bluuebunny/crossref_metadata_2025 huggingface dataset:
Free‐running of plasma melatonin rhythm prior to full manifestation of a non‐24 hour sleep‐wake syndrome
Authors: HASHIMOTO SATOKO , NAKAMURA KOUJI , HONMA SATO , HONMA KEN ICHI
Published: March 2008

Abstract A long‐term observation of a sighted man who developed a non‐24 h sleep‐wake syndrome is reported. A partial entrainment was observed first, whereby the sleep‐wake rhythm was entrained by the day‐night alternation whereas the circadian rhythm in plasma melatonin was free‐running. Two years later, the sleep‐wake rhythm of this subject started to free‐run together with the melatonin rhythm. Oral administration of melatonin for 2 weeks improved the entrainability of both rhythms but failed to entrain the rhythms completely. It is concluded that the free‐running of the circadian pacemaker preceded a full manifestation of a non‐24 h sleep‐wake syndrome in this particular subject.
Time course of saliva and serum melatonin levels after ingestion of melatonin
Authors: SHIRAKAWA SHIN‐ICHIROU , TSUCHIYA SATOSHI , TSUTSUMI YASUMASA , KOTORII TSUYOSHI , UCHIMURA NAOHISA , SAKAMOTO TETSUROU , YAMADA SHIGETO
Published: March 2008

Abstract Salival and serum melatonin levels after melatonin ingestion were measured by gas chromatography‐mass spectrometry. Ingestion of 3 mg melatonin caused a marked increase in serum melatonin (3561 ± 1201 pg/mL) within 20 min, followed by a gradual decrease, but the level still remained higher than the basal level at 240 min after the ingestion. The saliva melatonin 60 min after the ingestion showed the highest level (1177 ± 403 pg/mL) which was one‐third of the plasma level. The saliva melatonin level was highly correlated with the serum level throughout the experimental period (r= 0.82, P= 0.0001). These data indicate that the measurement of saliva melatonin level may be a suitable indicator for the melatonin secretion into general circulation.
A quantitative study of neurofibrillary tangles, senile plaques and astrocytes in the hippocampal subdivisions and entorhinal cortex in Alzheimer's disease, normal controls and non‐Alzheimer neuropsychiatric diseases
Authors: MURAMORI FUMIHIKO , KOBAYASHI KATSUJI , NAKAMURA ICHIROU
Published: March 2008

Abstract  The present quantitative study was performed in order to discriminate pathological substrates for dementia from Alzheimer changes in normal controls (NC) and non‐Alzheimer neuropsychiatric diseases (NAND). Regional densities of senile plaques (SP), neurofibrillary tangles (NFT) and astrocytes in the cornu ammonis (CA), subiculum and entorhinal cortex were measured and differences in these densities among Alzheimer's disease (AD), NAND and NC were statistically compared. Densities of NFT in the CA and subiculum were significantly higher in AD than in NAND, and densities of SP in all regions were significantly higher in AD than in NAND. Similarly, NFT density in the subiculum and SP density in all regions were higher in AD than in NC. Regional densities of astrocytes in most regions were closely correlated with those of Alzheimer changes. In conclusion, the attribution of the Alzheimer changes, particularly of NFT, to dementia is neglected when they are confined to the entorhinal cortex. However, the attribution of the Alzheimer changes to dementia should be appreciated when they spread from the entorhinal cortex to the subiculum and/or CA.
Were British railway companies well managed in the early twentieth century?1
Authors: CRAFTS NICHOLAS , LEUNIG TIMOTHY , MULATU ABAY
Published: March 2008

This paper examines major privately owned British railway companies before the First World War. Quantitative evidence is presented on return on capital employed (ROCE), total factor productivity (TFP) growth, cost inefficiency, and speed of passenger services. There were discrepancies in performance across companies but ROCE and TFP typically fell during our period. Cost inefficiency rose before 1900 but then was brought under control as a profits collapse loomed. Without the discipline of either strong competition or effective regulation, managerial failure was common. This sector is an important qualification to the conventional wisdom that late Victorian Britain did not fail.
Electron transfer at the microbe–mineral interface: a grand challenge in biogeochemistry
Authors: FREDRICKSON J. K. , ZACHARA J. M.
Published: March 2008

The interplay between microorganisms and minerals is a complex and dynamic process that has sculpted the geosphere for nearly the entire history of the Earth. The work of Dr Terry Beveridge and colleagues provided some of the first insights into metal–microbe and mineral–microbe interactions and established a foundation for subsequent detailed investigations of interactions between microorganisms and minerals. Beveridge also envisioned that interdisciplinary approaches and teams would be required to explain how individual microbial cells interact with their immediate environment at nano‐ or microscopic scales and that through such approaches and using emerging technologies that the details of such interactions would be revealed at the molecular level. With this vision as incentive and inspiration, a multidisciplinary, collaborative team‐based investigation was initiated to probe the process of electron transfer (ET) at the microbe–mineral interface. The grand challenge to this team was to address the hypothesis that multiheme c‐type cytochromes of dissimilatory metal‐reducing bacteria localized to the cell exterior function as the terminal reductases in ET to Fe(III) and Mn(IV) oxides. This question has been the subject of extensive investigation for years, yet the answer has remained elusive. The team involves an integrated group of experimental and computational capabilities at US Department of Energy's Environmental Molecular Sciences Laboratory, a national scientific user facility, as the collaborative focal point. The approach involves a combination of in vitro and in vivo biologic and biogeochemical experiments and computational analyses that, when integrated, provide a conceptual model of the ET process. The resulting conceptual model will be evaluated by integrating and comparing various experimental, i.e. in vitro and in vivo ET kinetics, and theoretical results. Collectively, the grand challenge will provide a detailed view of how organisms engage with mineral surfaces to exchange energy and electron density as required for life function.
“Spread your ass cheeks”: And other things that should not be said in indigenous languages
Authors: MUEHLMANN SHAYLIH
Published: March 2008

