Differential effects of the CCKA receptor ligands PD-140, 548 and A-71623 on latent inhibition in the rat.

Latent inhibition (LI) is a behavioural paradigm in which repeated exposure to a stimulus without consequence inhibits the formation of any new associations with that stimulus. To the extent that LI reflects a process of learning to ignore irrelevant stimuli, disrupted LI has been suggested as an animal model for the attentional deficits observed in schizophrenia. The antipsychotic potential of cholecystokinin (CCK) stems from its colocalization with dopamine (DA) in the mesolimbic pathway, where it demonstrates both excitatory and inhibitory effects on dopaminergic activity. This may be explained by mediation through different receptor subtypes. A variety of hypotheses has emerged regarding the potential clinical application of subtype-selective CCK-based drugs. The present experiments examined the effects on LI of two selective CCKA ligands: PD-140,548 (a CCKA antagonist, Experiment 1: 0.001, 0.01, and 0.1 mg/kg) and A-71623 (a CCKA agonist, Experiment 2: 0.02, 0.05, and 0.1 mg/kg). In both experiments, the effects of haloperidol (0.1 mg/kg) were also investigated. Animals receiving 0.1 mg/kg of haloperidol or 0.001 or 0.1 mg/kg (but not 0.01 mg/kg) of PD-140,548 treated the preexposed stimulus as irrelevant after a low number of preexposures. In contrast, no facilitatory effect on LI was detectable at any of the A-71623 doses. The finding that A-71623 failed to enhance LI indicates that it is unlikely that this compound would have any antipsychotic effect within the clinical setting. Considering the facilitatory effect exerted by PD-140,548 on LI, it is probable that the inhibition of CCK activity might prove a more promising strategy for the pharmacological treatment of schizophrenia.

Effects of amisulpride, risperidone and chlorpromazine on auditory and visual latent inhibition, prepulse inhibition, executive function and eye movements in healthy volunteers.

In view of the evidence that cognitive deficits in schizophrenia are critically important for long-term outcome, it is essential to establish the effects that the various antipsychotic compounds have on cognition, particularly second-generation drugs. This parallel group, placebo-controlled study aimed to compare the effects in healthy volunteers (n = 128) of acute doses of the atypical antipsychotics amisulpride (300 mg) and risperidone (3 mg) to those of chlorpromazine (100 mg) on tests thought relevant to the schizophrenic process: auditory and visual latent inhibition, prepulse inhibition of the acoustic startle response, executive function and eye movements. The drugs tested were not found to affect auditory latent inhibition, prepulse inhibition or executive functioning as measured by the Cambridge Neuropsychological Test Battery and the FAS test of verbal fluency. However, risperidone disrupted and amisulpride showed a trend to disrupt visual latent inhibition. Although amisulpride did not affect eye movements, both risperidone and chlorpromazine decreased peak saccadic velocity and increased antisaccade error rates, which, in the risperidone group, correlated with drug-induced akathisia. It was concluded that single doses of these drugs appear to have little effect on cognition, but may affect eye movement parameters in accordance with the amount of sedation and akathisia they produce. The effect risperidone had on latent inhibition is likely to relate to its serotonergic properties. Furthermore, as the trend for disrupted visual latent inhibition following amisulpride was similar in nature to that which would be expected with amphetamine, it was concluded that its behaviour in this model is consistent with its preferential presynaptic dopamine antagonistic activity in low dose and its efficacy in the negative symptoms of schizophrenia.

A cephalometric study of class II malocclusions treated with mandibular surgery

INTRODUCTION:

Class II malocclusion is often associated with retrognathic mandible. Some of these problems require surgical correction. The purposes of this study were to investigate treatment outcomes in patients with Class II malocclusions whose treatment included mandibular advancement surgery and to identify predictors of good outcomes.
METHODS:

Pretreatment and posttreatment cephalometric radiographs of 90 patients treated with mandibular advancement surgery by 57 consultant orthodontists in the United Kingdom before September 1998 were digitized, and cephalometric landmarks were identified. Paired samples t tests were used to compare the pretreatment and posttreatment cephalometric values for each patient. For each cephalometric variable, the proportion of patients falling within the ideal range was identified. Multiple logistic regression analysis was performed to identify predictors of achieving ideal range outcomes for the key skeletal (ANB and SNB angles), dental (overjet and overbite), and soft-tissue (Holdaway angle) measurements.
RESULTS:

