Back to (non)-Basics: Recent developments in neutral and charge-balanced glycosidase inhibitors

Certain glycosidase inhibitors possess potent antiviral, antitumour and antidiabetic properties. Glyconic acid lactones, the earliest glycosidase inhibitors identified, have planar anomeric carbons that mimic the transition state of glycoside hydrolysis. Other classes include lactams, glycals, epoxides, halides and sulfonium ions, the latter based on the natural product salacinol from an antidiabetic herb.

Acquired myasthenia gravis associated with a non-invasive thymic carcinoma in a dog

An 8 1/2-year-old neutered male Beagle was diagnosed with acquired myasthenia gravis associated with a non-invasive thymic carcinoma. The thymic mass was surgically excised and the dog was treated with pyridostigmine, prednisolone and azathioprine. Serial acetylcholine receptor antibody titres were increased initially but slowly declined to normal values over a period of 24 weeks. Improved exercise tolerance was seen following therapy, however, oesophageal dysfunction persisted. The dog was euthanased 26 weeks after initial presentation due to a complicating illness. A necropsy showed no regrowth or metastasis of the thymic carcinoma.

Reproducibility of a laboratory-based 40-km cycle time-trial on a stationary wind-trainer in highly trained cyclists

The purpose of the present study was to examine the reproducibility of laboratory-based 40-km cycle time-trial performance on a stationary wind-trainer. Each week, for three consecutive weeks, and on different days, forty-three highly trained male cyclists ((x) over bar +/- SD; age = 25 +/- 6 y; mass = 75 +/- 7 kg; peak oxygen uptake [(V) over dot O-2 peak] = 64.8 +/- 5.2 ml x kg(-1) x min(-1)) performed: 1) a (V) over dot O-2 peak test, and 2) a 40-km time-trial on their own racing bicycle mounted to a stationary wind-trainer (Cateye - Cyclosimulator). Data from all tests were compared using a one-way analysis of variance. Performance on the second and third 40-km time-trials were highly related (r = 0.96; p < 0.001), not significantly different (57:21 +/- 2:57 vs. 57:12 +/- 3:14 min:s), and displayed a low coefficient of variation (CV) = 0.9 +/- 0.7%. Although the first 40-km time-trial (58:43 +/- 3:17min:s) was not significantly different from the second and third tests (p = 0.06), inclusion of the first test in the assessment of reliability increased within-subject CV to 3.0 +/- 2.9%. 40-km time-trial speed (km x h(-1)) was significantly (p < 0.001) related to peak power output (W; r = 0.75), (V) over dot O-2 peak (1 x min(-1); r = 0.53), and the second ventilatory turnpoint (1 x min(-1); r = 0.68) measured during the progressive exercise tests. These data demonstrate that the assessment of 40-km cycle time-trial performance in well-trained endurance cyclists on a stationary wind-trainer is reproducible, provided the athletes perform a familiarization trial.

Geometric nonlinear analysis of thin plates by a refined nonlinear non-conforming triangular plate element

Based on the refined non-conforming element method for geometric nonlinear analysis, a refined nonlinear non-conforming triangular plate element is constructed using the Total Lagrangian (T.L.) and the Updated Lagrangian (U.L.) approach. The refined nonlinear non-conforming triangular plate element is based on the Allman's triangular plane element with drilling degrees of freedom [1] and the refined non-conforming triangular plate element RT9 [2]. The element is used to analyze the geometric nonlinear behavior of plates and the numerical examples show that the refined non-conforming triangular plate element by the T.L. and U.L. approach can give satisfactory results. The computed results obtained from the T.L. and U.L. approach for the same numerical examples are somewhat different and the reasons for the difference of the computed results are given in detail in this paper. © 2003 Elsevier Science Ltd. All rights reserved.

