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Biomedical subjects

S M Clarke

Publications and source records attributed to S M Clarke.

At least 19 recordsLinked to original sources
PubMed2006

Filtration of deformable emulsion droplets.

Oil-in-water (o/w) emulsions of different droplet size were filtered on membranes of various pore sizes to investigate the growth and behaviour of o/w filter cakes. The cake desorptivity S and the filter membrane resistance R were measured at various filtration pressures P. The variation of S with P shows that filter cake oil droplets of radius a are effectively rigid for P << gamma/a and fully deformable for P >> gamma/a, where gamma is the oil-water interfacial tension. For the largest P, when S became P-independent, the filter cake remained water-permeable as expected from theory.

Journal Article↗
PubMed2006

The crystalline structures of carboxylic acid monolayers adsorbed on graphite.

X-ray and neutron diffraction have been used to investigate the formation of solid crystalline monolayers of all of the linear carboxylic acids from C(6) to C(14) at submonolayer coverage and from C(8) to C(14) at multilayer coverages, and to characterize their structures. X-rays and neutrons highlight different aspects of the monolayer structures, and their combination is therefore important in structural determination. For all of the acids with an odd number of carbon atoms, the unit cell is rectangular of plane group pgg containing four molecules. The members of the homologous series with an even number of carbon atoms have an oblique unit cell with two molecules per unit cell and plane group p2. This odd-even variation in crystal structure provides an explanation for the odd-even variation observed in monolayer melting points and mixing behavior. In all cases, the molecules are arranged in strongly hydrogen-bonded dimers with their extended axes parallel to the surface and the plane of the carbon skeleton essentially parallel to the graphite surface. The monolayer crystal structures have unit cell dimensions similar to certain close-packed planes of the bulk crystals, but the molecular arrangements are different. There is a 1-3% compression on increasing the coverage over a monolayer.

Journal Article↗
PubMed2003

Liquid crystalline elastomers: dynamics and relaxation of microstructure.

The equilibrium mechanical response of nematic elastomers can be soft or hard depending on the relation between the imposed strains and the nematic director, in particular, if the local nematic director is able to respond by rotating. The dynamical response proves to be equally unusual. We examine the linear dynamic mechanical response of monodomain nematic elastomers under shear and the aspects of time-temperature superposition of the dynamical data across phase-transition regions. In the low-frequency region of the master curves, one finds a dramatic reduction of rubber plateau modulus and the rise in internal dissipation: in the shear geometries compatible with dynamic soft elasticity. Power-law variation of the storage modulus with frequency G' proportional, variant omega(a) agrees very well with the results of static stress relaxation, where each relaxation curve obeys the analogous power law G' proportional, variant t(-a) in the corresponding region of long times and temperatures.

Elastomers↗
PubMed2003

NMR study of n-dodecane adsorbed on graphite.

In this brief contribution we demonstrate that 1H and 2H NMR spectroscopy can be an effective method of investigating adsorption from liquids at the solid-liquid interface. The method is illustrated here with the adsorption of a simple alkane adsorbed on graphite, in particular the system n-dodecane and graphite at coverages of 1 and 5 monolayers. Static single-pulse proton nuclear magnetic resonance and static quadrupolar echo deuterium nuclear magnetic resonance spectra were recorded for both coverages. The experimental NMR results presented here show features clearly consistent with earlier calorimetric and neutron scattering work and demonstrate the formation of solid adsorbed layers that coexist with the bulk adsorbate with both isotopes. This ability to probe both deuterated and protonated materials simultaneously illustrates that this experimental approach can be readily extended to investigate the adsorption behaviour of multicomponent mixtures.

Adsorption↗
PubMed2002

Effect of cross-linker geometry on dynamic mechanical properties of nematic elastomers.

We study three monodomain (single-crystal) nematic elastomer materials, all side-chain siloxane polymers with the same mesogenic groups but with different types of cross linking: (i) short flexible siloxane linkage affine to the network backbone, (ii) short flexible aliphatic cross links miscible with mesogenic side-chain groups, and (iii) long segments of main-chain nematic polymer. The dynamic mechanical response of these three systems shows a characteristically universal decrease of storage modulus and a corresponding increase of loss factor. This effect of "dynamic soft elasticity" is strongly anisotropic, depending on the nematic director orientation. We examine the important role of the average backbone chain anisotropy r(T)=l(parallel)/l(perpendicular), which is affected by the cross-linking geometry and contributes to the magnitude and frequency dependence of the dynamic anomaly, and discuss possible applications in mechanical damping and polarized acoustic technology.

Journal Article↗
PubMed2001

Effect of crosslinker geometry on equilibrium thermal and mechanical properties of nematic elastomers.

