Biomedical subjects

S Pratt

Publications and source records attributed to S Pratt.

At least 19 recordsLinked to original sources

PubMed2006

Synthesis and SAR study of acridine, 2-methylquinoline and 2-phenylquinazoline analogues as anti-prion agents.

Transmissible spongiform encephalopathies (TSEs) are thought to arise from aggregation of a protease resistant protein denoted PrP(Sc), which is a misfolded isoform of the normal cellular prion protein PrP(C). Using virtual high-throughput screening we have selected structures analogous to acridine, 2-methyquinoline and 2-phenylquinazoline as potential therapeutic candidates for the treatment of TSEs. From the synthesis and screening of constructed libraries we have shown that an electron-rich aromatic ring attached through an amine linker to the position para to the ring nitrogen is beneficial to both binding to PrP(C) and the suppression of PrP(Sc) accumulation for acridine and 2-methylquinoline analogues. 2-Phenylquinazoline analogues appear to utilise a different mode of action by binding at a different location and/or pose. We report IC50s in the nanomolar range.

Acridines↗

PubMed2006

Modelling biological processes under anaerobic conditions through integrating titrimetric and off-gas measurements-applied to EBPR systems.

An innovative method for modelling biological processes under anaerobic conditions is presented and discussed. The method is based on titrimetric and off-gas measurements. Titrimetric data is recorded as the addition rate of hydroxyl ions or protons that is required to maintain pH in a bioreactor at a constant level. An off-gas analysis arrangement measures, among other things, the transfer rate of carbon dioxide. The integration of these signals results in a continuous signal which is solely related to the biological reactions. When coupled with a mathematical model of the biological reactions, the signal allows a detailed characterisation of these reactions, which would otherwise be difficult to achieve. Two applications of the method to the enhanced biological phosphorus removal processes are presented and discussed to demonstrate the principle and effectiveness of the method.

Bacteria, Anaerobic↗

PubMed2005

'Active' filters for upgrading phosphorus removal from pond systems.

This paper investigates limestone and iron slag filters as an upgrade option for phosphorus removal from wastewater treatment ponds. A review of 'active' filter technology and the results from laboratory and field research using packed columns of the different media is presented. It is shown that both limestone and iron slag can remove phosphorus but highlights that different types of limestone give markedly different performance. Filter performance appears to be improved by increasing temperature and by the presence of algae, presumably because of its tendency to elevate pH. Performance is related to hydraulic retention time (HRT), but this relationship is not linear, particularly at low HRTs. Importantly for future research, the results from field-testing with pond effluent show significant differences compared to those obtained when using a synthetic feed in the laboratory. For the iron slag filter, higher performance was observed in the field (72% in field vs. 27% in laboratory, at a 12 hour-HRT), while the opposite was observed for the limestone (64% in laboratory vs. 18% in field, at a 12-hour HRT).

Calcium Carbonate↗

PubMed2004

Rate of nitrate production during a two-stage nitrification batch reaction.

The two steps of nitrification, namely the oxidation of ammonia to nitrite and nitrite to nitrate, often need to be considered separately in process studies. It has been assumed that these two reactions can be described by single Monod models. In this paper, the suitability of the single Monod model for describing nitrite oxidation to nitrate is discussed. The measured rate of nitrate production during a batch reaction is presented. For the system studied it was found that nitrate production actually increased after the completion of ammonia oxidation. It is suggested that the reason for the increase was a combination of: (i) likely competition for oxygen when both substrates were present, and (ii) a decrease in ammonia inhibition of nitrite oxidisers with the removal of ammonia. The result is that a single Monod expression (based on nitrite as the substrate) could not be used to describe nitrate production. In these types of systems the consequence of oxygen limitation and substrate inhibition should also be considered.

Ammonia↗

PubMed2004

Comparison of methods for the determination of K(L)aO2 for respirometric measurements.

