A variational principle for singular integral equations with bounded solutions

In many boundary value problems involving triple integral equations or triple series relations, it is required to solve a single singular integral equation with constant but unknown limits of integration. In this paper we present a variational method to determine approximately the bounded unknown function, if it exists, together with the unknown limits of integration for a type of such singular integral equations. The method is used to recover the exact solution of an integral equation and is applied to a contact problem in the theory of elasticity which is intractable otherwise.     

Development and internal validation of an in vitro-in vivo correlation for a hydrophilic metoprolol tartrate extended release tablet formulation

PURPOSE: To develop and validate internally an in vitro-in vivo correlation (IVIVC) for a hydrophilic matrix extended release metoprolol tablet. METHODS: In vitro dissolution of the metoprolol tablets was examined using the following methods: Apparatus II, pH 1.2 & 6.8 at 50 rpm and Apparatus I, pH 6.8, at 100 and 150 rpm. Seven healthy subjects received three metoprolol formulations (100 mg): slow, moderate, fast releasing and an oral solution (50 mg). Serial blood samples were collected over 48 hours and analyzed by a validated HPLC assay using fluorescence detection. The f2 metric (similarity factor) was used to analyze the dissolution data. Correlation models were developed using pooled fraction dissolved (FRD) and fraction absorbed (FRA) data from various combinations of the formulations. Predicted metoprolol concentrations were obtained by convolution of the in vivo dissolution rates. Prediction errors were estimated for Cmax and AUC to determine the validity of the correlation. RESULTS: Apparatus I operated at 150 rpm, and pH of 6.8 was found to be the most discriminating dissolution method. There was a significant linear relationship between FRD and FRA when using either two or three of the formulations. An average percent prediction error for Cmax and AUC for all formulations of less than 10% was found for all IVIVC models. CONCLUSIONS: The relatively low prediction errors for Cmax and AUC observed strongly suggest that the metoprolol IVIVC models are valid. The average percent prediction error of less than 10% indicates that the correlation is predictive and allows the associated dissolution data to be used as a surrogate for bioavailability studies.     

Use of polymerase chain reaction to assess efficacy of leprosy chemotherapy

The assessment of chemotherapy efficacy in leprosy is difficult, since the only reliable method for determining whether the causative organism, Mycobacterium leprae, is viable depends on its growth in mouse foot pads. In an attempt to replace this expensive, time-consuming test, methods based on the polymerase chain reaction (PCR) have been developed. These methods depend on detection of DNA, which is more susceptible to degradation on cell death than are other cell components, so should be a more accurate indicator of viability. We have used a specific PCR assay to detect M leprae DNA in skin biopsy samples from leprosy patients. By use of limiting dilution PCR (LD-PCR), the concentration of M leprae DNA in the original sample could be measured. The DNA concentration was more closely correlated with the morphological index (derived from a staining technique that distinguishes morphologically intact and damaged bacteria) than with the number of bacteria visible (bacterial index, BI, which counts both alive and dead bacteria). In a longitudinal study of multibacillary patients on multi-drug therapy, skin biopsy samples were collected before treatment and 3, 6, 12, and 24 months after the start of therapy. While the BI showed little or no change during treatment, the number of genomes detected by PCR fell sharply, in parallel with the MI. We propose that PCR can be used as a rapid measure of M leprae viability and that this approach can be used for monitoring individual leprosy patients and for assessment of existing and new regimens. The method may be applicable to other infectious diseases in which culture of the causative organism is slow or impossible.     

X-ray photoelectron spectroscopy and Fourier transform-infrared studies of transition metal phosphate glasses

X-ray photoelectron spectroscopy and Fourier transform-infrared studies were carried out on phosphate glasses containing oxides of iron, cobalt, nickel, copper and zinc. The results suggest that the glasses containing iron and zinc may have structures in which both the phosphorus and the iron (or zinc) atoms are tetrahedrally coordinated by oxygen into three-dimensional structures which resemble the polymorphic forms of silica, whereas the glasses containing cobalt, nickel and copper may consist of polymeric chains of PO₄ tetrahedra bonded to adjacent tetrahedra via bridging oxygens. These polyphosphate chains are linked together by the interaction between the metal cation and the oxygens of the network former. In addition, the core level 2p shake-up satellites of the 3d-transition metal ions in these glasses were studied. The results support a suggestion that the satellites in the glass are most likely due to the electron transfer from ligand to metal 3d orbitals.     

