Angular redistribution of nonlinear perturbations: a universal feature of nonuniform flows.

Classically, the net action of nonlinear turbulent processes is interpreted as either a direct or inverse cascade. However, in nonuniform/shear flows the dominant process is a nonlinear redistribution over wave number angle of perturbation spatial Fourier harmonics. We call this process a nonlinear transverse redistribution (NTR). This phenomenon is demonstrated for a simple two-dimensional constant shear (non-normal) flow by numerically simulating the nonlinear dynamics of coherent and stochastic vortical perturbations in the flow. NTR is a general feature of nonlinear processes that should manifest itself in nonuniform engineering, environmental, and astrophysical flows. The conventional characterization of turbulence in terms of direct and inverse cascades, which ignores NTR, appears to be misleading for shear flow turbulence. We focus on the action of nonlinear processes on the spectral energy. NTR redistributes perturbations over different quadrants of the wave number plane and the interplay of this nonlinear redistribution with linear phenomena becomes intricate: it can realize either positive or negative feedback. In the case of positive feedback, it repopulates the quadrants in wave number space where the shear flow induces linear transient growth.

Efficacy of caspofungin against Aspergillus flavus, Aspergillus terreus, and Aspergillus nidulans.

The echinocandin caspofungin is a potent inhibitor of the activity of 1,3-beta-D-glucan synthase from Aspergillus flavus, Aspergillus terreus, and Aspergillus nidulans. In murine models of disseminated infection, caspofungin prolonged survival and reduced the kidney fungal burden. Caspofungin was at least as effective as amphotericin B against these filamentous fungi in vivo.

Seasonal variability in the concentrations of Irgarol 1051 in Brighton Marina, UK; including the impact of dredging.

Variations in Irgarol 1051 concentrations in the UK's largest marina at Brighton were determined regularly over a period of one year. Aqueous concentrations ranged from <1 to 960 ngl(-1) with highest mean concentrations generally associated with berths for larger vessels and with the main channels. Temporally, highest concentrations were recorded in November through to January and were probably associated with maintenance of vessels in an adjacent boatyard. Elevated levels were also encountered at the beginning of the season, coinciding with the introduction of newly antifouled vessels. Increased concentrations also followed dredging, possibly through re-mobilisation of Irgarol 1051. No correlations were found between dissolved Irgarol 1051 concentrations and pH, temperature or salinity. With the exception of sporadically high concentrations recorded for water samples (probably taken in close proximity to recently antifouled vessels), concentrations rarely exceeded the no observed effect concentration for marine periphyton of 63 ngl(-1). Concentrations of Irgarol 1051 in sediments sampled from the marina ranged from <1 to 77 ngg(-1). Apparent distribution coefficients (K(d)) calculated from sedimentary and aqueous samples (collected simultaneously) are generally within the range of K(d)'s reported from laboratory experiments.

Sorption and desorption of benzo(a)pyrene in aquatic systems.

The sorptive behaviour of polycyclic aromatic hydrocarbons (PAHs) is critical to controlling their transport, fates and effects in the environment. Experiments are described which detail the behaviour of a model compound (benzo(a)pyrene) under simulated aquatic conditions. The kinetics of sorption were comparable to those of other PAH compounds. The sorption equilibrium was extensively studied and found to be affected by several key parameters, notably sediment concentration. The sorption coefficient decreased substantially with the sediment concentration, from 9580 ml g(-1) at a sediment concentration of 0.067 g l(-1) to 1,110 ml g(-1) at a sediment concentration of 9.8 g l(-1). The results are consistent with previous reports and often explained by the presence of colloids. In this paper the dry weight concentration of colloids was determined and used for deriving the true sorption coefficient, which is up to an order of magnitude higher than the observed partition coefficient. The sorption of benzo(a)pyrene was also dependent on some of the particle properties, and the sorption coefficient was found to increase with the organic carbon content and specific surface area of sediment particles. The desorption of benzo(a)pyrene from sediment was shown to be relatively rapid, with implications for the potential remobilisation of benzo(a)pyrene and similar compounds.

The antifungal echinocandin caspofungin acetate kills growing cells of Aspergillus fumigatus in vitro.

