Flexible modeling via a hybrid estimation scheme in generalized mixed models for longitudinal data

To circumvent the computational complexity of likelihood inference in generalized mixed models that assume linear or more general additive regression models of covariate effects, Laplace's approximations to multiple integrals in the likelihood have been commonly used without addressing the issue of adequacy of the approximations for individuals with sparse observations. In this article, we propose a hybrid estimation scheme to address this issue. The likelihoods for subjects with sparse observations use Monte Carlo approximations involving importance sampling, while Laplace's approximation is used for the likelihoods of other subjects that satisfy a certain diagnostic check on the adequacy of Laplace's approximation. Because of its computational tractability, the proposed approach allows flexible modeling of covariate effects by using regression splines and model selection procedures for knot and variable selection. Its computational and statistical advantages are illustrated by simulation and by application to longitudinal data from a fecundity study of fruit flies, for which overdispersion is modeled via a double exponential family.     

北京门头沟牛眼洞晚更新世哺乳动物化石

北京市门头沟牛眼洞产有豹、岩羊和纳呼尔绵羊等３种哺乳动物化石。其中豹化石尺 寸相当小,小于所有已知的化石记录,根据贝格曼法则以及与现代豹不同亚种的对比,表明它 应该是一种热带和亚热带的动物,这一发现指示当时的气候环境正处于间冰阶的暖期中。结 合整个哺乳动物化石的性质,说明其时代为晚更新世晚期。     

Osmotic properties of large unilamellar vesicles prepared by extrusion.

We have examined the morphology and osmotic properties of large unilamellar vesicles (LUVs) prepared by extrusion. Contrary to expectations, we observe by cryo-electron microscopy that such vesicles, under isoosmotic conditions, are non-spherical. This morphology appears to be a consequence of vesicle passage through the filter pores during preparation. As a result when such LUVs are placed in a hypoosmotic medium they are able to compensate, at least partially, for the resulting influx of water by "rounding up" and thereby increasing their volume with no change in surface area. The increase in vesicle trapped volume associated with these morphological changes was determined using the slowly membrane-permeable solute [3H]-glucose. This allowed calculation of the actual osmotic gradient experienced by the vesicle membrane for a given applied differential. When LUVs were exposed to osmotic differentials of sufficient magnitude lysis occurred with the extent of solute release being dependent on the size of the osmotic gradient. Surprisingly, lysis was not an all-or-nothing event, but instead a residual osmotic differential remained after lysis. This differential value was comparable in magnitude to the minimum osmotic differential required to trigger lysis. Further, by comparing the release of solutes of differing molecular weights (glucose and dextran) a lower limit of about 12 nm diameter can be set for the bilayer defect created during lysis. Finally, the maximum residual osmotic differentials were compared for LUVs varying in mean diameter from 90 to 340 nm. This comparison confirmed that these systems obey Laplace's Law relating vesicle diameter and lysis pressure. This analysis also yielded a value for the membrane tension at lysis of 40 dyn cm-1 at 23 degrees C, which is in reasonable agreement with previously published values for giant unilamellar vesicles.     

Remodeling of conduit arteries in hypertension and flow-overload obeys a minimum energy principle

Arterial remodeling is an important process in physiology and pathophysiology. Based on an energy minimization method, Murray's law predicts the optimal inner radius. Application of Darcy's law in the wall results in an optimal outer radius. The average wall stress is computed by the Laplace's law. Using these formulas, a large porcine coronary artery in hypertension is studied. The results reveal how wall thickness and average circumferential stress change after increasing blood pressure and volume flow rate. The theoretical predictions are in good qualitative agreement with experimental observations. The advantage and limitation of the current approach are discussed.     

Effect of conductivity interfaces in electrocardiography

This paper develops numerical techniques for two problems of interest in electrocardiography: (1) the determination of infinite-media surface potential gradients from boundedmedia torso potentials, and (2) the effects of lung-torso, blood mass-torso, and torso-air conductivity interfaces on torso surface potentials. This paper is an extension of a previous paper on the effects of conductivity interfaces which also utilized an integral equation formulation of Laplace's equation. Supported in part by USPHS Grants HE 05716 and HE 11307 and American Heart Grant 67-850.     

Interpretation of water desorption isotherms of lysozyme

The interrelationship between water desorption isotherms and the humidity dependences of the Young's modulus and volume strains of different lysozyme crystals and films has been analysed. The strain of protein samples is shown to be dependent on their elastic properties and to be induced by Laplace's pressure which can be calculated from the Thomson (Kelvin) relation. The energy of the mechanical deformation of protein samples expended for repacking and deformation of protein molecules considerably contributes to the integral change of free energy upon dehydration. Solid protein samples should be considered as deformable porous materials whose water sorption isotherms are determined not only by the number and properties of individual hydration centres but also by the macroscopic properties of protein solids.     

