Oxidative degradation of triblock-copolymer surfactant and its effects on self-assembly.

We investigate the degradation behaviour of a triblock-copolymer surfactant made from polyethylene oxide (PEO) and polypropylene oxide (PPO) (PEO-PPO-PEO), highlighting how the aggregation behaviour of this polymer in water alters with ageing. Samples aged at room temperature were compared to samples degraded using accelerated ageing at elevated temperatures. We find that large mass losses occurred to the polymer surfactant which resulted in a change in the aggregation behaviour, with larger, rod-like or planar aggregates forming at longer degradation times. We look at how this change in aggregation behaviour changes the formulation stability of these polymers, specifically, the interaction of the polymer surfactant with poly(N-isopropylacrylamide) microgels. It is known that these species associate and form gels at elevated temperatures. This paper highlights how commonly used polymeric surfactants can degrade over time, resulting in dramatic changes to aggregation behaviour and therefore, formulation properties.

Gambling problems, risk factors, community knowledge, and impact in a US Lao immigrant and refugee community sample.

OBJECTIVES: The objectives of this study were to examine gambling-related problems, risk factors, help-seeking attitudes, community perceptions, and correlates of problem gambling in a Lao sample of Southeast Asian refugees and immigrants and to discuss cultural implications for the treatment and prevention of gambling problems in Southeast Asian refugee and immigrant populations. STUDY DESIGN: This was a cross-sectional, community-based interview study. METHODS: Participants (N = 200, males = 51%, females = 49%) were recruited from a Lao community center in a major US metropolitan area (convenience sample; community center recruitment and peer nomination). Structured interviews on gambling and substance use were conducted by Lao center staff members in both English and Lao languages. RESULTS: Gambling-related problems were measured using the South Oaks Gambling Screen (SOGS), gambling frequency, and quantity measures. In a previous study, we reported a substantial number of participants from the sample endorsed gambling-related harms and problems (SOGS score of five or more = 24%) and common methods of play were slots, house betting, cards at a casino, and sports betting. Among those endorsing five or more gambling problems, reasons for gambling included making money (68%), social life (31.3%), entertainment (58.3%), and reducing boredom (35.4%). Less commonly endorsed reasons were depression or stress (14.6%) and escape (10.4%). Many participants reported a family history of gambling problems. Those with problem gambling had twice the level of sibling problem gambling histories relative to those without problem gambling (35.4% vs. 11.1%). There were substantially more participants in the problem gambling group who had started gambling before the age of 13 years than in non-problem gamblers (P < .05). Many recognized gambling as a significant issue in the community and reported knowing several individuals affected by gambling-related problems. CONCLUSIONS: Many participants recognized gambling as a significant issue in the Lao community. We include insights gleaned from a research partnership with a community organization. Although data cannot be generalized to the Lao community because of limitations in sampling methodology, participants viewed gambling as a culturally common social practice. Cultural norms affected where community members gamble, types of games, and betting practices. In this context, community members may view gambling-related harms as both a community-level and individual-level concern. These data suggest a significant need for rigorous research to inform policies and a culturally sensitive approach to public health prevention, intervention, and education. We discuss the challenges and cultural barriers to research and community engagement and offer suggestions for prevention and intervention ideas efforts.

Self-assembly and surface behaviour of pure and mixed zwitterionic amphiphiles in a deep eutectic solvent.

Recent investigations have shown that deep eutectic solvents provide a suitable environment for self-organisation of biomolecules, in particular phospholipids and proteins. However, the solvation of complex lyophilic moieties by deep eutectic solvents still remains unclear. Here we explore the behaviour of zwitterionic surfactants in choline chloride:glycerol eutectic mixture. Dodecyl-2-(trimethylammonio)ethylphosphate and N-alkyl-N,N-dimethyl-3-ammonio-1-propanesulfonate (alkyl = dodecyl, tetradecyl) surfactants were investigated by means of surface tension, X-ray reflectivity and small-angle neutron scattering. These surfactants were found to remain surface active and form globular micelles in deep eutectic solvents. Still, the surface behaviour of these species was found to differ depending on the headgroup and tail structure. The morphology of the micelles also slightly varies between surfactants, demonstrating differences in the packing of individual monomers. The characteristics of mixtures of the dodecyl surfactants is also reported, showing a deviation from ideal mixing associated with attractive interactions between sulfobetaine and phosphocholine headgroups. Such non-ideality results in variation of the surface behaviour and self-assembly of these surfactant mixtures. The results presented here will potentially lead to the development of new alternatives for drug-delivery, protein solubilisation and biosensing through a better fundamental understanding of the behaviour of zwitterionic surfactants in deep eutectic solvents.

