Factors Affecting Volterra Kernel Estimation: Emphasis on Lung Tissue Viscoelasticity

The goal of this study is to quantitatively investigate how the memory length, order of nonlinearity, type of input, and measurement noise can affect the identification of the Volterra kernels of a nonlinear viscoelastic system, and hence the inference on system structure. We explored these aspects with emphasis on nonlinear lung tissue mechanics around breathing frequencies, where the memory length issue can be critical and a ventilatory input is clinically demanded. We adopted and examined Korenberg's fast orthogonal algorithm since it is a least-squares technique that does not demand white Gaussian noise input and makes no presumptions on the kernel shape and system structure. We then propose a memory autosearch method, which incorporates Akaike's final production error criterion into Korenberg's fast orthogonal algorithm to identify the memory length simultaneously with the kernels. Finally, we designed a special ventilatory flow input and evaluated its potential for the kernel identification of the nonlinear systems requiring oscillatory forcing. We found that the long memory associated with soft tissue viscoelasticity may prohibit correct identification of the higher-order kernels of the lung. However, the key characteristics of the first-order kernel may be revealed through averaging over multiple experiments and estimations. © 1998 Biomedical Engineering Society. PAC98: 8745Bp, 8710+e, 8350Gd, 8380Lz     

实验性急性坏死性胰腺炎狗血液粘弹性改变

为研究血液流变学在急性出血性坏死性胰腺炎(AHNP)发病机理中的作用,将44条杂种狗分成5组。第Ⅰ、Ⅱ组分别为手术对照组和急性间质性胰胰炎组(两组各有8条狗)。第Ⅲ、Ⅳ、Ⅴ组狗的主管内注入牛磺胆酸钠溶液形成实验性急性出血性坏死性胰腺炎。而第Ⅳ、Ⅴ组分别用低分子右旋糖酐40(DX40)和丹参溶液静脉注入作为治疗。在所有5组中动脉血压和中心静脉压于手术前后均未见显著性改变。第Ⅲ、Ⅳ、Ⅴ组的血清淀粉酶和脂肪酶水平在实验性AHNP形成后明显增高。但在第Ⅳ、Ⅴ组用药物治疗后,此两酶水平迅速降低。用Low Shear-30流变测定仪测定血液流变学改变。所有5组血浆粘度在手术前、后无明显变化。第Ⅰ、Ⅱ组狗全血的红细胞压积(HCT),在0.512秒~(-1)和51.2秒~(-1)下的表观粘度(η0.512,η51.2),红细胞聚集指数(AI),复粘度的粘性分量(η′)和弹性分量(η″)、以及弹性模量(G′)在手术前后均无明显改变。然而,上述这些参数在实验性AHNP形成后的第Ⅲ、Ⅳ、Ⅴ组有明显增高。但在第Ⅳ和Ⅴ组用药物治疗后,这些参数持续下降;而且,第Ⅴ组丹参溶液比第Ⅳ组的DX40对于血液流变学改变有更好的改善作用。结果证明血液流变学异常是AHNP时引起胰腺微循环障碍的重要因素,并且血液流变学异常的纠正能改善出血性坏死性胰腺炎的症状。     

Endocytic proteins with prion-like domains form viscoelastic condensates that enable membrane remodeling

Membrane invagination and vesicle formation are key steps in endocytosis and cellular trafficking. Here, we show that endocytic coat proteins with prion-like domains (PLDs) form hemispherical puncta in the budding yeast, Saccharomyces cerevisiae. These puncta have the hallmarks of biomolecular condensates and organize proteins at the membrane for actin-dependent endocytosis. They also enable membrane remodeling to drive actin-independent endocytosis. The puncta, which we refer to as endocytic condensates, form and dissolve reversibly in response to changes in temperature and solution conditions. We find that endocytic condensates are organized around dynamic protein–protein interaction networks, which involve interactions among PLDs with high glutamine contents. The endocytic coat protein Sla1 is at the hub of the protein–protein interaction network. Using active rheology, we inferred the material properties of endocytic condensates. These experiments show that endocytic condensates are akin to viscoelastic materials. We use these characterizations to estimate the interfacial tension between endocytic condensates and their surroundings. We then adapt the physics of contact mechanics, specifically modifications of Hertz theory, to develop a quantitative framework for describing how interfacial tensions among condensates, the membrane, and the cytosol can deform the plasma membrane to enable actin-independent endocytosis.