High rate of detection of primary aldosteronism, including surgically treatable forms, after 'non-selective' screening of hypertensive patients

Background Wide testing of the aldosterone: renin ratio among hypertensive individuals has revealed primary aldosteronism to be common, with most patients normokalaemic. Some investigators, however, have reported aldosterone-producing adenoma to be rare among patients so detected. Objective To test the hypothesis that differences among reported studies in the rate of detection of aldosterone-producing adenoma (as opposed to bilateral adrenal hyperplasia) reflect differences in the procedures used for diagnosis of primary aldosteronism, and the methods used to identify aldosterone-producing adenomas. Methods In the newly established Princess Alexandra Hospital Hypertension Unit (PAHHU), we used procedures developed by Greenslopes Hospital Hypertension Unit (which reports that more than 30% of patients with primary aldosteronism have aldosterone-producing adenomas) to diagnose primary aldosteronism and determine the subtype. All patients with an increased aldosterone: renin ratio (measured after correction for hypokalaemia and while the patient was not receiving interfering medications) underwent fludrocortisone suppression testing to confirm or exclude primary aldosteronism; if they were positive, they underwent genetic testing to exclude glucocorticoid-remediable aldosteronism before adrenal venous sampling was used to differentiate lateralizing from bilateral primary aldosteronism. Results This approach allowed PAHHU to diagnose, within 2 years, 54 patients [only seven (13%) hypokalaemic] with primary aldosteronism. All tested negative for glucocorticoid-remediable aldosteronism. Aldosterone production was lateralized to one adrenal in 15 patients (31%; only six hypokalaemic) and was bilateral in 34 (69%; all normokalaemic) of 49 patients who underwent adrenal venous sampling. Among patients with lateralizing adrenal hyperplasia, computed tomography revealed an ipsilateral mass in only six and a contralateral lesion in one. Fourteen patients underwent unilateral adrenalectomy, which cured the hypertension in seven and improved it in the remainder. In patients with bilateral primary aldlosteronism, hypertension responded to spironolactone (112.5-50 mg/ day) or amiloride (2.5-10 mg/day). Conclusion When performed with careful regard to confounding factors, measurement of the aldosterone: renin ratio in all hypertensive individuals, followed by fludrocortisone suppression testing to confirm or exclude primary aldosteronism and adrenal venous sampling to determine the subtype, can result in the detection of significant numbers of patients with specifically treatable or potentially curable hypertension. (C) 2003 Lippincott Williams Wilkins.

Time will tell: Ambiguous non-responses on internet relay chat

The design of Internet Relay Chat (IRC) affords for, and itself produces, non-response situations that are not possible in FTF or telephone interaction. These system-occasioned nonresponses produce almost isomorphic stimuli to participant non-responses. Situations thus arise in which non-responses are interpersonally accountable despite agentive ambiguity. This study explores four intersections of participant-action and system-occasioned non-responses. An extension to Pomerantz's (1984b) 'pursuing a response' problems/solutions is proposed. The impact of IRC's design on its popularity is discussed in contrast to more recent chat systems. Suggestions are made for active and passive presence and non-response accounting features in future chat systems.

The use of 16s rDNA restriction fragment length polymorphism analysis for the identification of non-fermenting gram negative bacilli in a cystic fibrosis microbiology referral service

The utility of 16s rDNA restriction fragment length polymorphism (RFLP) analysis for the partial genomovar differentiation of Burkholderia cepacia complex bacterium is well documented. We compared the 16s rDNA RFLP signatures for a number of non-fermenting gram negative bacilli (NF GNB) LMG control strains and clinical isolates pertaining to the genera Burkholderia, Pseudomonas, Achromobacter (Alcaligenes), Ralstonia, Stenotrophomonas and Pandoraea. A collection of 24 control strain (LMG) and 25 clinical isolates were included in the study. Using conventional PCR, a 1.2 kbp 16s rDNA fragment was generated for each organism. Following restriction digestion and electrophoresis, each clinical isolate RFLP signature was compared to those of the control strain panel. Nineteen different RFLP signatures were detected from the 28 control strains included in the study. TwentyoneyTwenty- five of the clinical isolates could be classified by RFLP analysis into a single genus and species when compared to the patterns produced by the control strain panel. Four clinical B. pseudomallei isolates produced RFLP signatures which were indistinguishable from B. cepacia genomovars I, III and VIII. The identity of these four isolates were confirmed using B. pseudomallei specific PCR. 16s rDNA RFLP analysis can be a useful identification strategy when applied to NF GNB, particularly for those which exhibit colistin sulfate resistance. The use of this molecular based methodology has proved very useful in the setting of a CF referral laboratory particularly when utilised in conjunction with B. cepacia complex and genomovar specific PCR techniques. Species specific PCR or sequence analysis should be considered for selected isolates; especially where discrepancies between epidemiology, phenotypic and genotypic characteristics occur.

