An experimental study of OH(A2Σ+) + H2: Electronic quenching, rotational energy transfer, and collisional depolarization.

Zeeman quantum beat spectroscopy has been used to determine the thermal (300 K) rate constants for electronic quenching, rotational energy transfer, and collisional depolarization of OH(A2Σ+) by H2. Cross sections for both the collisional disorientation and collisional disalignment of the angular momentum in the OH(A2Σ+) radical are reported. The experimental results for OH(A2Σ+) + H2 are compared to previous work on the OH(A2Σ+) + He and Ar systems. Further comparisons are also made to the OH(A2Σ+) + Kr system, which has been shown to display significant non-adiabatic dynamics. The OH(A2Σ+) + H2 experimental data reveal that collisions that survive the electronic quenching process are highly depolarizing, reflecting the deep potential energy wells that exist on the excited electronic state surface.

Observation of the de Vries behavior in SmA* phase of a liquid crystal using polarised Raman scattering and infrared spectroscopy.

Two approaches exist in the literature for describing the orientational distribution function (ODF) of the molecular directors in SmA* phase of liquid crystals, though several models are recently proposed in the literature for explaining the de Vries behaviour. These ODFs correspond to either the conventional unimodal arrangements of molecular directors arising from the mean field theory that leads to the broad or sugar-loaf like distribution or to the "diffuse-cone-shaped" type distribution proposed by de Vries. The hypothesis by de Vries provides for a realistic explanation as to how at a molecular level, a first-order SmA* to SmC* transition can occur where the uniform molecular director azimuthal distributions condense to values lying within a narrow range of angles; finally these condense to a single value while at the same time ensuring a little or no concomitant shrinkage in the layer spacing. The azimuthal distribution of the in-layer directors is probed using IR and polarized Raman spectroscopic techniques. The latter allows us to obtain the ODF and the various order parameters for the uniaxial and the biaxial phases. Based on the results of these measurements, we conclude that the "cone-shaped" (or volcano-shaped) de Vries type of distribution can most preferably describe SmA* where "a first-order phase transition from SmA* to SmC*" and a low layer shrinkage can both be easily explained.

Pseudomonas aeruginosa biofilm disruption using microbial surfactants.

AIMS: To establish the ability of the rhamnolipids biosurfactants from Pseudomonas aeruginosa, in the presence and absence of caprylic acid and ascorbic acid, to disrupt bacterial biofilms, compared with the anionic alkyl sulphate surfactant Sodium dodecyl sulphate (SDS). METHODS AND RESULTS: Pseudomonas aeruginosa ATCC 15442 biofilms were disrupted by rhamnolipids at concentrations between 0·5 and 0·4 g l(-1) and with SDS at 0·8 g l(-1) . The combination of rhamnolipids 0·4 g l(-1) and caprylic acid at 0·1 g l(-1) showed a remarkable effect on biofilm disruption and cell killing. After 30 min of treatment most of the biofilm was disrupted and cell viability was significantly reduced. Neither caprylic acid nor ascorbic acid has any effect on biofilm disruption at 0·1 g l(-1) . SDS is an effective antimicrobial agent; however, in the presence of caprylic acid its effect was neutralized. CONCLUSIONS: The results show that rhamnolipids at low concentration in the presence of caprylic acid are promising molecules for inhibition/disruption of biofilms formed by Ps. aeruginosa ATCC 15442. SIGNIFICANCE AND IMPACT OF THE STUDY: The disruption of biofilms has major significance in many industrial and domestic cleaning applications and in medical situations.

Effect of biosurfactants on Pseudomonas aeruginosa and Staphylococcus aureus biofilms in a BioFlux channel.

