A theoretically-based experimental approach for identifying vascular constitutive relations

We employ a structurally-motivated phenomenological formulation to identify biomechanical experiments which can be used to determine a vascular constitutive relation directly from data. Large deformations, nonlinear material behavior, load-dependent anisotropy, material heterogeneity and incompressibility are accounted for in the analysis. For purposes of illustration, we outline a procedure for studying elastic arteries wherein the behavior of the media and adventitia is considered separately. This general approach for identifying vascular constitutive relations can be applied to any vessel or airway, however, and should provide certain advantages over previous microstructural or purely phenomenological formulations.     

Quantification of the mechanical behavior of carotid arteries from wild-type, dystrophin-deficient, and sarcoglycan-delta knockout mice

As patients with muscular dystrophy live longer because of improved clinical care, they will become increasingly susceptible to many of the cardiovascular diseases that affect the general population. There is, therefore, a pressing need to better understand both the biology and the mechanics of the arterial wall in these patients. In this paper, we use nonlinear constitutive relations to model, for the first time, the biaxial mechanical behavior of carotid arteries from two common mouse models of muscular dystrophy (dystrophin-deficient and sarcoglycan-delta null) and wild-type controls. It is shown that a structurally motivated four-fiber family stress-strain relation describes the passive behavior of all three genotypes better than does a commonly used phenomenological exponential model, and that a Rachev-Hayashi model describes the mechanical contribution of smooth muscle contraction under basal tone. Because structurally motivated constitutive relations can be extended easily to model adaptations to altered hemodynamics, results from this study represent an important step toward the ultimate goal of understanding better the mechanobiology and pathophysiology of arteries in muscular dystrophy.     

Homology in classical and molecular biology

Hypotheses of homology are the basis of comparative morphology and comparative molecular biology. The kinds of homologous and nonhomologous relations in classical and molecular biology are explored through the three tests that may be applied to a hypothesis of homology: congruence, conjunction, and similarity. The same three tests apply in molecular comparisons and in morphology, and in each field they differentiate eight kinds of relation. These various relations are discussed and compared. The unit or standard of comparison differs in morphology and in molecular biology; in morphology it is the adult or life cycle, but with molecules it is the haploid genome. In morphology the congruence test is decisive in separating homology and nonhomology, whereas with molecular sequence data similarity is the decisive test. Consequences of this difference are that the boundary between homology and nonhomology is not the same in molecular biology as in morphology, that homology and synapomorphy can be equated in morphology but not in all molecular comparisons, and that there is no detected molecular equivalent of convergence. Since molecular homology may reflect either species phylogeny or gene phylogeny, there are more kinds of homologous relation between molecular sequences than in morphology. The terms paraxenology and plerology are proposed for two of these kinds--respectively, the consequence of multiple xenology and of gene conversion.     

Arterial intima-media thickness: site-specific associations with HRT and habitual exercise

We determined the site-specific relations of hormone replacement therapy (HRT) and habitual exercise status with intima-media thickness (IMT) in both elastic (carotid) and muscular (femoral) arteries in 77 healthy postmenopausal women: 43 women were sedentary (20 no-HRT and 23 HRT users) and 34 women were endurance trained (14 no-HRT and 20 HRT users). Femoral IMT was not different among the sedentary HRT and endurance-trained no-HRT and HRT groups, but was lower (P < 0.005) in these three groups than in the sedentary no-HRT women. There were no significant group differences in carotid IMT. However, in older women (> or =65 yrs) carotid IMT was smaller (P < 0.05) in HRT compared with no-HRT women. We conclude that both endurance training and HRT status are independently associated with a smaller IMT and these effects are evident primarily in muscular arteries. These results suggest that HRT and habitual exercise may protect postmenopausal women against cardiovascular disease through influences on IMT. The site-specific relations may be due to a greater number of smooth muscle cells and plasticity of muscular arteries compared with elastic arteries and/or differences in heterogeneous influences such as metabolic requirements and hydrostatic pressures.     

Elastic properties of arteries and their influence on the cardiovascular system

Pressure-volume relations of aorta and arteries are considered using a fiber-fluid continuum analysis. A Windkessel model is revised to investigate the effects of the exponential pressure-volume relation of the present study on the cardiovascular system. It is shown that the elastic properties of the fibers in large blood vessels play an important role in the circulation of blood in health and in disease.     

