1964: The first model for the shape of a transfer RNA molecule. An account of an unpublished small-angle X-ray scattering study

The shape of non-fractionated Escherichia coli transfer RNA molecules in solution was investigated using small-angle X-ray scattering during the years 1960-1962 at the Centre de Recherche sur les Macromolécules in Strasbourg. The innermost region of the scattering curve yielded the average molecular weight (Mr) and the radius of gyration (Rg) of the particles, whereas the experimental data at large angles could be approximated at best by the scattering curve of a kinked rod-shaped molecule. The simplest model that was compatible with Mr, Rg, and the mass per unit length of the rod was a boomerang-shaped particle made of two double helical stems connected by a sharp kink. This model that eventually proved similar to the high-resolution L-shaped structure, was presented in my Ph.D. dissertation (J. Witz, Etude de la structure de quelques polynucléotides en solution par diffusion centrale des rayons X, Ph.D. dissertation, University of Strasbourg, France, 1964) but has never been published in detail. It is the purpose of this note to recall this story.     

Matrix decomposition model for investigating prehistoric intracemetery biological variation

A matrix decomposition model for analyzing prehistoric intracemetery biological variability is presented. The model, based on the correlation between interindividual biological and burial distance matrices, provides an estimate of the number of distinct burial populations interred within a single cemetery, which effectively ameliorates identifiability problems typical of general variability analyses (Raemsch [1995] Ph.D. dissertation, SUNY at Albany). Unlike other methods for analyzing intrasite variability analysis (e.g., kinship analysis and microchronology), this method is not reliant on a priori subgroup definition. Assuming a kin-structured burial pattern, a residual matrix is defined based on the raw data matrices; the proportion of negative or zero residuals to the total number of residuals provides an estimate of the number of hidden subgroupings (lineages) within the cemetery. The comparative utility of the model is demonstrated on a series of protohistoric and historic period skeletal samples from the Georgia coast, where it demonstrated that the increase in phenotypic variability during the early mission period is the result of population aggregation at the missions and not necessarily genetic admixture between local and nonlocal groups.     

Confocal arthroscopy-based patient-specific constitutive models of cartilaginous tissues—II: prediction of reaction force history of meniscal cartilage specimens

The theoretical framework developed in a companion paper (Part I) is used to derive estimates of mechanical response of two meniscal cartilage specimens. The previously developed framework consisted of a constitutive model capable of incorporating confocal image-derived tissue microstructural data. In the present paper (Part II) fibre and matrix constitutive parameters are first estimated from mechanical testing of a batch of specimens similar to, but independent from those under consideration. Image analysis techniques which allow estimation of tissue microstructural parameters form confocal images are presented. The constitutive model and image-derived structural parameters are then used to predict the reaction force history of the two meniscal specimens subjected to partially confined compression. The predictions are made on the basis of the specimens' individual structural condition as assessed by confocal microscopy and involve no tuning of material parameters. Although the model does not reproduce all features of the experimental curves, as an unfitted estimate of mechanical response the prediction is quite accurate. In light of the obtained results it is judged that more general non-invasive estimation of tissue mechanical properties is possible using the developed framework.     

Confocal arthroscopy-based patient-specific constitutive models of cartilaginous tissues - II: prediction of reaction force history of meniscal cartilage specimens

The theoretical framework developed in a companion paper (Part I) is used to derive estimates of mechanical response of two meniscal cartilage specimens. The previously developed framework consisted of a constitutive model capable of incorporating confocal image-derived tissue microstructural data. In the present paper (Part II) fibre and matrix constitutive parameters are first estimated from mechanical testing of a batch of specimens similar to, but independent from those under consideration. Image analysis techniques which allow estimation of tissue microstructural parameters form confocal images are presented. The constitutive model and image-derived structural parameters are then used to predict the reaction force history of the two meniscal specimens subjected to partially confined compression. The predictions are made on the basis of the specimens' individual structural condition as assessed by confocal microscopy and involve no tuning of material parameters. Although the model does not reproduce all features of the experimental curves, as an unfitted estimate of mechanical response the prediction is quite accurate. In light of the obtained results it is judged that more general non-invasive estimation of tissue mechanical properties is possible using the developed framework.     

