A stabilized finite element method for finite-strain three-field poroelasticity

We construct a stabilized finite-element method to compute flow and finitestrain deformations in an incompressible poroelastic medium. We employ a three- field mixed formulation to calculate displacement, fluid flux and pressure directly and introduce a Lagrange multiplier to enforce flux boundary conditions. We use a low order approximation, namely, continuous piecewise-linear approximation for the displacements and fluid flux, and piecewise-constant approximation for the pressure. This results in a simple matrix structure with low bandwidth. The method is stable in both the limiting cases of small and large permeability. Moreover, the discontinuous pressure space enables efficient approximation of steep gradients such as those occurring due to rapidly changing material coefficients or boundary conditions, both of which are commonly seen in physical and biological applications

Neural responses to others’ pain vary with psychopathic traits in healthy adult males

Disrupted empathic processing is a core feature of psychopathy. Neuroimaging data have suggested that individuals with high levels of psychopathic traits show atypical responses to others' pain in a network of brain regions typically recruited during empathic processing (anterior insula, inferior frontal gyrus, and mid- and anterior cingulate cortex). Here, we investigated whether neural responses to others' pain vary with psychopathic traits within the general population in a similar manner to that found in individuals at the extreme end of the continuum. As predicted, variation in psychopathic traits was associated with variation in neural responses to others' pain in the network of brain regions typically engaged during empathic processing. Consistent with previous research, our findings indicated the presence of suppressor effects in the association of levels of the affective-interpersonal and lifestyle-antisocial dimensions of psychopathy with neural responses to others' pain. That is, after controlling for the influence of the other dimension, higher affective-interpersonal psychopathic traits were associated with reduced neural responses to others' pain, whilst higher lifestyle-antisocial psychopathic traits were associated with increased neural responses to others' pain. Our findings provide further evidence that atypical function in this network might represent neural markers of disrupted emotional and empathic processing; that the two dimensions of psychopathy might tap into distinct underlying vulnerabilities; and, most importantly, that the relationships observed at the extreme end of the psychopathy spectrum apply to the nonclinical distribution of these traits, providing further evidence for continuities in the mechanisms underlying psychopathic traits across the general population

As Far as the Eye Can See: Relationship between Psychopathic Traits and Pupil Response to Affective Stimuli

Psychopathic individuals show a range of affective processing deficits, typically associated with the interpersonal/affective component of psychopathy. However, previous research has been inconsistent as to whether psychopathy, within both offender and community populations, is associated with deficient autonomic responses to the simple presentation of affective stimuli. Changes in pupil diameter occur in response to emotionally arousing stimuli and can be used as an objective indicator of physiological reactivity to emotion. This study used pupillometry to explore whether psychopathic traits within a community sample were associated with hypo-responsivity to the affective content of stimuli. Pupil activity was recorded for 102 adult (52 female) community participants in response to affective (both negative and positive affect) and affectively neutral stimuli, that included images of scenes, static facial expressions, dynamic facial expressions and sound-clips. Psychopathic traits were measured using the Triarchic Psychopathy Measure. Pupil diameter was larger in response to negative stimuli, but comparable pupil size was demonstrated across pleasant and neutral stimuli. A linear relationship between subjective arousal and pupil diameter was found in response to sound-clips, but was not evident in response to scenes. Contrary to predictions, psychopathy was unrelated to emotional modulation of pupil diameter across all stimuli. The findings were the same when participant gender was considered. This suggests that psychopathy within a community sample is not associated with autonomic hypo-responsivity to affective stimuli, and this effect is discussed in relation to later defensive/appetitive mobilisation deficits

Discrimination of meniscal cell phenotypes using gene expression profiles

The lack of quantitative and objective metrics to assess cartilage and meniscus cell phenotypes contributes to the challenges in fibrocartilage tissue engineering. Although functional assessment of the final resulting tissue is essential, initial characterization of cell sources and quantitative description of their progression towards the natural, desired cell phenotype would provide an effective tool in optimizing cell-based tissue engineering strategies. The purpose of this study was to identify quantifiable characteristics of meniscal cells and thereby find phenotypical markers that could effectively categorize cells based on their tissue of origin (cartilage, inner, middle, and outer meniscus). The combination of gene expression ratios collagen VI/collagen II, ADAMTS-5/collagen II, and collagen I/collagen II was the most effective indicator of variation among different tissue regions. We additionally demonstrate a possible application of these quantifiable metrics in evaluating the use of serially passaged chondrocytes as a possible cell source in fibrocartilage engineering. Comparing the ratios of the passaged chondrocytes and the native meniscal cells may provide direction to optimize towards the desired cell phenotype. We have thus shown that measurable markers defining the characteristics of the native meniscus can establish a standard by which different tissue engineering strategies can be objectively assessed. Such metrics could additionally be useful in exploring the different stages of meniscal degradation in osteoarthritis and provide some insight in the disease progression