Homo-FRET Imaging Enables Quantification of Protein Cluster Sizes with Subcellular Resolution

Fluorescence-anisotropy-based homo-FRET detection methods can be employed to study clustering of identical proteins in cells. Here, the potential of fluorescence anisotropy microscopy for the quantitative imaging of protein clusters with subcellular resolution is investigated. Steady-state and time-resolved anisotropy detection and both one- and two-photon excitation methods are compared. The methods are evaluated on cells expressing green fluorescent protein (GFP) constructs that contain one or two FK506-binding proteins. This makes it possible to control dimerization and oligomerization of the constructs and yields the experimental relation between anisotropy and cluster size. The results show that, independent of the experimental method, the commonly made assumption of complete depolarization after a single energy transfer step is not valid here. This is due to a nonrandom relative orientation of the fluorescent proteins. Our experiments show that this relative orientation is restricted by interactions between the GFP barrels. We describe how the experimental relation between anisotropy and cluster size can be employed in quantitative cluster size imaging experiments of other GFP fusions. Experiments on glycosylphosphatidylinisotol (GPI)-anchored proteins reveal that GPI forms clusters with an average size of more than two subunits. For epidermal growth factor receptor (EGFR), we observe that ∼40% of the unstimulated receptors are present in the plasma membrane as preexisting dimers. Both examples reveal subcellular heterogeneities in cluster size and distribution.     

Orthogonal Invariant Sets of the Diffusion Tensor and the Development of a Curvilinear Set Suitable for Low-Anisotropy Tissues

We develop a curvilinear invariant set of the diffusion tensor which may be applied to Diffusion Tensor Imaging measurements on tissues and porous media. This new set is an alternative to the more common invariants such as fractional anisotropy and the diffusion mode. The alternative invariant set possesses a different structure to the other known invariant sets; the second and third members of the curvilinear set measure the degree of orthotropy and oblateness/prolateness, respectively. The proposed advantage of these invariants is that they may work well in situations of low diffusion anisotropy and isotropy, as is often observed in tissues such as cartilage. We also explore the other orthogonal invariant sets in terms of their geometry in relation to eigenvalue space; a cylindrical set, a spherical set (including fractional anisotropy and the mode), and a log-Euclidean set. These three sets have a common structure. The first invariant measures the magnitude of the diffusion, the second and third invariants capture aspects of the anisotropy; the magnitude of the anisotropy and the shape of the diffusion ellipsoid (the manner in which the anisotropy is realised). We also show a simple method to prove the orthogonality of the invariants within a set.     

A comparison of normalization methods for high density oligonucleotide array data based on variance and bias

MOTIVATION: When running experiments that involve multiple high density oligonucleotide arrays, it is important to remove sources of variation between arrays of non-biological origin. Normalization is a process for reducing this variation. It is common to see non-linear relations between arrays and the standard normalization provided by Affymetrix does not perform well in these situations. RESULTS: We present three methods of performing normalization at the probe intensity level. These methods are called complete data methods because they make use of data from all arrays in an experiment to form the normalizing relation. These algorithms are compared to two methods that make use of a baseline array: a one number scaling based algorithm and a method that uses a non-linear normalizing relation by comparing the variability and bias of an expression measure. Two publicly available datasets are used to carry out the comparisons. The simplest and quickest complete data method is found to perform favorably. AVAILABILITY: Software implementing all three of the complete data normalization methods is available as part of the R package Affy, which is a part of the Bioconductor project http://www.bioconductor.org. SUPPLEMENTARY INFORMATION: Additional figures may be found at http://www.stat.berkeley.edu/~bolstad/normalize/index.html     