Orange-eye: A sex-linked recessive mutation in Ephestia cautella (Walker) (Lepidoptera: Pyralidae)

A new eye color mutant, orange eye (O), is described for Ephestia cautella. Preliminary data revealed that this mutation was inherited as a sex-linked recessive. The character is generally recognizable in only the late pupae and adult stages. The viability and reproductive potential of this strain are not significantly different from the wild type.     

Adaptive instantaneous frequency estimation of multicomponent FMsignals using quadratic time-frequency distributions

An adaptive approach to the estimation of the instantaneous frequency (IF) of nonstationary mono- and multicomponent FM signals with additive Gaussian noise is presented. The IF estimation is based on the fact that quadratic time-frequency distributions (TFDs) have maxima around the IF law of the signal. It is shown that the bias and variance of the IF estimate are functions of the lag window length. If there is a bias-variance tradeoff, then the optimal window length for this tradeoff depends on the unknown IF law. Hence, an adaptive algorithm with a time-varying and data-driven window length is needed. The adaptive algorithm can utilize any quadratic TFD that satisfies the following three conditions: First, the IF estimation variance given by the chosen distribution should be a continuously decreasing function of the window length, whereas the bias should be continuously increasing so that the algorithm will converge at the optimal window length for the bias-variance tradeoff, second, the time-lag kernel filter of the chosen distribution should not perform narrowband filtering in the lag direction in order to not interfere with the adaptive window in that direction; third, the distribution should perform effective cross-terms reduction while keeping high resolution in order to be efficient for multicomponent signals. A quadratic distribution with high resolution, effective cross-terms reduction and no lag filtering is proposed. The algorithm estimates multiple IF laws by using a tracking algorithm for the signal components and utilizing the property that the proposed distribution enables nonparametric component amplitude estimation. An extension of the proposed TFD consisting of the use of time-only kernels for adaptive IF estimation is also proposed     

Structure-activity relationships and physico-chemical properties of synthetic lipopeptide inhibitors of PKC

Four synthetic lipopeptides, (K-pm 19,31), (K-pm 19,21,31), (K-pm 19,28,31) and (K-pm 19,21,28,31) with the lysine-palmitoyl (K-pm) residue as a lipophilic moiety, based on the pseudosubstrate sequence 19RFARKGALRQKNV31 (R19-V31), were found to be potent protein kinase C (PKC) inhibitors. However, the lipopeptides (K-pm 19,21,31), (K-pm 19,28,31) and (K-pm 19,21,28,31) were also found to act as protein kinase cAMP-dependent (PKA) inhibitors. Peptide (K-pm 19,31), the least water soluble, is marginally selective towards PKC, unlike the other palmitoyl derivatives studied here. Since the non-palmitoylated analogues (K 19,31), (K-ac 19,31), (K 19,21,31) and (K-ac 19,21,31) were inhibitors of PKC but not of PKA, the palmitoyl moiety must play a role in the specificity of protein kinase inhibition. In vitro, the lipophilic peptides showed greater stability to protease-mediated hydrolysis than the pseudosubstrate peptide depending upon the number of lipophilic (K-pm) residues. CD studies showed that in comparison with the peptide analogues, the remarkable resistance of the pseudosubstrate (R19-V31) to adopt an alpha-helix conformation in TFE, known to be strongly alpha-helix inducing, rules out this structure as the peptide binding conformation to PKC. By contrast, in aqueous media all the peptides show an extended conformation that correlates well with their inhibitory activity. This is in compliance with the crystallographic observation that an extended structure has been observed for the (5-24) PKI peptide inhibitor bound to PKA.     

Volatiles Retention in the Drying of Skin Forming Materials PART 1: Materials Which Gelatinise at Moderately High Temperatures

Single droplets were dried whilst suspended from a rotating thermocouple in a horizontal wind tunnel, to study the effect of skin formation upon the retention of flavours. Native rice starch, wheat starch, or dextrin were used to encapsulate ethanol as a simulated flavour. The ethanol content of the dried droplets was measured using gas liquid chromatography and the crusts were examined using a scanning electron microecope. The effects of variations in encapsulant concentration, drying air temperature, and air flow rates upon flavour retention were determined.

With the rice starch, the 'final retention' of ethanol, defined as the ethanol content of the droplet after drying for ten minutes, was largely independent of initial solids