Endocytosis in eukaryotic cells can occur via two separate mechanisms: actin-dependent and actin-independent pathways. In this study, we used the budding yeast Saccharomyces cerevisiae as a tractable model system to uncover the mechanistic basis for actin-independent endocytosis. This is directly relevant to the early stages of endocytic membrane invagination that occurs in mammalian cells through homologs of the proteins that we identify and study here in yeast (1, 2). In S. cerevisiae, membrane invagination that enables endocytosis is normally driven by growth of membrane-bound branched actin (3). A second actin-independent route to endocytosis is realized when intracellular turgor pressure is reduced. This reduction of turgor pressure alleviates the tension on plasma membranes that would normally oppose membrane invagination (1, 4). Although this actin-independent mechanism is not evident under laboratory conditions, it does occur at the hyperosmotic, high-sucrose concentrations that can be found in the wild when yeast grow on rotting fruit and under industrial fermentation conditions, particularly in the context of bioethanol production (1).In both mechanisms, endocytosis is initiated by the coordinated recruitment of a number of proteins associated with distinct stages of endocytic maturation (5). Clathrin heavy and light chains first interact with initiator proteins (Ede1 and Syp1) to form a lattice on the membrane. Subsequently, early coat proteins such as Sla1, Sla2, Ent1, Ent2, and Yap1801 (6) bind directly to the adaptor–clathrin lattice and form the cortical body (5). Electron microscopy data highlight the existence of hemispherical membraneless bodies around endocytic sites. These bodies are identifiable by following the localization of labeled endocytic coat proteins such as Sla1. The observed Sla1-labeled bodies are known to exclude ribosomes from regions that are near the cortical sites in the cytosol. Importantly, these endocytic bodies form even when actin is not polymerized, and the membrane is flat (7).Many of the coat proteins in bodies that form around endocytic sites include prion-like domains (PLDs). These are low-complexity intrinsically disordered domains that are enriched in polar amino acids such as glutamine, asparagine, glycine, and serine and are interspersed by aromatic residues (6, 8). Proteins with PLDs have the ability to drive the formation of membraneless biomolecular condensates through phase separation in cells (9) and in vitro (10). Condensates are mesoscale, nonstoichiometric macromolecular assemblies that concentrate biomolecules (11–13). Here, we show that endocytosis in S. cerevisiae involves the concentration of PLD-containing proteins, including the essential protein Sla1, within biomolecular condensates that form at cortical sites (14). Inferences from indirect measurements suggest that these condensates have viscoelastic properties and that they are scaffolded by a dense network of PLD-containing proteins. We show that condensate formation requires an intact PLD and the coat protein Sla1 is at the hub of the condensate-driving protein–protein interaction network. The distinctive compositional biases within PLDs of coat proteins contribute to condensate formation and function. We present a model, motivated by Hertz contact theory (15–17), to provide a plausible explanation for how interfacial tensions among condensates, the membrane, and the cytosol can enable membrane invagination and drive actin-independent endocytosis. This model shows that the formation of condensates and cohesiveness of molecular interactions within them are likely to be essential for mechanoactive processes associated with actin-independent endocytosis.     

Environmental effects on pulmonary mechanics and the response to inhaled methacholine

To investigate the role of environmental exposure from birth on airway and lung parenchymal responsiveness to inhaled methacholine (Mch), three litters of puppies (n = 14) were studied when 8–10 weeks of age. Two litters, one mongrel (n = 7) and one foxhound-beagle cross (n = 3), were born and raised in a clean animal house environment (clean mongrels and clean cross, respectively). Another litter of mongrels was born (n = 4) and raised in an external environment (external mongrels), exposed to normal rural environmental contaminants. Animals were studied open-chested with alveolar capsules used to partition mechanics into airway and parenchymal components. Lung mechanics were measured after abrupt flow interruptions. The animals born and raised in the external environment were significantly more responsive to inhaled Mch than those born and raised in the clean environment. This finding was true for both airway and parenchymal responsiveness. The group mean effective dose of Mch that produced a doubling of airway resistance (ED₂₀₀Raw) for the external mongrel group was 4.40 mg/ml compared with 19.44 mg/ml for the clean mongrel group and 16.34 mg/ml for the clean cross group (P < 0.02). The group mean effective dose of Mch that produced a doubling of pressure difference in airways after the initial rapid rise in airway pressure (ED₂₀₀Pdif) for the external mongrel group was 0.79 mg/ml compared with 3.90 mg/ml for the clean mongrel group and 10.78 mg/ml for the clean cross group (P < 0.01). Generalized linear modeling analysis showed that both “environment” and “breed” were significant factors in determining ED₂₀₀Pdif, but only “environment” significantly influenced ED₂₀₀Raw. In summary, the present study has demonstrated that the environment in which an animal is born and raised can influence lung mechanics and responsiveness to methacholine. This finding is particularly true for the lung parenchyma. Pediatr Pulmonol. 1998; 25:332–337. © 1998 Wiley-Liss, Inc.     