The mass transfer coefficient for oxygen in water (K(L)aO2) is an important parameter for respirometric studies. But determination of K(L)aO2 in process conditions is not straightforward, In this paper, two distinct procedures for determining K(L)aO2 in process conditions are outlined and tested. The off-gas method relies on a gas mass balance over a bioreactor while the non-steady state methods rely on analysing DO recovery after perturbation. Various means for inducing perturbation are tested and compared. K(L)aO2 values for a bioreactor are determined by the listed methods. It was found that the off-gas method resulted in the highest K(L)aO2 for the given reactor, while the non-steady state method, whereby perturbation is caused by exogenous activity on acetate, resulted in the lowest K(L)aO2. It is shown that the gas mass balancing technique is robust to unexpected exogenous activity (caused by for example, the oxidation of storage polymers formed or nitrite accumulated), while the non-steady state methods that involve inducing perturbations by exogenous activity appear susceptible to such continued exogenous activity in the DO recovery period.

Ammonia↗

PubMed2003

Comparison of source images for protons, pi-'s, and lambda's in 6A GeV Au+Au collisions.

Source images are extracted from two-particle correlations constructed from strange and nonstrange hadrons produced in 6A GeV Au+Au collisions. Very different source images result from pp vs p Lambda vs pi(-)pi(-) correlations. Scaling by transverse mass can describe the apparent source size ratio for p/pi(-) but not for Lambda/pi(-) or Lambda/p. These observations suggest important differences in the space-time emission histories for protons, pions, and neutral strange baryons produced in the same events.

Journal Article↗

PubMed2003

Improving titrimetric techniques by modelling pH change in activated sludge systems.

Existing titrimetric techniques rely on a well defined hydrogen ion production rate. In particular, they are only suitable in circumstances in which constant background pH influencing reactions take place. This is rarely the case due to the presence of the carbonate acid/base system. In this paper, a model, which describes the influence of the nitrification process on pH and accounts for the action of the carbonate system, is presented. The validity of the model is tested by comparison of model predictions for the important state variables with that of experimental data from a batch oxidation of ammonium nitrogen. The two cases studied are the responses of an endogenously respiring nitrifying sludge to: an ammonium chloride pulse and a pulse of both bicarbonate and ammonium chloride. The results are most encouraging as the dynamic HPR response is mirrored by the model simulation. Furthermore, using the model for data interpretation, the initial nitrogen substrate levels are recovered. It is shown that this could not have been achieved in either case using existing titrimetric techniques.

Bioreactors↗

PubMed2001

Event-by-event analysis of proton-induced nuclear multifragmentation: determination of the phase transition universality class in a system with extreme finite-size constraints.

A percolation model of nuclear fragmentation is used to interpret 10.2 GeV/c p+197Au multifragmentation data. Emphasis is put on finding signatures of a continuous nuclear matter phase transition in finite nuclear systems. Based on model calculations, corrections accounting for physical constraints of the fragment detection and sequential decay processes are derived. Strong circumstantial evidence for a continuous phase transition is found, and the values of two critical exponents, sigma = 0.5+/-0.1 and tau = 2.35+/-0.05, are extracted from the data. A critical temperature of T(c) = 8.3+/-0.2 MeV is found.

Journal Article↗

PubMed2001

Amino acids in the cytoplasmic C terminus of the parathyroid Ca2+-sensing receptor mediate efficient cell-surface expression and phospholipase C activation.