Left Ventricular Stresses in the Intact Human Heart

A set of stress differential equations of equilibrium is presented for a thick prolate spheroid which is the assumed shape for the left ventricle. An analysis for the stresses in the ventricular wall indicates that maximum stresses occur at the inner layers and decrease to a minimum at the epicardial surface, a result that is partially validated by experiment. Simple expressions are available for the evaluation of maximum stresses which occur at the equator and are suitable for small laboratory-oriented digital computers employed in the clinical evaluation of patient status. The surprising result is that Laplace's law yields practical values for mean stresses in thick-walled ventricles.     

Laplace's law and the alveolus: a misconception of anatomy and a misapplication of physics

Both the anatomy and the mechanics of inflation of the alveoli, as presented in most textbooks of physiology, have been misunderstood and misrepresented. The typical representation of the acinus as a "bunch of grapes" bears no resemblance to its real anatomy; the alveoli are not independent little balloons. Because of the prevalence of this misconception, Laplace's law, as it applies to spheres, has been invoked as a mechanical model for the forces of alveolar inflation and as an explanation for the necessity of pulmonary surfactant in the alveolus. Alveoli are prismatic or polygonal in shape, i.e., their walls are flat, and Laplace law considerations in their inflation apply only to the very small curved region in the fluid where these walls intersect. Alveoli do not readily collapse into one another because they are suspended in a matrix of connective tissue "cables" and share common, often perforated walls, so there can be no pressure differential across them. Surfactant has important functions along planar surfaces of the alveolar wall and in mitigating the forces that tend to close the small airways. Laplace's law as it applies to cylinders is an important feature of the mechanics of airway collapse, but the law as it applies to spheres is not relevant to the individual alveolus.     

A calculation of the magnetic field of a nerve action potential.

The magnetic field outside an isolated axon is calculated using transmembrane potential data to specify the boundary conditions to a solution of Laplace's equation. It is shown that the contribution to the magnetic field from the current inside the membrane is two orders of magnitude larger than that from the external current. The contribution from current within the membrane is negligible. Comparisons are made between waveforms calculated for a crayfish lateral axon and those measured for a frog sciatic nerve. This calculation suggests that the magnetic field measured outside nerves can be used to determine their internal current without puncturing the nerve membrane.     

Stresses in the closed mitral valve: a model study

In the present model study on the closed mitral valve, tensile force in the chordae tendineae is related to transvalvular pressure using a mathematical model of mechanics of the closed mitral valve. Circumferential stress as well as bending stress in the valve leaflets were neglected. Without precisely knowing the mechanical properties of the leaflet material, geometry of the leaflets was estimated by applying Laplace's law, which relates leaflet stress to leaflet curvature. Independent of shape of the mitral valve orifice, under all circumstances tensile force in the chordae tendineae was calculated to be equal or greater than half the force exerted on the mitral valve orifice by the transvalvular pressure.     

Measurements of transmitter action: the problem of voltage dependence

Conventional intracellular recordings, from central mammalian neurones, are used to assess the actions of putative transmitters on neuronal membrane parameters such as input conductance and to determine reversal potentials. Ohm's Law and constant current methods can be employed to accurately assess such parameters provided the putative transmitter activates a voltage-independent response. However, several likely transmitter candidates act via voltage-dependent mechanisms to alter neuronal excitability; as a consequence, results from this method of analysis must be cautiously interpreted. Under this constraint of possible voltage dependence, constant current methods can lead to spurious conclusions about the physiological and pharmacological characterization of the response.     

Structural color production by constructive reflection from ordered collagen arrays in a bird (Philepitta castanea: Eurylaimidae)

Ordered hexagonal arrays of parallel collagen fibers produce the brilliant green structural color of the fleshy, supraorbital caruncles of male Velvet Asity (Philepitta castanea; Aves: Eurylaimidae). The collagen arrays are organized in larger macrofibrils that are packed irregularly within cone-shaped papillae that cover the surface of the caruncle. The color of the caruncle conforms closely to the wavelengths predicted by applying Bragg's Law of constructive reflection to measurements of the size and spatial organization of the collagen arrays. These observations constitute a novel mechanism of structural color production in animals. These collagen arrays are convergently similar to the smaller, highly structured collagen arrays in the mammalian cornea, which exploit the same physical mechanism to produce optical transparency. © 1994 Wiley-Liss, Inc.     

Location of the motor unit electrical axis and determination of the muscle anisotropy ratio

A method to localize the electrical axis of a motor unit (MU) and to simultaneously determine the anisotropy ratio (the ratio between the transverse and the longitudinal extracellular conductivity) of the muscle is proposed. The method is based on the use of Laplace's equation. Particular attention is paid to the theoretical consideration of an asymmetric MU. The method is tested utilizing simulation data on the extracellular potentials of a MU in which the propagation of two depolarized zones along a participant muscle fiber is accounted for. It is shown that the method is reliable and the calculation accurate mostly for the moments of time associated with small changes in the MU potential.     

