Reactions of artemisinin and arteether with acid: Implications for stability and mode of antimalarial action

The currently accepted mechanism of trioxane antimalarial action involves generation of free radicals within or near susceptible sites probably arising from the production of distonic radical anions. An alternative mechanistic proposal involving the ionic scission of the peroxide group and consequent generation of a carbocation at C-4 has been suggested to account for antimalarial activity. We have investigated this latter mechanism using DFT (B3LYP/6-31+G* level) and established the preferred Lewis acid protonation sites (artemisinin O5a >> O4a approximate to O3a > O2a > O1a; arteether O4a >= O3a > O5b >> O2a > O1a; Figure 3) and the consequent decomposition pathways and hydrolysis sites. In neither molecule is protonation likely to occur on the peroxide bond O1-O2 and therefore lead to scission. Therefore, the alternative radical pathway remains the likeliest explanation for antimalarial action.

On the stability and convergence of the finite section method for integral equation formulations of rough surface scattering

We consider the Dirichlet and Robin boundary value problems for the Helmholtz equation in a non-locally perturbed half-plane, modelling time harmonic acoustic scattering of an incident field by, respectively, sound-soft and impedance infinite rough surfaces.Recently proposed novel boundary integral equation formulations of these problems are discussed. It is usual in practical computations to truncate the infinite rough surface, solving a boundary integral equation on a finite section of the boundary, of length 2A, say. In the case of surfaces of small amplitude and slope we prove the stability and convergence as A→∞ of this approximation procedure. For surfaces of arbitrarily large amplitude and/or surface slope we prove stability and convergence of a modified finite section procedure in which the truncated boundary is ‘flattened’ in finite neighbourhoods of its two endpoints. Copyright © 2001 John Wiley & Sons, Ltd.

Biomineralisation by earthworms: an investigation into the stability and distribution of amorphous calcium carbonate

Background Many biominerals form from amorphous calcium carbonate (ACC), but this phase is highly unstable when synthesised in its pure form inorganically. Several species of earthworm secrete calcium carbonate granules which contain highly stable ACC. We analysed the milky fluid from which granules form and solid granules for amino acid (by liquid chromatography) and functional group (by Fourier transform infrared (FTIR) spectroscopy) compositions. Granule elemental composition was determined using inductively coupled plasma-optical emission spectroscopy (ICP-OES) and electron microprobe analysis (EMPA). Mass of ACC present in solid granules was quantified using FTIR and compared to granule elemental and amino acid compositions. Bulk analysis of granules was of powdered bulk material. Spatially resolved analysis was of thin sections of granules using synchrotron-based μ-FTIR and EMPA electron microprobe analysis. Results The milky fluid from which granules form is amino acid-rich (≤ 136 ± 3 nmol mg−1 (n = 3; ± std dev) per individual amino acid); the CaCO3 phase present is ACC. Even four years after production, granules contain ACC. No correlation exists between mass of ACC present and granule elemental composition. Granule amino acid concentrations correlate well with ACC content (r ≥ 0.7, p ≤ 0.05) consistent with a role for amino acids (or the proteins they make up) in ACC stabilisation. Intra-granule variation in ACC (RSD = 16%) and amino acid concentration (RSD = 22–35%) was high for granules produced by the same earthworm. Maps of ACC distribution produced using synchrotron-based μ-FTIR mapping of granule thin sections and the relative intensity of the ν2: ν4 peak ratio, cluster analysis and component regression using ACC and calcite standards showed similar spatial distributions of likely ACC-rich and calcite-rich areas. We could not identify organic peaks in the μ-FTIR spectra and thus could not determine whether ACC-rich domains also had relatively high amino acid concentrations. No correlation exists between ACC distribution and elemental concentrations determined by EMPA. Conclusions ACC present in earthworm CaCO3 granules is highly stable. Our results suggest a role for amino acids (or proteins) in this stability. We see no evidence for stabilisation of ACC by incorporation of inorganic components.

Design and fabrication of infrared filters for remote sounding instrumentation

Cooled infrared filters have been used in pressure modulation and filter radiometry to measure the dynamics, temperature distribution and concentrations of atmospheric elements in various satellite radiometers. Invariably such instruments use precision infrared bandpass filters and coatings for spectral selction, often operating at cryogenic temperatures. More recent developments in the use of spectrally-selective cooled detectors in focal plane arrays have simplified the optical layout and reduced the component count of radiometers but have placed additional demands on both the spectral and physical performance requirements of the filters. This paper describes and contrasts the more traditional radiometers using discrete detectors with those which use focal plane detector array technology, with particular emphasis on the function of the filters and coatings in the two cases. Additionally we discuss the spectral techniques and materials used to fabricate infrared coatings and filters for use in space optics, and give examples of their application in the fabrication of some demanding long wavelength dichroics and filters. We also discuss the effects of the space environment on the stability and durability of high performance infrared filters and materials exposed to low Earth orbit for 69 months on the NASA Long Duration Exposure Facility (LDEF).