We study three monodomain (single-crystal) nematic elastomer materials, all side-chain siloxane polymers with the same mesogenic groups but with different types of crosslinking: (i) short flexible siloxane linkage affine to the network backbone, (ii) short flexible aliphatic crosslinks miscible with mesogenic side chain groups, and (iii) long segments of main-chain nematic polymer. Equilibrium physical properties of these three systems are very different, especially the spontaneous thermal expansion and anisotropic stress-strain response along and perpendicular to the uniform nematic director. In the latter case, we examine the soft elastic plateau during the director reorientation. We compare the nematic order-parameter Q(T), provided primarily by the side mesogenic groups and relatively constant between the samples, and the average backbone chain anisotropy r(T)=l( parallel)/l( perpendicular), which is strongly affected by the crosslinking geometry. The experimental data is compared quantitatively with theoretical models of nematic elastomers.

Journal Article↗
PubMed2001

Anomalous viscoelastic response of nematic elastomers.

We report a combined theoretical and experimental study of linear viscoelastic response in oriented monodomain nematic elastomers. The model predicts a dramatic decrease in the dynamic modulus in certain deformation geometries in an elastic medium with an independently mobile internal degree of freedom, the nematic director with its own relaxation dynamics. Dynamic mechanical measurements on monodomain nematic elastomers confirm our predictions of dependence on shear geometry and on nematic order, and also show a very substantial mechanical loss clearly associated with director relaxation.

Journal Article↗
PubMed2001

The pharmacokinetics of methadone in HIV-positive patients receiving the non-nucleoside reverse transcriptase inhibitor efavirenz.

AIMS: Methadone is predominantly metabolized by cytochrome P450 3A4 and the non nucleoside reverse transcriptase inhibitor (NNRTI) efavirenz is a recognized inducer of this enzyme. We evaluated the pharmacokinetics of methadone in the presence and absence of efavirenz when administered to HIV infected patients with a history of injection drug use (IDU). METHODS: Eleven patients on stable methadone maintenance therapy, due to commence antiretroviral therapy (ART), participated in this study. Steady state methadone kinetic profiles were obtained on two occasions 0, 1, 2, 3, 4, 5, 6, 7, 8 and 24 h post dosing. Following centrifugation, separated plasma was heated at 58 degrees C for 30 min to inactivate HIV and stored at -80 degrees C until methadone analysis by high performance liquid chromatography. RESULTS: When combined with efavirenz there was a marked decrease in the maximum plasma concentration (Cmax) of methadone from 689 (range 212-1568) to 358 (range 205-706) ng ml(-1), P = 0.007 : 95% confidence interval (CI) 112-549. The mean area under the methadone concentration curve 0-24 h (AUC(0,24 h)) was also significantly reduced from 12341 (range 3682-34147) to 5309 (range 2430-10349) ng ml(-1) h in the presence of efavirenz, P = 0.012 : 95% CI 1921-12143. Nine patients described symptoms of methadone withdrawal and received a dose increase. Although methadone AUC(0,24 h) was reduced by over 50% following efavirenz the mean increase in methadone dose required was 22% (range 15-30 mg). CONCLUSION: The inclusion of the NNRTI efavirenz in once daily ART for HIV patients with a history of IDU receiving methadone maintenance results in a significant reduction in methadone plasma concentrations mediated by enzyme induction. It is important to distinguish efavirenz neurological effects which were observed between days 1-5 of therapy from symptoms of methadone withdrawal which occurred from day 8 onwards. The dose of methadone was adjusted by increments of 10 mg to counteract the efavirenz inducing effect.

Adult↗
PubMed2000

Amino acid deletions in loop C of the chlorophyll a-binding protein CP47 alter the chloride requirement and/or prevent the assembly of photosystem II.

The chlorophyll a-binding protein CP47 directs excitation energy to the reaction center of photosystem II (PSII) during oxygenic photosynthesis and has additional structural and functional roles associated with the PSII water-oxidizing complex. Oligonucleotide-directed mutagenesis was employed to study loop C of CP47 (approximately Trp-162 to Gly-197) which faces the thylakoid lumen. Five short amino acid deletion strains, delta(S169-P171), delta(Y172-G176), delta(G176-P180), delta(E184-A188) and delta(F190-N194), were created that span this domain. The deletion between Gly-176 and Pro-180, located around the middle of loop C, produced an obligate photoheterotroph that could not assemble functional PSII centers. The deletions in mutants delta(S169-P171) and delta(Y172-G176) reduced PSII levels to < or = 20% of the control and thus impaired photoautotrophic growth. In contrast, mutants delta(E184-A188) and delta(F190-N194) were photoautotrophic even though the number of photosystems was decreased by 50%. All PSII complexes assembled in the deletion strains had an increased susceptibility to photoinactivation and deletion of Glu-184 to Ala-188 prevented photoautotrophic growth under chloride-limiting conditions. Furthermore, the removal of the extrinsic PSII-O, PSII-U and PSII-V proteins from mutants delta(E184-A188) and delta(F190-N194) reduced the rates of oxygen evolution and, in the strains lacking either the PSII-O or PSII-V proteins, also increased the photoautotrophic doubling times. These effects were greater in mutant delta(E 184-A188) than in mutant delta(F190-N194) and the order of importance for the removal of the extrinsic proteins was found to be deltaPSII-V > or = deltaPSII-O > deltaPSII-U.