Triceratops Marsh 1889

A recently unearthed Triceratops sp. pelvis from the Hell Creek Formation of Montana (USA) bears dozens of large bite marks (Fig. 1)8. Casts ofsome of the deeper punctures show that an adult T. rex produced the marks using its longer anterior caniniform teeth8. The bitten bones are predominantly composed of cancellous bone tissue, capped only by a thin layer of dense cortical bone8. On the basis of these marks, it is difficult to gauge whether the teeth that produced the bite marks were particularly robust. We attempted to quantify the forces that the tyrannosaur dentition absorbed when biting the Triceratops ilium, by using laboratory simulations. W e contrasted the results with those for extant taxa to place them in a comparative context, and assessed the functional and behavioural implications of these comparisons. Using histological examination we determined that extant bovine ilia exhibit comparable microstructure to Triceratops ilia. Consequently, bovine ilia were used to model the bitten Triceratops bones. Sections of ili a with cortices ofvarying thickness were penetrated with a T rex tooth replica to a depth of 11.5 mm (the depth of the deepest ilium bite mark8) using a servohydraulic mechanical loading frame. The forces produced throughout these simulations were recorded. When indented, the bovine ilia exhibited localized crushing as the only mode of failure, and the punctures produced were comparable in morphology to the T rex bite marks. The forces during testing increased with increasing penetration depths (Fig. 2). Peak forces ranged from 1,900 to 15,100 N (Fig. 3). A positive correlation between peak penetration force and cortical thickness was found (Fig. 3). A bone sample removed from the bitten Triceratops ilium within 2cm of the deepest bite mark (11.5mm) revealed a cortical thickness of 2.5 mm. From a linear regression of our data (Fig. 3), we determined that roughly 6,410N of force was required to produce the bite mark. E stimates as great as 13,400 N for posterior teeth were obtained when biting velocity, energy absorptio n by flesh, and the mechanical advantage of poste rior teeth relative to more anterior teeth were taken into consideration (Fig. 3). These bite-force estimates make it possible to evaluate speculations on tyrannosaur tooth strength and potential behaviours using comparisons with extant taxa. The largest m aximum bite force measureme nts or estimates for extant vertebrates at posterior tooth positions are: 550 N for labrador dogs9, 749 N for humans10, 1,412 N for wolves11, 1,446 N for dusky sharks (location of force measurement within jaw not given)n, 1,712 N for orangutans1.1, 4,168 for lions11, and 13,300 N for American alligators14 (K. A Vliet, personal communication). Using bite force as a relative indicator of dental strength, the results suggest that T rex teeth were as strong as, or in most cases substantially stronger than, those of any extant taxa tested to date. Consequently speculations that their dentition was mechanically weak were not supported. Peak bite-force estimates for large American alligators (Alligator mississipiensis) are within the range we calculated for a feeding T. rex. This taxon shares many dental attributes with T. rex (including thecodont implantation15,16, stout semi-sharp caniniform teeth that are transversely rounded6,7, 16, and nearly identical histological structures17, 18). These morphological similarities imply similarity in function19 Alligators use their teeth to procure large prey and to engage conspecifics during confrontations20 Both activities demand teeth that can sustain large compression and bending forces, particularly because impacts with bones are frequent20 The bite-force estimates and tooth mark evidence show that T. rex teeth could similarly withstand large bite forces and sustain repetitive bone impacts. Therefore, it is not unreasonable to suspect that the T. rex dentition could be used in behaviours similar to those of alligators, and with some mechanical safety21 Physical evidence supports this reasoning. Bony calli on adult tyrannosaur crania attest to biting injuries during intraspccific aggression22, 23, and a healed hadrosaur tail injury has been attributed to biting by a T. rex during a failed predation attempt5. Although our data suggest that T. rex could produce enormous bite forces and possessed a dentition that could endure stresses associated with prey struggles, they by no means prove that T. rex was predacious. Indeed it could be argued that these characteristics enhanced their utilization of scavenged carcasses. Nevertheless, these results refute assertions that T. rex was mechanically limited by its dentition to scavenging carrion. We contend that if T. rex could consistently manoeuvre into a position to engage prey with its dentition, it could have exploited a predatory niche. It has been shown recently that theropod bite marks are much more common in the fossil record that was once suspected8 24 25 Consequently, the methods used here could be used to assess biteforce estimates for other tyrannosaur individuals, as well as for many theropod species. Such data would greatly augment our understanding of dinosaur tooth form and function, the physical capacities of their teeth and jaws (ontogenetically and interspecifically), and provide new insight into the musculoskeletal biomechanics of dinosaur crania.Published as part of Erickson, Gregory M., Van Kirk, Samuel D., Su, Jinntung, Levenston, Marc E., Caler, William E. & Carter, Dennis R., 1996, Bite-force estimation for Tyrannosaurus rex from tooth-marked bones, pp. 706-708 in Nature 382 (6593) on pages 706-707, DOI: 10.1038/382706a0, http://zenodo.org/record/373096