Recent studies have indicated that biosurfactants play a role both in maintaining channels between multicellular structures in biofilms and in dispersal of cells from biofilms. A combination of caprylic acid (0.01 % v/v) together with rhamnolipids (0.04 % v/v) was applied to biofilms of Pseudomonas aeruginosa ATCC 15442, Staphylococcus aureus ATCC 9144 and a mixed culture under BioFlux flowthrough conditions and caused disruption of the biofilms. The biofilms were also treated with a combination of rhamnolipids (0.04 % v/v) and sophorolipids (0.01 %). Control treatments with PBS 1× had no apparent effect on biofilm disruption. The Gram-positive bacterium (S. aureus ATCC 9144) was more sensitive than P. aeruginosa ATCC 15442 in terms of disruption and viability as shown by Live/Dead staining. Disruption of biofilms of P. aeruginosa ATCC 15442 was minimal. Oxygen consumption by biofilms, after different treatments with biosurfactants, confirms that sophorolipid on its own is unable to kill/inhibit cells of P. aeruginosa ATCC 15442, and even when used in combination with rhamnolipids, under static conditions, no decrease in the cell viability was observed. Cells in biofilms exposed to mono-rhamnolipids (0.04 % v/v) showed behaviour typical of exposure to bacteriostatic compounds, but when exposed to di-rhamnolipids (0.04 % v/v), they displayed a pattern characteristic of bactericidal compounds.

Maintenance rituximab after autologous stem cell transplantation in patients with mantle cell lymphoma.

BACKGROUND: High-dose therapy and autologous stem cell transplantation (ASCT) improves outcomes for patients with mantle cell lymphoma (MCL), but relapse ultimately occurs in most patients. Recently presented interim results from a phase III prospective trial suggest maintenance rituximab (MR) after ASCT for MCL improves progression-free survival (PFS). The maturation of these data and any benefit of MR on overall survival (OS) remain to be defined. PATIENTS AND METHODS: In this retrospective study, we examined a cohort of consecutive patients with MCL that underwent ASCT for MCL at our center and evaluated their outcomes according to whether they received MR after ASCT (n = 50) or did not (n = 107). MR was treated as a time-dependent covariate to account for variation in timing of its initiation. RESULTS: MR was associated with an improved PFS [hazard ratio (HR) 0.44; confidence interval (CI) (0.24-0.80), P = 0.007] and overall survival (OS; HR 0.46; CI 0.23-0.93, P = 0.03) following a multivariate adjustment for confounding factors with a median follow-up of ∼5 years. Grade 4 neutropenia was increased (34% versus 18%, P = 0.04) in the MR group, but no effect on the rate of mortality unrelated to relapse was observed. CONCLUSIONS: These data support that MR after ASCT for MCL confers a benefit in PFS and additionally suggest it may improve OS. General application of this strategy will require confirmation of benefit in prospective randomized trials.

Modelling proton tunnelling in the adenine-thymine base pair.

The energies of the canonical (standard, amino-keto) and tautomeric (non-standard, imino-enol) charge-neutral forms of the adenine-thymine base pair (A-T and A*-T*, respectively) are calculated using density functional theory. The reaction pathway is then computed using a transition state search to provide the asymmetric double-well potential minima along with the barrier height and shape, which are combined to create the potential energy surface using a polynomial fit. The influence of quantum tunnelling on proton transfer within a base pair H-bond (modelled as the DFT deduced double-well potential) is then investigated by solving the time-dependent master equation for the density matrix. The effect on a quantum system by its surrounding water molecules is explored via the inclusion of a dissipative Lindblad term in the master equation, in which the environment is modelled as a heat bath of harmonic oscillators. It is found that quantum tunnelling, due to transitions to higher energy eigenstates with significant amplitudes in the shallow (tautomeric) side of the potential, is unlikely to be a significant mechanism for the creation of adenine-thymine tautomers within DNA, with thermally assisted coupling of the environment only able to boost the tunnelling probability to a maximum of 2 × 10(-9). This is barely increased for different choices of the starting wave function or when the geometry of the potential energy surface is varied.

Responses to colour and host odour cues in three cereal pest species, in the context of ecology and control.