Response-reinforcer relations and resistance to change

Behavioral momentum theory suggests that the relation between a response and a reinforcer (i.e., response-reinforcer relation) governs response rates and the relation between a stimulus and a reinforcer (i.e., stimulus-reinforcer relation) governs resistance to change. The present experiments compared the effects degrading response-reinforcer relations with response-independent or delayed reinforcers on resistance to change in conditions with equal stimulus-reinforcer relations. In Experiment 1, pigeons responded on equal variable-interval schedules of immediate reinforcement in three components of a multiple schedule. Additional response-independent reinforcers were available in one component and additional delayed reinforcers were available in another component. The results showed that resistance to disruption was greater in the components with added reinforcers than without them (i.e., better stimulus-reinforcer relations), but did not differ for the components with added response-independent and delayed reinforcement. In Experiment 2, a component presenting immediate reinforcement alternated with either a component that arranged equal rates of reinforcement with a proportion of those reinforcers being response independent or a component with a proportion of the reinforcers being delayed. Results showed that resistance to disruption tended to be either similar across components or slightly lower when response-reinforcer relations were degraded with either response-independent or delayed reinforcers. These findings suggest that degrading response-reinforcer relations can impact resistance to change, but that impact does not depend on the specific method and is small relative to the effects of the stimulus-reinforcer relation.     

Role of elastin anisotropy in structural strain energy functions of arterial tissue

The vascular wall exhibits nonlinear anisotropic mechanical properties. The identification of a strain energy function (SEF) is the preferred method to describe its complex nonlinear elastic properties. Earlier constituent-based SEF models, where elastin is modeled as an isotropic material, failed in describing accurately the tissue response to inflation–extension loading. We hypothesized that these shortcomings are partly due to unaccounted anisotropic properties of elastin. We performed inflation–extension tests on common carotid of rabbits before and after enzymatic degradation of elastin and applied constituent-based SEFs, with both an isotropic and an anisotropic elastin part, on the experimental data. We used transmission electron microscopy (TEM) and serial block-face scanning electron microscopy (SBFSEM) to provide direct structural evidence of the assumed anisotropy. In intact arteries, the SEF including anisotropic elastin with one family of fibers in the circumferential direction fitted better the inflation–extension data than the isotropic SEF. This was supported by TEM and SBFSEM imaging, which showed interlamellar elastin fibers in the circumferential direction. In elastin-degraded arteries, both SEFs succeeded equally well in predicting anisotropic wall behavior. In elastase-treated arteries fitted with the anisotropic SEF for elastin, collagen engaged later than in intact arteries. We conclude that constituent-based models with an anisotropic elastin part characterize more accurately the mechanical properties of the arterial wall when compared to models with simply an isotropic elastin. Microstructural imaging based on electron microscopy techniques provided evidence for elastin anisotropy. Finally, the model suggests a later and less abrupt collagen engagement after elastase treatment.     

A three-dimensional muscle model: a quantified relation between form and function of skeletal muscles

A three-dimensional muscle model with complex geometry is described and tested against experimental data. Using this model, several muscles were constructed. These muscles have equal optimum length but differ in architecture. The force exerted by the constructed muscles, in relation to their actual length and velocity of shortening, is discussed. Generally speaking, the constructed muscles with considerable pennation have great fiber angles, a great physiological cross section, a narrow active and steep passive length-force relation, and a low maximal velocity of shortening. The maximal power (force times velocity) delivered by the constructed muscles is shown to be almost independent of the architecture of the muscles. The steepness of the passive length-force relation is determined mainly by the shortest fibers within the group of constructed muscles, whereas maximal velocity of shortening and the width of the active length-force relation are determined mainly by the longest fibers. The validity of the three-dimensional muscle model with respect to some morphological and functional characteristics is tested. Length-force relations of constructed muscles are compared with the actual length-force relations of mm. gastrocnemii mediales and mm. semimembranosi of male Wistar rats. Moreover, actual fiber angle, fiber length, and muscle thickness of three mm. gastrocnemii mediales are compared with values found for constructed muscles. It is concluded that the three-dimensional muscle model closely approximates the actual muscle form and function.     

A Note on the Derivation of Epidemic Final Sizes

Final size relations are known for many epidemic models. The derivations are often tedious and difficult, involving indirect methods to solve a system of integro-differential equations. Often when the details of the disease or population change, the final size relation does not. An alternate approach to deriving final sizes has been suggested. This approach directly considers the underlying stochastic process of the epidemic rather than the approximating deterministic equations and gives insight into why the relations hold. It has not been widely used. We suspect that this is because it appears to be less rigorous. In this article, we investigate this approach more fully and show that under very weak assumptions (which are satisfied in all conditions we are aware of for which final size relations exist) it can be made rigorous. In particular, the assumptions must hold whenever integro-differential equations exist, but they may also hold in cases without such equations. Thus, the use of integro-differential equations to find a final size relation is unnecessary and a simpler, more general method can be applied.     