In this article, I describe the use of indigenous‐language swearwords by the younger generation in the Cucapá settlement of El Mayor in northern Mexico. I argue that this vocabulary functions as a critique of and a challenge to the increasingly formalized imposition of indigenous‐language capacity as a measure of authenticity and as both a formal and an informal criterion for the recognition of indigenous rights. I argue that this ethnographic case can also be read as a critique of the notion of language as a cultural repository popularized in recent linguistic anthropological literature on language endangerment. For the youth in El Mayor, indigenous identity is not located in the Cucapá language but in an awareness of a shared history of the injustices of colonization and a continuing legacy of state indifference. [language death, indigenous people, politics of recognition, Mexico, swearwords, identity, language ideology]
The lessons of slavery: Discourses of slavery,mestizaje,andblanqueamientoin an elementary school in Puerto Rico
Authors: GODREAU ISAR P. , REYES CRUZ MARIOLGA , FRANCO ORTIZ MARILUZ , CUADRADO SHERRY
Published: March 2008

On the basis of ethnographic research conducted in an elementary public school in Puerto Rico, we maintain in this article that subduing and narrowing the history of slavery is instrumental in the reproduction of national ideologies ofmestizajein Afro‐Latin America. We explore how school texts and practices silence, trivialize, and simplify the history of slavery and conclude that these maneuvers distance blackness from Puerto Rican identity and silence racism while upholding racial democracy andblanqueamientoas a social value. [slavery, racism in education, Puerto Rico, blanqueamiento, mestizaje, blackness, public history]
Of hungry ghosts and other matters of consumption in the Republic of Korea: The commodity becomes a ritual prop
Authors: KENDALL LAUREL
Published: March 2008

Contemporary South Korean shaman rituals(kut)incorporate new consumer goods as agentive “props,” foci that provoke mime and commentary in dramatic interactions between shamans, clients, gods, and ancestors. In the 1990s, much of this object‐centered performance concerned the moral ambiguities of consumption, an appreciation facilitated by an analytic focus on the prop itself. In this study, I argue that the play of props in ritual conveys otherwise elusive nuances regarding the play of things in everyday life and that, when new consumer goods assume the status of props, they enable commentary on the moral paradox of getting and having. [prop, consumption, commodity, South Korea, shaman, ritual, materiality]
Effect ofWithania somniferaon Insulin Sensitivity in Non‐Insulin‐Dependent Diabetes Mellitus Rats
Authors: Anwer Tarique , Sharma Manju , Pillai Krishna Kolappa , Iqbal Muzaffar
Published: March 2008

Abstract: We investigated the effect of an aqueous extract ofWithania somnifera(WS) on insulin sensitivity in non‐insulin‐dependent diabetes mellitus (NIDDM) rats. NIDDM was induced by single intraperitoneal injection of streptozotocin (100 mg/kg) to 2 days old rat pups. WS (200 and 400 mg/kg) was administered orally once a day for 5 weeks after the animals were confirmed diabetic (i.e. 75 days after streptozotocin injection). A group of citrate control rats (group I) were also maintained that has received citrate buffer on the second day of their birth. A significant increase in blood glucose, glycosylated haemoglobin (HbA1c) and serum insulin levels were observed in NIDDM control rats. Treatment with WS reduced the elevated levels of blood glucose, HbA1c and insulin in the NIDDM rats. An oral glucose tolerance test was also performed in the same groups, in which we found a significant improvement in glucose tolerance in the rats treated with WS. The insulin sensitivity was assessed for both peripheral insulin resistance and hepatic insulin resistance. WS treatment significantly improved insulin sensitivity index (KITT) that was significantly decreased in NIDDM control rats. There was significant rise in homeostasis model assessment of insulin resistance (HOMA‐R) in NIDDM control rats whereas WS treatment significantly prevented the rise in HOMA‐R in NIDDM‐treated rats. Our data suggest that aqueous extract of WS normalizes hyperglycemia in NIDDM rats by improving insulin sensitivity.
The Prescribing Pattern of a New Antipsychotic: A Descriptive Study of Aripiprazole for Psychiatric In‐Patients*
Authors: Andersen Stig Ejdrup , Johansson Majka , Manniche Charlotte
Published: March 2008

