Determination of 4-methylpropranolol in cerebrospinal fluid,serum, and urine by nonprotected fluid room-temperature phosphorescence using simplex optimization

A direct and simple procedure for the determination of 4-methylpropranolol, a specific beta-adrenergic receptor blocking agent, in biological fluids was developed. The method was based on the measurement of the nonprotected fluid room-temperature phosphorescence of the drug. This technique enables us to determine analytes in complex matrices without the need for a tedious prior separation process. The appropriate experimental conditions to obtain suitable reproducibility and maximum phosphorescence signal, when sodium sulfite is used to eliminate the oxygen from the solution and when potassium iodide is used as heavy atom, were studied. The optimum concentration of KI was 3.2 M. The optimization of Na(2)SO(3) (7.0 x 10(-3) M) and the accurate value of pH (10.88) were determined using a simplex as the method of optimization. A sodium carbonate-hydrogen carbonate buffer solution (5.0 x 10(-2) M) was used to adjust the value of pH. The delay time (124 micros), gate time (206 micros), and time between flashes (5 ms) were also optimized using a simplex. Under the above conditions, the maximum signal of phosphorescence appears instantly once the sample has been prepared, and the intensity was measured at lambda(ex) = 300 nm and lambda(em) = 537 nm, in the concentration range 25-500 ng/ml. Overall least-squares regression was used to find the straight line that fit the experimental data. The detection limit according to the error propagation theory was 6.2 ng/ml and the detection limit calculated as proposed by C. A. Clayton et al. (1987, Anal. Chem. 59, 2506) was 11.7 ng/ml. The repeatability was studied using 10 solutions of 200 ng/ml 4-methylpropranolol; if error propagation theory was assumed, the relative error was 1.78% and the standard deviation for replicate samples was 3.5 ng/ml. This method was successfully applied to the determination of 4-methylpropranolol in urine, serum, and cerebrospinal fluid, with recoveries of 99.3 +/- 0.5% in the case of urine, 99.8 +/- 0.2% for serum, and 101.5 +/- 1.5% for cerebrospinal fluid.     

Evidence for time-dependent maximum increase of free radical damage and eicosanoid formation in the brain as related to duration of cardiac arrest and cardio-pulmonary resuscitation

Recovery of neurological function in patients following cardiac arrest and cardiopulmonary resuscitation (CPR) is a complex event. Free radical induced oxidative stress is supposed to be involved in this process. We studied levels of 8-iso-PGF2alpha (indicating oxidative injury) and 15-keto-dihydro-PGF2alpha (indicating inflammatory response) in venous plasma obtained from the jugular bulb in a porcine model of experimental cardiopulmonary resuscitation (CPR) where 2, 5, 8, 10 or 12 min of ventricular fibrillation (VF) was followed by 5 or 8 min of closed-chest CPR. A significant increase of 8-iso-PGF2alpha was observed immediately following restoration of spontaneous circulation in all experiments of various duration of VF and CPR. No such increase was seen in a control group. When compared between the groups there was a duration-dependent maximum increase of 8-iso-PGF2alpha which was greatest in animals subjected to the longest period (VF12 min + CPR8 min) of no or low blood flow. In contrast, the greatest increase of 15-keto-dihydro-PGF2alpha was observed in the 13 min group (VF8 min + CPR5 min). Thus, a time-dependent cerebral oxidative injury occurs in conjunction which cardiac arrest and CPR.     

Error-free recombinational repair predominates over mutagenic translesion replication in E. coli

Tolerance mechanisms are important in the ability of cells to cope with DNA damage. In E. coli, the two main damage tolerance mechanisms are recombinational repair (RR) and translesion replication (TLR). Here we show that RR effectively repairs gaps opposite DNA lesions. When both mechanisms are functional, RR predominates over TLR, being responsible for 86% of the repair events. This predominance of RR is determined by the high concentration of RecA present under SOS conditions, which causes a differential inhibition of TLR. Further inhibition of TLR is caused by the RecA-catalyzed strand exchange reaction of RR. This molecular hierarchy in the tolerance of DNA lesions ensures that the nonmutagenic RR predominates over the mutagenic TLR, thereby contributing to genetic stability.     