The C-terminal tail of the calcium receptor (CaR) regulates the affinity of the receptor for ligand, desensitization, and membrane localization. To determine the role of specific amino acids in the bovine parathyroid CaR in mediating signal transduction and cell-surface expression, we transfected truncated and mutated CaR cDNAs into HEK-293 cells. The ability of high extracellular [Ca(2+)] ([Ca(2+)](o)) to increase total inositol phosphate (InsP) production, an index of phospholipase C (PLC) activation, was determined. Receptor expression was assessed by immunoblotting and immunocytochemistry. In cells transiently or stably expressing receptors with the C-terminal tail truncated after residue 895 (CaR-(1-895)) or 929 (CaR-(1-929)), raising [Ca(2+)](o) increased InsPs to levels comparable with those of cells expressing wild-type CaRs. There were no PLC responses to high [Ca(2+)](o) (up to 30 mm) in cells expressing CaRs with C-terminal tails of only 3 residues (CaR-(1-866)), even though these receptors were expressed in the membrane. We scanned the residues between Ser(866) and Val(895) using tandem-Ala and single-site mutagenesis. Two point mutants (His(880) --> Ala and Phe(882) --> Ala CaR) showed 50-70% reductions in high [Ca(2+)](o)-induced InsP production. The levels of expression and glycosylation of these mutants were comparable with wild-type CaRs, but both receptors were profoundly retained in intracellular organelles and co-localized with the endoplasmic reticulum marker BiP. This suggested that the signaling defects of these receptors were likely because of defective trafficking of receptors to the cell surface. Modeling of the C-terminal domain of the CaR indicated that His(880) and Phe(882) are situated in a putative alpha-helical structure of 15 amino acids between residues 877 and 891 in the C-terminal tail. Our studies support the idea that specific amino acids, and possibly a unique secondary structure in the C-terminal tail, are required for the efficient targeting of the CaR to the cell surface required for PLC activation.

Amino Acid Sequence↗

PubMed2001

Quality of life in schizophrenia: contributions of anxiety and depression.

A number of studies have demonstrated a strong relationship between quality of life in schizophrenia and general psychopathology measures, and moreover, that the positive, negative, and disorganized symptoms are less related to quality of life. The current investigation examined the relationship between quality of life and symptomatology in 63 stabilized outpatients diagnosed with schizophrenia or schizoaffective disorder. Consistent with other findings, more severe depression, as rated on the Brief Psychiatric Rating Scale (BPRS) was associated with lower general life satisfaction and lower satisfaction with daily living, finances, health, and social life. In addition, higher anxiety ratings on the BPRS were associated with less satisfaction with global quality of life, daily activities, family, health and social relationship, even when controlling for positive symptoms, negative symptoms, or depression. No other symptoms of schizophrenia were as strongly associated with subjective quality of life. Anxiety was also significantly correlated with a number of positive and negative symptoms while depression was substantially less related. These findings, suggest that more precise analyses of general psychopathology, and anxiety in particular, may be necessary to further clarify the factors involved in quality of life in schizophrenia. In addition, these findings suggest future directions for theories of affect and treatment in schizophrenia.

Adolescent↗

PubMed2000

Clocking hadronization in relativistic heavy-Ion collisions with balance functions

A novel state of matter has been hypothesized to exist during the early stage of relativistic heavy-ion collisions, with normal hadrons not appearing until several fm/c after the start of the reaction. To test this hypothesis, correlations between charges and their associated anticharges are evaluated with the use of balance functions. It is shown that late-stage hadronization is characterized by tightly correlated charge-anticharge pairs when measured as a function of relative rapidity.

Journal Article↗

PubMed2000

Amino acids in the second and third intracellular loops of the parathyroid Ca2+-sensing receptor mediate efficient coupling to phospholipase C.

To determine the role of amino acids in the second and third intracellular (IC) loops of the Ca(2+)-sensing receptor (CaR) in phospholipase C (PLC) activation, we mutated residues in these loops either singly or in tandem to Ala and assessed PLC activity by measuring high extracellular [Ca(2+)] ([Ca(2+)](o))-induced inositol phosphate accumulation and protein expression by immunoblotting and immunocytochemistry in human embryonic kidney 293 cells. Two CaR constructs in the second IC loop, F707A CaR and to a lesser extent L704A CaR, demonstrated reduced activation of PLC, despite levels of protein expression comparable with the wild-type (wt) CaR. Substitution of Tyr or His for Phe-707, but not Leu, Val, Glu, or Trp, partially restored the ability of high [Ca(2+)](o) to activate PLC. Eight residues in the third IC loop were involved in PLC signaling. The responses to high [Ca(2+)](o) in cells expressing CaRs with Ala substitutions at these sites were <35% of the wt CaR. The L798A, F802A, and E804A CaRs were dramatically impaired in their responses to [Ca(2+)](o) even up to 30 mm. Substitutions of Leu-798 with other hydrophobic residues (Ile, Val, or Phe), but not with acidic, basic, or polar residues, produced reduced responses compared with wt. Phe-802 could be replaced with either Tyr or Trp with partial retention of the ability to activate PLC. Glu-804 could only be substituted with Asp or Gln and maintain its signaling capacity. Cell surface expression of the CaRs mutated at Leu-798 and Phe-802 appeared normal compared with wt CaR. Cell surface CaR expression was, however, reduced substantially in cells expressing several mutants at position Glu-804 by confocal microscopy. These studies strongly implicate specific hydrophobic and acidic residues in the second and third IC loops of the parathyroid CaR (and potentially larger stretches of the third loop) in mediating efficient high [Ca(2+)](o)-induced PLC activation and or CaR expression.