Ultrastructural,cytochemical, and enzymatic studies on the adhesive “plaques” of the brown algaeLaminaria saccharina (L.) lamour. andNereocystis luetkeana (nert.) post. et rupr. 1

Summary Newly settled zoospores of bothLaminaria saccharina andNereocystis luetkeana are surrounded by adhesive plaques. At this stage cell wall deposition has not occurred and similar structures cannot be detected in the cytoplasm. In free swimming zoospores, however, plaques are observed exclusively in small vesicles within the cytoplasm. Enzymatic extractions and cytochemical tests indicate that plaques are glycoproteid in nature. Studies on the influence of several enzymes on the attachment of zoospores show that plaques are involved in the adhesion of zoospores to the substratum.Project supported by NRC grant #A2288. Nereocystis data are part of a Ph.D. dissertation presented by this author to the University of British Columbia.     

Identifying a minimal rheological configuration: a tool for effective and efficient constitutive modeling of soft tissues

We describe a modeling methodology intended as a preliminary step in the identification of appropriate constitutive frameworks for the time-dependent response of biological tissues. The modeling approach comprises a customizable rheological network of viscous and elastic elements governed by user-defined 1D constitutive relationships. The model parameters are identified by iterative nonlinear optimization, minimizing the error between experimental and model-predicted structural (load-displacement) tissue response under a specific mode of deformation. We demonstrate the use of this methodology by determining the minimal rheological arrangement, constitutive relationships, and model parameters for the structural response of various soft tissues, including ex vivo perfused porcine liver in indentation, ex vivo porcine brain cortical tissue in indentation, and ex vivo human cervical tissue in unconfined compression. Our results indicate that the identified rheological configurations provide good agreement with experimental data, including multiple constant strain rate load/unload tests and stress relaxation tests. Our experience suggests that the described modeling framework is an efficient tool for exploring a wide array of constitutive relationships and rheological arrangements, which can subsequently serve as a basis for 3D constitutive model development and finite-element implementations. The proposed approach can also be employed as a self-contained tool to obtain simplified 1D phenomenological models of the structural response of biological tissue to single-axis manipulations for applications in haptic technologies.     

The evolution of the protein synthesis system

An evolutionary picture of the early protein synthesis was presented in relation to the problem of the origin and the evolution of life. A model of an autocatalytic system was studied in this connection. The system in this model included a template nucleotide and two activated amino acid polymerases with or without a nucleotide polymerase. Variables defining the system were: (1) Catalytic activity of the polymerases, (2) Number of amino acid residues at the activity site of the polymerases, (3) Number of amino acid residues at the selectivity site of the polymerases, (4) Number of the polymerases, (5) Accuracy of polymerization and activity of the polymerases, (6) Number of evolutionary improvements, and (7) The probability of an occurrence of beneficial mutations. The population changes of the systems were obtained by computer calculations. The simulation results indicated that even a very small enzymic activity and specificity of the polymerases could eventually lead the system to the most accurate protein synthesis, as far as transitions to systems with higher accuracy were allowed. The model study would encourage further quantiative investigations on catalytic activities of synthetic peptides, and on interactions between nucleotides and amino acids, and constructions of autocatalytic systems from a chemical evolutionary point of view.This is a part of a dissertation of HM to be presented to the Graduate School of the University of Maryland in partial fulfilment of the requirements for the Ph.D.     

A note on the covariance of the Mantel-Haenszel log-odds-ratio estimator and the sample marginal rates

A simple technique, developed in Phillips (unpublished Ph.D. dissertation, University of Windsor, Windsor, Ontario, 1987), is used to approximate cov(theta MH, pi), i = 1, 2, where theta MH is the Mantel-Haenszel log-odds-ratio estimator for a 2 x 2 x K table and the pi are the sample marginal proportions. These results are then applied to obtain an approximate variance estimate of an adjusted risk difference based on the Mantel-Haenszel odds-ratio estimator.     