Distortion of Chain Conformation and Reduced Entanglement in Polymer-Graphene Oxide Nanocomposites.

We study the conformations of polymer chains in polymer-graphene oxide nanocomposites. We show that the chains have a reduced radius of gyration that is consistent with confinement at a solid interface in the melt, as is expected for well-dispersed, high aspect ratio nanoparticles that are much larger than the polymer coil size. We show that confinement of the polymer chains causes a corresponding reduction in interchain entanglements, and we calculate a contribution to the plateau modulus from the distorted polymer network via a simple scaling argument. Our results are a significant step forward in understanding how two-dimensional nanoparticles affect global material properties at low loadings.

Enhancing electron affinity and tuning band gap in donor-acceptor organic semiconductors by benzothiadiazole directed C-H borylation.

Electrophilic borylation using BCl3 and benzothiadiazole to direct the C-H functionalisation of an adjacent aromatic unit produces fused boracyclic materials with minimally changed HOMO energy levels but significantly reduced LUMO energy levels. In situ alkylation and arylation at boron using Al(alkyl)3 or Zn(aryl)2 is facile and affords boracycles that possess excellent stability towards protic solvents, including water, and display large bathochromic shifts leading to far red/NIR emission in the solid state with quantum yields of up to 34%. Solution fabricated OLEDs with far red/NIR electroluminescence are reported with EQEs > 0.4%.

Rainforest aerosols as biogenic nuclei of clouds and precipitation in the Amazon.

The Amazon is one of the few continental regions where atmospheric aerosol particles and their effects on climate are not dominated by anthropogenic sources. During the wet season, the ambient conditions approach those of the pristine pre-industrial era. We show that the fine submicrometer particles accounting for most cloud condensation nuclei are predominantly composed of secondary organic material formed by oxidation of gaseous biogenic precursors. Supermicrometer particles, which are relevant as ice nuclei, consist mostly of primary biological material directly released from rainforest biota. The Amazon Basin appears to be a biogeochemical reactor, in which the biosphere and atmospheric photochemistry produce nuclei for clouds and precipitation sustaining the hydrological cycle. The prevailing regime of aerosol-cloud interactions in this natural environment is distinctly different from polluted regions.

Reprogrammed streptokinases develop fibrin-targeting and dissolve blood clots with more potency than tissue plasminogen activator.

BACKGROUND: Given the worldwide epidemic of cardiovascular diseases, a more effective means of dissolving thrombi that cause heart attacks, could markedly reduce death, disability and healthcare costs. Plasminogen activators (PAs) such as streptokinase (SK) and tissue plasminogen activator (TPA) are currently used to dissolve fibrin thrombi. SK is cheaper and more widely available, but it appears less effective because it lacks TPA's fibrin-targeted properties that focus plasminogen activation on the fibrin surface. OBJECTIVE: We examined whether re-programming SK's mechanism of action would create PAs with greater fibrin-targeting and potency than TPA. METHODS AND RESULTS: When fibrinogen consumption was measured in human plasma, reprogrammed molecules SKDelta1 and SKDelta59 were 5-fold and > 119-fold more fibrin-dependent than SK (P < 0.0001), and 2-fold and > 50-fold more fibrin-dependent than TPA (P < 0.001). The marked fibrin-targeting of SKDelta59 was due to the fact that: (i) it did not generate plasmin in plasma, (ii) it was rapidly inhibited by alpha2-antiplasmin, and (iii) it only processed fibrin-bound plasminogen. To assess the fibrin-targeting and therapeutic potential of these PAs in vivo, a novel 'humanized' fibrinolysis model was created by reconstituting plasminogen-deficient mice with human plasminogen. When compared with TPA, SKDelta1 and SKDelta59 were 4-fold (P < 0.0001) and 2-fold (P < 0.003) more potent at dissolving blood clots in vivo, respectively, on a mass-dose basis and 2-3 logs more potent than TPA (P < 0.0001) when doses were calibrated by standard activity assays. CONCLUSION: These experiments suggest that reprogramming SK's mechanism of action markedly enhances fibrin-targeting and creates, in comparison with TPA, activators with greater fibrinolytic potency.

