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Biomedical subjects

A C Scott

Publications and source records attributed to A C Scott.

At least 19 recordsLinked to original sources
PubMed2006

Capillary HPLC/QTOF-MS for characterizing complex naphthenic acid mixtures and their microbial transformation.

A rapidly expanding oil sands industry in Canada produces and indefinitely stores large volumes of toxic aqueous tailings containing high concentrations of naphthenic acids (NAs), a complex mixture of naturally occurring aliphatic or alicyclic carboxylic acids. Although there is an acknowledged need to reduce the environmental risks posed by NAs, little is understood about their environmental fate due to a lack of appropriate analytical methods. A dilute-and-shoot reversed-phase capillary HPLC/QTOF-MS method was developed that combines high specificity and sensitivity, quantitative capabilities, the ability to detect novel transformation products, and new structural information within each NA isomer class. HPLC separated NAs, based on carbon number, degree of cyclization, and the extent of alkyl branching, and in so doing increased analytical sensitivity up to 350-fold while providing additional specificity compared to infusion techniques. For tailings water, an interlaboratory study revealed many differences in isomer class profiles compared to an established GC/MS method, much of which was attributed to the misclassification of oxidized NAs (i.e., NA + O) by low-resolution GC/MS. HPLC/QTOF-MS enabled the detection of oxidized products in the same chromatographic run, and Van Krevelen diagrams were adapted to visualize the complex data. A marked decrease of retention times was evident in Syncrude tailings water compared to a commercial mixture, suggesting that tailings water is dominated by highly persistent alkyl-substituted isomers. A biodegradation study revealed that tailings water microorganisms preferentially deplete the least alkyl-substituted fraction and may be responsible for the NA profile in aged tailings water.

Biodegradation, Environmental↗
PubMed2004

Quantum signatures of breather-breather interactions.

The spectrum of the quantum discrete nonlinear Schrödinger equation, or boson Hubbard Hamiltonian, on a periodic 1D lattice shows some interesting detailed band structure, which may be interpreted as the quantum signature of a two-breather interaction in the classical case. This fine structure is studied using degenerate perturbation theory. We also present a modification to this model, which increases the mobility of bound states.

Journal Article↗
PubMed2003

The serotonin transporter intronic VNTR enhancer correlated with a predisposition to affective disorders has distinct regulatory elements within the domain based on the primary DNA sequence of the repeat unit.

We have demonstrated that a variable number tandem repeat domain (VNTR) within intron 2 of the serotonin transporter gene is a transcriptional regulatory domain which is potentially correlated with a predisposition to affective disorders and other behavioural conditions. This correlation based on copy number of the VNTR alone (nine, 10 or 12 copies of 16/17 base-pair element) has been controversial and not reproduced in all studies. We demonstrate that individual repeat elements within the VNTR domain differ in their enhancer activity in an embryonic stem cell model. This has implications for both the mechanism by which these VNTRs are correlated with the progression of the disease and suggests that clinical analysis should now be extended to correlate sequence variation within the VNTR with the disorder. The latter may resolve some of the conflicting data published to date.

Animals↗
PubMed2002

Mode locking in reversed-field pinch experiments.

The MHD mode trajectory in the Madison Symmetric Torus reversed-field pinch has been found to obey the sine-Gordon equation. Corresponding to experiment, a perturbation analysis predicts the locations of mode locking to be at the vacuum chamber poloidal and/or toroidal gaps. The mode's energy dissipates when it locks, as shown by a decaying spiral phase-plane trajectory. Unlocked modes travel around the torus without an abrupt energy loss. By varying key machine parameters obtained by statistical analysis, the probability of locking in accordance with the experimental results can be predicted.

Journal Article↗
PubMed2002

Femtosecond study of self-trapped vibrational excitons in crystalline acetanilide.