Cyclic Tensile Culture Promotes Fibroblastic Differentiation of Marrow Stromal Cells Encapsulated in Poly(Ethylene Glycol)-Based Hydrogels

To inform future efforts in tendon/ligament tissue engineering, our laboratory has developed a well-controlled model system with the ability to alter both external tensile loading parameters and local biochemical cues to better understand marrow stromal cell differentiation in response to both stimuli concurrently. In particular, the synthetic, poly(ethylene glycol)-based hydrogel material oligo(poly(ethylene glycol) fumarate) (OPF) has been explored as a cell carrier for this system. This biomaterial can be tailored to present covalently incorporated bioactive moieties and can be loaded in our custom cyclic tensile bioreactor for up to 28 days with no loss of material integrity. Human marrow stromal cells encapsulated in these OPF hydrogels were cultured (21 days) under cyclic tensile strain (10%, 1 Hz, 3 h of strain followed by 3 h without) or at 0% strain. No difference was observed in cell number due to mechanical stimulation or across time (n = 4), with cells remaining viable (n = 4) through 21 days. Cyclic strain significantly upregulated all tendon/ligament fibroblastic genes examined (collagen I, collagen III, and tenascin-C) by day 21 (n ≥ 6), whereas genes for other pathways (osteogenic, chondrogenic, and adipogenic) did not increase. After 21 days, the presence of collagen I and tenascin-C was observed via immunostaining (n = 2). This study demonstrates the utility of this hydrogel/bioreactor system as a versatile, yet well-controlled, model environment to study marrow stromal cell differentiation toward the tendon/ligament phenotype under a variety of conditions

Validating MRI-Derived Myocardial Stiffness Estimates Using In Vitro Synthetic Heart Models

Impaired cardiac filling in response to increased passive myocardial stiffness contributes to the pathophysiology of heart failure. By leveraging cardiac MRI data and ventricular pressure measurements, we can estimate in vivo passive myocardial stiffness using personalized inverse finite element models. While it is well-known that this approach is subject to uncertainties, only few studies quantify the accuracy of these stiffness estimates. This lack of validation is, at least in part, due to the absence of ground truth in vivo passive myocardial stiffness values. Here, using 3D printing, we created soft, homogenous, isotropic, hyperelastic heart phantoms of varying geometry and stiffness and simulate diastolic filling by incorporating the phantoms into an MRI-compatible left ventricular inflation system. We estimate phantom stiffness from MRI and pressure data using inverse finite element analyses based on a Neo-Hookean model. We demonstrate that our identified softest and stiffest values of 215.7 and 512.3 kPa agree well with the ground truth of 226.2 and 526.4 kPa. Overall, our estimated stiffnesses revealed a good agreement with the ground truth (< 5.8 % error) across all models. Our results suggest that MRI-driven computational constitutive modeling can accurately estimate synthetic heart material stiffnesses in the range of 200–500 kPa.Green Open Access added to TU Delft Institutional Repository 'You share, we take care!' - Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Medical Instruments & Bio-Inspired Technolog