Amino Acid Sequence↗
PubMed2000

Antiretroviral therapy for drug users.

Injection drug use represents the primary risk factor for up to 40% of patients with HIV infection. Physicians are generally reluctant to prescribe antiretroviral therapy (ART) for these patients due to possible poor adherence, and the potential for complex drug interactions to occur. Providing daily observed ART in conjunction with methadone maintenance therapy (MMT) has significantly improved accessibility of ART for many drug users. Knowledge of potential drug interactions between methadone, ART, and both legally and illegally prescribed drugs has permitted such interactions to be anticipated and either avoided or treated appropriately. Optimizing ART for drug users therefore demands a multidisciplinary approach from medical, clinical pharmacology and psychiatric services.

Anti-HIV Agents↗
PubMed2000

The efficacy and tolerability of combination antiretroviral therapy in pregnancy: infant and maternal outcome.

Antiretroviral therapy (ART) and Caesarean section (CS) delivery significantly reduce the risk of vertically transmitted HIV infection. Attention must focus on determining the optimal management strategy for HIV-positive pregnancies. Guidelines must reflect not only the activity and tolerability of combination ART in pregnancy for mother and infant and the potential short and long-term infant toxicity, but also whether surgical delivery can confer an added benefit if combination ART had reduced plasma viraemia to undetectable levels. To aid the development of management strategies for the Republic of Ireland, a retrospective detailed review of all HIV-positive pregnancies since the introduction of combination ART was undertaken. Since 1997 there have been 25 deliveries to 24 women. Combination ART reduced plasma viraemia to undetectable levels in 76% mothers at delivery. The CS rate was 28% and no unanticipated infant toxicity was encountered. To date no infant has proven infected. Three infants have seroreverted and 24 of 26 infants have had at least 2 negative HIV ribonucleic acid (RNA) and polymerase chain reaction (PCR) tests. Two infants are less than one month old. In this study, the CS rate of 28% is below that reported from many centres yet no vertical transmission was found. Given the efficacy of ART in reducing plasma viraemia, the additional benefit of CS for these women is questionable.

Adolescent↗
PubMed1999

Mutation of Phe-363 in the photosystem II protein CP47 impairs photoautotrophic growth, alters the chloride requirement, and prevents photosynthesis in the absence of either PSII-O or PSII-V in Synechocystis sp. PCC 6803.

The deletion of the amino acids between Gly-351 and Thr-365 within the large, lumen-exposed, hydrophilic region (loop E) of the photosystem II (PSII) chlorophyll a-binding protein CP47 produced a strain of Synechocystis sp. PCC 6803 that failed to assemble stable PSII centers [Eaton-Rye, J. J., and Vermaas, W. F. J. (1991) Plant Mol. Biol. 17, 1165-1177]. The importance of two conserved Phe residues at positions 362 and 363 within this deletion has been investigated. The F363R strain had impaired photoautotrophic growth and an enhanced sensitivity to photoinactivation, demonstrating that Phe is required at position 363 for normal PSII function. In contrast, photoautotrophic growth in strains N361K and F362R was unaffected. Uniquely, among the mutant strains tested, F363R was unable to grow under chloride-limiting conditions, and this effect was reversed by replacing chloride with bromide. The removal of the manganese-stabilizing protein (PSII-O), the 12 kDa extrinsic protein (PSII-U), and cytochrome c-550 (PSII-V) was investigated in each mutant in vivo. In N361K and F362R, removal of PSII-V produced a more deleterious effect than the removal of PSII-O, but even so, all strains remained photoautotrophic. In contrast, the absence of PSII-V and PSII-O in F363R produced obligate photoheterotrophic strains. The removal of PSII-U increased the susceptibility of PSII to heat inactivation and further decreased the stability of PSII in F363R, demonstrating that PSII-U can contribute to the stabilization of mutations that have been introduced into CP47. The order of importance of the selective removal of the extrinsic proteins in strains carrying mutations in loop E of CP47 was found to be as follows: DeltaPSII-V >/= DeltaPSII-O > DeltaPSII-U.