Caspofungin acetate is an antifungal antibiotic that inhibits synthesis of 1,3-beta-D-glucan, an essential component of the fungal cell wall. While caspofungin causes cell death in yeasts and dimorphic fungi such as Candida albicans, its effect on Aspergillus fumigatus is less well understood. We used the fluorescent dyes 5,(6)-carboxyfluorescein diacetate (CFDA) and bis-(1,3-dibutylbarbituric acid) trimethine oxonol (DiBAC), which stain live and dead cells, respectively, to further characterize the antifungal activity of caspofungin. For comparison, compounds whose mode of action was either fungistatic (fluconazole, itraconazole) or fungicidal (amphotericin B) were also evaluated. A correlation between caspofungin-induced loss of viability, decreased CFDA staining, and increased DiBAC staining was established first with C. albicans. For A. fumigatus, caspofungin caused similar dye-staining changes, which were quantified by fluorimetric analysis of stained hyphae grown in a medium that promoted dispersed growth. The minimum concentration of caspofungin required to produce these changes also decreased the level of growth-dependent reduction of the indicator dye Alamar Blue. We observed a differential effect of caspofungin as a function of cell position: 88% of apical cells and 61% of subapical branching cells failed to stain with the viable dye CFDA, but only 24% of subapical cells were unstained. Complementary results were seen with germlings from DiBAC-stained, caspofungin-treated cultures. Extended incubation of A. fumigatus with a single dose of caspofungin affected the same proportion of apical and subapical branching cells for up to 72 h. The dye-staining patterns illustrate that the cells at the active centers for new cell wall synthesis within A. fumigatus hyphae are killed when they are exposed to caspofungin.

Quantitative PCR assay to measure Aspergillus fumigatus burden in a murine model of disseminated aspergillosis: demonstration of efficacy of caspofungin acetate.

Caspofungin acetate (MK-0991) is an antifungal antibiotic that inhibits the synthesis of 1,3-beta-D-glucan, an essential component of the cell wall of several pathogenic fungi. Caspofungin acetate was recently approved for the treatment of invasive aspergillosis in patients who are refractory to or intolerant of other therapies. The activity of 1,3-beta-D-glucan synthesis inhibitors against Aspergillus fumigatus has been evaluated in animal models of pulmonary or disseminated disease by using prolongation of survival or reduction in tissue CFU as assay endpoints. Because these methods suffer from limited sensitivity or poor correlation with fungal growth, we have developed a quantitative PCR-based (qPCR) (TaqMan) assay to monitor disease progression and measure drug efficacy. A. fumigatus added to naïve, uninfected kidneys as either ungerminated conidia or small germlings yielded a linear qPCR response over at least 4 orders of magnitude. In a murine model of disseminated aspergillosis, a burden of A. fumigatus was detected in each of five different organs at 4 days postinfection by the qPCR assay, and the mean fungal load in these organs was 1.2 to 3.5 log(10) units greater than mean values determined by CFU measurement. When used to monitor disease progression in infected mice, the qPCR assay detected an increase of nearly 4 log(10) conidial equivalents/g of kidney between days 1 and 4 following infection, with a peak fungal burden that coincided with the onset of significant mortality. Traditional CFU methodology detected only a marginal increase in fungal load in the same tissues. In contrast, when mice were infected with Candida albicans, which does not form true mycelia in tissues, quantitation of kidney burden by both qPCR and CFU assays was strongly correlated as the infection progressed. Finally, treatment of mice with induced disseminated aspergillosis with either caspofungin or amphotericin B reduced the A. fumigatus burden in infected kidneys to the limit of detection for the qPCR assay. Because of its much larger dynamic range, the qPCR assay is superior to traditional CFU determination for monitoring the progression of disseminated aspergillosis and evaluating the activity of antifungal antibiotics against A. fumigatus.

Levels of antifoulant Irgarol 1051 in the Conwy Marina, North Wales.

Irgarol 1051 (2-methylthio-4-tert-butylamino-6-cyclopropylamino-s-triazine) is an antifouling agent used in paint formulations that are applied to the hulls of ships. A survey was carried out at Conwy Marina in North Wales to determine the levels of the herbicide over a period of three months. Liquid/liquid extraction was used to concentrate the analyte for quantitative analysis using gas chromatography/mass spectrometry (GC/MS) in the selected ion monitoring (SIM) mode. The concentrations of Irgarol 1051 in Conwy marina ranged from 7 to 543 ng/l, similar to the levels found in many other marinas, estuaries and ports in England, although much lower than those in Côte d'Azur, France. The concentrations of Irgarol 1051 were not found to be influenced by salinity, pH or temperature, although there is a strong correlation between the average concentrations of Irgarol 1051 and the density of boating activity. At the levels found in the marina, it is possible that non-target photosynthetic inhibition could occur.

