Showing papers by "University of Hertfordshire published in 1995"

The science of complexity: An alternative perspective for strategic change processes

Abstract: The two perspectives of strategy process most firmly established in the literature—strategic choice and ecology—assume the same about system dynamics: negative feedback processes driving successful systems (individual organizations or populations of organizations) toward predictable equilibrium states of adaptation to the environment. This paper proposes a third perspective, that of complex adaptive systems. The framework is provided by the modern science of complexity: the study of nonlinear and network feedback systems, incorporating theories of chaos, artificial life, self-organization and emergent order. Here system dynamics are characterized by positive and negative feedback as systems coevolve far from equilibrium, in a self-organizing manner, toward unpredictable long-term outcomes.

Examination of drug-induced and isolation-induced disruptions of prepulse inhibition as models to screen antipsychotic drugs

Abstract: Prepulse inhibition (PPI) of an acoustic startle response is impaired in schizophrenics. PPI can also be studied in the rat, and is impaired by dopamine (DA) D2/3 receptor agonists such as apomorphine. This disruption is reversed by DA antagonists, leading to proposals that this approach may be a useful means to identify novel antipsychotics. There is also evidence to suggest a role of serotonergic (5-HT) and glutamatergic systems in schizophrenia, and accordingly PPI can be disrupted by the 5-HT2 agonist DOI, and the non-competitive NMDA antagonist, dizocilpine. In the present study we have examined the effect of four antipsychotic drugs, haloperidol (0.1–0.3 mg/kg), raclopride (0.03–0.3 mg/kg), risperidone (0.3–3 mg/kg) and clozapine (0.0001–10 mg/kg), against the PPI disruptions induced by apomorphine (0.5 mg/kg), DOI (3 mg/kg) and dizocilpine (0.15 mg/kg). Furthermore, these drugs have been examined for their ability to restore a PPI deficit produced by housing rats under conditions of social isolation. All drugs except clozapine reversed an apomorphine-induced disruption. However, clozapine and risperidone, but not raclopride and haloperidol, reversed a DOI-induced disruption. Only risperidone was effective in restoring a PPI deficit produced by dizocilpine. In contrast to the drug-induced disruptions which were differentially sensitive to the various neuroleptics, isolation-induced disruptions were restored by each drug. These results support the idea that non-drug induced disruptions of PPI, such as social isolation, may be a more viable approach to identify novel antipsychotics.

The efficient analysis of neutral and highly polar pharmaceutical compounds using reversed-phase and ion-exchange electrochromatography

Abstract: Highly polar compounds, such as tricyclic antidepressants are very difficult to analyse by electrochromatography with conventional reversed-phase silica-based chromatography packings. At high pH (high electroosmotic flow) the test compounds were not eluted from a Spherisorb ODS-1 column, as a result of strong interactions between the analyte and residual silanol groups on the packing material. By lowering the pH of the mobile phase, whereby the highly basic test compounds become positively charged, it was possible to elute the samples but only with severe peak tailing. Because cause the electroosmotic flow was greatly reduced, the elution time for neutral species became prohibitively long. By use of a strong cation exchanger in place of C18-silica it was found possible to resolve a series of highly basic compounds with very high efficiencies, with very little evidence of peak tailing. Plate numbers in excess of 8 million per metre were observed.

Nebulization of Fluids of Different Physicochemical Properties with Air-Jet and Ultrasonic Nebulizers

Abstract: Purpose. Empirical formulae relate the mean size of primary droplets from jet and ultrasonic nebulizers to a fluid's physicochemical properties. Although the size selective “filtering” effects of baffling and evaporation may modify the secondary aerosol produced, this research sought to evaluate whether viscosity and surface tension of nebulized fluids influenced the aerosol's size and output characteristics.

Groundwater Exploration Using Remote Sensing And A Low-Cost Geographical Information System

Abstract: Now that personal computers (pc's) have become more powerful, potable, and affordable, geoscientists can make full use of developments in computer-aided mapping, particularly Geographical Information Systems (GIS). The IDRISI GIS was used to 1) carry out image processing on satellite images; 2) assess the reliability of the interpreted lineaments; 3) create maps showing individual lineament lengths, areal extent of interconnected lineaments, and targets for groundwater boreholes; and 4) incorporate socio-economic factors, by creating maps that show the proximity of villages to sites considered favourable for boreholes. The exact location of each site for drilling was decided on the basis of geophysical surveys over the areas that had been targeted by the remote sensing and GIS analysis. Most of the remote sensing and GIS work was carried out in Ghana in two weeks, during which the ‘ground truth’ of lineament maps was checked. The total cost of the hardware and software used in this project (16-colour laptop pc, portable colour printer, and IDRISI) was slightly less than US$ 2,600. The relatively low cost and ease of use of this system make it a technology that is readily transferable to developing countries.