Enhanced triplet formation by twisted intramolecular charge-transfer excited states in conjugated oligomers and polymers.

The triplet yield and intersystem crossing rate of a set of conjugated oligomers and polymers that, in polar solvents, form a charge-transfer state with a twisted conformation has been investigated. It was observed that in these dibenzothiophene-fluorene oligomers a greater than 10-fold increase on the triplet yield is achieved by simply changing the medium polarity to favor the formation of the twisted charge-transfer state, while the fluorescence lifetime is only slightly increased. The increase in the intersystem crossing rate is attributed to the improved mixing between the singlet and triplet states in the twisted excited state. In analogous polymers, the intersystem crossing rate does not show the same increase, most likely because of the greater energetic and conformational disorder increasing the intersystem crossing rate at all times, regardless of the formation of the twisted charge-transfer state or not.

Self-assembly of Peptide nanotubes in an organic solvent.

The self-assembly of a modified fragment of the amyloid beta peptide, based on sequence Abeta(16-20), KLVFF, extended to give AAKLVFF is studied in methanol. Self-assembly into peptide nanotubes is observed, as confirmed by electron microscopy and small-angle X-ray scattering. The secondary structure of the peptide is probed by FTIR and circular dichroism, and UV/visible spectroscopy provides evidence for the important role of aromatic interactions between phenylalanine residues in driving beta-sheet self-assembly. The beta-sheets wrap helically to form the nanotubes, the nanotube wall comprising four wrapped beta-sheets. At higher concentration, the peptide nanotubes form a nematic phase that exhibits spontaneous flow alignment as observed by small-angle neutron scattering.

Spontaneous clearance of childhood hepatitis C virus infection.

To describe the spontaneous clearance rate of childhood hepatitis C virus (HCV) infection, to determine whether route of transmission affects the clearance rate and to identify other predictors of clearance. Children with chronic hepatitis C were identified between 1990 and 2001. The rate of spontaneous clearance (defined as >or=2 positive anti-HCV antibody test but negative HCV RNA) was calculated using survival analysis. Univariate and multivariate predictor variables [route of transmission, age at infection, age at last follow-up, alanine aminotransferase (ALT) and gender] for clearance were evaluated. Of 157 patients, 28% of children cleared infection (34 transfusional and 10 nontransfusional cases). The 123 transfusional cases were older at time of infection and at follow-up, compared with the 34 nontransfusional cases. Younger age at follow-up (p < 0.0001) and normal ALT levels (p < 0.0001) favoured clearance. Among cases of neonatal infection, 25% demonstrated spontaneous clearance by 7.3 years. The rate of spontaneous clearance of childhood HCV infection was comparable between transfusional and nontransfusional cases. If clearance occurs, it tends to occur early in infection, at a younger age.

Mass spectral evidence that small changes in composition caused by oxidative aging processes alter aerosol CCN properties.

Oxidative processing (i.e., "aging") of organic aerosol particles in the troposphere affects their cloud condensation nuclei (CCN) activity, yet the chemical mechanisms remain poorly understood. In this study, oleic acid aerosol particles were reacted with ozone while particle chemical composition and CCN activity were simultaneously monitored. The CCN activated fraction at 0.66 +/- 0.06% supersaturation was zero for 200 nm mobility diameter particles exposed to 565 to 8320 ppmv O3 for less than 30 s. For greater exposure times, however, the particles became CCN active. The corresponding chemical change shown in the particle mass spectra was the oxidation of aldehyde groups to form carboxylic acid groups. Specifically, 9-oxononanoic acid was oxidized to azelaic acid, although the azelaic acid remained a minor component, comprising 3-5% of the mass in the CCN-inactive particles compared to 4-6% in the CCN-active particles. Similarly, the aldehyde groups of alpha-acyloxyalkylhydroperoxide (AAHP) products were also oxidized to carboxylic acid groups. On a mass basis, this conversion was at least as important as the increased azelaic acid yield. Analysis of our results with Köhler theory suggests that an increase in the water-soluble material brought about by the aldehyde-to-carboxylic acid conversion is an insufficient explanation for the increased CCN activity. An increased concentration of surface-active species, which decreases the surface tension of the aqueous droplet during activation, is an interpretation consistent with the chemical composition observations and Köhler theory. These results suggest that small changes in particle chemical composition caused by oxidation could increase the CCN activity of tropospheric aerosol particles during their atmospheric residence time.