Life history, enamel formation, and linear enamel hypoplasia in the Ceboidea

Linear enamel hypoplasia (LEH), a developmental defect of enamel, increases in frequency from prosimian to monkey to lesser ape to great ape grades (Guatelli-Steinberg 2000 Am. J. Phys. Anthropol. 112:395-410, [2001] Evol. Anthropol. 10:138-151; Newell 1998 Ph.D. dissertation, Temple University). This taxonomic pattern in the distribution of LEH is closely related to maturation length across the primate order (Newell 1998 Ph.D. dissertation, Temple University, 2000 Am. J. Phys. Anthropol. [Suppl.] 30:236). Longer maturation periods are associated with higher LEH frequencies; they appear to provide greater opportunity for defects to form. The present study explores the relationship between maturation length and LEH frequency within the Ceboidea. Because of its prolonged period of growth, Cebus is predicted to manifest LEH at a higher frequency than the more rapidly maturing ceboid genera. To test this hypothesis, two separate researchers (E.A.N. and D.G.-S.) examined LEH in nonoverlapping museum series of ceboids. The results support the hypothesis: in 13 genera (n = 1,276), E.A.N. found that LEH frequencies ranged from 0% in Callicebus, Cebuella, and Saimiri to 20% in Cebus. D.G.-S. found similar frequencies among five genera (n = 107), from 0% in Saimiri to 32% in Cebus. Thus, the broad pattern of LEH distribution evident across major taxonomic groups of primates is repeated within the Ceboidea. We also examined a related hypothesis linking the spacing of perikymata, which is influenced by enamel extension rates (Shellis 1998 J. Hum. Evol. 35:387-400), to LEH. The most likely areas of tooth crowns to exhibit LEH in human teeth are those in which perikymata are most closely spaced (Hillson and Bond 1997 Am. J. Phys. Anthropol. 104:89-103). We hypothesized that the longer-maturing Cebus, with its elevated LEH frequency, will also exhibit more closely spaced perikymata than other ceboids. Analysis of a small microscopic subsample (n = 8) lends limited support to this second hypothesis.     

Mechanical identification of layer-specific properties of mouse carotid arteries using 3D-DIC and a hyperelastic anisotropic constitutive model

The role of mechanics is known to be of primary order in many arterial diseases; however, determining mechanical properties of arteries remains a challenge. This paper discusses the identifiability of the passive mechanical properties of a mouse carotid artery, taking into account the orientation of collagen fibres in the medial and adventitial layers. On the basis of 3D digital image correlation measurements of the surface strain during an inflation/extension test, an inverse identification method is set up. It involves a 3D finite element mechanical model of the mechanical test and an optimisation algorithm. A two-layer constitutive model derived from the Holzapfel model is used, with five and then seven parameters. The five-parameter model is successfully identified providing layer-specific fibre angles. The seven-parameter model is over parameterised, yet it is shown that additional data from a simple tension test make the identification of refined layer-specific data reliable.     

A Three-Dimensional Analytical (Rheological) Model of the Human Left Ventricle in Passive-Active States: Nontraumatic Determination of the In Vivo Values of the Rheological Parameters