Long-term expression of protein kinase C in adult mouse hearts improves postischemic recovery.

Activation of protein kinase C (PKC) protects the heart from ischemic injury; however, its mechanism of action is unknown, in part because no model for chronic activation of PKC has been available. To test whether chronic, mild elevation of PKC activity in adult mouse hearts results in myocardial protection during ischemia or reperfusion, hearts isolated from transgenic mice expressing a low level of activated PKCbeta throughout adulthood (beta-Tx) were compared with control hearts before ischemia, during 12 or 28 min of no-flow ischemia, and during reperfusion. Left-ventricular-developed pressure in isolated isovolumic hearts, normalized to heart weight, was similar in the two groups at baseline. However, recovery of contractile function was markedly improved in beta-Tx hearts after either 12 (97 +/- 3% vs. 69 +/- 4%) or 28 min of ischemia (76 +/- 8% vs. 48 +/- 3%). Chelerythrine, a PKC inhibitor, abolished the difference between the two groups, indicating that the beneficial effect was PKC-mediated. (31)P NMR spectroscopy was used to test whether modification of intracellular pH and/or preservation of high-energy phosphate levels during ischemia contributed to the cardioprotection in beta-Tx hearts. No difference in intracellular pH or high-energy phosphate levels was found between the beta-Tx and control hearts at baseline or during ischemia. Thus, long-term modest increase in PKC activity in adult mouse hearts did not alter baseline function but did lead to improved postischemic recovery. Furthermore, our results suggest that mechanisms other than reduced acidification and preservation of high-energy phosphate levels during ischemia contribute to the improved recovery.

Expression of protein kinase C beta in the heart causes hypertrophy in adult mice and sudden death in neonates.

Protein kinase C (PKC) activation in the heart has been linked to a hypertrophic phenotype and to processes that influence contractile function. To establish whether PKC activation is sufficient to induce an abnormal phenotype, PKCbeta was conditionally expressed in cardiomyocytes of transgenic mice. Transgene expression in adults caused mild and progressive ventricular hypertrophy associated with impaired diastolic relaxation, whereas expression in newborns caused sudden death associated with marked abnormalities in the regulation of intracellular calcium. Thus, the PKC signaling pathway in cardiocytes has different effects depending on the timing of expression and, in the adult, is sufficient to induce pathologic hypertrophy.

Early luteal progesterone supplementation during in vitro fertilization cycles. A randomized trial.

The effects of early luteal phase progesterone (P) supplementation were studied in women with endogenous serum P levels less than or equal to 12 ng/mL prior to embryo transfer. From a total of 129 cycles that received the same ovarian hyperstimulation protocol, 72 cycles were characterized by levels less than 12 ng/mL on the day prior to embryo transfer. Of those women, 42 (group B) were started on P supplementation one day prior to embryo transfer, and 30 (group C) were started according to the standard protocol after embryo transfer. The clinical course and outcomes in both groups were compared with 57 cycles that had P levels greater than or equal to 12 ng/mL (group A). The early P supplementation in group B resulted in a transient increase in P levels on the morning of embryo transfer as compared with group C. It did not, however, approach the levels seen in group A, which had higher P levels from the early luteal phase through embryo transfer and more favorable oocyte recovery, fertilization and cleavage rates. We were unable to improve the clinical outcome in group B as compared with group C by providing earlier P supplementation.

Balance sheet for phosphorus in the UK.

A balance sheet for the inputs, uses and outputs of phosphorus in the UK economy has been drawn up. The major import is fertilizer, amounting to about 200 kt P per year. After fertilizers, the other imports (in kt P) are in animal feeds (63), detergents (38) and human food (14). The major outputs are sewage (50), animal excreta (26) and refuse (21); soil losses are about 20 kt. The flowpaths for phosphorus through humans, animals and plants are described. The discrepancy of about 210 kt P/yr is explained by the fact that the amount of phosphorus in the soil increases each year by almost as much as the amount of fertilizer phosphorus added. In view of UK dependence on this imported resource it is suggested that priority is given to work which might eventually have some practical application in preventing or reversing the immobilization of phosphorus in the soil.