Many insects show a greater attraction to multimodal cues, e.g. odour and colour combined, than to either cue alone. Despite the potential to apply the knowledge to improve control strategies, studies of multiple stimuli have not been undertaken for stored product pest insects. We tested orientation towards a food odour (crushed white maize) in combination with a colour cue (coloured paper with different surface spectral reflectance properties) in three storage pest beetle species, using motion tracking to monitor their behaviour. While the maize weevil, Sitophilus zeamais (Motsch.), showed attraction to both odour and colour stimuli, particularly to both cues in combination, this was not observed in the bostrichid pests Rhyzopertha dominica (F.) (lesser grain borer) or Prostephanus truncatus (Horn) (larger grain borer). The yellow stimulus was particularly attractive to S. zeamais, and control experiments showed that this was neither a result of the insects moving towards darker-coloured areas of the arena, nor their being repelled by optical brighteners in white paper. Visual stimuli may play a role in location of host material by S. zeamais, and can be used to inform trap design for the control or monitoring of maize weevils. The lack of visual responses by the two grain borers is likely to relate to their different host-seeking behaviours and ecological background, which should be taken into account when devising control methods.

Charge radius isotope shift across the N=126 shell gap.

We revisit the problem of the kink in the charge radius shift of neutron-rich even isotopes near the N=126 shell closure. We show that the ability of a Skyrme force to reproduce the isotope shift is determined by the occupation of the neutron 1i(11/2) orbital beyond N=126 and the corresponding change it causes to deeply-bound protons orbitals with a principal quantum number of 1. Given the observed position of the single-particle energies, one must either ensure occupation is allowed through correlations, or not demand that the single-particle energies agree with experimental values at the mean-field level.

Pharmacokinetics of micafungin in HIV positive patients with confirmed esophageal candidiasis.

Esophageal candidiasis (EC) is a common and serious complication in patients infected with the human immunodeficiency virus (HIV). Micafungin has been shown to have dose-related efficacy and to be well tolerated in patients with HIV and EC. This analysis of data from a randomized, double-blind study examined pharmacokinetic parameters of micafungin (dosed at 50, 100, and 150 mg/day) and its metabolites in a subset of patients with HIV and EC. Micafungin exhibited linear, predictable pharmacokinetics, similar to the previous observations in healthy control subjects. Micafungin peak plasma concentration and exposure were increased with dose, while half-life and clearance remained consistent with increasing dose. Plasma concentrations of the metabolites M-1, M-2, and M-5 remained low throughout the study (24 h exposure ≤14% relative to micafungin at end of therapy for each). No differences in micafungin pharmacokinetic parameters were observed according to the sex or race of the patients. The high systemic exposures associated with micafungin 100 and 150 mg/day relative to micafungin 50 mg/day were found to directly correlate with endoscopic clearance. These data provide evidence that the pharmacokinetics of micafungin underlie the dose-related efficacy in patients with HIV and EC.

Comparison of three stationary phases in the separation of polyphenyls by liquid chromatography.

We present herein new analytical protocols for the separation and structural elucidation of polyphenyls. Three commercially available chromatographic stationary phases are compared in the separation of these non-polar, unfunctionalized, positional isomers. Baseline separation of nine terphenyl and quaterphenyl isomers is achieved in under ten minutes using a rapid gradient elution HPLC method. Complete separation of these, and a further five polyphenyls, is demonstrated. We finally present a linear correlation between solvent accessible surface area and the retention times of these closely related compounds.

Critical links between biodiversity and health in wild bee conservation.

Wild bee populations are declining due to human activities, such as land use change, which strongly affect the composition and diversity of available plants and food sources. The chemical composition of food (i.e., nutrition) in turn determines the health, resilience, and fitness of bees. For pollinators, however, the term 'health' is recent and is subject to debate, as is the interaction between nutrition and wild bee health. We define bee health as a multidimensional concept in a novel integrative framework linking bee biological traits (physiology, stoichiometry, and disease) and environmental factors (floral diversity and nutritional landscapes). Linking information on tolerated nutritional niches and health in different bee species will allow us to better predict their distribution and responses to environmental change, and thus support wild pollinator conservation.

A secreted chemokine binding protein encoded by murine gammaherpesvirus-68 is necessary for the establishment of a normal latent load.

