Continuous Wave Analysis Research Articles

Conformational Response of Influenza A M2 Transmembrane Domain to Amantadine Drug Binding at Low pH (pH 5.5).

The M2 protein from influenza A plays important roles in its viral cycle. It contains a single transmembrane helix, which oligomerizes into a homotetrameric proton channel that conducts in the low-pH environment of the host-cell endosome and Golgi apparatus, leading to virion uncoating at an early stage of infection. We studied conformational rearrangements that occur in the M2 core transmembrane domain residing on the lipid bilayer, flanked by juxtamembrane residues (M2TMD21−49 fragment), upon its interaction with amantadine drug at pH 5.5 when M2 is conductive. We also tested the role of specific mutation and lipid chain length. Electron spin resonance (ESR) spectroscopy and electron microscopy were applied to M2TMD21−49, labeled at the residue L46C with either nitroxide spin-label or Nanogold® reagent, respectively. Electron microscopy confirmed that M2TMD21−49 reconstituted into DOPC/POPS at 1:10,000 peptide-to-lipid molar ratio (P/L) either with or without amantadine, is an admixture of monomers, dimers, and tetramers, confirming our model based on a dimer intermediate in the assembly of M2TMD21−49. As reported by double electron-electron resonance (DEER), in DOPC/POPS membranes amantadine shifts oligomer equilibrium to favor tetramers, as evidenced by an increase in DEER modulation depth for P/L's ranging from 1:18,000 to 1:160. Furthermore, amantadine binding shortens the inter-spin distances (for nitroxide labels) by 5–8 Å, indicating drug induced channel closure on the C-terminal side. No such effect was observed for the thinner membrane of DLPC/DLPS, emphasizing the role of bilayer thickness. The analysis of continuous wave (cw) ESR spectra of spin-labeled L46C residue provides additional support to a more compact helix bundle in amantadine-bound M2TMD 21−49 through increased motional ordering. In contrast to wild-type M2TMD21−49, the amantadine-bound form does not exhibit noticeable conformational changes in the case of G34A mutation found in certain drug-resistant influenza strains. Thus, the inhibited M2TMD21−49 channel is a stable tetramer with a closed C-terminal exit pore. This work is aimed at contributing to the development of structure-based anti-influenza pharmaceuticals.

Feasibility study of optically pumped molecular lasers with small quantum defect

An analytical analysis of continuous wave (CW) optically pumped molecular lasers with small quantum defect is presented. The results show the conditions under which lasing with small Stokes shifts are possible. The general results are applied to HCN as an example gas. The predictions from the analytical approach are in good quantitative agreement with numerical calculations. The effective vibrational lifetimes and rotational relaxation rates of the molecule determine the principal behavior of such lasers. High overall laser efficiencies are possible for long interaction length of pump laser and gas media, which for example can be achieved in waveguide structures. This makes such lasers potentially interesting for coherently combining the output of mutually incoherent fiber and or diode lasers.

Continuous wave and ultra-fast reflectivity studies for the determination of GaN excitonic oscillator strengths as a function of the in-plane biaxial strain

Abstract Up to now, many works have been dedicated to the study of the excitonic parameters of GaN by analyzing cw-spectroscopy results. In this work, time-resolved reflectivity experiments are carried out to record the impulse response of excitons at the femtosecond scale. By combining the analysis of continuous wave and time-resolved reflectivity spectra recorded on high quality GaN samples, the excitonic parameters are determined with accuracy. The oscillator strength evolutions of A, B and C free excitons are analysed versus the in-plane biaxial stress and compared with theoretical predictions.

Factors affecting the continuous wave Doppler spectrum for the diagnosis of carotid arterial disease

Spectral analysis of continuous wave (CW) Doppler signals is used for the diagnosis of carotid arterial disease. Previous clinical and in vitro studies have documented that the peak Doppler frequency is increased in recordings made directly over a stenosis and that spectral broadening is observed beyond a stenosis in the region of disturbed flow. However, certain hemodynamic and technical factors can effect the Doppler spectrum and in particular cause spectral broadening although they are not related to the severity of the arterial stenosis. In this in vitro study, Doppler spectra were quantified by (1) measurements of the peak, mean and mode frequencies, and (2) measurements that quantify changes in the shape of the spectra and thus can potentially detect the presence of spectral broadening. The latter measurements included the spectral broadening index (SBI), coefficient of variation (CV), coefficient of skewedness (CS), and coefficient of kurtosis (CK). Using straight tubes without a bifurcation in a steady flow model, we found that the peak frequency and the extent of spectral broadening were dependent upon the severity of the stenosis, the relation of the recording site to the stenosis or bulb, and the flow rate. Comparison of the severity of Doppler spectral broadening from bulb and stenosis recordings allowed us to conclude that any observed changes in spectral broadening measurements are probably due to a significant stenosis and not to the presence of a normal bulb. If the tube is not completely insonated by the CW Doppler beam, an error of between 4 and 35% can be read in the spectral broadening measurements. The peak frequency, mean frequency, and SBI are not altered significantly by the automatic gain control or dynamic range and noise level settings usually chosen by the spectrum analyzer. Because of the variability of individual Doppler spectra, one should be cautious about deriving quantitative data from one individual spectrum. The results of quantitative analysis of the amplitude spectrum are different from the power spectrum. In conclusion, this in vitro study identified several hemodynamic and technical factors that affect the CW Doppler spectrum; however, in the clinical setting, their influence on quantitative measurements of the extent of spectral broadening likely can be minimized by a skilled technologist who uses a standardized technique.

In vitro study of continuous wave Doppler spectral changes resulting from stenoses and bulbs.

Quantitative analysis of continuous wave (CW) Doppler spectra by measurements of peak frequency and spectral broadening is an important non-invasive method for detecting disturbed flow caused by carotid arterial stenosis. It is known that severe stenoses can be detected; however, the spectral changes associated with minor or moderate stenoses may not be detected or can potentially be confused with those produced by flow disturbances in the normal carotid bulb. In order to determine if the flow disturbances in a normal bulb and those associated with a minor stenosis produce significant spectral changes, Doppler spectra were recorded from straight tubes with bulbs or stenoses in an in vitro model with steady flow rates of 400, 600, and 800 cc/min (Reynolds numbers of 1700, 2600, and 3500). Stenoses greater than approximately 30% cross-sectional area were associated with an increased peak frequency and increased spectral broadening as measured by spectral broadening index (SBI), coefficient of variation (CV), coefficient of skewedness (CS) and coefficient of kurtosis (CK). Stenoses less than 30% were not detected. With flow rates of 400 and 600 cc/min, the presence of a bulb did not affect peak frequency or the extent of spectral broadening. With a higher flow rate (800 cc/min), there was an increase in SBI, CV and CS but no increase in peak frequency. Based on the results of these in vitro steady flow experiments in straight tubes, we conclude that increased peak frequency and spectral broadening are the result of a stenosis greater than 30% cross-sectional area.(ABSTRACT TRUNCATED AT 250 WORDS)

Computer-Based Analysis oc Continuous Wave Operation of Distribution Feeders

This paper describes a set of computer programs developed for the analysis of continuous wave, steady-state operation of distribution feeders. The programs are designed for distribution feeders which are tree configured. They use a recursive algorithm and require only small dimensioned matrix operations. They are application user-oriented and, while they make an exact representation of the feeder, are easy to use, since they make extensive use of precomputed data bases.