On nonlinear symmetric stability and the nonlinear saturation of symmetric instability

A nonlinear symmetric stability theorem is derived in the context of the f-plane Boussinesq equations, recovering an earlier result of Xu within a more general framework. The theorem applies to symmetric disturbances to a baroclinic basic flow, the disturbances having arbitrary structure and magnitude. The criteria for nonlinear stability are virtually identical to those for linear stability. As in Xu, the nonlinear stability theorem can be used to obtain rigorous upper bounds on the saturation amplitude of symmetric instabilities. In a simple example, the bounds are found to compare favorably with heuristic parcel-based estimates in both the hydrostatic and non-hydrostatic limits.

Instability of surface-temperature filaments in strain and shear

The effects of uniform straining and shearing on the stability of a surface quasi-geostrophic temperature filament are investigated. Straining is shown to stabilize perturbations for wide filaments but only for a finite time until the filament thins to a critical width, after which some perturbations can grow. No filament can be stabilized in practice, since there are perturbations that can grow large for any strain rate. The optimally growing perturbations, defined as solutions that reach a certain threshold amplitude first, are found numerically for a wide range of parameter values. The radii of the vortices formed through nonlinear roll-up are found to be proportional to θ/s, where θ is the temperature anomaly of the filament and s the strain rate, and are not dependent on the initial size of the filament. Shearing is shown to reduce the normal-mode growth rates, but it cannot stabilize them completely when there are temperature discontinuities in the basic state; smooth filaments can be stabilized completely by shearing and a simple scaling argument provides the shear rate required. Copyright © 2010 Royal Meteorological Society

Flow structure and variability in the subtropical Indian Ocean: Instability of the South Indian Ocean Countercurrent

The origin of the eddy variability around the 25°S band in the Indian Ocean is investigated. We have found that the surface circulation east of Madagascar shows an anticyclonic subgyre bounded to the south by eastward flow from southwest Madagascar, and to the north by the westward flowing South Equatorial Current (SEC) between 15° and 20°S. The shallow, eastward flowing South Indian Ocean Countercurrent (SICC) extends above the deep reaching, westward flowing SEC to 95°E around the latitude of the high variability band. Applying a two-layer model reveals that regions of large vertical shear along the SICC-SEC system are baroclinically unstable. Estimates of the frequencies (3.5–6 times/year) and wavelengths (290–470 km) of the unstable modes are close to observations of the mesoscale variability derived from altimetry data. It is likely then that Rossby wave variability locally generated in the subtropical South Indian Ocean by baroclinic instability is the origin of the eddy variability around 25°S as seen, for example, in satellite altimetry.

Effect of disease-selective predation on prey infected by contact and external sources

We propose and analyze a simple mathematical model for susceptible prey (S)–infected prey (I)–predator (P) interaction, where the susceptible prey population (S) is infected directly from external sources as well as through contact with infected class (I) and the predator completely avoids consuming the infected prey. The model is analyzed to obtain different thresholds of the key parameters under which the system exhibits stability around the biologically feasible equilibria. Through numerical simulations we display the effects of external infection and the infection through contact on the system dynamics in the absence as well as in the presence of the predator. We compare the system dynamics when infection occurs only through contact, with that when it occurs through contact and external sources. Our analysis demonstrates that under a disease-selective predation, stability and oscillations of the system is determined by two key parameters: the external infection rate and the force of infection through contact. Due to the introduction of external infection, the predator and the prey population show limit-cycle oscillations over a range parametric values. We suggest that while predicting the dynamics of such an eco-epidemiological system, the modes of infection and the infection rates might be carefully investigated.

Predictability and skill of boreal winter forecasts made with the ECMWF Seasonal Forecasting System II

The performance of boreal winter forecasts made with the European Centre for Medium-Range Weather Forecasts (ECMWF) System 11 Seasonal Forecasting System is investigated through analyses of ensemble hindcasts for the period 1987-2001. The predictability, or signal-to-noise ratio, associated with the forecasts, and the forecast skill are examined. On average, forecasts of 500 hPa geopotential height (GPH) have skill in most of the Tropics and in a few regions of the extratropics. There is broad, but not perfect, agreement between regions of high predictability and regions of high skill. However, model errors are also identified, in particular regions where the forecast ensemble spread appears too small. For individual winters the information provided by t-values, a simple measure of the forecast signal-to-noise ratio, is investigated. For 2 m surface air temperature (T2m), highest t-values are found in the Tropics but there is considerable interannual variability, and in the tropical Atlantic and Indian basins this variability is not directly tied to the El Nino Southern Oscillation. For GPH there is also large interannual variability in t-values, but these variations cannot easily be predicted from the strength of the tropical sea-surface-temperature anomalies. It is argued that the t-values for 500 hPa GPH can give valuable insight into the oceanic forcing of the atmosphere that generates predictable signals in the model. Consequently, t-values may be a useful tool for understanding, at a mechanistic level, forecast successes and failures. Lastly, the extent to which t-values are useful as a predictor of forecast skill is investigated. For T2m, t-values provide a useful predictor of forecast skill in both the Tropics and extratropics. Except in the equatorial east Pacific, most of the information in t-values is associated with interannual variability of the ensemble-mean forecast rather than interannual variability of the ensemble spread. For GPH, however, t-values provide a useful predictor of forecast skill only in the tropical Pacific region.