Abstract:  In June 2004, aripiprazole was marketed as a second‐generation antipsychotic with an entire new mechanism of action. The objective of this descriptive study is to examine the day‐to‐day prescriptions of aripiprazole to an unselected population of psychiatric in‐patients. From 1 February to 1 May 2006, present and former in‐patients treated with aripiprazole were identified. Prescriptions of aripiprazole and psychoactive comedication were collected retrospectively from the patient records. Seventy‐one patients, mainly schizophrenic, received aripiprazole 2.5 to 55 mg/day for median 350 days. The median average exposure was 18.9 mg/day (range 2.5–45 mg/day) and exceeded 15 and 30 mg/day in 63% and 4.2% of the patients, respectively. Generally, aripiprazole was either added to the existing antipsychotic treatment or replaced other antipsychotics; only 17% of the patients were treatment‐naïve. In 25% aripiprazole, monotherapy was commenced whereas aripiprazole‐antipsychotic combinations were initially prescribed in 75%. Overall, 85% of the patients received periods of antipsychotic polypharmacy and aripiprazole was combined with 17 different antipsychotics. Each patient received median three (range 0–8) psychoactive drugs parallel with aripiprazole. This study demonstrates reality in psychopharmacology and quote aripiprazole as example. In day‐to‐day practice, aripiprazole is used as part of highly individualized regimens comprising polypharmacy and excessive dosing. Although theoretically appropriate for some patients, this approach also implies conducting unblinded and uncontrolled mini‐experiments. Sparse evidence supports this practice and effectiveness studies of aripiprazole that takes into account the true complexity of clinical prescribing are urgently needed.
Stiffness Characteristics of the Circular Ilizarov Device as Opposed to Conventional External Fixators
Authors: Gasser B. , Boman B. , Wyder D. , Schneider E.
Published: March 2008

Ilizarov proposes the use of a special circular fixation device for treatment of bone defects and nonunions or for limb lengthening. Supposition was that the success of this method has to do with the specific mechanical behavior of the device. This behavior is a result of the configuration of the fixation elements. Therefore, a mechanical study of the sensitivity of the circular compression and distraction device (CDD) to configuration parameters was performed. The CDD was found to exhibit a nonlinear stiffness behavior, in particular under axial load. This may be favorable for the induction and tolerance of bone formation. Among the different parameters tested the ring radius was the most important with respect to stiffness. In general, the stiffness of the CDD allows adjustment during postoperative management. In magnitude, it is equal or lower when compared to other fixator types.
Cracks Emanating From Circular Voids or Elastic Inclusions in PMMA Near a Bone-Implant Interface
Authors: Gharpuray V. M. , Keer L. M. , Lewis J. L.
Published: March 2008

Mechanical fracture is believed to be a primary reason for loss of fixation at the bone-cement-implant interface. In addition to the expected cracks at the bone-cement interface, cracks are also observed to be formed at voids and inclusions within the cement. An analytical solution is presented for cracks emanating from circular voids or elastic inclusions under uniaxial tension using the solution for a single dislocation as a Green’s function. Stress intensity factors are calculated for arbitrary orientations of the cracks, and for varying relative stiffnesses of the inclusion and the matrix, to determine the most favorable combination of parameters for crack growth.
Large Deformation Analysis of Orthodontic Appliances
Authors: Lipsett A. W. , Faulkner M. G. , El-Rayes K.
Published: March 2008

The deformations of orthodontic appliances used for space closure are large so that any mathematical analysis will require a nonlinear approach. Existing incremental finite element and finite difference numerical methods suffer from excessive computational effort when analyzing these problems. An accurate segmental technique is proposed to handle these difficulties in an extremely efficient fashion. The segmental technique starts by assuming that an orthodontic appliance is composed of a number of smaller segments, the ends of which undergo small relative rotation. With an appropriate choice of local coordinate system the equilibrium equations for each segment are linearized and solved in a straightforward manner. The segments are then assembled using geometric and force compatibility relations similar to the transfer matrix method. Consequently, the original nonlinear boundary value problem is solved as a sequence of linear initial value problems which converge to the required boundary conditions. As only one segment need be considered at a time, the computations can be performed accurately and efficiently on a PC type computer. Although an iterative solution is used to match the boundary conditions, the time required to solve a given problem ranges from a few seconds to a couple of minutes depending on the initial geometric complexity. The accuracy of the segmental technique is verified by comparison with an exact solution for an initially curved cantilever beam with an end load. In addition, comparisons are made with existing experimental and numerical results as well as with a new set of experimental data. In all cases the segmental technique is in excellent agreement with the results of these other studies.
Surface Strain Variation in Human Patellar Tendon and Knee Cruciate Ligaments
Authors: Butler D. L. , Sheh M. Y. , Stouffer D. C. , Samaranayake V. A. , Levy M. S.
Published: March 2008