Amino Acid Sequence↗

PubMed2000

Canonical and microcanonical calculations for fermi systems

Recursion relations are presented that allow exact calculation of canonical and microcanonical partition functions of degenerate Fermi systems, assuming no explicit two-body interactions. Calculations of the level density, sorted by angular momentum, are presented for 56Ni. The issue of treating unbound states is also addressed.

Journal Article↗

PubMed2000

Accumulation of carbon monoxide and carbon dioxide in stored canola.

Production of carbon monoxide (CO) and carbon dioxide (CO(2)) from canola was studied in the laboratory and in commercial storage. Canola rapidly produced amounts of CO and CO(2) far exceeding those reported for dry cereal grain and dried peas and at levels dangerous to human health. In the laboratory, canola (5.8% m.c.) was stored in sealed flasks at 25, 35 and 45 degrees C for 12 weeks. Levels of CO, CO(2) and oxygen (O(2)) were then measured by gas chromatography. Average levels of CO and CO(2) increased with storage temperature. Levels of CO peaked at 6 weeks, exceeding 10,000 ppm v/v (1%) at 45 degrees C. CO(2) levels peaked at 11.9% after 10 weeks storage at 45 degrees C. In field measurements, CO levels in a steel bin (7000 tonne capacity) filled with canola ranged from 1100 to 800 ppm in the grain bulk before sealing, 1050-370 ppm in the grain bulk after sealing, and 290-440 ppm in the head space of the sealed bin. CO(2) concentrations were >3% in the grain bulk and averaged 1.5% in the headspace. CO production rate was estimated at 200 ng g(-1) day(-1). Canola storage poses a greater potential safety hazard than storage of cereals.

Journal Article↗

PubMed2000

Sugar transport regulation: comparative characterization of the effect of NADH CoQ reductase deficiency in two cell culture systems.