Mast cells in neuroimmune function: neurotoxicological and neuropharmacological perspectives.

Abstract: Mast cells are located in close proximity to neurons in the peripheral and central nervous systems, suggesting a functional role in normal and aberrant neurodegenerative states. They also possess many of the features of neurons, in terms of monoaminergic systems, responsiveness to neurotrophins and neuropeptides and the ability to synthesise and release bioactive neurotrophic factors. Mast cells are able to secrete an array of potent mediators which may orchestrate neuroinflammation and affect the integrity of the blood-brain barrier. The ‘cross-talk’ between mast cells, lymphocytes, neurons and glia constitutes a neuroimmune axis which is implicated in a range of neurodegenerative diseases with an inflammatory and/or autoimmune component, such as multiple sclerosis and Alzheimer's disease. Mast cells appear to make an important contribution to developing, mature and degenerating nervous systems and this should now be recognised when assessing the neurotoxic potential of xenobiotics.

High-throughput screen for detecting antimycobacterial agents.

Abstract: A simple, robust assay system which can be used to screen for inhibitors of mycobacterial growth has been developed. A strain of the rapidly growing saprophyte Mycobacterium aurum is used as the test organism. Inhibition of its growth is highly predictive of activity against Mycobacterium tuberculosis, which cannot itself be used in screening because of its growth characteristics and highly infectious nature. The viability of M. aurum in the presence of a test sample is monitored by measuring the uptake of radiolabelled uracil into the cells. In a microtiter plate format, the screen has the potential for testing several thousand samples per day.

Effect of scopolamine on visual attention in rats.

Abstract: In the present study, the effects of scopolamine (SCOP) were determined upon the performance of rats in the five-choice serial reaction time task, a test of attention analogous to the continuous performance test in man. Rats were trained to detect and respond to brief flashes of light presented randomly in one of five locations until a stable level of performance was reached. SCOP (0.03–0.1 mg/kg SC) was administered 30 min prior to testing under standard conditions of stimulus presentation. SCOP reduced response accuracy at the highest dose and dose-dependently increased omissions and perseverative responses. However, these effects were mimicked by scopolamine methylbromide (SCOPMBr) which might suggest a peripheral site of action. When the task difficulty was increased by manipulating the stimulus presentation parameters, i.e. reduced stimulus intensity, duration or temporal predictability, SCOP (0.075 mg/kg SC) failed further to impair performance accuracy. However, in two separate experiments, SCOP (0.075 mg/kg SC) robustly increased the distractibility caused by a burst of loud white-noise occurring unpredictably during the intertrial-interval: SCOP significantly decreased accuracy and increased omissions, magazine latency, premature and perseverative responses compared with vehicle and the equivalent dose of SCOPMBr. These findings provide further evidence of a role for the central cholinergic system in attention.

Antecedents of schizophrenia and affective illness. Obstetric complications.

Abstract: Original article can be found at: http://bjp.rcpsych.org/ Copyright The Royal College of Psychiatrists [Full text of this article is not available in the UHRA]

The three-dimensional solution structure of RANTES.

Abstract: The solution structure of the chemokine RANTES (regulated on activation, normal T-cell expressed and secreted) has been determined using NMR spectroscopy Backbone and side-chain 1H and 15N assignments have been obtained using a combination of two-dimensional homonuclear and three-dimensional heteronuclear spectra Regular elements of secondary structure have been identified on the basis of a qualitative interpretation of NOE data, J(NH-H alpha) coupling constants, and amide exchange rates Three-dimensional structures were calculated from a total of 2146 experimental restraints using a combination of distance geometry and simulated annealing protocols For the 13 best structures the average backbone (N, C alpha, C) atomic rmsd from the mean coordinates for residues 5-65 is 064 A (+/- 014 A) for the dimer and 050 A (+/- 008 A) for the individual monomers Each monomer consists of a three-stranded antiparallel beta-sheet (residues 26-30, 38-43, 48-51) in a Greek key motif with a C-terminal helix (56-65) packed across the sheet, an arrangement similar to the monomeric structure of other members of this chemokine family (IL-8, PF4, MGSA/Gro alpha, and MIP-1 beta) Overall, the RANTES dimer resembles that previously reported for MIP-1 beta