Local surface strains in bone-fascicle-bone subunits from human patellar tendon and anterior and posterior cruciate ligaments were measured between markers using low-speed photography during low rate subfailure testing. A simple stress-strain relationship of the power form was found to describe the bone-to-bone responses up to four percent strain for all three tissue types examined. The regional material behavior were best fit using an inverted strain-stress relationship, however. The power model, fitted to the experimental data, conformed to the expected stress-strain relationship better than either the quadratic or cubic models. With few exceptions, for a given stress, the strains near the proximal and distal bone ends were not significantly different from each other, but were significantly higher than the strains in the tissue midregions. Local strain patterns generally varied among subunits from the same tissue.
In-Vivo Indentation of Human Skin
Authors: Lanir Y. , Dikstein S. , Hartzshtark A. , Manny V.
Published: March 2008

Indentation tests were carried out on the forehead skin of volunteers under loading pressures of 0–5 KPa. The indentation was found to increase asymptomatically with loading pressure. In an attempt to develop a quantitative index for aging of the skin, its response to indentation loading was analyzed in reference to its glycosaminoglycan (GAG) containing ground substance and fibers’ network microstructure. An analytic model that considers the skin as an incompressible solid-fluid mixture was developed and utilized to simulate the skin’s indentation response. Following parameter fitting, the predicted results are in close agreement with the data. The model can thus serve as a tool for evaluating the effect of changes in the dermis components which accompany aging.
Effect of Hypertension on Elasticity and Geometry of Aortic Tissue From Dogs
Authors: Vaishnav Ramesh N. , Vossoughi Jafar , Patel Dali J. , Cothran LaVal N. , Coleman Bernell R. , Ison-Franklin Eleanor L.
Published: March 2008

Inflation-extension experiments were carried out on segments of the descending thoracic aortas from 4 normotensive and 4 hypertensive dogs rendered hypertensive using either unilateral or bilateral renal artery constriction. Intravascular pressures up to 200 mm Hg and axial forces up to 200 g were used. The external diameter of the segment and the distance between two longitudinally spaced gage marks were recorded photographically at each pressure-force level combination. Dimensions in the undeformed configuration were measured at the end of the inflation-extension experiment. Data were analyzed for changes in geometry and force-deformation response. Results indicate that: 1. Under sustained hypertension the wall thickness in the undeformed configuration increases with a concurrent reduction in the in-situ longitudinal extension ratio. 2. This dual tissue response accomplishes substantial reductions in the circumferential and longitudinal stresses from the levels that would be reached at equivlaent pressures in the absence of these geometric changes. 3. At comparable intravascular pressures the extensibility in the circumferential direction is slightly greater for the hypertensive aortas as compared to normals. However, the stress-extension ratio relationship in the circumferential direction is similar in the two groups. 4. The stress-extension ratio relationship in the longitudinal direction indicates that the hypertensive aorta is stiffer than its normotensive counterpart.
An Evaluation of the Weinbaum-Jiji Bioheat Equation for Normal and Hyperthermic Conditions
Authors: Charny C. K. , Weinbaum S. , Levin R. L.
Published: March 2008

The predictions of the simplified Weinbaum-Jiji (WJ) bioheat transfer equation in one dimension are compared to those of the complete one-dimensional three-equation model that represented the starting point for the derivation of the WJ equation, as well as results obtained using the traditional bioheat transfer equation of Pennes [6]. The WJ equation provides very good agreement with the three-equation model for vascular generations 2 to 9, which are located in the outer half of the muscle layer, where the paired vessel diameters are less than 500 μm, under basal blood flow conditions. At the same time, the Pennes equation yields a better description of heat transfer in the first generation, where the vessels’ diameters are greater than 500 μm and ε, the vessels’ normalized thermal equilibration length, is greater than 0.3. These results were obtained under both normothermic and hyperthermic conditions. A new conceptual view of the blood source term in the Pennes equation has emerged from these results. This source term, which was originally intended to represent an isotropic heat source in the capillaries, is shown to describe instead the heat transfer from the largest countercurrent microvessels to the tissue due to small vessel bleed-off. The WJ equation includes this effect, but significantly overestimates the second type of tissue heat transfer, countercurrent convective heat transfer, when ε > 0.3. Indications are that a “hybrid” model that applies the Pennes equation in the first generation (normothermic) and first two to three generations (after onset of hyperthermia) and the Weinbaum-Jiji equation in the subsequent generations would be most appropriate for simulations of bioheat transfer in perfused tissue.
The Dynamics of the Subtalar Joint in Sudden Inversion of the Foot
Authors: Mizrahi Joseph , Ramot Yair , Susak Zev
Published: March 2008

The human subtalar joint was modelled as a quasi-linear second-order underdamped system to simulate sudden inversion motion of the foot relative to the shank. The model was fed with experimental data obtained from six subjects on a specially constructed apparatus. A total of 35 deg inversion was produced on the tested leg rapidly enough (lasting less than 40 ms) in order to ensure that the protective muscles are not activated. The parameters of the joint were evaluated and the following ranges were obtained at 35 deg inversion: elastic stiffness 14–52 Nm rad-1, damping coefficient 1.4–2.9 Nms rad-1, and natural frequency 78–125 Hz. The effects on the test parameters of weight bearing amount, foot dominance, and protective footwear were studied on one subject.
Simultaneous Convective and Diffusive Mass Transfers in a Hemodialyser
Authors: Jaffrin Michel Y. , Ding Luhui , Laurent Jean Marc
Published: March 2008