In this paper a three-dimensional continuum model of a mammalian left ventricle is formulated. The stresses in the model satisfy the conditions of zero stress on the outer (epicardial surface-representing) boundary. The strains of the model are obtained from the actual dynamic geometry measurements (obtained from cineangiocardiography). Since the left ventricular muscle is incompressible, the dilatational strain is zero and hence the (three-dimensional) deviatric stress components are related to the corresponding strain components by Maxwell and Voigt rheological model analogues of one-dimensional systems; the parameters of the model are series and parallel elastic (SE, PE) elements and the contractile element (CE) (representing the sarcomere). The incorporation of the rheological features of the cardiac muscle into the three-dimensional constitutive equations (for the three-dimensional continuum model of the left ventricle) is a feature of this paper. A procedure is presented to determine the parameters of the constitutive equations (i.e., the SE, PE, and the parameters of the force-velocity relation for the CE) for the left ventricle of a subject from data on the dimensions and chamber pressure of the left ventricle. The values of these parameters characterize the rheology of the left ventricular muscle of the subject. In order to demonstrate clinical application of the analyses, in vivo data of the subjects' left ventricular pressure and dimensions are obtained, and the analyses are applied to the data to determine (for each subject) the values and characteristics of the elastic elements and CEs.     

Survival analysis in clinical trials: past developments and future directions

The field of survival analysis emerged in the 20th century and experienced tremendous growth during the latter half of the century. The developments in this field that have had the most profound impact on clinical trials are the Kaplan-Meier (1958, Journal of the American Statistical Association 53, 457-481) method for estimating the survival function, the log-rank statistic (Mantel, 1966, Cancer Chemotherapy Report 50, 163-170) for comparing two survival distributions, and the Cox (1972, Journal of the Royal Statistical Society, Series B 34, 187-220) proportional hazards model for quantifying the effects of covariates on the survival time. The counting-process martingale theory pioneered by Aalen (1975, Statistical inference for a family of counting processes, Ph.D. dissertation, University of California, Berkeley) provides a unified framework for studying the small- and large-sample properties of survival analysis statistics. Significant progress has been achieved and further developments are expected in many other areas, including the accelerated failure time model, multivariate failure time data, interval-censored data, dependent censoring, dynamic treatment regimes and causal inference, joint modeling of failure time and longitudinal data, and Baysian methods.     

Determination of material parameters of the two-dimensional Holzapfel–Weizsäcker type model based on uniaxial extension data of arterial walls

Soft tissues are anisotropic materials yet a majority of mechanical property tests have been uniaxial, which often failed to recapitulate the tensile response in other directions. This paper aims to study the feasibility of determining material parameters of anisotropic tissues by uniaxial extension with a minimal loss of anisotropic information. We assumed that by preselecting a certain constitutive model, we could give the constitutive parameters based on uniaxial extension data from orthogonal strip samples. In our study, the Holzapfel–Weizsäcker type strain energy density function (H–W model) was used to determine the material parameters of arterial walls from two fresh donation bodies. The key points we applied were the relationships between strain components in uniaxial tensile tests and the methods of stochastic optimisation. Further numerical experiments were taken. The estimate–effect ratio, defined by the number of data with the precision of estimation less than 0.5% over whole size of data, was calculated to demonstrate the feasibility of our method. The material parameters for Chinese aorta and pulmonary artery were given with the maximum root mean square (RMS) errors 0.042, and the minimal estimate–effect ratio in numerical experiments was 90.79%. Our results suggest that the constitutive parameters of arterial walls can be determined from uniaxial extension data, given the passive mechanical behaviour governed by H–W model. This method may apply to other tissues using different constitutive models.     

Microplane constitutive model and computational framework for blood vessel tissue