Age-associated impairments in a test of attention: evidence for involvement of cholinergic systems

Abstract: We trained three groups of rats, young (Y; 3 months at the start of study), middle aged (MA; 15 months), and aged (AG; 22 months), in the serial five-choice serial reaction time task, a test of attention. There were clear age-related differences in task acquisition Y acquired the task quicker than MA rats, which learned faster than AG rats. A subgroup of AG rats [AG(I)] could not reach criterion (> 80% correct, < 20% omissions under standard conditions of 0.5 sec stimulus duration, 5 sec limited hold). Accordingly, they were tested under conditions of 1 sec stimulus duration. Having acquired the task, under standard conditions both MA and AG groups were slower to make a correct response but not to collect the food reward. Furthermore, parameter changes, particularly reductions in stimulus duration and intensity, revealed further age-related changes in accuracy. Following completion of these studies, animals were trained in a simpler one-choice task. Importantly, reducing stimulus duration/intensity in this task revealed no differences between Y and MA/AG groups, although AG(I) rats were impaired. This dissociation between MA/AG impairments in the one- and five-choice task suggests that these animals may show attentional deficits compared with Y rats, which are independent of changes in sensory (visual), motor function, or motivation. Finally, the MA deficit in attention was partially reversed by tacrine pretreatment (3 mg/kg). Also scopolamine (0.01–0.075 mg/kg) and mecamylamine (0.3–5 mg/kg) pretreatment impaired choice accuracy of MA but not Y rats. Taken together, the drug studies imply that the attentional deficits may at least be partially due to changes in cholinergic function.

Can, may, must and should : A Relevance theoretic account

Abstract: In this paper I argue that the polysemy view is not capable of giving a unified account of the meanings of CAN, MAY, MUST and SHOULD, whereas the unitary meaning view does not encounter the problems facing the polysemy view. I propose unitary meanings which are rich enough to account for the range of interpretations these modals can have, but which are specific enough to account for why they get these interpretations and not others. Proposing unitary meanings implies that we have to look for a theory of pragmatics which can explain how we achieve the different interpretations of these modals in use. I will argue that adopting the Relevance theory view of what drives interpretation gives us the basis for such an explanation.

Pumping and pressure detection using flexible tubes

Abstract: A peristaltic pump unit (18) has a flexible infusate line (28) which is repeatedly compressed by a flat plate like pusher (30). Transverse valve plates (32, 34), on either side of the pusher (30), operate sequentially to close the line in front of and behind the pusher. A resistive pressure sensor (50), between the two valves, provides signals to a microprocessor (46) which provides the system monitoring capabilities. Consistency in dose rate is provided by arranging for the flexible line (28) to be received in an elongate groove or channel (58) which acts to restrain sideways bulging of the line as it is being compressed by the pusher.

Role of aldehyde oxidase in the in vitro conversion of famciclovir to penciclovir in human liver.

Abstract: Famciclovir is the diacetyl 6-deoxy derivative of the active antiviral penciclovir that is for use in the treatment of infections caused by the herpes family of viruses. The major pathway of conversion is via di-deacetylation to BRL 42359, followed by oxidation to penciclovir. On oral dosing of famciclovir to humans, only penciclovir and BRL 42359 can be detected consistently in the plasma; thus, attention was focused on the oxidation reaction. This 6-oxidation occurred rapidly in human liver cytosol, had no requirement for cofactors, and followed simple Michaelis-Menten kinetics with a KM of 115 microM +/- 23 (N = 3). Using inhibitors of xanthine oxidase (allopurinol) and aldehyde oxidase (menadione and isovanillin), the relative roles of these enzymes in this process were determined. At a concentration of BRL 42359 that reflected plasma concentrations observed in humans (4 microM), both menadione (IC50 7 microM) and isovanillin (IC50 15 microM) caused extensive inhibition of the 6-oxidation reaction. In contrast, allopurinol caused no significant inhibition, confirming earlier in vivo work. At higher substrate concentrations (50 and 200 microM), the results with these inhibitors were broadly similar. These results provide strong evidence that aldehyde oxidase and not xanthine oxidase is responsible for the 6-oxidation of BRL 42359 to penciclovir in human liver cytosol, and this is likely to reflect the in vivo situation.