The mass transfer in a hemodialyser in the presence of combined dialysis and ultrafiltration has been calculated by integration of mass fluxes across the boundary layers in blood and dialysate phase taking into account the partial rejection of solute as well as changes in local blood flow and ultrafiltration flux along the membrane. Clearances of creatinin, vitamin B12, and myoglobin have been calculated as a function of blood and ultrafiltrate flow rate and were found to be in good agreement with in vitro measurements. The data suggest the following empirical correlation for the hemodiafiltration clearance CL=CLD+0.46QF where QF is the ultrafiltration flow rate and CLD is the clearance at QF=0.
Extensional Recovery of an Intact Erythrocyte From a Tank-Treading Motion
Authors: Sutera S. P. , Mueller E. R. , Zahalak G. I.
Published: March 2008

Normal human erythrocytes suspended in shear flow are stretched into quasi ellipsoidal forms while their membranes rotate smoothly (tank-treading). Following abrupt cessation of shear the cells recover their discoidal shapes approximately exponentially, in the manner of a Kelvin-Voigt (K-V) solid. To test the hypothesis that the recovery process is membrane-controlled, the effects of initial deformation, cytoplasmic viscosity and membrane surface-to-volume ratio were studied. It was concluded that the membrane dynamics dominates the transient shape recovery, and that the characteristic recovery time is dependent on the initial deformation. Hence, the usual simplified analysis based on retraction of a plane sheet of K-V material with constant moduli appears to be an inadequate treatment of transient whole cell recovery.
Application of the Micropipette Technique to the Measurement of Cultured Porcine Aortic Endothelial Cell Viscoelastic Properties
Authors: Sato M. , Theret D. P. , Wheeler L. T. , Ohshima N. , Nerem R. M.
Published: March 2008

The viscoelastic deformation of porcine aortic endothelial cells grown under static culture conditions was measured using the micropipette technique. Experiments were conducted both for control cells (mechanically or trypsin detached from the substrate) and for cells in which cytoskeletal elements were disrupted by cytochalasin B or colchicine. The time course of the aspirated length into the pipette was measured after applying a stepwise increase in aspiration pressure. To analyze the data, a standard linear viscoelastic half-space model of the endothelial cell was used. The aspirated length was expressed as an exponential function of time. The actin microfilaments were found to be the major cytoskeletal component determining the viscoelastic response of endothelial cells grown in static culture.
The Behavior of Human Neutrophils During Flow Through Capillary Pores
Authors: Frank R. S. , Tsai M. A.
Published: March 2008

The passage times of individual human neutrophils through single capillary-sized pores in polycarbonate membranes were measured with the resistive pulse technique, and results were compared to those obtained from the micropipette aspiration of entire cells. Pore transit measurement serves as a useful means to screen populations of cells, and allows for protocols that measure time dependent changes to the population. Neutrophils exhibited a highly linear pressure/flow rate relationship at aspiration pressures from 200 Pa to 1,500 Pa in both the pore and pipette systems. Cellular viscosity, as determined by the method of Hochmuth and Needham, was 89.0 Pa·s for the pore systems and 134.9 Pa·s for the pipette systems. These results are in general agreement with recent values of neutrophil viscosity published in the literature. Extrapolation of the observed linear flow response revealed an apparent minimum pressure for whole cell aspiration significantly above the threshold pressure predicted by Evans’ liquid drop model. However, whole cell aspiration was achieved in both the pore and pipette systems at pressures below this extrapolated minimum, although the calculated cellular viscosity was greatly increased. The implications of these two regimes of cell deformation is unclear. This behavior could be explained by shear thinning of the material in the cell body. However the origin of this phenomenon may be in the cortical region of the cell, which exhibits an elastic tension that may be deformation rate dependent.
Passive Deformations and Active Motions of Leukocytes
Authors: Skalak Richard , Dong Cheng , Zhu Cheng
Published: March 2008

The purpose of this paper is to review the development of continuum mechanics models of single leukocytes in both passive deformations and active motions and to indicate some future directions. Models of passive deformations describe the overall rheological behavior of single leukocytes under externally applied forces and predict the average mechanical properties from experimental data. Various “apparent” viscoelastic coefficients are obtained depending on the models assumed and the types of test used. Models of spontaneous motions postulate active driving mechanisms which must be derived internally from the cell itself and probably have different bases for different kind of motions. For pseudopod protrusion on leukocytes, energy transduction from chemical potential to mechanical work associated with actin polymerization at the tip of the projection is assumed to supply the motive power. For pseudopod retraction, active contraction due to actin-myosin interaction is assumed to be the driving force. The feasibility of the hypotheses are tested via numerical examples and comparison of the theoretical results with experimental measurements.
Determination of a Constitutive Relation for Passive Myocardium: I. A New Functional Form
Authors: Humphrey J. D. , Strumpf R. K. , Yin F. C. P.
Published: March 2008