Herpesviruses encode a variety of proteins with the potential to disrupt chemokine signaling, and hence immune organization. However, little is known of how these might function in vivo. The B cell-tropic murine gammaherpesvirus-68 (MHV-68) is related to the Kaposi's sarcoma-associated herpesvirus (KSHV), but whereas KSHV expresses small chemokine homologues, MHV-68 encodes a broad spectrum chemokine binding protein (M3). Here we have analyzed the effect on viral pathogenesis of a targeted disruption of the M3 gene. After intranasal infection, an M3 deficiency had surprisingly little effect on lytic cycle replication in the respiratory tract or the initial spread of virus to lymphoid tissues. However, the amplification of latently infected B cells in the spleen that normally drives MHV-68-induced infectious mononucleosis failed to occur. Thus, there was a marked reduction in latent virus recoverable by in vitro reactivation, latency-associated viral tRNA transcripts detectable by in situ hybridization, total viral DNA load, and virus-driven B cell activation. In vivo CD8(+) T cell depletion largely reversed this deficiency, suggesting that the chemokine neutralization afforded by M3 may function to block effective CD8(+) T cell recruitment into lymphoid tissue during the expansion of latently infected B cell numbers. In the absence of M3, MHV-68 was unable to establish a normal latent load.

Long-term persistence of activated cytotoxic T lymphocytes after viral infection of the central nervous system.

Mice intranasally inoculated with influenza A/X-31 are protected against a subsequent intracerebral challenge with the neurovirulent influenza A/WSN and this heterotypic protection is mediated by CD8(+) cytotoxic T lymphocytes. We have studied the kinetics of this secondary immune response and found that despite the elimination of replication-competent virus by day 10, we were able to recover activated influenza-specific cytotoxic T lymphocytes (CTLs) that killed freshly ex vivo from the brains of mice for at least 320 d after the intracerebral inoculation. The activated antiviral CTLs expressed high levels of the early activation marker CD69, suggesting continuing TCR signaling despite a lack of viral protein and major histocompatibility complex staining by immunohistochemistry in the brain parenchyma and barely detectable levels of viral nucleic acid by single and two-step reverse transcription PCR. Local persistence of activated lymphocytes may be important for efficient long-term responses to viruses prone to recrudesce in sites of relative immune privilege.

Mixing behavior of the biosurfactant, rhamnolipid, with a conventional anionic surfactant, sodium dodecyl benzene sulfonate.

The use of small angle neutron scattering, SANS, neutron reflectivity, NR, and surface tension to study the mixing properties of the biosurfactant rhamnolipid with a conventional anionic surfactant, sodium dodecyl 6-benzene sulfonate, LAS, is reported. The monorhamnose rhamnolipid, R1, mixes close to ideally with LAS at the air-water interface, whereas for mixtures of LAS with the dirhamnose rhamnolipid, R2, the LAS strongly partitions to the air-water interface relative to R2, probably because of the steric hindrance of the larger R2 headgroup. These trends in the binary mixtures are also reflected in the ternary R1/R2/LAS mixtures. However, for these ternary mixtures, there is also a pronounced synergy in the total adsorption, which reaches a maximum for a LAS/rhamnolipid mole ratio of about 0.6 and a R1/R2 mol ratio of about 0.5, an effect which is not observed in the binary mixtures. In solution, the R1/LAS mixtures form relatively small globular micelles, L(1), at low surfactant concentrations (<20 mM), more planar structures (lamellar, L(α), unilamellar/multilamellar vesicles, ulv/mlv) are formed at higher surfactant concentrations for R1 and LAS rich compositions, and a large mixed phase (L(α)/L(1) and L(1)/L(α)) region forms at intermediate surfactant compositions. In contrast, for the R2/LAS mixtures, the higher preferred curvature of R2 dominates the phase behavior. The predominant microstructure is in the form of small globular micelles, except for solution compositions rich in LAS (>80 mol % LAS) where more planar structures are formed. For the ternary mixtures, there is an evolution in the resulting phase behavior from one dominated by L(1) (R2 rich) to one dominated by planar structures, L(α), (R1, LAS rich), and which strongly depends upon the LAS/rhamnolipid and R1/R2 mole ratio.

Solution self-assembly and adsorption at the air-water interface of the monorhamnose and dirhamnose rhamnolipids and their mixtures.