An overjet within the ideal range of 1 to 4 mm was achieved in 72% of patients and was more likely with larger initial ANB angles. Horizontal correction of the incisor relationship was achieved by a combination of 75% skeletal movement and 25% dentoalveolar change. An ideal posttreatment ANB angle was achieved in 42% of patients and was more likely in females and those with larger pretreatment ANB angles. Ideal soft-tissue Holdaway angles (7 degrees to 14 degrees ) were achieved in 49% of patients and were more likely in females and those with smaller initial SNA angles. Mandibular incisor decompensation was incomplete in 28% of patients and was more likely in females and patients with greater pretreatment mandibular incisor proclination. Correction of increased overbite was generally successful, although anterior open bites were found in 16% of patients at the end of treatment. These patients were more likely to have had initial open bites.
CONCLUSIONS:

Mandibular surgery had a good success rate in normalizing the main dental and skeletal relationships. Less ideal soft-tissue profile outcomes were associated with larger pretreatment SNA-angle values, larger final mandibular incisor inclinations, and smaller final maxillary incisor inclinations. The use of mandibular surgery to correct anterior open bite was associated with poor outcomes.

Analysis and Synthesis of pHEMT Class-E Amplifiers with Shunt Inductor including ON-State Active-Device Resistance Effects

In this theoretical paper, the analysis of the effect that ON-state active-device resistance has on the performance of a Class-E tuned power amplifier using a shunt inductor topology is presented. The work is focused on the relatively unexplored area of design facilitation of Class-E tuned amplifiers where intrinsically low-output-capacitance monolithic microwave integrated circuit switching devices such as pseudomorphic high electron mobility transistors are used. In the paper, the switching voltage and current waveforms in the presence of ON-resistance are analyzed in order to provide insight into circuit properties such as RF output power, drain efficiency, and power-output capability. For a given amplifier specification, a design procedure is illustrated whereby it is possible to compute optimal circuit component values which account for prescribed switch resistance loss. Furthermore, insight into how ON-resistance affects transistor selection in terms of peak switch voltage and current requirements is described. Finally, a design example is given in order to validate the theoretical analysis against numerical simulation.

The Agent-Rule-Class Framework for Multi-Agent Systems

Multi-agent systems have become increasingly mature, but their appearance does not make the traditional OO approach obsolete. On the contrary, OO methodologies can benefit from the principles and tools designed for agent systems. The Agent-Rule-Class (ARC) framework is proposed as an approach that builds agents upon traditional OO system components and makes use of business rules to dictate agent behaviour with the aid of OO components. By modelling agent knowledge in business rules, the proposed paradigm provides a straightforward means to develop agent-oriented systems based on the existing object-oriented systems and offers features that are otherwise difficult to achieve in the original OO systems. The main outcome of using ARC is the achievement of adaptivity. The framework is supported by a tool that ensures agents implement up-to-date requirements from business people, reflecting desired current behaviour, without the need for frequent system rebuilds. ARC is illustrated with a rail track example.

A novel structural class of photoswitchable oligonucleotide

Directed Michaelis–Arbuzov reactions of support-bound internucleotide O-benzyl- or O-methyl-phosphite triesters with meta-phenylazobenzylamine or alkane-/glycol-linked a,x-diamines were effected in the presence of iodine. The corresponding tritylated phosphoramidate-linked 11-mers were fully deprotected and released from the support under standard conditions and the fast- and slow-diastereoisomers of both the E- and the Z-meta-phenylazobenzyl-appended oligomers were readily resolved by RP-HPLC. The primary amine-functionalised oligonucleotides were either purified, detritylated and then finally treated with Nhydroxysuccinimidyl carboxylic acid ester derivatives of photoswitchable moieties (Route A) or first derivatised and then subsequently purified and detritylated (Route B). This latter route enabled resolution of fast- and slow-isomers of the trityl-on oligomers bearing novel photoswitchable azopyridine or 9-alkoxyanthracene moieties using RP-HPLC, following which the pure diastereoisomers were detritylated and characterised by MALDI-MS.

Analysis of Latent Tracks for MeV protons in CR-39

For protons of energy up to a few MeV, the temporal evolution of etched latent tracks in CR-39 nuclear track detector has been numerically modeled by assuming that the electronic energy loss of the protons governs the latent track formation. The technique is applied in order to obtain the energy spectrum of high intensity laser driven proton beams, with high accuracy. The precise measurement of the track length and areal track density have been achieved by scanning short etched, highly populated CR-39 employing atomic force microscope.