The specific aim of this study is to determine a constitutive relation for non-contracting myocardium in terms of a pseudostrain-energy function W whose form is guided by both theory and experiment. We assume that the material symmetry of myocardium is initially and locally transversely-isotropic, and seek a W which depends upon only two coordinate invariant measures of the finite deformation. The specific functional form of such a W is inferred directly from experimental protocols in which one invariant is held constant while the other is varied, and vice versa. On the basis of data from families of these “constant invariant” tests on thin slabs of myocardium taken from the mid-walls of six canine left ventricles, we propose a new polynomial form of W containing only five material parameters.
Nonlinear Analysis of Intervertebral Disk Under Dynamic Load
Authors: Natali A. , Meroi E.
Published: March 2008

This study pertains to the response of intervertebral joint under dynamic axial load. The numerical model represents two vertebral bodies with an interposed disk and uses three-dimensional elements. A transversely isotropic material law is adopted for cortical bone and an isotropic law for cancellous bone. Annulus collagen fibers are modelled using truss elements with no compressive resistance. The disk material is assumed hyperelastic, using a mixed finite element approach, allowing a representation of the disk involving the incompressibility characteristics for the material. The analysis considers finite displacement and strain fields under dynamic load. Intensity, trend and distribution of loads on the vertebral body are deduced from the literature. The problem is investigated with reference to different compressibility levels of disk material related to disk degeneration phenomena.
The Joint Distribution Problem With Multiple Articular Contact Forces
Authors: Andrews J. G. , Cheng C. K.
Published: March 2008

The single joint distribution problem with two or more unknown bony contact forces is considered, and an optimal solution procedure free of ad hoc assumptions is described. If two bony contact forces are present, a strictly muscle force dependent equality constraint exists that allows for initial independent estimation of muscle forces, followed by unique estimation of all bony contact force components perpendicular to the straight line connecting their known points of application. However, if three or more bony contact forces are present, no strictly muscle force dependent equality constraint exists, solution separability is lost, and optimal muscle and bony contact forces are obtained simultaneously.
Implementation of a Five Degree of Freedom Automated System to Determine Knee Flexibility In Vitro
Authors: Berns G. S. , Hull M. L. , Patterson H. A.
Published: March 2008

This article describes an automated system designed to study the complete flexibility functions of the knee in vitro. The system allows five degrees of freedom with flexion angle being fixed, though adjustable from 0 to 45 deg. Loads corresponding to each of the five motions can be applied independently and in any combination. The effect of weight bearing on knee flexibility can also be studied by including axial force as one of the five loads. The relative motions are measured with LVDT’s and RVDT’s, and the loads are measured with strain gage transducers. The system is digitally controlled with a closed feedback loop, allowing for any combination of programmed loads. A control algorithm on an IBM PC/AT monitors the loads on each axis and continuously adjusts stepping motors to correctly follow programmed loads. The machine coordinate system corresponds to clinically accepted definitions of motion yet retains sequence independence for rotations. Results are presented demonstrating the repeatability of using a functional definition of axis placement to align the leg within the machine. Results are also presented demonstrating the utility of the full flexibility functions of the knee, notably in the determination of significant load interactions between anterior/posterior force and internal/external torque, and varus/valgus torque and internal/external torque.
An Analytical Model of Joint Contact
Authors: Eberhardt A. W. , Keer L. M. , Lewis J. L. , Vithoontien V.
Published: March 2008

The stress distribution in the region of contact between a layered elastic sphere and a layered elastic cavity is determined using an analytical model to simulate contact of articulating joints. The purpose is to use the solution to analyze the effects of cartilage thickness and stiffness, bone stiffness and joint curvature on the resulting stress field, and investigate the possibility of cracking of the material due to tensile and shear stresses. Vertical cracking of cartilage as well as horizontal splitting at the cartilage-calcified cartilage interface has been observed in osteoarthritic joints. The current results indicate that for a given system (material properties μ and ν constant), the stress distribution is a function of the ratio of contact radius to layer thickness (a/h), and while tensile stresses are seen to occur only when a/h is small, tensile strain is observed for all a/h values. Significant shear stresses are observed at the cartilage-bone interface. Softening of cartilage results in an increase in a/h, and a decrease in maximum normal stress. Cartilage thinning increases a/h and the maximum contact stress, while thickening has the opposite effect. A reduction in the indenting radius reduces a/h and increases the maximum normal stress. Bone softening is seen to have negligible effect on the resulting contact parameters and stress distribution.
Pulsatile Pressure and Flow in the Skeletal Muscle Microcirculation
Authors: Lee Shou-Yan , Schmid-Scho¨nbein G. W.
Published: March 2008

Although blood flow in the microcirculation of the rat skeletal muscle has negligible inertia forces with very low Reynolds number and Womersley parameter, time-dependent pressure and flow variations can be observed. Such phenomena include, for example, arterial flow overshoot following a step arterial pressure, a gradual arterial pressure reduction for a step flow, or hysteresis between pressure and flow when a pulsatile pressure is applied. Arterial and venous flows do not follow the same time course during such transients. A theoretical analysis is presented for these phenomena using a microvessel with distensible viscoelastic walls and purely viscous flow subject to time variant arterial pressures. The results indicate that the vessel distensibility plays an important role in such time-dependent microvascular flow and the effects are of central physiological importance during normal muscle perfusion. In-vivo whole organ pressure-flow data in the dilated rat gracilis muscle agree in the time course with the theoretical predictions. Hemodynamic impedances of the skeletal muscle microcirculation are investigated for small arterial and venous pressure amplitudes superimposed on an initial steady flow and pressure drop along the vessel.
A Numerical Model for Studying the Effect of Plasma Layer on the Process of Blood Oxygenation in the Pulmonary Capillaries
Authors: Sharan Maithili , Singh M. P. , Aminataei A.
Published: March 2008

