Basilar membrane mechanics at the base of the chinchilla cochlea. I. Input-output functions, tuning curves, and response phases

Basilar membrane (BM) velocity was measured at a site 3.5 mm from the basal end of the chinchilla cochlea using the M?ssbauer technique. The threshold of the compound action potential recorded at the round window in response to tone bursts was used as an indicator of the physiological state of the cochlea. The BM input-output functions display a compressive nonlinearity for frequencies around the characteristic frequency (CF, 8 to 8.75 kHz), but are linear for frequencies below 7 and above 10.5 kHz. In preparations with little surgical damage, isovelocity tuning curves at 0.1 mm/s are sharply tuned, have Q10's of about 6, minima as low as 13 dB SPL, tip-to-tail ratios (at 1 kHz) of 56 to 76 dB, and high-frequency slopes of about 300 dB/oct. These mechanical responses are as sharply tuned as frequency-threshold curves of chinchilla auditory nerve fibers with corresponding CF. There is a progressive loss of sensitivity of the mechanical response with time for the frequencies around CF, but not for frequencies on the tail of the tuning curve. In some experiments the nonlinearity was maintained for several hours, in spite of a considerable loss of sensitivity of the BM response. High-frequency plateaus were observed in both isovelocity tuning curves and phase-frequency curves.     

Simultaneous determination of two anti-inflammatory drugs in serum using isopotential fluorimetry

The simultaneous determination of 6-methoxy-2-naphthylacetic acid (6MNA) and diflunisal in serum samples using the combination of matrix isopotential synchronous fluorescence (MISF) and first derivative technique is proposed. 6MNA and diflunisal exhibit overlapped spectra and serum produces background fluorescence that precludes the direct determination of these anti-inflammatory drugs by conventional fluorimetry. This method provides good analytical results for determination of compounds in samples with unknown background fluorescence. The method was applied for the simultaneous determination of 6MNA and diflunisal in serum samples at concentrations between 20-200 and 100-1000 ng mL⁻¹, respectively, by means of absolute values of first derivative of synchronous scan at 247.9/364.0 and 262.6/392.4 nm for 6MNA and diflunisal, respectively. In order to obtain maximum sensitivity and adequate selectivity, factors affecting fluorescence intensity were studied. As a result, the analyses were performed in water at a pH of 7.2, adjusted by using sodium dihydrogen phosphate/hydrogen phosphate (0.1 M) as a buffer solution. Serum samples were diluted 200 times. Analytical parameters of the proposed method were calculated according to the error propagation theory. The limit of detection calculated according to Clayton was 15.8 and 63.0 ng mL⁻¹ for 6MNA and diflunisal, respectively. The sensitivity, repeatability and reproducibility achieved with the proposed method were adequate for the determination of these anti-inflammatory agents in serum samples.     

Direct determination of closely overlapping drug mixtures of diflunisal and salicylic acid in serum by means of derivative matrix isopotential synchronous fluorescence spectrometry

A direct method for the simultaneous fluorimetric determination of two anti-inflammatory drugs in serum is proposed. The combination of matrix isopotential synchronous fluorescence (MISF) and first derivative technique provides good analytical results and permits the simultaneous determination of diflunisal and salicylic acid in human serum. MISF spectra are obtained by calculating the isopotential trajectory in the three-dimensional fluorescence spectrum for a serum solution. In the spectral contour, the trajectory is taken to be the portion of the line that passes by the fluorescence maxima of both compounds ensuring a sensitivity level similar to that of a direct determination in absence of background fluorescence. Analysis was carried out in water using a pH of 7.2 provides by 0.1 M sodium dihydrogen phosphate buffer. Serum samples are diluted 100 times and provide linear calibration plots at diflunisal and salicylic acid concentrations up to 800 ng mL⁻¹. The goodness of the analytical signal was checked by using variance analysis. Signals recorded throughout the calibration range were subjected to three calibrations per each analyte, both in the absence and in the presence of variable amounts of the other analyte. Differences between individual calibrations and slopes were compared with those within individual calibrations. Based on the results, diflunisal and salicylic acid can be accurately quantified in the presence of each other. The limit of detection calculated according to Clayton who uses error propagation throughout the calibration curve and a non-centralized security factor was 36.8 and 37.3 ng mL⁻¹ for diflunisal and salicylic acid, respectively.     

A Routley–Meyer Semantics for Gödel 3-Valued Logic and Its Paraconsistent Counterpart

Routley–Meyer semantics (RM-semantics) is defined for Gödel 3-valued logic G3 and some logics related to it among which a paraconsistent one differing only from G3 in the interpretation of negation is to be remarked. The logics are defined in the Hilbert-style way and also by means of proof-theoretical and semantical consequence relations. The RM-semantics is defined upon the models for Routley and Meyer’s basic positive logic B₊, the weakest positive RM-semantics. In this way, it is to be expected that the models defined can be adapted to other related many-valued logics.     

An Investigation of the N-Arylsulfonylation of 2-Azetidinones

N-Arylsulfonylation of 2-azetidinones can lead to the diastereoselective formation of oligomerization products. However, a simple increase of arylsulfonyl chloride concentration minimized oligomerization and allowed preparation of 1-arylsulfonyl-2-azetidinones in good yield.     

Optimizing logistic regression coefficients for discrimination and calibration using estimation of distribution algorithms

Logistic regression is a simple and efficient supervised learning algorithm for estimating the probability of an outcome or class variable. In spite of its simplicity, logistic regression has shown very good performance in a range of fields. It is widely accepted in a range of fields because its results are easy to interpret. Fitting the logistic regression model usually involves using the principle of maximum likelihood. The Newton–Raphson algorithm is the most common numerical approach for obtaining the coefficients maximizing the likelihood of the data. This work presents a novel approach for fitting the logistic regression model based on estimation of distribution algorithms (EDAs), a tool for evolutionary computation. EDAs are suitable not only for maximizing the likelihood, but also for maximizing the area under the receiver operating characteristic curve (AUC). Thus, we tackle the logistic regression problem from a double perspective: likelihood-based to calibrate the model and AUC-based to discriminate between the different classes. Under these two objectives of calibration and discrimination, the Pareto front can be obtained in our EDA framework. These fronts are compared with those yielded by a multiobjective EDA recently introduced in the literature.      

Basilar membrane mechanics at the base of the chinchilla cochlea. II. Responses to low-frequency tones and relationship to microphonics and spike initiation in the VIII nerve

Low-frequency stimuli (40- to 1000-Hz tones) have been used to correlate the motion of the 8-to 9-kHz place of the chinchilla basilar membrane with the cochlear microphonics recorded at the round window and with the responses of auditory nerve fibers with appropriate characteristic frequency. At the lowest stimulus frequencies, maximum displacement of the basilar membrane toward scala tympani occurs in near synchrony with maximum rarefaction at the eardrum and maximum negativity at the round window; at higher frequencies, the mechanical and microphonic response phases progressively lag rarefaction, reaching - 240 deg at 1000 Hz. At most frequencies (40-1000 Hz) near-threshold neural responses, once corrected for neural travel-time and synaptic delays, somewhat lead (by some 40 deg) maximal scala tympani displacement and maximal negativity of the round window microphonics. The variation of sensitivity with frequency is similar for basilar membrane displacement and microphonic responses: Under open-bulla conditions, sensitivity is constant for frequencies between 100 and 1000 Hz; below 100 Hz, sensitivity decreases at rates close to 12 dB/oct toward lower frequencies. Neural response sensitivity matches BM displacement more closely than BM velocity.