中国木兰科各属次生木质部的解剖特征及系统演化

综述了中国木兰科10属的次生木质部解剖学特征,包括导管分子,纤维管胞和木射线。同时,进一步讨论了其系统演化。这10属分为两亚科,即:木兰亚科(Magnoliodeae),包括木兰族(Magnolieae)和含笑族(Michelieae Law),木兰族有木莲属(Maglietia Bl.)、华盖木属(Manglietiastrum Law)、木兰属(Magnolia L.)、拟单性木兰属(Parakmeria Hu et Cheng)、单性木兰属[Kmeria(Pierre) Dandy]、长蕊木兰属(Alcimandra Dandy)共六属;含笑族有含笑属(Michelia L.)、合果木属(Paramichelia Hu)、观光木属(Tsoongiodendron Chun)共三属。鹅掌楸亚科[Liriodendroideae(Bark) Law],仅鹅掌楸属(Liriodendron L.)一属。大量的木材解剖学研究表明,木兰科的原始性很明显,但也有一些进化特征。可以通过属间的差别来分析本科的系统演化。木兰科的系统演化可简单总结为:木兰亚科[木兰族(木莲属,华盖木属,拟单性木兰属,单性木兰属→木兰属,长蕊木兰属)→含笑族]→鹅掌楸亚科。     

Membrane potential induced by external electric field pulses can be followed with a potentiometric dye.

A potential-sensitive dye was recently used to measure the spatial variation in the membrane potential induced by an externally applied electric field. In this work, we demonstrate that the time course of these induced potentials can also be followed. Two experimental systems were explored. Dye fluorescence from HeLa cells could be modulated by a train of field pulses; the relative fluorescence change measured with a lock-in amplifier was linear with the field and similar to the fluorescence responses obtained in the static measurements. A model membrane system consisting of a hemispherical bilayer allowed convenient measurement of the dye absorbance change as a function of the bathing solution conductivity. The charging time of the membrane was inversely related to the aqueous conductance as predicted by the theoretical solution to Laplace's equation.     

以国家公园为主体的自然保护地体系立法思考

实现十九大报告提出的建立以国家公园为主体的自然保护地体系的改革目标需要法治保障。建设自然保护地体系涉及的不同生态系统和多个管理部门、多方利益主体, 是一个巨大的复杂系统, 需要进行整体性、系统性的立法研究。目前, 国家正在推进国家公园体制改革并已将《国家公园法》列入十三届全国人大常委会立法计划。更需要我们从自然保护地立法体系建设的高度, 正确处理《国家公园法》与未来可能制定的《自然保护地法》的关系, 在《国家公园法》制定过程中为今后出台《自然保护地法》预留空间, 并建立相应的衔接机制, 统筹谋划并协同推进国家公园法与自然保护地立法。     

Book Reviews

Book reviewed in this article:
Ethnology: A Chief is a Chief by the People: The Autobiography of Stimela Jason Jingoes. Stimela Jason Jingoes .
Ethnology: Family Law and Litigation in Basotho Society. Sebastian Poulter .
Ethnology: Chieftainship and Legitimacy: An Anthropological Study of Executive Law in Lesotho. Ian Hamnett .     

Prediction of internal pressure profile of compression bandages using stress relaxation parameters

The efficacy of compression therapy using compression bandages is highly dependent on the level of compression applied and the sustenance of the pressure during the course of treatment. This study attempts to predict the pressure profile generated by compression bandages using constitutive equations describing relaxation behavior of viscoelastic materials. It is observed that this pressure profile is highly correlated with the stress relaxation behavior of the bandage. To model the pressure profile, the stress relaxation behavior of compression bandages was studied and modeled using three mechanical models: the Maxwell model, the standard linear solid model and the two-component Maxwell model with a nonlinear spring. It was observed that the models with more component values explained the experimental relaxation curves better. The parameters used for modelling relaxation behavior were used to describe the pressure profile, which is significantly dependent on the longitudinal stress relaxation behavior of the bandage, using the modified Laplace's law equation. This approach thus helps in evaluating the bandage performance with time during compression therapy as novel wound care management.     

Analysis of the effect of medium and membrane conductance on the amplitude and kinetics of membrane potentials induced by externally applied electric fields.

The kinetics and amplitudes of membrane potential induced by externally applied electric field pulses are determined for a spherical lipid bilayer using a voltage-sensitive dye. Several experimental parameters were systematically varied. These included the incorporation of gramicidin into the membrane to alter its conductivity and the variation of the external electrolyte conductivity via changes in salt concentration. The ability of the solution to Laplace's equation for a spherical dielectric shell to quantitatively describe the membrane potential induced on a lipid bilayer could thus be critically evaluated. Both the amplitude and the kinetics of the induced potential were consistent with the predictions of this simple model, even at the extremes of membrane conductance or electrolyte concentration. The success of the experimental approach for this system encourages its application to more complex problems such as electroporation and the influences of external electric fields in growth and development.