Femtosecond IR spectroscopy of delocalized NH excitations of crystalline acetanilide confirms that self-trapping in hydrogen-bonded peptide units exists and does stabilize the excitation. Two phonons with frequencies of 48 and 76 cm (-1) are identified as the major degrees of freedom that mediate self-trapping. After selective excitation of the free exciton, self-trapping occurs within a few 100 fs. Excitation of the self-trapped states disappears from the spectral window of this investigation on a 1 ps time scale, followed by a slow ground state recovery of the hot ground state within 18 ps.

Acetanilides↗
PubMed2001

Excitation wave propagation as a possible mechanism for signal transmission in pancreatic islets of Langerhans.

In response to glucose application, beta-cells forming pancreatic islets of Langerhans start bursting oscillations of the membrane potential and intracellular calcium concentration, inducing insulin secretion by the cells. Until recently, it has been assumed that the bursting activity of beta-cells in a single islet of Langerhans is synchronized across the whole islet due to coupling between the cells. However, time delays of several seconds in the activity of distant cells are usually observed in the islets of Langerhans, indicating that electrical/calcium wave propagation through the islets can occur. This work presents both experimental and theoretical evidence for wave propagation in the islets of Langerhans. Experiments with Fura-2 fluorescence monitoring of spatiotemporal calcium dynamics in the islets have clearly shown such wave propagation. Furthermore, numerical simulations of the model describing a cluster of electrically coupled beta-cells have supported our view that the experimentally observed calcium waves are due to electric pulses propagating through the cluster. This point of view is also supported by independent experimental results. Based on the model equations, an approximate analytical expression for the wave velocity is introduced, indicating which parameters can alter the velocity. We point to the possible role of the observed waves as signals controlling the insulin secretion inside the islets of Langerhans, in particular, in the regions that cannot be reached by any external stimuli such as high glucose concentration outside the islets.

Animals↗
PubMed2001

Federico Cesi and his field studies on the origin of fossils between 1610 and 1630.

In 1603 Federico Cesi, along with four of his friends, founded the first Scientific Academy in Europe, the Accademia dei Lincei, which included Galileo Galillei as a member. Between 1611 and 1630 Cesi undertook an ambitious project to collect and record fossils from his lands around Acquasparta in Umbria. He had drawings and descriptions made of all the excavated fossils, fossil woods and their sites of origin. He died before his work could be published and it was left to his friend Francesco Stelluti to publish a monograph in which he claimed that evidence demonstrated that the fossil woods were formed from stone and were 'not once living'. The corpus of drawings, now in the Royal Collection at Windsor, has allowed the project to be reconstructed and fieldwork in Italy has shown that the complex nature of the fossil preservation could have easily confused the researchers and have led to misinterpretation of the fossils. This research by Cesi is the first to combine field and specimen data to interpret the origin of fossils and has been widely neglected by historians of Science.

Art↗
PubMed2001

Skeletal muscle training in chronic heart failure.

Patients with heart failure are limited in their ability to tolerate exercise. Recent research has suggested that this limitation cannot be entirely attributed to cardiac or lung impairment but rather that changes in peripheral muscles may play an important role. There are objective similarities between heart failure and muscular deconditioning. Deficiencies in peripheral blood flow and skeletal muscle function, morphology, metabolism and function are present in both conditions. Moreover, an exaggerated activity of the receptors sensitive to exercise-derived metabolic signals (muscle ergoreceptors and peripheral and central chemoreceptors) leads to early and profound exercise-induced fatigue and dyspnoea. These muscle afferents contribute to the ventilatory, haemodynamic and autonomic responses to exercise both in physiological and pathological conditions, including chronic heart failure. Against this background, a skeletal muscle origin of symptoms in heart failure has been proposed. The protective effects of physical training have been described in many recent studies: training improves ventilatory control, skeletal muscle metabolism and autonomic nervous system activity. The exercise training appears to induce its beneficial effects on skeletal muscle both directly (on muscle function, histological and biochemical features) and indirectly (by reducing the activation of the muscle afferents). The metabolic mediators of these muscle afferents may become a potential target in the future therapy of heart failure symptoms.

Autonomic Nervous System↗
PubMed2001

Effect of altering conditions of the sequence method on baroreflex sensitivity.

