this showed a circadian dependence. Mainly carbohydrates (rise in RQ) were used during the light phase stimulation whereas lipids (decrease in RQ) were released in the dark phase.

A technique for concurrently checking faults in static CMOS circuits is proposed. It performs concurrent monitoring of static current by means of built-in current sensors (BICS) and detects the leakage current that accompanies the parametric shifts. Using BICs also allows the selection of high-quality circuits during manufacturing testing, resulting in a higher mean time to failure.<>

This paper reals with the design of a microprocessor dedicated to safety applications and more particularly to Automatic Train Control. This microprocessor Is self-checking i.e. able to detect its own errors. Its name is COBRA for Controller with Built in self-checking for Real-time Applications.

The synthesis and characterization of an octahedral cobalt(III) complex of the octaamine ligand 5,5-bis(4-amino-2-azabutyl)-3,7-diazanonane-1,9-diamine, [co( asen )]3+, is described. Two approaches to the preparation of encapsulated derivatives of [Co(asen)]3+ are also described. The first approach involves reaction of [Co(asen)]3+ with nitromethane and formaldehyde in the presence of base. After extensive chromatographic purification [(1-(4-amine-2-azabutyl)-8-nitro-3,6,10,13,16,19-hexaazabicyclo[6.6.6] icosane )cobalt(III)]5+ was isolated. The second more convenient method employs precautionary protection of the pendant primary amine of [Co( asen )]3+, as the benzenesulfonate, prior to reaction with the same capping reagents. Both approaches result in an encapsulated complex bearing a pendant 4-amine-2-azabutyl moiety. The protecting group is stable under reaction conditions required for successive chemical modifications of the capping nitro group to amine, chloro and proton capped cages, but is readily removed in refluxing acidic solution.

In normal rats, hypoglycemic doses of intravenous insulin bring about glucoprivic feeding but the same doses of insulin inhibit feeding when combined with doses of glucose that prevent hypoglycemia. In this study, these effects were compared between obese Zucker rats (fa-fa), known to present several abnormalities related to insulin, and normal Wistar rats by infusion of insulin (1 IU over 1 h), insulin plus glucose (5·1 g over 2 h) or vehicle. Feeding patterns and microstructure were automatically monitored. Contrary to its effect in the normal rats, insulin infusion did not enhance feeding in the Zucker rats but rather slightly decreased total food intake and meal duration. The insulin plus glucose infusion produced a total anorexia in normal rats but only a partial reduction in total food intake and metal duration was observed in Zucker rats. The impaired feeding effect of insulin in the Zucker rat may be related to its peripheral resistance to insulin which prevents a severe hypoglycemia and therefore glucoprivic feeding. The lack of inhibition of feeding when both insulin and glucose are infused may account for the well-known delayed satiation and large meals in the Zucker rat, possibly involving impaired hypothalamic action of insulin. Copyright 1994, 1999 Academic Press

DNA-envelope complexes isolated from osmotically lysed spheroplasts of Escherichia coli contained 0.2 to 1% of the total cellular DNA after labeling with [3H]thymidine. Molecular weight determinations indicated that the amount of bound DNA was equivalent in most cases to a maximum of three binding sites per chromosome. Bound DNA from E. coli B/r was distributed approximately equally between inner and outer membrane components when envelopes were fractionated on sucrose equilibrium gradients. Outer membrane-DNA complexes, in particular, fraction H1, with a density of 1.24 g/cm3, were quite stable against shearing and against Sarkosyl NL97. In the case of E. coli B/r, H1-DNA was also relatively resistant to deoxyribonuclease. Inner membrane-DNA complexes, in contrast, were quite labile and readily dissociated to release free DNA. The outer membrane fractions did not appear to contain replication fork DNA, but small amounts may have been present in the inner membrane complexes. A two- to eightfold enrichment for chromosomal origin DNA in the envelope was obtained when cultures of E. coli K-12, synchronized for DNA replication, were pulse labeled at different times in the replication cycle. This enrichment was found invariably in the outer membrane fractions. However, the data do not exclude the possibility that this DNA is bound to regions of adhesion between inner and outer membranes which sediment with a density indistinguishable from that of the outer membrane.

In homozygous β-thalassemia, the organ damage is mainly attributed to excessive iron deposition through the formation of oxygen free radicals. Despite appropriate transfusion and chelation therapy and low ferritin levels, patients still develop organ failure, heart failure being the main cause of death. This study was designed to determine whether the decreased antioxidant activity of the apolipoprotein E (APOE) ε4 allele could represent a genetic risk factor for the development of left ventricular failure (LVF) in β-thalassemia homozygotes. A total of 251 Greek β-thalassemia homozygotes were studied. Patients were divided in three groups: group A (n = 151) with no cardiac impairment, group C (n = 47) with LVF, and 53 patients with LV dilatation and normal LV systolic function constituted the group B. DNA was obtained from all patients, and the polymerase chain reaction was used to analyze the polymorphism at the APOE locus. The APOE allele frequencies were compared with those of a Greek control sample of 216 healthy blood donors. Patients with no cardiac impairment had an APOE ε4 allele frequency (7.9%) not different from population controls (6.5%, P> .05), while patients with LVF had a significantly higher frequency of APOE ε4 (12.8%) than the controls (P< .05, odds ratio = 2.11, 95% confidence interval 1.03 to 4.32). The APOE ε4 allele may represent an important genetic risk factor for the development of organ damage in homozygous β-thalassemia.

IT is usually assumed that absorbed nutrients have effects which contribute to the control of food intake. Indeed, we have suggested that the rate of flow of energy to working tissues is the basic controlling factor in appetite and satiety1,2. The chief absorbed energy substrate in the rat on a laboratory diet is glucose: yet glucose administration does not always produce a decrease in energy intake which compensates for all the glucose energy administered. Such negative findings may be artefacts of failure to mimic the absorption of glucose during normal satiety; sometimes, for instance, as has been pointed out3,4, undetectably low doses, unphysiological concentrations and volumes, and starved rats that are not easily satiated have been used. Furthermore, it may be necessary to produce the normal context for nutrient utilisation, such as adequate secretion of insulin. For example, the reduction in food intake during continuous intravenous infusion of glucose is at most 0.6 kcal per kcal infused: coinfusion of insulin corrects this incomplete compensation5. We report here that the context of the initial absorption of a meal on familiar diet permits full compensation for infused glucose by a decrease in meal size. In contrast, when an unfamiliar cue is added to the diet, conditioning of appetite6,7by the infusion is sufficient to overwhelm satiety, disrupting compensation and causing faster weight gain.