The number of clonogenic cells in a mouse jejunal crypt

A study of eight deaths involving the benzodiazepine flunitrazepam was performed to assess the contribution of this drug to the fatalities. Coronial deaths in Victoria in the 2-year period to mid-1991 were selected in which either flunitrazepam or flunitrazepam and ethanol were the principal toxicological findings. All bodies were subject to a full autopsy by forensic pathologists, and a full toxicological examination. No significant pathology was found at autopsy in any case. Very high concentrations of 7-aminoflunitrazepam, a metabolite of flunitrazepam, were present in all cases. In four cases no other significant drug was detected, whereas in the other four cases there were significant concentrations of ethanol (mean 1.6 g/L). In these two groups of cases the concentrations of 7-aminoflunitrazepam were 0.45 mg/L and 0.16 mg/L, respectively. Only moderate levels of flunitrazepam were detected, suggesting that 7-aminoflunitrazepam is produced postmortem and may be an important marker of flunitrazepam usage. The causes of death in these eight cases were probably either flunitrazepam toxicity or a combination of flunitrazepam and ethanol toxicity. Only one case appeared likely to have been a suicide. Our observations in these cases suggest that flunitrazepam may cause death in the absence of other drugs or significant disease. The presence of ethanol reduces the amount of flunitrazepam needed to cause death.     

Managing patients with vulvovaginal candidiasis

Epidemiologic studies have demonstrated a continuing increase in the prevalence of vulvovaginal candidiasis. Although in the past most of these infections were caused by Candida albicans, an increasing percentage are caused by non-albicans Candida species that are less sensitive to the most frequently used antifungal agents. An accurate diagnosis of these infections and the subsequent choice of the most appropriate therapy can only be made after a thorough evaluation of the patient. Successful treatment of vulvovaginal candidiasis is dependent on compliance with therapy; thus, the treatment regimen chosen should fit the patient's daily lifestyle. Newer single-dose regimens offer the option of completing therapy with a single treatment for most patients with uncomplicated vaginal candidiasis. Use of topical agents avoids the potential systemic adverse effects and drug interactions that have been noted with oral antifungals. Patient education and support can also enhance satisfaction with the treatment plan and promote compliance.     

Identification of potent P2Y-purinoceptor agonists that are derivatives of adenosine 5'-monophosphate

1. A series of chain-extended 2-thioether derivatives of adenosine monophosphate were synthesized and tested as agonists for activation of the phospholipase C-linked P2Y-purinoceptor of turkey erythrocyte membranes, the adenylyl cyclase-linked P2Y-purinoceptor of C6 rat glioma cells, and the cloned human P2U-receptor stably expressed in 1321N1 human astrocytoma cells. 2. Although adenosine monophosphate itself was not an agonist in the two P2Y-purinoceptor test systems, eleven different 2-thioether-substituted adenosine monophosphate analogues were full agonists. The most potent of these agonists, 2-hexylthio AMP, exhibited an EC50 value of 0.2 nM for activation of the C6 cell receptor. This potency was 16,000 fold greater than that of ATP and was only 10 fold less than the potency of 2-hexylthio ATP in the same system. 2-hexylthio adenosine was inactive. 3. Monophosphate analogues that were the most potent activators of the C6 cell P2Y-purinoceptor were also the most potent activators of the turkey erythrocyte P2Y-purinoceptor. However, agonists were in general more potent at the C6 cell receptor, and potency differences varied between 10 fold and 300 fold between the two receptors. 4. Although 2-thioether derivatives of adenosine monophosphate were potent P2Y-purinoceptor agonists no effect of these analogues on the human P2U-purinoceptor were observed. 5. These results support the view that a single monophosphate is sufficient and necessary for full agonist activity at P2Y-purinoceptors, and provide insight for strategies for development of novel P2Y-purinoceptor agonists of high potency and selectivity.     

"Psychology" or "the psychological studies"?