A two layer model for the blood oxygenation in pulmonary capillaries is proposed. The model consists of a core of erythrocytes surrounded by a symmetrically placed plasma layer. The governing equations in the core describe the free molecular diffusion, convection, and facilitated diffusion due to the presence of haemoglobin. The corresponding equations in the plasma layer are based on the free molecular diffusion and the convective effect of the blood. According to the axial train model for the blood flow proposed by Whitmore (1967), the core will move with a uniform velocity whereas flow in the plasma layer will be fully developed. The resulting system of nonlinear partial differential equations is solved numerically. A fixed point iterative technique is used to deal with the nonlinearities. The distance traversed by the blood before getting fully oxygenated is computed. It is shown that the concentration of O2 increases continuously along the length of the capillary for a given ratio of core radius to capillary radius. It is found that the rate of oxygenation increases as the core to capillary ratio decreases. The equilibration length increases with a heterogeneous model in comparison to that in a homogeneous model. The effect of capillary diameters and core radii on the rate of oxygenation has also been examined.
Recipes for Reconstituting Skin
Authors: Bell E. , Rosenberg M. , Kemp P. , Gay R. , Green G. D. , Muthukumaran N. , Nolte C.
Published: March 2008

Reconstituted Living Skin Equivalent™ (LSE™) is made up of a dermal equivalent (DE) on which keratinocytes are plated where they give rise to a multilayered differentiated epidermis. The dermal equivalent develops through interactions between fibroblasts and collagen fibrils that begin to form after the cell-matrix precursor is cast. The gel that forms as a result of collagen polymerization and fluid trapping is contracted uniformly in all dimensions. By securing it at ends and edges in the mold in which it is cast, the final dimensions, strength and morphology of the forming tissue are altered. The same phenomena are seen in casting tubular tissues for the fabrication of small caliber blood vessel equivalents. The cells of the dermal equivalent are biosynthetically active and enrich the matrix to different degrees with secretory products, depending on how the cells are stimulated and on the presence or absence of an epidermis. Collagen biosynthesis by dermal cells in the DE is sensitive to growth factors, ascorbate concentrations and amino acid pools. Both ascorbate and TGFβ1 increase total collagen biosynthesis at least two-fold by one week after tissue formation. With TGFβ1 present, the capacity of cells in the DE to synthesize collagen increases with time, over a two-week period. If ascorbate (200 μg/ml) is added just after the tissue is cast and daily thereafter, contraction lattice is blocked, and collagen biosynthesis is enhanced relative to contracted controls that had received 200 μg/ml ascorbate once. The increase was nearly an order of magnitude over that of controls and was coordinate with a comparable increase in hyaluronate and sulfated glycosaminoglycan (GAG) production as shown by TCA-precipitable glucosamine in the intercellular matrix of the DE. Both the LSE and the Living Dermal Equivalent™ (LDE™) exhibit complex responses to UV radiation and to various chemicals that are greatly different from responses given by monolayered cells. In general, threshold doses are elevated by one or more orders of magnitude for the tissues as compared with cells in monolayer, with the LSE exhibiting higher thresholds than the DE. The immunogenicity of the human LSE has been tested in vitro. Its cells are shown to be unable to stimulate a response in a mixed lymphocyte reaction (MLR) even after Class II antigens are induced by exposure to cytokines. The basis for the immunologic neutrality of the LSE can be referred to the absence of immune system (IS) cells normally present in skin and to the specific antigenic profiles of nonimmune system (NIS) cells that must be different from those of IS cells and which, even after Class II induction, are not allostimulatory. The generality of immunologic neutrality is an essential consideration in the fabrication of tissue and organ equivalents for grafting. The idea that it can be made a graft property has been formalized in the Neutral Allograft Hypothesis.
Endothelialization of the Luminal Sac in Artificial Cardiac Prostheses: A Challenge for Both Biologists and Engineers
Authors: Lelkes P. I. , Samet M. M.
Published: March 2008