Direct measurement of the singlet generation yield in polymer light-emitting diodes.

In this study, the singlet and triplet exciton generation yields of a representative blue-emitting conjugated polymer are directly compared using simultaneous optical and electrical excitation measurements. After carefully accounting for bimolecular triplet annihilation and knowing the independently measured solid state inter-system-crossing yield of the polymer, a singlet generation yield of 44% is obtained, in the working device, which is clearly in excess of the simple quantum statistical 25% limit.

Transmission of Mycobacterium tuberculosis from an infant.

SETTING: This report investigates the unusual transmission of Mycobacterium tuberculosis from a 12-week-old infant with nosocomially acquired tuberculosis (TB). Compliance with recommendations on the post-exposure management of young children is described. DESIGN: Contacts of an infant case of TB were identified and recommended to undergo baseline and post-exposure tuberculin skin tests (TST) as per Canadian TB standards. TST conversion was measured at least 8 weeks post exposure. Children aged <6 years were recommended to initiate preventive treatment with isoniazid (INH) until their post-exposure TST. Information on TST results and adherence to therapy were analysed from existing medical records. RESULTS: Overall, 17 TST conversions were documented among 732 contacts: both parents, two health care workers (HCWs) who provided close care, and several patients, visitors and one staff member without obvious close contact. Of 65 eligible children, 46% completed post-exposure therapy as recommended. The most common reasons for treatment failure were concern about side effects, perception of low risk and lack of physician support. CONCLUSION: This investigation suggests that all children, including infants, with cough and numerous bacilli or extensive pulmonary disease should be considered infectious. Health care provider education is necessary to resolve the observed low compliance with current post-exposure management guidelines.

Femtosecond ground state recovery: measuring the intersystem crossing yield of polyspirobifluorene.

Measurement of the quantum yield of triplet formation has been made for the prototypical conjugated polymer polyspirobifluorene in solution and solid state. An updated method has been described based on femtosecond time resolved ground state recovery following photoexcitation of the polymer. The two components to the recovery of the ground state due to the decay of the singlet and triplet excited states are clearly visible and from these it is possible to calculate Phi(T)=0.05+/-0.01 in solution, this gives k(isc)=5.4 x 10(7) s(-1) which compares favorably with other conjugated polymers. In polymer films an increased triplet yield of Phi(T)=0.12+/-0.02 is found to be independent of temperature, the increased yield is attributed to triplet recombination from charged states.

Variegated micelle surfaces: correlating the microstructure of mixed surfactant micelles with bulk solution properties.

Electron paramagnetic resonance, viscosity, and small-angle neutron scattering (SANS) measurements have been used to study the interaction of mixed anionic/nonionic surfactant micelles with the polyampholytic protein gelatin. Sodium dodecyl sulfate (SDS) and the nonionic surfactant dodecylmalono-bis-N-methylglucamide (C12BNMG) were chosen as "interacting" and "noninteracting" surfactants, respectively; SDS micelles bind strongly to gelatin but C12BNMG micelles do not. Further, the two surfactants interact synergistically in the absence of the gelatin. The effects of total surfactant concentration and surfactant mole fraction have been investigated. Previous work (Griffiths et al. Langmuir 2000, 16 (26), 9983-9990) has shown that above a critical solution mole fraction, mixed micelles bind to gelatin. This critical mole fraction corresponds to a micelle surface that has no displaceable water (Griffiths et al. J. Phys. Chem. B 2001, 105 (31), 7465). On binding of the mixed micelle, the bulk solution viscosity increases, with the viscosity-surfactant concentration behavior being strongly dependent on the solution surfactant mole fraction. The viscosity at a stoichiometry of approximately one micelle per gelatin molecule observed in SDS-rich mixtures scales with the surface area of the micelle occupied by the interacting surfactant, SDS. Below the critical solution mole fraction, there is no significant increase in viscosity with increasing surfactant concentration. Further, the SANS behavior of the gelatin/mixed surfactant systems below the critical micelle mole fraction can be described as a simple summation of those arising from the separate gelatin and binary mixed surfactant micelles. By contrast, for systems above the critical micelle mole fraction, the SANS data cannot be described by such a simple approach. No signature from any unperturbed gelatin could be detected in the gelatin/mixed surfactant system. The gelatin scattering is very similar in form to the surfactant scattering, confirming the widely accepted picture that the polymer "wraps" around the micelle surface. The gelatin scattering in the presence of deuterated surfactants is insensitive to the micelle composition provided the composition is above the critical value, suggesting that the viscosity enhancement observed arises from the number and strength of the micelle-polymer contact points rather than the gelatin conformation per se.