On both historical and principled grounds, the author has long argued that psychology cannot be a single or coherent discipline, whether conceived in scientific or sui generis terms. Instead, the desirability of renaming psychology as the psychological studies has been argued. The present article is a synoptic review of the basis for such a position and its entailments for the future. These are seen to be rather inviting ones for all competent persons engaged in psychological inquiry. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Image-based rendering of complex scenes from a multi-camera rig

Image-based rendering is a method to synthesise novel views from a set of given real images. Two methods to extrapolate novel views of complex scenes with occlusions and large depth discontinuities from images of a moving uncalibrated multi-camera rig are described. The real camera viewpoints are calibrated from the image data and dense depth maps are estimated for each real view. Novel views are synthesised from this representation with view-dependent image-based rendering techniques at interactive rates. Since the 3D scene geometry is available in this approach, it is well suited for mixed reality applications where synthetic 3D objects are seamlessly embedded in the novel view.     

Classification of model transformation techniques used in UML-based Web engineering

Software development techniques are continuously evolving with the goal of solving the main problems that still affect the building and maintenance of software systems: time, costs and error-proneness. Model-driven engineering (MDE) approaches aim to reduce at least some of these problems providing techniques for the construction of models and the specification of transformation rules, tool support and automatic generation of code and documentation. The method of resolution of MDE is to first build models, which are independent of the platform, transforming them in later stages to technological-dependent models, and to achieve automatic model and code generation based on transformation rules. Web engineering is a domain where model-driven approaches can be used to address evolution and adaptation of Web software to continuously emerging new platforms and changes in technologies. We present an overview of the development process of the Unified Modelling Language (UML)-based Web engineering (UWE) defined as an MDE approach. The main characteristic of UWE is the use of standards including the UML, XML metadata interchange as model exchange, meta-object facility for metamodelling, model-driven architecture and the transformation language query-view-transformation. We focus on the model transformation aspects of the UWE process.     

Hybrid finite-element method for discretising cylindrically symmetric parts in electrotechnical models

In many technical devices such as transformers and electrical machines, large differences in geometric dimensions are observed. As a consequence, the generation of a 3D computational grid for the whole device leads to unacceptably large numbers of elements or can even fail. In addition to the commonly applied cartesian or cylindrical symmetries of the overall geometry, the model can be subdivided into parts featuring translational or cylindrical symmetries. Such parts are discretised separately, accounting for the local symmetry, and are then combined with the surrounding 3D model. Excitations and boundary conditions of the submodels are not necessarily symmetric but are expected to be smooth in the direction of the symmetry. Then, the field distribution at the interface is well approximated by a set of spectral elements along the dimension of symmetry. Coupling between the model parts is carried out by means of Lagrange multipliers. A single-phase transformer with thin insulation sheets is taken as an example to illustrate the proposed hybrid discretisation. The cross-section of the cylindrically symmetric part containing thin sheets, is represented by a fine 2D finite-element mesh so that all the geometrical details can be resolved, and the rest of the structure is discretised by a 3D mesh. Nevertheless, a fully 3D field distribution is calculated in all model parts. Only a small number of harmonic functions is needed to account for the azimuthal field variation at the cylindrical interface. Hence, the number of unknowns in the numerical model is reduced significantly, while a high level of accuracy is maintained     

Nicotine-stimulated release of [3H]norepinephrine from fetal rat locus coeruleus cells in culture

Acute nicotine administration stimulated [3H]norepinephrine ([3H]NE) release from cultured fetal locus coeruleus (LC) cells. The effect was concentration dependent, with an EC50 of 0.9 microM, and was abolished by removal of calcium from, or addition of tetrodotoxin (500 nM) to, the assay buffer. Other nicotinic receptor agonists stimulated [3H]NE release, with the rank order of potency being (+)-epibatidine > (-)-nicotine > 1,1-dimethyl-4-phenylpiperazinium (DMPP). Whereas (-)-nicotine and (+/-)-epibatidine exhibited equal maximal responses, DMPP was a partial agonist and (-)-cytisine had no agonist activity. Nicotine-stimulated release of [3H]NE was blocked by nicotinic receptor antagonists, with an order of potency of mecamylamine > lobeline > cytisine > methyllycaconitine > dihydro-beta-erythroidine. The pharmacological profile of this nicotinic receptor is largely consistent with that described previously for an alpha4beta2 subunit combination, although discrepancies in the efficacies of agonists were observed. No additivity in NMDA- and nicotine-stimulated [3H]NE release was observed, suggesting a common signal transduction mechanism. However, the pharmacological characteristics of MK-801 blockade of nicotine-induced responses were not consistent with those of an NMDA receptor. We therefore conclude that nicotine directly releases [3H]NE from LC cells and does not act indirectly via activation of glutamate release.