BACKGROUND: The sequence method is widely used as a simple, non-invasive measure of baroreflex sensitivity (BRS). This technique, originally described in anaesthetized cats, has been transferred virtually unchanged to humans, without evidence that the optimal values in cats are the same as those in patients with cardiovascular disease. OBJECTIVE: To study the effect of altering the components of the sequence method on the measured BRS in patients with chronic heart failure (CHF) and in normal individuals. METHODS: Eighty patients with CHF [aged 62 +/- 12 years (mean +/- SD)] and 40 normal control individuals [aged 38 +/- 15 years (mean +/- SD)] underwent measurement of heart rate and non-invasive blood pressure. Altering only the shift between blood pressure and R-R interval and the required correlation coefficient of the regression line had no effect on the value of BRS, but had a significant effect on the number of valid sequences. Alteration of the blood pressure or R-R interval thresholds, however, affected not only the number of valid sequences, but also the value of BRS in both groups. In normal controls, agreement with the bolus phenylephrine method was improved by increasing the blood pressure threshold, although this led to a reduction in the number of valid sequences. In patients with CHF, agreement was optimized by decreasing both the blood pressure and R-R interval thresholds. This also had the effect of increasing the number of valid sequences. CONCLUSION: Changes should be made to this technique, to optimize its validity in conscious humans, particularly when applied to patients with attenuated BRS.

Adult↗
PubMed2000

Contribution of skeletal muscle 'ergoreceptors' in the human leg to respiratory control in chronic heart failure.

The role of skeletal muscle ergoreceptors (afferents sensitive to muscle contraction, differentiated into metaboreceptors, sensitive to metabolic changes, and mechanoreceptors, sensitive to mechanical changes) in the genesis of the increased ventilatory drive in chronic heart failure is controversial. We have aimed to clarify the contribution of muscle metaboreceptors in the leg to ventilation and to compare this with the contribution of mechanoreceptors. Eighteen heart failure patients and 12 controls were studied. Metaboreceptor and mechanoreceptor responses were measured in the leg by bicycle exercise with and without regional circulatory occlusion during recovery, and by active and equivalent passive limb movement, respectively.Patients, in comparison with controls, had a lower peak VO2 (Oxygen uptake) (18.1+/-1.6 vs. 24.5+/-2.5 ml min(-1) kg(-1), P< 0.05), and an evident metaboreceptor contribution to the ventilatory response (3.5+/-1.6 vs. -4.0+/-1.3 l min(-1), P<0.001). Passive limb movement increased ventilation in both patients and controls (+3.7+/-0.4 and +2.9+/-0.5 l min(-1) from baseline, P<0.003), but this was associated with an increase in VO2 (+0.1+/-0.01 and +0.1+/-0.02 l min(-1) from baseline, P<0.001). The ratio of the increase in ventilation to the increase in VO2 during passive movement was not significantly higher than that during active exercise for either patients or controls, suggesting a limited contribution from the mechanoreceptors. In chronic heart failure the presence of a muscle metaboreceptor reflex is also demonstrated in the leg, while mechanoreceptors exhibited a non-significant contribution in both patients and controls. The hypothesis of a peripheral origin of symptoms of exertional intolerance in this syndrome is confirmed as being mainly due to metabolic stimulation of the muscle metaboreceptors.

Bicycling↗
PubMed2000

Technical advance: stringent control of transgene expression in Arabidopsis thaliana using the Top10 promoter system.