Spatial and Temporal Genetic Variation in British Field Populations of the Grain Aphid Sitobion avenae (F.) (Hemiptera: Aphididae) Studied Using RAPD-PCR

Abstract: The grain aphid Sitobion avenae (F.) was collected from winter wheat and adjacent cocksfoot grass at two locations in southern England and at four times in the year (April-July). Genetic variation between individual aphids was then investigated using random amplified polymorphic DNA polymerase chain reaction. Individuals caught in wheat and cocksfoot during April provided very different and highly diagnostic banding patterns that were independent of location. This host-based genetic differentiability was less evident as the season progressed, largely as a result of genetic drift and local movement between adjacent host species, which appeared to be predominantely in the direction from cocksfoot to wheat. The diversity of putative clones fell significantly, the mean number of individuals per clone rose and clones became more exclusively associated with certain sites which suggests that long-distance migration may have less of a homogenizing effect than hitherto thought for this species.

In situ detection and identification of trace explosives by raman microscopy

Abstract: The innovative design of the newly developed Renishaw Raman Microscope system and its application to the in situ detection and identification of plastic explosives contained in fingerprint samples are presented. Raman microscopy is a nondestructive inspection method. Our experimental results show that Raman spectra and Raman band images can be obtained from explosive particles as small as 1 µm3 in size or 1 picogram in mass. After exploring the full potential of the Raman microscopic technique, the aim of this research is to develop a real-time and field-deployable plastic explosive detection system.

Sodium transport measured in plasma membrane vesicles isolated from wheat genotypes with differing K+/Na+ discrimination traits

Abstract: Right-side-out plasma membrane vesicles were isolated from wheat roots using an aqueous polymer two-phase system. The purity and orientation of the vesicles were confirmed by marker enzyme analysis. Membrane potential (Ψ)-dependent 22Na+ influx and sodium/proton (Na+/ H+) antiport-mediated efflux across the plasma membrane were studied using these vesicles. Membrane potentials were imposed on the vesicles using either K+ gradients in the presence of valinomycin or H+ gradients. The ΔΨ was quantified by the uptake of the lipophilic cation tetraphenylphosphonium. Uptake of Na+ into the vesicles was stimulated by a negative ΔΨ and had a Km for extrav-esicular Na+ of 34.8 ± 5.9 mol m3. The ΔΨ-dependent uptake of Na+ was similar in vesicles from roots of hexaploid (cv. Troy) and tetraploid (cv. Langdon) wheat differing in a K+/Na+ discrimination trait, and was also unaffected by growth in 50 mol m−3 NaCl. Inhibition of ΔΨ-dependent Na+ uptake by Ca2+ was greater in the hexaploid than in the tetraploid. Sodium/proton antiport was measured as Na+-dependent, amiloride-inhibited pH gradient formation in the vesicles. Acidification of the vesicle interior was measured by the uptake of 14C-methylamine. The Na+/H+ antiport had a Km, for intravesicular Na+ of between 13 and 19 mol m−3. In the hexaploid, Na+/H+ antiport activity was greater when roots were grown in the presence of 50 mol m−3NaCl, and was also greater than the activity in salt-grown tetraploid wheat roots. Antiport activity was not increased in a Langdon 4D chromosome substitution line which carries a trait for K+/Na+ discrimination. It is concluded that neither of the transport processes measured is responsible for the Na+/K+ discrimination trait located on the 4D chromosome of wheat.

Simultaneous Measurement of Intracellular pH and K+ or NO3- in Barley Root Cells Using Triple-Barreled, Ion-Selective Microelectrodes.