不同祖师麻提取物对后交联凝胶贴膏基质的性能影响

目的 以祖师麻Daphnes Giraldii Cortex不同体积分数乙醇渗漉流浸膏为药物模型,研究其对后交联凝胶基质黏弹性及释药性的影响。方法 结合黏附力测试、流变学指标、体外释放度试验及相关性分析,考察不同祖师麻提取物出膏率、软化点及pH值对后交联凝胶基质成型过程中关键流变学参数及贴膏释药性的影响。结果 当乙醇体积分数在75%～95%时,祖师麻提取物出膏率及pH值随乙醇体积分数的升高而显著降低,软化点则相反。出膏率主要通过影响基质的复合模量（G^*）及屈服应力（τ）值来影响贴膏内聚力及抗剪切能力,软化点和pH值主要通过影响基质G^*、τ、弹性模量（G′）、G值来影响贴膏的结构稳定性、抗剪切性、初黏力及剥离强度。体外释药结果显示,祖师麻甲素10 h内的累积释药率随提取物醇提体积分数的升高而增大,但提取物3个理化性质对释药率的影响并不显著。结论 不同祖师麻提取物对后交联基质的性能影响总体差异不大,通过检测基质相关的流变学指标可以有目的地对基质配方进行相应调整,从而进一步提高贴膏的成型质量和后交联基质的普遍适用性。     

兔盆底组织力学特性的实验研究

目的研究分娩与未分娩兔盆底组织的生物力学特性。方法以14只新西兰雌性大白兔盆底组织为拉伸试样，分娩与未分娩分组对照，用WDW4100微机控制电子万能实验机进行拉伸实验，测定其应力应变关系，蠕变和应力松弛特性。结果得到了闭孔内肌和孑子肌肌腱的极限强度、最大刚度、应力应变关系和粘弹性特征。结论分娩与未分娩兔盆底组织生物力学特性存在明显的差异，这对临床上研究人类盆底组织有一定的参考价值，有助于妇产泌尿科学的发展。     

血液粘弹性和触变性的数学表征：新型5参数时变性本构方程及其适应性研究

研究了新型５参数时变性本构方程表征血液粘弹性和触变性的适应性；分别探讨了各模型参数对表因液粘弹性和触变性的影响；     

Comparison of viscoelasticity between normal human sciatic nerve and amniotic membrane

Sciatic nerve tissue was obtained from the gluteus maximus muscle segment of normal human cadavers and amniotic membrane tissue was obtained from healthy human puerperant placentas.Both tissues were analyzed for their stress relaxation and creep properties to determine suitability for transplantation applications.Human amniotic membrane and sciatic nerve tissues had similar tendencies for stress relaxation and creep properties.The stress value of the amniotic membrane stress relaxation group decreased to a greater extent compared with the sciatic nerve stress relaxation group.Similarly,the stress value of the amniotic membrane creep group increased to a greater extent compared with the sciatic nerve creep group.The stress relaxation curve for human amniotic membrane and sciatic nerve showed a logarithm correlation,while the creep curve showed an exponential correlation.These data indicate that amniotic membrane tissue has better stress relaxation and creep properties compared with sciatic nerve tissue.     

润滑油抗泡机理的研究 Ⅰ.泡沫的流变行为及表面粘弹性能

从流体力学角度研究了泡沫膜的流变行为,并结合表面化学原理,指出抗泡剂需具有较高表面活性,才能在泡沫表面很好铺展、消泡。高度铺展的抗泡剂才能在泡沫表面形成不溶吸附层,从而改变液膜流变性质。抗泡剂表面活性不溶吸附层的存在,不仅影响泡沫的动力学稳定性,也对泡沫的表面膨胀弹性和表面膨胀粘度产生较大影响。泡沫膜表面膨胀弹性和表面膨胀粘度的降低,将使得泡沫在受到外界应力的作用下,易于形变、破裂。