Effect of ethanol on the interaction between poly(vinylpyrrolidone) and sodium dodecyl sulfate.

The effect of ethanol on the interaction between the anionic surfactant sodium dodecyl sulfate (SDS) and the nonionic polymer poly(vinylpyrrolidone) (PVP) has been investigated using a range of techniques including surface tension, fluorescence, electron paramagnetic resonance (EPR), small-angle neutron scattering (SANS), and viscosity. Surface tension and fluorescence studies show that the critical micelle concentration (cmc) of the surfactant decreases to a minimum value around 15 wt % ethanol; that is, it follows the cosurfactant effect. However, in the presence of PVP, the onset of the interaction, denoted cmc(1), between the surfactant and the polymer is considerably less dependent on ethanol concentration. The saturation point, cmc(2), however, reflects the behavior of the cmc in that it decreases upon addition of ethanol. This results in a decrease in the amount of surfactant bound to the polymer [C(bound) = cmc(2) - cmc] at saturation. The viscosity of simple PVP solutions depends on ethanol concentration, but since SANS studies show that ethanol has no effect on the polymer conformation, the changes observed in the viscosity reflect the viscosity of the background solvent. There are significant increases in bulk viscosity when the surfactant is added, and these have been correlated with the polymer conformation extracted from an analysis of the SANS data and with the amount of polymer adsorbed at the micelle surface. Competition between ethanol and PVP to occupy the surfactant headgroup region exists; at low ethanol concentration, the PVP displaces the ethanol and the PVP/SDS complex resembles that formed in the absence of the ethanol. At higher ethanol contents, the polymer does not bind to the ethanol-rich micelle surface.

Understanding the mechanism of action of poly(amidoamine)s as endosomolytic polymers: correlation of physicochemical and biological properties.

Bioresponsive poly(amidoamine)s (PAA)s are currently under development as endosomolytic polymers for intracellular delivery of proteins and genes. Here for the first time, small-angle neutron scattering (SANS) is used to systematically investigate the pH-dependent conformational change of an endosomolytic polymer, the PAA ISA 23. The radius of gyration of the ISA23 was determined as a function of pH and counterion, the aim being to correlate changes in polymer conformation with membrane activity assessed using a rat red blood cell haemolysis assay. With decreasing pH, the ISA23 radius of gyration increased to a maximum (R(g) approximately 80 A) around pH = 3, before subsequently decreasing once more. At high pH and therefore high ionic strengths, the polymer is negatively charged and adopts a rather compact structure (R(g) approximately 20 A), presumably with the dissociated carboxylic groups on the exterior of the polymer coil. At low pH, the coil again collapses (R(g) < 20 A), presumably due to the effects of the high ionic strength. It is concluded that the nature of the salt form has no direct bearing on the size of the polymer coil, but it does indirectly determine the prevailing pH and, hence, polymer conformation. Pulsed-gradient spin-echo NMR measurements were in good agreement with the SANS estimates of the radius of gyration, although ISA23 polydispersity does complicate the data interpretation/comparison. These results support the proposed mode of action of PAAs, namely a coil expansion on passing from a neutral pH (extracellular) to an acidic pH (endosomal and lysosomal) environments. The results do, however, suggest that the charge on the polymer shows a closer correlation with the haemolysis activity rather than the polymer conformation.

The structure of metallomicelles.