The self-assembly in solution and adsorption at the air-water interface, measured by small-angle neutron scattering, SANS, and neutron reflectivity, NR, of the monorhamnose and dirhamnose rhamnolipids (R1, R2) and their mixtures, are discussed. The production of the deuterium-labeled rhamnolipids (required for the NR studies) from a Pseudomonas aeruginosa culture and their separation into the pure R1 and R2 components is described. At the air-water interface, R1 and R2 exhibit Langmuir-like adsorption isotherms, with saturated area/molecule values of about 60 and 75 Å(2), respectively. In R1/R2 mixtures, there is a strong partitioning of R1 to the surface and R2 competes less favorably because of the steric or packing constraints of the larger R2 dirhamnose headgroup. In dilute solution (<20 mM), R1 and R2 form small globular micelles, L(1), with aggregation numbers of about 50 and 30, respectively. At higher solution concentrations, R1 has a predominantly planar structure, L(α) (unilamellar, ULV, or bilamellar, BLV, vesicles) whereas R2 remains globular, with an aggregation number that increases with increasing surfactant concentration. For R1/R2 mixtures, solutions rich in R2 are predominantly micellar whereas solutions rich in R1 have a more planar structure. At an intermediate composition (60 to 80 mol % R1), there are mixed L(α)/L(1) and L(1)/L(α) regions. However, the higher preferred curvature associated with R2 tends to dominate the mixed R1/R2 microstructure and its associated phase behavior.

Gamow's cyclist: a new look at relativistic measurements for a binocular observer.

The visualization of objects moving at relativistic speeds has been a popular topic of study since Special Relativity's inception. While the standard exposition of the theory describes certain shape-changing effects, such as the Lorentz-contraction, it makes no mention of how an extended object would appear in a snapshot or how apparent distortions could be used for measurement. Previous work on the subject has derived the apparent form of an object, often making mention of George Gamow's relativistic cyclist thought experiment. Here, a rigorous re-analysis of the cyclist, this time in three dimensions, is undertaken for a binocular observer, accounting for both the distortion in apparent position and the relativistic colour and intensity shifts undergone by a fast-moving object. A methodology for analysing binocular relativistic data is then introduced, allowing the fitting of experimental readings of an object's apparent position to determine the distance to the object and its velocity. This method is then applied to the simulation of Gamow's cyclist, producing self-consistent results.

Scope for non-crop plants to promote conservation biological control of crop pests and serve as sources of botanical insecticides.

Besides providing food and shelter to natural enemies of crop pests, plants used in conservation biological control interventions potentially provide additional ecosystem services including providing botanical insecticides. Here we concurrently tested the strength of these two services from six non-crop plants in managing cabbage pests in Ghana over three successive field seasons. Crop margin plantings of Ageratum conyzoides, Tridax procumbens, Crotalaria juncea, Cymbopogon citratus, Lantana camara and Talinum triangulare were compared with a bare earth control in a three-way split plot design such that the crop in each plot was sprayed with either a 10% (w/v) aqueous extract from the border plant species, a negative control (water) and a positive control (emamectin benzoate 'Attack' insecticide). Pests were significantly less numerous in all unsprayed treatments with non-crop plant margins and in corresponding sprayed treatments (with botanical or synthetic insecticide positive control) while treatments with bare earth margin or sprayed with water (negative controls) had the highest pest densities. Numbers of predators were significantly depressed by synthetic insecticide but higher in other treatments whether unsprayed or sprayed with botanical insecticide. We conclude that some plant species have utility in both conservation biological control and as source of botanical insecticides that are relatively benign to natural enemies. In this crop system, however, the additional cost associated with using botanical insecticides was not justified by greater levels of pest suppression than achieved from border plants alone.

Immune control of mammalian gamma-herpesviruses: lessons from murid herpesvirus-4.