In this report, we have characterized the upregulation of glucose transport in two different respiration-deficient fibroblast cell cultures. We have demonstrated that glucose transport increases in respiration-deficient cells as measured by 2 deoxy D-glucose transport and is readily observed in both the WG750 human and G14 Chinese hamster fibroblast respiration-deficient cell lines when compared with the MCH55 normal human and V79 parental Chinese hamster cell lines, respectively. Using subcellular fractionation techniques, the GLUT 1 glucose transporter was found located predominantly in the plasma membrane-enriched fraction of the human and hamster cell lines. In human cells, the expression of the GLUT 1 glucose transporter was elevated three-fold in the plasma membrane-enriched fraction of the WG750 respiration-deficient mutant cells. In the Chinese hamster cell lines, the respiration-deficient G14 cells exhibited no such GLUT 1 glucose transporter elevation in the plasma membrane-enriched fraction, yet expressed a >2-fold increase in glucose transport. Furthermore, the G14 cells had a similar content of GLUT 1 glucose transporter in the plasma membrane fraction when compared with the V79 parental cell line. Using Western blot analysis, the GLUT 1 glucose transporter in G14 cells exhibited a different mobility on a polyacrylamide gel when compared with the mobility of the GLUT 1 glucose transporter of the V79 cell line. This differential mobility of the glucose transporters in the hamster cells appeared to be related to glycosylation differences of the glucose transporters. Although normal human and hamster cell lines exhibited significant increases in insulin-stimulated sugar transport (P < 0.05), the two respective respiration-deficient cell lines exhibited no significant increases in insulin-stimulated sugar transport (P > 0.05). Additionally, the expression of the GLUT 1 mRNA in the human WG750 mutant cells was elevated when compared with GLUT 1 mRNA in normal cells. Insulin exposure significantly increased GLUT 1 mRNA in human cells (P < 0.05). No differences in the GLUT 1 mRNA were observed between both hamster cell lines. Thus, both respiration-deficient cell lines are insulin resistant (i.e., regarding their insulin-stimulated sugar transport). The respiration-deficient mutation results in an increased sugar transport in the human and hamster cells; however, the human cells adapt to the mutation by increasing their levels of GLUT 1 mRNA and eventually membrane-located glucose transporters. On the other hand, the hamster cells adapt by apparently modifying their glucose transporters' intrinsic activity via glycosylation. We feel that these cell systems can be effective models to study the multiple factors involved in sugar transport regulation in vertebrate cells.

Animals↗

PubMed2000

Adaptation to loudness and environmental stimuli in three newly fitted hearing aid users.

Hearing aid fitting strategies can be categorized according to whether a loudness normalization or a loudness equalization rationale is employed. Regardless of the underlying rationale, the amount of patient participation in determining the initial hearing aid settings will vary when an audiologist-driven (AD) versus a patient-driven protocol is employed. When an AD protocol is used, few changes are made during the initial fitting session based on user feedback. It is assumed that the patient will adapt to the loudness and/or sound quality provided by the hearing aids if not immediately acceptable. The following three case reports document varying degrees of adaptation to hearing aid settings derived using an AD approach. Clinical implications will be discussed.

Adaptation, Physiological↗

PubMed1999

Protein kinase C activation blocks calcium receptor signaling in Xenopus laevis oocytes.

We examined whether calcium receptor (CaR) signaling is affected by protein kinase C (PKC) activation by assessing the effects of phorbol-12-myristate-13-acetate (PMA) on 45Ca2+ efflux from Xenopus laevis oocytes expressing wild-type (WT) and mutant bovine parathyroid CaRs. Raising extracellular [Ca2+] ([Ca2+]0) from 0.5 to 5.5 mM increased 45Ca efflux (26 +/- 3-fold) in oocytes expressing full-length and C-terminally truncated receptor (amino acid 1-895). These increases in 45Ca efflux were blocked by 88 +/- 3% after PMA treatment for 20 min. Three consensus PKC phosphorylation sites (Thr-647, Ser-795, and Thr-889) were mutated in the context of the full-length and truncated CaR. PMA treatment inhibited high [Ca2+]0-induced responses in oocytes expressing the Ser795Ala CaR (1-895), Thr889Ala CaR (1-895), and Ser795Ala/Thr889Ala CaR (1-895) by 30-40% compared with untreated controls (P < 0.05). A triple mutant of the full-length CaR demonstrated similarly reduced susceptibility to inhibition of 45Ca efflux by PMA. Thus, these sites are important in mediating the effects of PKC activation on CaRs, but other residues and effector molecules are likely to participate in the effects of PKC on CaR-induced signal transduction in target cells.

Animals↗

PubMed1999

Possible ancient oceans on Mars: evidence from Mars Orbiter Laser Altimeter data.

High-resolution altimetric data define the detailed topography of the northern lowlands of Mars, and a range of data is consistent with the hypothesis that a lowland-encircling geologic contact represents the ancient shoreline of a large standing body of water present in middle Mars history. The contact altitude is close to an equipotential line, the topography is smoother at all scales below the contact than above it, the volume enclosed by this contact is within the range of estimates of available water on Mars, and a series of extensive terraces parallel the contact in many places.

Evolution, Planetary↗