We show that the tightly regulated tetracycline-sensitive Top10 promoter system (Weinmann et al. Plant J. 1994, 5, 559-569) is functional in Arabidopsis thaliana. A pure breeding A. thaliana line (JL-tTA/8) was generated which expressed a chimeric fusion of the tetracycline repressor and the activation domain of Herpes simplex virus (tTA), from a single transgenic locus. Plants from this line were crossed with transgenics carrying the ER-targeted green fluorescent protein coding sequence (mGFP5) under control of the Top10 promoter sequence. Progeny from this cross displayed ER-targeted GFP fluorescence throughout the plant, indicating that the tTA-Top10 promoter interaction was functional in A. thaliana. GFP expression was repressed by 100 ng ml-1 tetracycline, an order of magnitude lower than the concentration used previously to repress expression in Nicotiana tabacum. Moreover, the level of GFP expression was controlled by varying the concentration of tetracycline in the medium, allowing a titred regulation of transgenic activity that was previously unavailable in A. thaliana. The kinetics of GFP activity were determined following de-repression of the Top10:mGFP5 transgene, with a visible ER-targeted GFP signal appearing from 24 to 48 h after de-repression.

Arabidopsis↗
PubMed2000

Plant nuclei can contain extensive grooves and invaginations.

Plant cells can exhibit highly complex nuclear organization. Through dye-labeling experiments in untransformed onion epidermal and tobacco culture cells and through the expression of green fluorescent protein targeted to either the nucleus or the lumen of the endoplasmic reticulum/nuclear envelope in these cells, we have visualized deep grooves and invaginations into the large nuclei of these cells. In onion, these structures, which are similar to invaginations seen in some animal cells, form tubular or planelike infoldings of the nuclear envelope. Both grooves and invaginations are stable structures, and both have cytoplasmic cores containing actin bundles that can support cytoplasmic streaming. In dividing tobacco cells, invaginations seem to form during cell division, possibly from strands of the endoplasmic reticulum trapped in the reforming nucleus. The substantial increase in nuclear surface area resulting from these grooves and invaginations, their apparent preference for association with nucleoli, and the presence in them of actin bundles that support vesicle motility suggest that the structures might function both in mRNA export from the nucleus and in protein import from the cytoplasm to the nucleus.

Cell Nucleus↗
PubMed2000

Chronic heart failure in the elderly: value of cardiopulmonary exercise testing in risk stratification.

OBJECTIVE: To assess the value of cardiopulmonary exercise testing in predicting prognosis in a cohort of elderly patients with chronic heart failure (CHF). DESIGN: A retrospective cohort study of all patients with CHF over the age of 70 years assessed between January 1992 and May 1997. SETTING: Tertiary centre. PATIENTS: 50 patients (mean (SD) age 75.9 (4.5) years, 8 women) with CHF New York Heart Association (NYHA) class I (3 patients), II (25 patients), III (20 patients), and IV (2 patients). Follow up was complete for two years in all patients. RESULTS: The patients underwent cardiopulmonary exercise testing (peak oxygen consumption 15.2 (4.5) ml/kg/min, minute ventilation/carbon dioxide production (VE/VCO(2)) slope 38.7 (11.8)); radionucleide ventriculography (left ventricular ejection fraction 32.8 (14.3)%); serum sodium measurement (139 (2.8) mmol/l); and echocardiography (left ventricular end diastolic dimension 6.1 (1.1) cm, left ventricular end systolic dimension 4.7 (1.5) cm). At the end of follow up in May 1999, 26 patients had died. The median follow up of the survivors was 47.7 months (interquartile range 31. 5-53.5 months). On univariate analysis VE/VCO(2) slope (p < 0.0001), NYHA class (p < 0.001), peak oxygen uptake (VO(2)) (p < 0.01), left ventricular end systolic dimension (p < 0.05), and serum sodium concentration (p < 0.05) had significant predictive power. Stepwise multivariate analysis identified only VE/VCO(2) slope (p < 0.01), NYHA class (p < 0.05), and peak VO(2) (p< 0.05) as conveying significant independent prognostic information. CONCLUSION: Elderly patients with CHF have a high mortality, with the majority dead within two years. Cardiopulmonary exercise testing provides important information for risk stratification within this group and its use should not be neglected.

Aged↗
PubMed1999

Changes in cytosolic pH within Arabidopsis root columella cells play a key role in the early signaling pathway for root gravitropism.