Thromboembolic complications are a major obstacle for the permanent use of artificial cardiac prostheses. Many of these complications are caused by the intrinsic thrombogenicity of the biomaterials, which are used to cast the luminal blood sac. Numerous attempts have been made to improve the hemocompatibility of the new generation of totally implantable blood pumps, mainly by physico-chemical modifications of the biopolymeric materials and the blood contacting surfaces. We, on the other hand, believe that the most promising and challenging approach, from both the biologists’ and engineers’ point of view, is to coat the luminal surfaces of cardiac prostheses with a functional monolayer of autologous endothelial cells (ECs) and thus reproduce “nature’s biocompatible blood container.” The key to lining an artificial heart with a nonthrombogenic monolayer of endothelial cells is to explore the molecular and cellular mechanisms which render the EC lining inside the beating ventricle nonthrombogenic and resistant to flow-induced shear stresses and cyclic, tensional deformations. This knowledge has then to be translated into biotechnological know-how, in order to maintain an intact EC monolayer inside the blood sac of an artificial device. In this paper we emphasize some of the bioengineering issues associated with the endothelialization of the luminal sac, and also discuss some aspects related to the blood sac itself.
Tissue Engineering by Cell Transplantation Using Degradable Polymer Substrates
Authors: Cima L. G. , Vacanti J. P. , Vacanti C. , Ingber D. , Mooney D. , Langer R.
Published: March 2008

This paper reviews our research in developing novel matrices for cell transplantation using bioresorbable polymers. We focus on applications to liver and cartilage as paradigms for regeneration of metabolic and structural tissue, but review the approach in the context of cell transplantation as a whole. Important engineering issues in the design of successful devices are the surface chemistry and surface microstructure, which influence the ability of the cells to attach, grow, and function normally; the porosity and macroscopic dimensions, which affect the transport of nutrients to the implanted cells; the shape, which may be necessary for proper function in tissues like cartilage; and the choice of implantation site, which may be dictated by the total mass of the implant and which may influence the dimensions of the device by the available vascularity. Studies show that both liver and cartilage cells can be transplanted in small animals using this approach.
Bioengineering in Development of the Hybrid Artificial Pancreas
Authors: Colton C. K. , Avgoustiniatos E. S.
Published: March 2008

The hybrid artificial pancreas for treatment of diabetes consists of insulin-secreting pancreatic tissue which is surrounded by a membrane that protects the tissue from rejection by the immune system following implantation. In this paper, we review the alternative therapeutic approaches for diabetes under study and then discuss the technical requirements that must be met by a hybrid device useful to humans. Previous work on intravascular and extravascular immunoisolation devices is reviewed from the standpoint of these requirements, and three critical unresolved issues are discussed: biocompatibility, oxygen supply limitations, and prevention of immune rejection.
Semipermeable Polymer Tubes Provide a Microenvironment for In Vivo Analysis of Dorsal Root Regeneration
Authors: Lustgarten J. H. , Proctor M. , Haroun R. I. , Avellino A. M. , Pindzola A. A. , Kliot M.
Published: March 2008

The regeneration of lesioned axons is critically influenced by the local microenvironment. In this study, semipermeable polymer tubes were used to provide a defined microenvironment in vivo to analyze the regeneration of dorsal root axons under various conditions in the adult rat. Cut dorsal root fibers grew across a 2.7 mm gap within enclosed polymer tubes by 4 weeks. The pattern of axonal outgrowth was dramatically influenced by mechanical factors such as the inner surface topography of the polymer tube. Tubes containing various molecular and cellular substrates were also used to study their effect on dorsal root regeneration.
Candidates for the Mechanosensory System in Bone
Authors: Cowin S. C. , Moss-Salentijn L. , Moss M. L.
Published: March 2008

Some potential mechanisms by which bone cells sense mechanical loads are described and hypotheses concerning the functioning of these mechanisms are explored. It is well known that bone tissue adapts its structure to its mechanical load environment. Recent research has illuminated the biological response of bone to mechanical loading at the cellular level, but the precise mechanosensory system that signals bone cells to deposit or resorb tissue has not been identifed. The purpose of this paper is to describe the current status of this research and to suggest some possible mechanosensory systems by which bone cells might sense environmental loads.
The Effects of Knee Motion and External Loading on the Length of the Anterior Cruciate Ligament (ACL): A Kinematic Study
Authors: Hollis J. M. , Takai S. , Adams D. J. , Horibe S. , Woo S. L.-Y.
Published: March 2008

A six-degrees-of-freedom mechanical linkage device was designed and used to study the unconstrained motion of ten intact human cadaver knees. The knees were subjected to externally applied varus and valgus (V-V) moments up to 14 N-m as well as anterior and posterior (A-P) loads up to 100 N. Tests were done at four knee flexion angles; 0, 30, 45, and 90 deg. Significant coupled axial tibial rotation was found, up to 21.0 deg for V-V loading (at 90 deg of flexion) and 14.2 deg for A-P loading (at 45 deg of flexion). Subsequently, the knees were dissected and the locations of the insertion sites to the femur and tibia for the anteromedial (AM), posterolateral (PL), and intermediate (IM) portions of the ACL were identified. The distances between the insertion sites for all external loading conditions were calculated. In the case when the external load was zero, the AM portion of the ACL lengthened with knee flexion, while the PL portion shortened and the intermediate (IM) portion did not change in length. With the application of 14 N-m valgus moment, the PL and IM portions of the ACL lengthened significantly more than the AM portion (p<0.001). With the application of 100 N anterior load, the AM portion lengthened slightly less than the PL portion, which lengthened slightly less than the IM portion (p<0.005). In general, the amount of lengthening of the three portions of the ACL during valgus and anterior loading was observed to increase with knee flexion angle (p< 0.001).