The variability of the circulus arteriosus (Willisii): order or anarchy?

The variation of the circulus arteriosus is studied using multivariate methods. The data which form the basis of this study are 19 measurements of half the circumference of the arteries that form the circle of Willis and its afferent and efferent branches; 100 circles of Willis were measured for this purpose. Since the number of variables per individual is large, multivariate statistical techniques are the most appropriate method to gain insight in the relations of vessel sizes that exist within the circle of Willis. So a principal component analysis was performed on the data. The results clearly show a number of relations between vessel sizes. In general, inverse relationships were found of vessels that have (at least partially) an identical irrigation area: both internal carotid arteries and the ipsilateral posterior communicating artery show an intimate relationship and are together inversely related to the basilar artery and the precommunicating part of the posterior cerebral artery. Inverse relationships are also found for both vertebral arteries and both precommunicating parts of the anterior cerebral arteries. The homonymous efferent arteries appear to be closely related and show an independent variation. Together the first six principal components explain 69% of the variance. These results support a haemodynamical hypothesis on the explanation of the variability of the circle of Willis. Moreover, the differential growth in the head-neck region during the first two decades of life is postulated to be the origin of a part of the variation.     

Who Owns the Water? The Relation as Unfinished Objectivation in the Mapuche Lived World

Anthropological approaches to relations have customarily relied on ethnographic accounts of relations empirically observed through fieldwork, overlooking, in general, the ways in which the very notion of relation is locally conceptualised and put into practice. In this article, we provide a general characterisation of how relations are theorised and practiced in indigenous southern Chile. We propose the expression ‘unfinished objectivation’ to refer to an ideal type of relationship in the Mapuche lived world, which corresponds neither to a subject–object dichotomy nor to a totally intersubjective model. Unfinished objectivation presupposes a type of relation in which those entities that are connected are submitted to the force of one another, but only to the unstable and contingent point before which they lose their irreducible autonomy and agency. To explore the model of unfinished objectivation we focus on the human–water relationship, which illustrates the tension between the need for objectivation, as well as recognition of the subjectivity of beings involved in the relationship. Nowhere is this tension clearer than in conflicts over water rights and ownership status, which have arisen from the commodification of water resources in neoliberal Chile.     

Microanatomy of the heart and associated structures of two scorpions,Centruroides sculpturatus ewing and Uroctonus mordax thorell

Spiroid orientation of the circumferential heart wall muscles is described for Centruroides sculpturatus Ewing. This muscle arrangement accounts for differences in ostial position when the heart of this species is compared to that of Uroctonus mordax Thorell. Other differences, such as number of lateral arteries present, cannot be explained on the basis of circumferential muscle orientation. The histology of the heart and associated vessels, but not the supraneural vessel, was found to be similar in both species. The lateral, posterior, communicating and sternal arteries all possess a muscularis composed of irregularly spaced, apparently branched, striated muscle fibers. External to this is a covering of connective tissue. The lumina of these arteries, the aorta, and the supraneural vessel are lined with a homogeneous, PAS-positive membrane. This membrane is also seen in blood vessels which penetrate the nervous system. It was not observed in vessels accompanying major nerves. Findings are compared to those of other authors. Differences in the structure of the hearts of these two species are discussed in relation to the microanatomy of other arachnid hearts.     

An experimental analysis of a mother-daughter rank reversal in Japanese macaques (Macaca fuscata)

This paper describes in detail how a 2.5-year-old female belonging to the second-ranking family in a captive group of three families managed to outrank her healthy, three-times heavier mother with the aid of the two immature daughters of the alpha female who was not herself directly involved. After the outranking was completed, the two active allies were removed. This had no effect on the rank relation between the female and her daughter. It is only after the mother of the two allies was removed (in addition to her daughters) that the mother recovered her rank above her daughter. This case study and the few other reported cases of changes in rank among females are discussed in relation to the issue of the stability of rank relations in hierarchical systems where rank is socially inherited rather than based solely on dyadic power contests. On the basis of this combined evidence, it appears that when attempting to rise in rank, females do not challenge dominants by allying with subordinates, but that they rather ally with an individual ranking above the target. This phenomenon, together with the fact that support is given to other females downwards the hierarchy, might explain the stability of female dominance relations and be the manifestation of an Evolutionarily Stable Strategy.     