Ratiometric wide-field fluorescence microscopy with 1',7'- bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein (BCECF)-dextran demonstrated that gravistimulation leads to rapid changes in cytoplasmic pH (pHc) in columella cells of Arabidopsis roots. The pHc of unstimulated columella cells in tiers 2 and 3, known sites of graviperception (E.B. Blancaflor, J.B. Fasano, S. Gilroy [1998] Plant Physiol 116: 213-222), was 7.22 +/- 0.02 pH units. Following gravistimulation, the magnitude and direction of pHc changes in these cells depended on their location in the columella. Cells in the lower side of tier 2 became more alkaline by 0.4 unit within 55 s of gravistimulation, whereas alkalinization of the cells on the upper side was slower (100 s). In contrast, all cells in tier 3 acidified by 0.4 pH unit within 480 s after gravistimulation. Disrupting these pHc changes in the columella cells using pHc modifiers at concentrations that do not affect root growth altered the gravitropic response. Acidifying agents, including bafilomycin A1, enhanced curvature, whereas alkalinizing agents disrupted gravitropic bending. These results imply that pHc changes in the gravisensing cells and the resultant pH gradients across the root cap are important at an early stage in the signal cascade leading to the gravitropic response.

Arabidopsis↗
PubMed1996

Comparison of biochemical extraction techniques for the detection of scrapie-associated fibrils in the central nervous system of sheep naturally affected with scrapie.

Standardized samples of brain material from four sheep naturally affected with scrapie and from four healthy control sheep were subjected to six different extraction techniques used for the detection of scrapie-associated fibrils by negative-contrast transmission electron microscopy. The six methods were compared in respect of fibril yield and clarity of ultrastructure. The simplest method consisting of a single N-lauroylsarcosine detergent extraction and differential centrifugation, followed by proteinase K enzyme digestion, gave the best overall results. The use of proteinase and nuclease inhibitors made no apparent difference to the yield or ultrastructural clarity of fibrils. Density gradient centrifugation appeared to reduce tungstate stain penetration and often obscured the ultrastructural clarity. The results suggested that the preferred technique could be improved by the use of a double homogenization stage at the beginning of the procedure and by adding an ultrasonic disintegration step to resuspend the final pellet prior to tungstate staining.

Animals↗
PubMed1996

Percutaneous vs modified phemister epiphysiodesis of the lower extremity.

Epiphysiodesis of the lower extremity for limb-length discrepancy has been performed on 24 patients by both the modified Phemister and a percutaneous method. The primary complication of epiphysiodesis by both methods was continued growth of the physeal plate (12% and 15%, respectively). Failure of epiphysiodesis was attributed to young skeletal age at surgery in three of five cases. Closer attention to physeal ablation and close follow up should prevent this complication. No angular deformities resulted in any patient. During 16 proximal fibular procedures, there were no neurologic complications. The percutaneous method is preferred due to ease of surgical procedure, minimal incisions, limited disability to the normal extremity, and equal results.

Adolescent↗
PubMed1995

Comparative study of electron microscopical techniques for the detection of scrapie-associated fibrils.

Samples of cervical spinal cord and four anatomical regions of the brains of 12 sheep with natural scrapie and six control sheep were examined by electron microscopy, after the tissues had been stored at 4 degrees C and -20 degrees C. The tissues were tested for the presence of scrapie-associated fibrils by a centrifugal extraction technique and by a touch-grid technique. The touch-grid technique was no better than the centrifugal extraction technique for the detection of fibrils. Structures which could have been classified as tubulofilaments were detected in touch-grid preparations without detergent treatment. With the centrifugal extraction technique there was a significant reduction of the fibril scores in some of the tissue extracts stored at -20 degrees C, but not in any of the extracts stored at 4 degrees C. There was, however, a reduction in the fibril scores when the final extracted pellets were stored at 4 degrees C. The stability of the fibrils on the test grids was unaffected by six months storage at room temperature but the clarity of their ultrastructure did deteriorate. Poor hydrophilic spread of the sample on the test grids did not have a significant effect on the fibril scores.

Animals↗