The effect of calcium removal from milk on casein micelle stability and structure

The total calcium level of raw skimmed milk was reduced by 10, 19, 29, 40 and 51% using Duolite® ion-exchange resin. The products were examined for concentrations of ionic calcium, sodium and potassium and the pH, ethanol stability, micelle diameter and ζ-potential were also measured. Ionic calcium decreased with removal of calcium and pH increased. Calcium removal resulted in an increase in the ethanol stability from 88% to above 100%. Casein micelle diameter increased as calcium was removed. The ζ-potential of the skimmed bulk milk was -24.4 mV, gradually becoming more negative with calcium removal to -30.6 mV after 51% calcium removal. The milk became more translucent as calcium was removed. To investigate the reversibility of this process, calcium chloride was added back to the depleted samples to restore their original total calcium content. At 51% removal, restoration of the total calcium level resulted in formation of clots. At levels of 10 and 19% calcium removal, the ethanol stability remained above 100%, but at higher levels of calcium removal the alcohol stability was adversely affected when the calcium was added back. Adding back calcium resulted in partial restoration of the original casein micelle diameter.

Stability in miniplasmids of Xanthomonas campestris pv. malvacearum during subculturing and storage - Abstract 7

Abstract 7

The effect of free Ca2+ on the heat stability and other characteristics of low-heat skim milk powder

Low-heat skim milk powder (SMP), reconstituted to 25% total solids, was found to have poor heat stability. This could be improved by reducing the free Ca2+ concentration to 1.14 mm, or lower, by the addition of either Amberlite IR-120 ion-exchange resin in its sodium form or tri-sodium citrate in skim milk prior to evaporation and spray drying. Reduction in Ca2+ concentration was accompanied by increases in pH, particle size, and kinematic viscosity, and by a reduction in zeta-potential and changes in colour. In-container sterilisation of the reconstituted powder increased particle size, zeta-potential, kinematic viscosity and a* and b* values. However. Ca2+ concentration, pH and whiteness decreased. This study elucidated the importance of Ca2+ concentration and pH on heat stability of low-heat SMP, suggesting that Ca2+ concentration and pH in bulk milk are useful indicators for ensuring that spray dried milk powder has good heat stability. (C) 2009 Elsevier Ltd. All rights reserved.

The synthesis, structure, and reactions of some simple unsaturated σ-hydrocarbylplatinum(II) complexes

Trimethyltin compounds Me3SnR(R = CHCH2, CFCF2, or CCPh) are selective reagents for the synthesis of unsaturated hydrocarbyl derivatives such as trans-PtCl(R)(PPhEt2)2, by R/Cl exchange or oxidative addition (e.g., to Pt(PPh3)3); single crystal X-ray analyses of two such compounds (R = CHCH2 or CCPh) show that the trans-influence of R has only a low sensitivity to hybridisation at carbon, with sp3 > sp ⩾ sp2.

Bistable systems with stochastic noise: virtues and limits of effective one-dimensional Langevin equations

The understanding of the statistical properties and of the dynamics of multistable systems is gaining more and more importance in a vast variety of scientific fields. This is especially relevant for the investigation of the tipping points of complex systems. Sometimes, in order to understand the time series of given observables exhibiting bimodal distributions, simple one-dimensional Langevin models are fitted to reproduce the observed statistical properties, and used to investing-ate the projected dynamics of the observable. This is of great relevance for studying potential catastrophic changes in the properties of the underlying system or resonant behaviours like those related to stochastic resonance-like mechanisms. In this paper, we propose a framework for encasing this kind of studies, using simple box models of the oceanic circulation and choosing as observable the strength of the thermohaline circulation. We study the statistical properties of the transitions between the two modes of operation of the thermohaline circulation under symmetric boundary forcings and test their agreement with simplified one-dimensional phenomenological theories. We extend our analysis to include stochastic resonance-like amplification processes. We conclude that fitted one-dimensional Langevin models, when closely scrutinised, may result to be more ad-hoc than they seem, lacking robustness and/or well-posedness. They should be treated with care, more as an empiric descriptive tool than as methodology with predictive power.