Differential passive and active biaxial mechanical behaviors of muscular and elastic arteries: basilar versus common carotid

Cerebrovascular disease continues to be responsible for significant morbidity and mortality. There is, therefore, a pressing need to understand better the biomechanics of both intracranial arteries and the extracranial arteries that feed these vessels. We used a validated four-fiber family constitutive relation to model passive biaxial stress-stretch behaviors of basilar and common carotid arteries and we developed a new relation to model their active biaxial responses. These data and constitutive relations allow the first full comparison of circumferential and axial biomechanical behaviors between a muscular (basilar) and an elastic (carotid) artery from the same species. Our active model describes the responses by both types of vessels to four doses of the vasoconstrictor endothelin-1 (10(-10)M, 10(-9)M, 10(-8)M, and 10(-7)M) and predicts levels of smooth muscle cell activation associated with basal tone under specific in vitro testing conditions. These results advance our understanding of the biomechanics of intracranial and extracranial arteries, which is needed to understand better their differential responses to similar perturbations in hemodynamic loading.     

A volumetric model for growth of arterial walls with arbitrary geometry and loads

Stress and deformation in arterial wall tissue are factors which may influence significantly its response and evolution. In this work we develop models based on nonlinear elasticity and finite element numerical solutions for the mechanical behaviour and the remodelling of the soft tissue of arteries, including anisotropy induced by the presence of collagen fibres. Remodelling and growth in particular constitute important features in order to interpret stenosis and atherosclerosis. The main object of this work is to model accurately volumetric growth, induced by fluid shear stress in the intima and local wall stress in arteries with patient-specific geometry and loads. The model is implemented in a nonlinear finite element setting which may be applied to realistic 3D geometries obtained from in vivo measurements. The capabilities of this method are demonstrated in several examples. Firstly a stenotic process on an idealised geometry induced by a non-uniform shear stress distribution is considered. Following the growth of a right coronary artery from an in vivo reconstructed geometry is presented. Finally, experimental measurements for growth under hypertension for rat carotid arteries are modelled.     

A model for the nonlinear elastic response of large arteries

The nonlinear elastic response of large arteries subjected to finite deformations due to action of biaxial principal stresses, is described by simple constitutive equations. Generalized measures of strain and stress are introduced to account for material nonlinearity. This also ensures the existence of a strain energy density function. The orthotropic elastic response is described via quasi-linear relations between strains and stresses. One nonlinear parameter which defines the measures of strain and stress, and three elastic moduli are assumed to be constants. The lateral strain parameters (equivalent to Poisson's ratios in infinitesimal deformations) are deformation dependent. This dependence is defined by empirical relations developed via the incompressibility condition, and by the introduction of a fifth material parameter. The resulting constitutive model compares well with biaxial experimental data of canine carotid arteries.     

Enhancing biomedical text summarization using semantic relation extraction

Automatic text summarization for a biomedical concept can help researchers to get the key points of a certain topic from large amount of biomedical literature efficiently. In this paper, we present a method for generating text summary for a given biomedical concept, e.g., H1N1 disease, from multiple documents based on semantic relation extraction. Our approach includes three stages: 1) We extract semantic relations in each sentence using the semantic knowledge representation tool SemRep. 2) We develop a relation-level retrieval method to select the relations most relevant to each query concept and visualize them in a graphic representation. 3) For relations in the relevant set, we extract informative sentences that can interpret them from the document collection to generate text summary using an information retrieval based method. Our major focus in this work is to investigate the contribution of semantic relation extraction to the task of biomedical text summarization. The experimental results on summarization for a set of diseases show that the introduction of semantic knowledge improves the performance and our results are better than the MEAD system, a well-known tool for text summarization.