Many acute viral infections can be controlled by vaccination; however, vaccinating against persistent infections remains problematic. Herpesviruses are a classic example. Here, we discuss their immune control, particularly that of gamma-herpesviruses, relating the animal model provided by murid herpesvirus-4 (MuHV-4) to human infections. The following points emerge: (i) CD8(+) T-cell evasion by herpesviruses confers a prominent role in host defence on CD4(+) T cells. CD4(+) T cells inhibit MuHV-4 lytic gene expression via gamma-interferon (IFN-gamma). By reducing the lytic secretion of immune evasion proteins, they may also help CD8(+) T cells to control virus-driven lymphoproliferation in mixed lytic/latent lesions. Similarly, CD4(+) T cells specific for Epstein-Barr virus lytic antigens could improve the impact of adoptively transferred, latent antigen-specific CD8(+) T cells. (ii) In general, viral immune evasion necessitates multiple host effectors for optimal control. Thus, subunit vaccines, which tend to prime single effectors, have proved less successful than attenuated virus mutants, which prime multiple effectors. Latency-deficient mutants could make safe and effective gamma-herpesvirus vaccines. (iii) The antibody response to MuHV-4 infection helps to prevent disease but is suboptimal for neutralization. Vaccinating virus carriers with virion fusion complex components improves their neutralization titres. Reducing the infectivity of herpesvirus carriers in this way could be a useful adjunct to vaccinating naive individuals with attenuated mutants.

Skin and systemic pharmacokinetics of tacrolimus following topical application of tacrolimus ointment in adults with moderate to severe atopic dermatitis.

BACKGROUND: Systemic exposure to tacrolimus following topical application of tacrolimus ointment is minimal. There are, however, no data on the distribution of tacrolimus in the skin. OBJECTIVES: To assess the distribution of tacrolimus in the skin and the systemic pharmacokinetics of tacrolimus in adults with moderate to severe atopic dermatitis after first and repeated application of tacrolimus ointment. METHODS: We investigated skin distribution of topically applied tacrolimus and systemic pharmacokinetics of percutaneously absorbed tacrolimus in adults with atopic dermatitis after topical application of tacrolimus 0.1% ointment twice daily for 2 weeks. Tacrolimus concentrations were assessed in full-thickness skin biopsies and blood samples. RESULTS: Of 14 patients, 11 completed treatment and were analysed. Mean +/- SD tacrolimus concentrations in the skin at 24 h after first and last ointment applications were 94 +/- 20 and 595 +/- 98 ng cm(-3), respectively. At 168 h after stopping treatment, values were 97% lower than at 24 h after last application. Tacrolimus concentration decreased with increasing skin depth. Systemic tacrolimus exposure after ointment application was low and highly variable, with 31% of samples below the limit of quantification (0.025 ng mL(-1)) and 94% below 1 ng mL(-1). Blood concentrations at 24 h after the first and last ointment applications were 750 and 1800 times lower, respectively, than those in skin. Physicians' assessments showed that tacrolimus ointment was effective and well tolerated. CONCLUSIONS: Tacrolimus was primarily partitioned in the skin, with minimal systemic absorption after topical application, in patients with atopic dermatitis.

The performance of surfactant mixtures at low temperatures.

Optimising detergency at lower temperatures is of increasing interest due to environmental and economic factors, and requires a greater understanding of the effects of temperature on the adsorption of surfactant mixtures at interfaces. The adsorption properties of surfactant mixtures and biosurfactant/surfactant mixtures have been studied at room temperatures and at temperatures below ambient using surface tension and neutron reflectivity measurements. For the ternary surfactant mixture of octaethylene monododecyl ether, C12E8, sodium dodecyl 6-benzene sulfonate, LAS, and sodium dioxyethylene glycol monododecyl sulfate, SLES, the surface tension at the air-water interface increases with decreasing temperature. In contrast, there is a notable reduction in the increase in the surface tension with a decrease in temperature from 25 °C to 10 °C for the 5 component rhamnolipid/surfactant mixture of the mono-rhamnose, R1, and di-rhamnose, R2, with C12E8/LAS/SLES. The associated neutron reflectivity data for the ternary C12E8/LAS/SLES mixture and the significant observation is that the 3, 4, and 5-component mixtures containing rhamnolipids in conjunction with the other surfactants show changes in composition and adsorbed amounts of the individual components which are close to the experimental error. However the significant observation is that the neutron reflectivity data indicate that the improved surface tension tolerance at lower temperatures is associated with the dominance of the rhamnolipid adsorption in such mixtures. Hence the introduction of the rhamnolipids provides a tolerance to the adverse effects associated with reduced temperatures, and a potential for improved detergency at relatively low temperatures.