Isoflavonoids from Myroxylon peruiferum

Considerable differences in flavonoid composition of the trunkwood characterize different specimens of Myroxylon balsamum (L.) Harms. Only calycosin among the 11 flavonoids found in M. peruiferum L.f., presently considered synonymous with M. balsamum, had previously been located in the latter species. Two of these flavonoids, 2′-hydroxy-7,3′,4′-trimethoxyisoflavanone and 2′-hydroxy-7,3′,4′-trimethoxyisoflavone are new natural products.     

Classification of Fricative Consonants for Speech Enhancement in Hearing Devices

Objective

To investigate a set of acoustic features and classification methods for the classification of three groups of fricative consonants differing in place of articulation.

Method

A support vector machine (SVM) algorithm was used to classify the fricatives extracted from the TIMIT database in quiet and also in speech babble noise at various signal-to-noise ratios (SNRs). Spectral features including four spectral moments, peak, slope, Mel-frequency cepstral coefficients (MFCC), Gammatone filters outputs, and magnitudes of fast Fourier Transform (FFT) spectrum were used for the classification. The analysis frame was restricted to only 8 msec. In addition, commonly-used linear and nonlinear principal component analysis dimensionality reduction techniques that project a high-dimensional feature vector onto a lower dimensional space were examined.

Results

With 13 MFCC coefficients, 14 or 24 Gammatone filter outputs, classification performance was greater than or equal to 85% in quiet and at +10 dB SNR. Using 14 Gammatone filter outputs above 1 kHz, classification accuracy remained high (greater than 80%) for a wide range of SNRs from +20 to +5 dB SNR.

Conclusions

High levels of classification accuracy for fricative consonants in quiet and in noise could be achieved using only spectral features extracted from a short time window. Results of this work have a direct impact on the development of speech enhancement algorithms for hearing devices.     

Apoptotic and anti-proliferative effects of all-trans retinoic acid. Adenine nucleotide translocase sensitizes HeLa cells to all-trans retinoic acid

We examined the apoptotic and anti-proliferative effects of all-trans retinoic acid (atRA) in HeLa cells. Our results demonstrated that HeLa cells were more sensitive to the anti-proliferative effects of atRA than to its apoptotic effects. Furthermore, we demonstrated that caspase inhibition attenuates cell death but does not alter the atRA-dependent reduction in cell proliferation, which suggests that atRA-induced apoptosis is independent of the arrest in cell proliferation. To check whether ANT proteins mediated these atRA effects, we transiently transfected cells with expression vectors encoding for individual ANT (adenine nucleotide translocase 1-3). Our results revealed that ANT1 and ANT3 over-expressing HeLa cells increased their atRA sensitivity. Thus, our results not only demonstrate the different functional activities of ANT isoforms, but also contribute to a better understanding of the properties of atRA as an anti-tumoral agent used in cancer therapy.     

RAPID DIVERSIFICATION OF SPERM PRECEDENCE TRAITS AND PROCESSES AMONG THREE SIBLING DROSOPHILA SPECIES

Postcopulatory sexual selection is credited with driving rapid evolutionary diversification of reproductive traits and the formation of reproductive isolating barriers between species. This judgment, however, has largely been inferred rather than demonstrated due to general lack of knowledge about processes and traits underlying variation in competitive fertilization success. Here, we resolved processes determining sperm fate in twice‐mated females, using transgenic Drosophila simulans and Drosophila mauritiana populations with fluorescently labeled sperm heads. Comparisons among these two species and Drosophila melanogaster revealed a shared motif in the mechanisms of sperm precedence, with postcopulatory sexual selection potentially occurring during any of the three discrete stages: (1) insemination; (2) sperm storage; and (3) sperm use for fertilization, and involving four distinct phenomena: (1) sperm transfer; (2) sperm displacement; (3) sperm ejection; and (4) sperm selection for fertilizations. Yet, underlying the qualitative similarities were significant quantitative differences in nearly every relevant character and process. We evaluate these species differences in light of concurrent investigations of within‐population variation in competitive fertilization success and postmating/prezygotic reproductive isolation in hybrid matings between species to forge an understanding of the relationship between microevolutionary processes and macroevolutionary patterns as pertains to postcopulatory sexual selection in this group.