This paper presents a nonlinearly elastic anisotropic microplane formulation in 3D for computational constitutive modeling of arterial soft tissue in the passive regime. The constitutive modeling of arterial (and other biological) soft tissue is crucial for accurate finite element calculations, which in turn are essential for design of implants, surgical procedures, bioartificial tissue, as well as determination of effect of progressive diseases on tissues and implants. The model presented is defined at a lower scale (mesoscale) than the conventional macroscale and it incorporates the effect of all the (collagen) fibers which are anisotropic structural components distributed in all directions within the tissue material in addition to that of isotropic bulk tissue. It is shown that the proposed model not only reproduces Holzapfel's recent model but also improves on it by accounting for the actual three-dimensional distribution of fiber orientation in the arterial wall, which endows the model with advanced capabilities in simulation of remodeling of soft tissue. The formulation is flexible so that its parameters could be adjusted to represent the arterial wall either as a single material or a material composed of several layers in finite element analyses of arteries. Explicit algorithms for both the material subroutine and the explicit integration with dynamic relaxation of equations of motion using finite element method are given. To circumvent the slow convergence of the standard dynamic relaxation and small time steps dictated by the stability of the explicit integrator, an adaptive dynamic relaxation technique that ensures stability and fastest possible convergence rates is developed. Incompressibility is enforced using penalty method with an updated penalty parameter. The model is used to simulate experimental data from the literature demonstrating that the model response is in excellent agreement with the data. An experimental procedure to determine the distribution of fiber directions in 3D for biological soft tissue is suggested in accordance with the microplane concept. It is also argued that this microplane formulation could be modified or extended to model many other phenomena of interest in biomechanics.     

On the propagation of a disturbance through a viscous liquid flowing in a distensible tube of appreciable mass

The velocity of propagation of a disturbance wave in a liquid flowing in a distensible tube is computed. The mathematical model is more general than those used in previous analyses: the tube wall properties are realistic; the convective part of the axial inertia forces is taken into account; radial inertia forces of both the fluid and tube wall are present; viscous stresses are present. Four parameters influencing the velocity of propagation are obtained and discussed. Curves are plotted illustrating the effects of the parameters. Contrary to the results of previous analyses, viscous effects are shown to be appreciable in blood flow. It is also shown that radial inertia effects can be important in laboratory set-ups. The material presented in this paper was adapted from the Ph.D. thesis written by the author at Harvard University.     

The influence of the material properties on the biomechanical behavior of the pelvic floor muscles during vaginal delivery

In this work, a finite element model intends to represent the effects that the passage of a fetal head can induce on the muscles of the pelvic floor, from a mechanical point of view.The finite element method is a valuable tool, that is contributing to the clarification of the mechanisms behind pelvic floor disorders related to vaginal deliveries, although some care is necessary in order to obtain correct results. The present work shows how the variation of the material parameters, used in the constitutive model, can affect the obtained results from a finite element simulation. The constitutive equation adopted in this work for the pelvic floor muscles is a modified form of the incompressible transversely isotropic hyperelastic model proposed earlier by Humphrey and Yin.Results for the pelvic floor strain and stresses obtained during the passage of the fetus head are presented. The results show the importance of the material parameters and the need for a correct constitutive model.     

The dissociation of insect embryos for cell culture

Summary Procedures and solutions were developed for dissociating embryos ofBlattella germanica in preparation for primary cell culture. Trypsin solutions were maximally effective at 0.01% for germ bands but higher concentrations, 0.05 to 0.1% were needed for embryos in later stages. This investigation was supported by U.S. Public Health Service Research Grant No. AI 09914 from the National Institute of Allergy and Infectious Diseases. This is paper No. 8855, Scientific Journal Series, Minnesota Agricultural Experiment Station. The work was selected from the dissertation of T. J. K. presented for the Ph. D. degree at the University of Minnesota.     

Mitosis in the protostelidPlanoprotostelium aurantium

Summary Mitosis in the protostelidPlanoprotostelium aurantium Olive andStoianovich is characterized by an open, centric spindle. The nuclear envelope breaks down prior to metaphase, begins to reform during late anaphase, and is complete by telophase. Centrioles are present at the poles throughout mitosis and are devoid of rootlet microtubules from metaphase to late anaphase. Chromosomes are small and numerous and are attached to single kinetochore microtubules during metaphase and early anaphase. Chromosome separation takes place by a presumed shortening of the chromosome to pole spindle followed by a lengthening of the interzonal spindle. Mitosis inP. aurantium is similar to that of certain other protostelid amoebae and to myxomycete amoebae, but it is considerably different from that of dictyostelid amoebae. The phylogenetic significance of this is discussed.This research represents part of a Ph.D. dissertation presented to the University of North Carolina.