Amino Acid Sequence↗
PubMed1998

Specific requirements for cytochrome c-550 and the manganese-stabilizing protein in photoautotrophic strains of Synechocystis sp. PCC 6803 with mutations in the domain Gly-351 to Thr-436 of the chlorophyll-binding protein CP47.

The requirement of cytochrome c-550 (PSII-V) in photosystem II (PSII) has been assessed in Synechocystis sp. PCC 6803 containing mutations between Gly-351 and Thr-436 of the loop E domain of the chlorophyll a-binding protein CP47. Six photoautotrophic strains were utilized to compare the effect of removal of either the manganese-stabilizing protein (PSII-O) or PSII-V on PSII activity in vivo. These were a wild-type control; two strains with amino acid deletions, Delta(R384-V392) and Delta(G429-T436); and three carrying specific amino acid substitutions, G351L/T365Q, G351L/E364Q/T365Q, and G351L/E353Q/E355Q/T365Q. The removal of PSII-O prevented the assembly of PSII in Delta(G429-T436) but not in Delta(R384-V392). Neither Delta(G429-T436) nor Delta(R384-V392) could support photoautotrophic growth in the absence of PSII-V. In chloride-limiting conditions, the photoautotrophic growth of Delta(R384-V392) was severely impaired and that of Delta(G429-T436) totally inhibited, and no strains lacking PSII-V could grow in chloride-limiting or calcium-limiting media. Substitutions at Gly-351, Glu-353, Glu-355, and Thr-365 produced phenotypes that were similar to those of the control in the presence or absence of PSII-O and PSII-V, but removal of PSII-O from G351L/E364Q/T365Q produced a significant reduction of assembled PSII centers and an enhanced sensitivity to photoinactivation while removal of PSII-V prevented photoautotrophic growth. The additional mutants E364Q:DeltaPSII-V and E364G:DeltaPSII-V demonstrated that this inhibition was a consequence of the mutation at Glu-364. These results also show that the removal of PSII-V, in vivo, produces phenotypes in the CP47 mutants examined that are either similar or more severe than those resulting from the removal of PSII-O.

Amino Acid Sequence↗
PubMed1994

Effect of gastric resection, Roux-en-Y diversion and vagotomy on gastric emptying in the rat.

Solid and liquid gastric emptying studies were conducted in 61 male Wistar rats. In 20 animals a two-thirds Pólya-type gastric resection was performed and 21 had a similar resection with a 10-cm Roux-en-Y diversion. In nine of the Roux diversions truncal vagotomy was also carried out. Twenty animals acted as controls: ten unoperated and ten that received laparotomy only. Body-weight and gastric emptying were measured weekly for 4 weeks and monthly for 4 months after surgery. Animals subjected to gastrectomy revealed a weight loss of approximately 16 per cent after operation. Weight gain was slower after Roux reconstruction than after Pólya-type anastomosis and slowest in animals with vagotomy and Roux drainage (P < 0.05). Gastric emptying was unchanged in unoperated controls. Animals in which a laparotomy was performed had delayed solid and liquid emptying for the first 4 weeks after operation (P < 0.05). Following Pólya-type gastrectomy, liquid emptying was delayed for 4 months. Solid emptying was unchanged, with no evidence of the delay present in animals with a laparotomy. Animals subjected to Roux-en-Y diversion showed a greater delay in liquid emptying than those with a Pólya resection; solid emptying was also delayed (P < 0.05). Severe gastric retention of liquids and solids occurred in the early postoperative phase when vagotomy was added to the Roux diversion (P < 0.01). Emptying of solids adopted a relatively normal linear pattern after this initial retention. Emptying of liquids, however, remained abnormal, appearing to adopt a biphasic pattern.

Anastomosis, Roux-en-Y↗
PubMed1991

A novel enzyme-linked immunosorbent assay (ELISA) for the detection of beryllium antibodies.

A novel immunological method has been developed for detecting antibodies (IgG molecules) specific to beryllium, a light metal used in industry and capable of causing chronic beryllium disease. Beryllium metal was vacuum deposited onto commercially available immunological microsticks, which were then exposed to test plasma containing the putative antibodies. Antigen-antibody complexes were located using a biotin-avidin amplification method. One employee diagnosed with chronic beryllium disease and one diagnosed as "sensitized" (lymphocyte transformation positive) exhibited antibody titers graphically and statistically different and higher than a pooled baseline control population. Plasma from these two employees (former beryllium workers) was used in four different approaches to validate the presence of beryllium antibodies. The assay proved to be reproducible.

Antibodies↗