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IR Titze 《Canadian Metallurgical Quarterly》1980,23(3):495-510
The myoelastic-aerodynamic theory of phonation has been quantified and tested with mathematical models. The models suggest that vocal fold oscillation is produced as a result of asymmetric forcing functions over closing and opening portions of the glottal cycle. For nearly uniform tissue displacements, as in falsetto voice, the asymmetry in the driving forces can result from the inertia of the air moving through the glottis. This inertia can in turn be enhanced or suppressed by supraglottal or subglottal vocal tract coupling. More obvious and pronounced asymmetries in the driving forces are associated with non-uniform vocal fold tissue displacements. These are combinations of normal tissue modes, and can result in vertical and horizontal phase differences along the surfaces, as observed in chest voice. The ranges of oscillation increase among various models as more freedom in the simulated tissue movement is incorporated. Of particular significance in initiating and maintaining oscillation are the vertical motions that facilitate coupling of aerodynamic energy into the tissues and allow tissue deformations under conditions of incompressibility. Vertical displacements also can have a significant on vocal tract excitation. Control of fundamental frequency of oscillation (FO) is basically myoelastic, partially as a result of deliberate or reflex adjustments of laryngeal muscles, and partially as a result of nonlinear tissue strain over the vibrational cycle. This places limits on the control of FO by subglottal pressure, and forces such control to be inseparably connected with vibrational amplitude, or less directly, with vocal intensity. 相似文献
476.
Neonates, as compared to older subjects, exhibit increased signs of relative respiratory suppression such as apnea, periodic breathing and only transient hyperventilatory response to hypoxia. Prenatal cocaine exposure exaggerates the respiratory pattern disturbances observed in infants. As endogenous opioids cause central suppression of breathing, we tested their possible involvement in these effects by assessing opioid content in respiratory-related brainstem regions of 2 to 5 (young) and 18 to 22 (older) day-old piglets, unexposed or preexposed to cocaine during 0.66 to 1.0 gestation. The selected ages represent distinct stages in the postnatal development of respiration. beta-Endorphin, methionine-enkephalin, dynorphin A and dynorphin B from the tractus solitarii, ambigualis, gigantoreticularis and parabrachialis medialis nuclei were separated by high performance liquid chromatography, then quantified by radioimmunoassays. Opioid content was higher in the brain regions of the young than of the older piglets, and increased after cocaine exposure in both age groups, but more in the young. These findings support the possible contribution of high opioid content to the relative suppression of respiratory function in early life, and to the exaggerated respiratory dysrhythmia observed in cocaine preexposed neonates. 相似文献
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RM Diaz S Todryk H Chong IR Hart K Sikora S Dorudi RG Vile 《Canadian Metallurgical Quarterly》1998,5(7):869-879
To develop protocols for the molecular immunotherapy of colorectal cancer, we compared the efficacy of three separate classes of therapeutic genes to induce antitumour responses in a murine colorectal cell model. Thus, the effects of two cytokines (IL-2 and GM-CSF) were compared with those of a costimulatory gene (B7.1) and a suicide gene (HSVtk). The rank order of efficacy against primary tumour growth was HSVtk[GCV], B7.1 > puro, IL-2 > GM-CSF, neo whereas the order of efficacy in inducing antitumour immunity was GM-CSF, IL-2, > B7.1, HSVtk[GCV] > puro, neo in a prophylactic vaccination model. To exploit these data in a clinically relevant and realistic way, we also demonstrated that colorectal tumours can reproducibly be explanted and established in short-term culture. Finally, a rapid transduction protocol has been developed by which, using adenoviral vectors, as many as 90% of the cells in these fresh tumour explants can be engineered to express high levels of the clinically relevant genes (GM-CSF or IL-2) within 1-2 weeks of surgery. Adenovirus-mediated gene delivery was reproducibly and significantly more efficient than retroviral transduction using the MFG-beta-Gal retroviral vector over the time-frame of importance for vaccination. Hence, combination of the animal model data with the ex vivo modification protocol suggests that vaccination of colorectal patients of the appropriate stage will be possible and effective. 相似文献
479.
CC Curtain MG Lowe IG Macreadie IR Gentle GA Lawrie AA Azad 《Canadian Metallurgical Quarterly》1998,14(17):1543-1551
We have found that the hemolytic and cytotoxic activities of myristoylated Nef N-terminal peptides require a net positive charge in the first seven amino residues of the sequence. The activities are considerably less dependent on the secondary structure of the peptides. Film balance studies showed that both active and inactive peptides interacted with neutral phospholipid monolayers, suggesting that binding to neutral lipids was not a sufficient condition for lytic activity. It was also found that nonmyristoylated N-terminal peptide did not interact to the same extent with the monolayer, indicating that myristoylation was essential for lipid interaction. It is considered that the positively charged residues of the proximate N terminus of Nef interact with acidic lipids of biological membranes, reinforcing the weak membrane-targeting properties of the myristyl chain. Parallels are drawn between this mode of interaction with membranes and that of members of the Src family of proteins, which are also myristoylated and have positively charged residues in their proximate N termini. In particular, these proteins and Nef also have serine residues in their proximal N-terminal regions, which when phosphorylated could neutralize the positive charge and thus provide a mechanism for modulating membrane interaction. 相似文献
480.
IR Marsden ML Allan RH Friend M Kurmoo D Kanazawa P Day G Bravic D Chasseau L Ducasse W Hayes 《Canadian Metallurgical Quarterly》1994,50(4):2118-2127