Variation of molecular alignment as a means of resolving orientational ambiguities in protein structures from dipolar couplings

Residual dipolar couplings for pairs of proximate magnetic nuclei in macromolecules can easily be measured using high-resolution NMR methods when the molecules are dissolved in dilute liquid crystalline media. The resulting couplings can in principle be used to constrain the relative orientation of molecular fragments in macromolecular systems to build a complete structure. However, determination of relative fragment orientations based on a single set of residual dipolar couplings is inherently hindered by the multi-valued nature of the angular dependence of the dipolar interaction. Even with unlimited dipolar data, this gives rise to a fourfold degeneracy in fragment orientations. In this Communication, we demonstrate a procedure based on an order tensor analysis that completely removes this degeneracy by combining residual dipolar coupling measurements from two alignment media. Application is demonstrated on (15)N-(1)H residual dipolar coupling data acquired on the protein zinc rubredoxin from Clostridium pasteurianum dissolved in two different bicelle media.     

Efficacy of a Behaviorally Based Voice Therapy Protocol for Vocal Nodules

The aim of this study was to assess the effects on vocal function of voice therapy for vocal nodules. Perceptual and physiological progressive changes were examined during a strictly structured, behaviorally based voice therapy protocol in which 11 women with vocal nodules participated. Randomized audio recordings from pretherapy and from each of the therapy approaches (vocal hygiene, respiration, direct facilitation, carryover) were used for perceptual evaluations. Six speech-language pathologists rated ten voice quality parameters. Two evaluation procedures were performed and compared. Interlistener reliability was sufficiently high in both tests. Significant effects of therapy were found for decreased overall dysphonia, press, instability, gratings, roughness, vocal fry, and "scrape." Nonsignificant group effects were found for breathiness, aphonic instances, and lack of sonority. No significant parameter changes occurred between baseline assessment and the completion of the initial (vocal hygiene) phase of therapy. Significant changes were found following the direct facilitation and respiration phases of therapy. Videostroboscopic evaluations made by two laryngologists showed that in no case were the nodules completely resolved. However, the nodules had decreased in size and edema was reduced after therapy for all clients, but one. Combined results suggest: (1) Alterations in vocal function were reflected in perceptual parameters, and (2) the voice therapy had a positive effect on voice quality, vocal status, and vocal function for the majority of the vocal nodule clients.     

Objective Voice Quality Analysis Before and After Onset of Unilateral Vocal Fold Paralysis

This study was designed to investigate objective voice quality measurements in unilateral vocal fold paralysis (UVFP) by eliminating intersubject variability. To our knowledge this is the first report objectively analyzing paralytic dysphonia as compared to the same voice before onset of UVFP. The voices of two male subjects were prospectively recorded before and after the onset of iatrogenic UVFP (thoracic surgery).The following acoustic measurements of the vowel /a/ were performed using the CSL and MDVP (Kay Elemetrics): jitter, shimmer, harmonics-to-noise ratio, cepstral peak prominence, the relative energy levels of the first harmonic, the first formant and the third formant, the spectral slope in the low-frequency zone (0-1 kHz and 0-2 kHz), and the relative level of energy above 6 kHz. Distribution of spectral energy was analyzed from a long-term average spectrum of 40 seconds of text. Laryngeal aerodynamic measurements were obtained for one patient before and after onset of paralysis using the Aerophone II (Kay Elemetrics). Pitch and amplitude perturbation increased secondary to UVFP, while the harmonics-to-noise ratio and the cepstral peak prominence decreased. A relative increase in the mid-frequency and high-frequency ranges and a decrease in the low-frequency spectral slope were observed. Mean airflow rate and intraoral pressure increased, and glottal resistance and vocal efficiency decreased secondary to UVFP. The findings of this self-paired study confirm some but not all the results of previous studies. Measures involving the fundamental and the formants did not corroborate previous findings. Further investigation with vocal tract modeling is warranted.     

Vocal Fold Mucosal Tears: Maintaining a High Clinical Index of Suspicion

Vocal fold mucosal tears have been discussed in the literature rarely, although they are not uncommon clinically. Disruptions in the epithelium usually follow trauma that may result from voice abuse and/or misuse, coughing, and other causes. A high index of suspicion is necessary to avoid missing vocal fold mucosal tears, and strobovideolaryngoscopy is indispensable in making the diagnosis. A brief period of complete voice rest is the standard of care and appears to be helpful in avoiding adverse sequelae and advancing the healing process, but there are no scientific studies to confirm its efficacy. Mucosal tears may heal completely or may be followed by the development of vocal fold masses, scar, and permanent dysphonia.     