Adsorption of supercritical fluids in non-porous and porous carbons: analysis of adsorbed phase volume and density

In this paper, we revisit the surface mass excess in adsorption studies and investigate the role of the volume of the adsorbed phase and its density in the analysis of supercritical gas adsorption in non-porous as well as microporous solids. For many supercritical fluids tested (krypton, argon, nitrogen, methane) on many different carbonaceous solids, it is found that the volume of the adsorbed phase is confined mostly to a geometrical volume having a thickness of up to a few molecular diameters. At high pressure the adsorbed phase density is also found to be very close to but never equal or greater than the liquid phase density. (C) 2003 Elsevier Science Ltd. All rights reserved.

Resolution enhancement by subtraction of confocal signals taken at different pinhole sizes

Subtractive imaging in confocal fluorescence light microscopy is based on the subtraction of a suitably weighted widefield image from a confocal image. An approximation to a widefield image can be obtained by detection with an opened confocal pinhole. The subtraction of images enhances the resolution in-plane as well as along the optic axis. Due to the linearity of the approach, the effect of subtractive imaging in Fourier-space corresponds to a reduction of low spatial frequency contributions leading to a relative enhancement of the high frequencies. Along the direction of the optic axis this also results in an improved sectioning. Image processing can achieve a similar effect. However, a 3D volume dataset must be acquired and processed, yielding a result essentially identical to subtractive imaging but superior in signal-to-noise ratio. The latter can be increased further with the technique of weighted averaging in Fourier-space. A comparison of 2D and 3D experimental data analysed with subtractive imaging, the equivalent Fourier-space processing of the confocal data only, and Fourier-space weighted averaging is presented. (C) 2003 Elsevier Ltd. All rights reserved.

Simultaneous observations of ionospheric quasiperiodic scintillations from short and long meridional baselines using VHF transmissions from transit satellites

For the first time it was possible to observe regular quasiperiodic scintillations (QPS) in VHF radio-satellite transmissions from orbiting satellites simultaneously at short (2.1 km) and long (121 km) meridional baselines in the vicinity of a typical mid-latitude station (Brisbane; 27.5degreesS and 152.9degreesE geog. and 35.6degrees invar.lat.), using three sites (St. Lucia-S, Taringa-T in Brisbane and Boreen Pt.-B, north of Brisbane). A few pronounced quasiperiodic (QP) events were recorded showing unambiguous regular structures at the sites which made it possible to deduce a time displacement of the regular fading minimum at S, T and B. The QP structure is highly dependent on the geometry of the ray-path from a satellite to the observer which is manifested as a change of a QP event from symmetrical to non-symmetrical for stations separated by 2.1 km, and to a radical change in the structure of the event over a distance of 121 km. It is suggested the short-duration intense QP events are due to a Fresnel diffraction (or a reflection mechanism) of radio-satellite signals by a single ionospheric irregularity in a form of an ellipsoid with a large ionization gradient along the major axis. The structure of a QP event depends on the angle of viewing of the irregular blob from a radio-satellite. In view of this it is suggested that the reported variety of the ionization formation, responsible for different types of QPS, is only apparent but not real. (C) 2003 Elsevier Science Ltd. All rights reserved.