Abstract: The manufacture and use of triple-barreled microelectrodes, which are capable of simultaneous in vivo measurement of intracellular pH and the activities of K+ or NO3- and cell membrane potential (Em), are described. Scanning electron micrographs showed that the three tips were aligned and that the overall tip diameter was approximately 0.8 [mu]m. When filled with 100 mM KCl, all three barrels simultaneously reported identical transmembrane potentials, showing that all three tips were located in the same subcellular compartment. Intracellular estimates of Em in barley (Hordeum vulgare L. cv Klaxon) root epidermal cells obtained with these triple-barreled microelectrodes were indistinguishable from those obtained using single- or double-barreled microelectrodes. Measurements made with triple-barreled K+ and pH-selective microelectrodes in root cells of 7-d-old barley plants grown in a nutrient solution containing 0.5 mM K+ yielded cytosolic and vacuolar populations having mean K+ activity values of 71.3 and 68.7 mM, respectively. The associated mean pH values ([plus or minus]SE) were 7.26 [plus or minus] 0.06 (cytosol) and 5.18 [plus or minus] 0.08 (vacuole). Analysis of whole-tissue digests confirmed the microelectrode measurements. Measurements made using triple-barreled pH- and nitrate-selective microelectrodes confirmed earlier double-barreled measurements of pH and nitrate in barley root epidermal cells growing in 10 mM nitrate.

Prevalence of penicillin resistant bacteria in acute suppurative oral infection

Abstract: Pus aspirated from acute suppurative oral infections in 78 patients (age range 13-76 years) yielded a total of 331 bacterial strains consisting of 143 facultative anaerobes (predominantly Streptococcus spp.) and 188 strict anaerobes (predominantly Prevotella spp.). Seventy-five isolates (23%) were resistant to penicillin (MIC > 1 mg/L), 37 (11%) were resistant to ampicillin (MIC > 2 mg/L) and 16 (5%) isolates were resistant to amoxycillin/clavulanic acid (MIC > 2 mg/L). Samples from 43 (55%) of the patients yielded at least one penicillin resistant isolate and within this group 30 samples (73%) contained at least one strain which produced beta-lactamase. A history of antibiotic therapy during the 6 months before enrollment in the study did not influence the isolation of penicillin resistant bacteria. It is concluded that penicillin resistant bacteria are often present in the microflora of acute dental infection.

Field and laboratory evaluation of a sex pheromone trap for the autodissemination of the fungal entomopathogen Zoophthora radicans (Entomophthorales) by the diamondback moth, Plutella xylostella (Lepidoptera: Yponomeutidae)

Abstract: The effectiveness of a sex pheromone trap designed specifically to deliver conidia (infective fungal propagules) of the entomopathogenic fungus Zoophthora radicans Brefeld (Zygomycetes: Entomophthorales) to male Plutella xylostella (Linnaeus) was investigated In field experiments in the Cameron Highlands of Malaysia, synthetic pheromone lures attracted adult males P xylostella at all times of the day whereas lures of virgin female moths attracted males only between the hours of dusk and dawn, when females are known to produce their pheromone Adult male moths attracted to traps baited with synthetic pheromone spent a geometric mean time of 88 seconds within the inoculation chamber, a time compatible with the period adults must spend within a shower of Z radicans conidia produced by uniform mycelial mats in order to become infected The field longevity of male and female P xylostella adults was found to be similar, with individuals living for a mean time of 49 days This was sufficient time for male moths to respond to the pheromone, enter the trap, become infected with Z radicans and succumb to that infection in the field (3-35 days) thereby releasing infective conidia into the cabbage crop

Changes in trace metal species and other components of the rhizosphere during growth of radish

Abstract: Changes in the properties of soil solution in the rhizosphere of developing radish plants were investigated. Variations in these properties were expected to affect the distribution and speciation of metals in the soil and soil solution. Applications of essential nutrients were linked to plant transpiration rates and prevented excess addition of nutrient ions, so that subtle changes in soil solution composition would not be obscured. Soil solution pH, the concentration of dissolved organic carbon (DOC) and the concentrations of major and trace elements in solution were found to vary over time. Strict control of fertilizer additions led to the maintenance of a relatively low ionic strength in the soil solution, and under such conditions trace metal solubility appeared to be highy influenced by the concentration of DOC. A chemical speciation analysis was performed which showed that, while dissolved Cd and Zn were largely uncomplexed in unplanted soil, Cd and Zn in the rhizosphere existed mainly as complexed forms. It is hypothesized that this is partly a result of Ca-metal-ligand equilibrium in solution, with higher Ca concentrations in unplanted soil leading to more of the Cd and Zn in solution existing in the uncomplexed state. Changes in the concentrations of uncomplexed Cd and Zn with time gave the best correlations with changes in plant uptake of these metals over time, supporting the hypothesis that plants mainly absorb the free metal ion from soil solution.