The Adjustable Laryngeal Implant

An adjustable laryngeal implant made of titanium has been developed for the treatment of unilateral vocal fold paralysis. The implant includes three parts: a plate that allows fixation to the thyroid cartilage, a block of titanium which includes the adjustable part, and a micrometric screw in the middle of the lateral side of the block, which moves the adjustable part. Precise medialization is accomplished by regulating the screw which also permits easy secondary adjustments, if needed in the future. This retrospective study assesses clinical outcomes of medialization laryngoplasty with the titanium adjustable implant, in patients with unilateral vocal fold paralysis. This study has the limitations of a retrospective study. However, preliminary results are encouraging. Analysis of subjective responses confirmed marked improvement in laryngeal function, speech, and swallowing. Objective voice analysis confirmed improvement in the aerodynamic measures. The adjustable laryngeal implant has many advantages including: precise medialization, ease of secondary adjustment, and preseveration of the mucosal wave. This implant is biocompatible, no migration is possible (it is fixed to the cartilage) and no extrusion of the implant has occurred. Titanium is magnetic resonance imaging (MRI)-safe.     

Qualitative and Quantitative Evaluation of Some Vocal Function Parameters Following Fitting of a Prosthesis

The insertion of a prosthesis and restoration with pectoralis major myocutaneous flaps for patients subjected to total pharyngolaryngectomy is a technique now universally accepted; however the literature on the subject is lacking. Our study considers 10 patients subjected to total pharyngolaryngecto-my and restoration with pectoralis major myocutaneous flaps who were fitted with vocal function prostheses and a control group of 50 subjects treated with a total laryngectomy without pectoralis major myocutaneous flaps and who were fitted with vocal function prostheses. Specific qualitative and quantitative parameters were compared. The quantitative measurement of the levels of voice intensity and the evaluation of the harmonics-to-noise ratio were not statistically significant (p > 0.05) between the two study groups at either high- or low-volume speech. On the contrary, statistically significant differences were found (p < 0.05) for the basic frequency of both the low and the high volume voice. For the qualitative analysis seven parameters were established for evaluation by trained and untrained listeners; on the basis of these parameters the control group had statistically better voices.     

The Effect of Cricothyroid Muscle Action on the Relation Between Subglottal Pressure and Fundamental Frequency in an In Vivo Canine Model

The relation between subglottal pressure (P_s) and fundamental frequency (F₀) in phonation was investigated with an in vivo canine model. Direct muscle stimulation was used in addition to brain stimulation. This allowed the P_s-F₀ slope to be quantified in terms of cricothyroid muscle activity. Results showed that, for ranges of 0–2 mA constant current stimulation of the cricothyroid muscle, the P_s-F₀ slope ranged from 10 Hz/kPa to 60 Hz/kPa. These results were compared to similar slopes obtained in a previous study on excised larynges in which the vocal fold length was varied instead of cricothyroid activation. A physical interpretation of the P_s-F₀ slope is that the amplitude-to-length ratio of the vocal folds decreases with CT activity, resulting in a smaller time-varying stiffness. In other words, there is less dependence of F₀ on amplitude of vibration when the vocal folds are long instead of short.     

圆形硐室岩爆机制及其突变理论分析

硐室岩爆机制是围岩中处于极限状态的塑性变形集中区承载能力下降时,其中完好岩体部分以弹性方式卸载,当后者释放的弹性能超过前者形变耗散的能量时便发生岩爆．以岩体等效应变为状态变量,建立了硐室岩爆的突变模型,给出岩爆释放地震能计算式．分析表明: 岩爆发生条件与岩体的升降模量比及岩体裂隙发育程度有关;对于特定冲击倾向的岩体,存在相应的临界软化区深度,当满足岩爆发生条件,且软化区深度达到临界深度时会发生岩爆．     

折线型非线性振动响应计算的时域有限元分段求解

本文研究折线型非线性振动系统响应的求解,按分段线性性质建立了分段线性的时域有限元离散模型。在求解中先计算当前段的振动响应,根据转折条件判断是否存在转折点。当存在多个转折点时,以最早出现的转折点作为下一段的起始点,否则以本时间段终点作为下一段的起始点,然后进入下一段的计算。本文方法能在每一段较精确地求出转折点,并同时给出该转折点之前各结点的响应解。较有效地解决了这类问题的数值求解。文中算例给出了相当精确的计算结果,验证了本文方法的有效性。