The morphology of micelles formed by two novel metallosurfactants has been studied by small-angle neutron scattering (SANS) and small-angle-X-ray scattering (SAXS). The two surfactants both contain a dodecyl chain as the hydrophobic moiety, but differ in the structure of the head group. The surfactants are Cu(II) complexes of monopendant alcohol derivatives of a) the face-capping macrocycle 1,4,7-triazacyclanonane (tacn), and b) an analogue based upon the tetraazamacrocycle 1,4,7,10-tetraazacyclododecane. Here, neutron scattering has been used to study the overall size and shape of the surfactant micelles, in conjunction with X-ray scattering to locate the metal ions. For the 1,4,7,10-tetraazacyclododecane-based surfactant, oblate micelles are observed, which are smaller to the prolate micelles formed by the 1,4,7-triazacyclononane analogue. The X-ray scattering analysis shows that the metal ions are distributed throughout the polar head-group region, rather than at a well-defined radius; this is in good agreement with the SANS-derived dimensions of the micelle. Indeed, the same model for micelle morphology can be used to fit both the SANS and SAXS data.

Interaction between a partially fluorinated alkyl sulfate and gelatin in aqueous solution.

The interaction of a partially fluorinated alkyl sulfate, sodium 1H,1H,2H,2H-perfluorooctyl sulfate (C6F13CH2CH2OSO3Na), with the polyampholyte gelatin has been examined in aqueous solution using surface tension and small-angle neutron scattering (SANS). The 19F chemical shift of each fluorine environment in the surfactant is unaltered by the addition of gelatin, indicating that there is no contact between the gelatin and the fluorocarbon core of the micelle. The chemical shift of the two methylene groups closest to the headgroup is altered when gelatin is present, disclosing the location of the polymer. The critical micelle concentration (cmc) of the surfactant, cmc = 17+/-1 mM, corresponds to an effective alkyl chain (CnH2n+1) length of n = 11. In the presence of gelatin, the cmc is substantially reduced as expected, cmc(1) = 4+/-1 mM, which is also consistent with an effective alkyl chain length of n = 11. In the presence of the fluorosurfactant, the monotonic decay of the SANS from the gelatin-only system is replaced by a substantial peak at an intermediate Q value mirroring the micellar interaction. At low ionic strengths, the gelatin/micelle complex can be described by an ellipsoid. At higher ionic strengths, the electrostatic interaction between the micelles is screened and the peak in the gelatin scattering disappears. The correlation length describing the network structure decreases with increasing SDS concentration as the bound micelles promote a collapse of the network.

Further evidence for the predictive validity of the unstable elevated exposed plus-maze, a behavioural model of extreme anxiety in rats: differential effects of fluoxetine and chlordiazepoxide.

The unstable elevated exposed plus-maze (UEEPM) is a novel model of extreme anxiety which elicits unconditioned flight/escape behaviour in rats. The current studies aimed to investigate further the predictive validity of the paradigm, by examining the effects on UEEPM behaviour of both clinically effective (chronic fluoxetine) and ineffective (acute fluoxetine and chlordiazepoxide) treatments for panic disorder. In the first experiment, male Brown Norway rats received a single injection of fluoxetine (1.0-10.0 mg/kg p.o.) or chlordiazepoxide (CDP, 1.0-10.0 mg/kg i.p.) 30 min prior to UEEPM exposure. In the second experiment, in order to assess the effects of chronic dosing or handling on baseline UEEPM behaviour, subjects received either 21 days vehicle injection (p.o.) or handling, before being exposed to the test. Finally, rats received 21 days fluoxetine (1.0-10.0 mg/kg) in their food, before being tested in the UEEPM. Acute CDP and fluoxetine had no effect on UEEPM behaviour. Chronic handling and vehicle administration (p.o.) significantly reduced escape in the UEEPM, hence preventing the effects of chronic fluoxetine administration from being investigated by p.o. dosing. Chronic fluoxetine in subjects' food (10.0 mg/kg) significantly attenuated animals' propensity to escape from the UEEPM. The results further support the pharmacological similarity between symptoms of panic in humans and escape in the UEEPM and suggest that the UEEPM may represent a paradigm to facilitate investigation into the neurochemical basis of extreme anxiety disorders.