Application of a Finite Element Model to a Cold-formed Steel C-section with a Bearing Stiffener

Described in this paper is the application of a finite element model to a cold-formed steel C-section with a bearing stiffener installed between its flanges. This model has been used to determine both the web crippling capacity of the joist, and the forces that develop in the fasteners connecting the bearing stiffener to the joist. The finite element model was also used to carry out parametric studies of the stiffened joist assembly to determine the impact on the web crippling capacity and the fastener forces caused by variations in the assembly. Based on the results of these finite element studies, combined with available experimental work, a design expression has been proposed that can calculate the web crippling capacity of a cold formed steel C-section joist that has a bearing stiffener installed between the joist flanges. A second design expression has been proposed for predicting the forces in the fasteners that connect the joist to the stiffener. Predictions of both the web crippling capacity and the fastener forces are necessary for determining the ultimate strength of the stiffened joist assembly

Digital tracking algorithm reveals the influence of structural irregularities on joint movements in the human cervical spine

The final publication is available at Elsevier via https://dx.doi.org/10.1016/j.clinbiomech.2018.04.015 © 2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/Background Disc height loss and osteophytes change the local mechanical environment in the spine; while previous research has examined kinematic dysfunction under degenerative change, none has looked at the influence of disc height loss and osteophytes throughout movement. Methods Twenty patients with pain related to the head, neck or shoulders were imaged via videofluoroscopy as they underwent sagittal-plane flexion and extension. A clinician graded disc height loss and osteophytes as “severe/moderate”, “mild”, or “none”. A novel tracking algorithm quantified motions of each vertebra. This information was used to calculate intervertebral angular and shear displacements. The digital algorithm made it practical to track individual vertebrae in multiple patients through hundreds of images without bias. Findings Cases without height loss/osteophytes had a consistent increase in intervertebral angular displacement from C2/C3 to C5/C6, like that of healthy individuals, and mild height losses did not produce aberrations that were systematic or necessarily discernable. However, joints with moderate to severe disc height loss and osteophytes exhibited reduced range of motion compared to adjacent unaffected joints in that patient and corresponding joints in patients without structural irregularities. Interpretation Digitally-obtained motion histories of individual joints allowed anatomical joint changes to be linked with changes in joint movement patterns. Specifically, disc height loss and osteophytes were found to influence cervical spine movement in the sagittal plane, reducing angular motions at affected joints by approximately 10% between those with and without height loss and osteophytes. Further, these joint changes were associated with perturbed intervertebral angular and shear movements.Natural Sciences and Engineering Research Council (NSERC) Discovery Grant

DRhoGEF2 Regulates Cellular Tension and Cell Pulsations in the Amnioserosa during Drosophila Dorsal Closure

Coordination of apical constriction in epithelial sheets is a fundamental process during embryogenesis. Here, we show that DRhoGEF2 is a key regulator of apical pulsation and constriction of amnioserosal cells during Drosophila dorsal closure. Amnioserosal cells mutant for DRhoGEF2 exhibit a consistent decrease in amnioserosa pulsations whereas overexpression of DRhoGEF2 in this tissue leads to an increase in the contraction time of pulsations. We probed the physical properties of the amnioserosa to show that the average tension in DRhoGEF2 mutant cells is lower than wild-type and that overexpression of DRhoGEF2 results in a tissue that is more solid-like than wild-type. We also observe that in the DRhoGEF2 overexpressing cells there is a dramatic increase of apical actomyosin coalescence that can contribute to the generation of more contractile forces, leading to amnioserosal cells with smaller apical surface than wild-type. Conversely, in DRhoGEF2 mutants, the apical actomyosin coalescence is impaired. These results identify DRhoGEF2 as an upstream regulator of the actomyosin contractile machinery that drives amnioserosa cells pulsations and apical constriction

Cell-Sorting at the A/P Boundary in the Drosophila Wing Primordium: A Computational Model to Consolidate Observed Non-Local Effects of Hh Signaling

Non-intermingling, adjacent populations of cells define compartment boundaries; such boundaries are often essential for the positioning and the maintenance of tissue-organizers during growth. In the developing wing primordium of Drosophila melanogaster, signaling by the secreted protein Hedgehog (Hh) is required for compartment boundary maintenance. However, the precise mechanism of Hh input remains poorly understood. Here, we combine experimental observations of perturbed Hh signaling with computer simulations of cellular behavior, and connect physical properties of cells to their Hh signaling status. We find that experimental disruption of Hh signaling has observable effects on cell sorting surprisingly far from the compartment boundary, which is in contrast to a previous model that confines Hh influence to the compartment boundary itself. We have recapitulated our experimental observations by simulations of Hh diffusion and transduction coupled to mechanical tension along cell-to-cell contact surfaces. Intriguingly, the best results were obtained under the assumption that Hh signaling cannot alter the overall tension force of the cell, but will merely re-distribute it locally inside the cell, relative to the signaling status of neighboring cells. Our results suggest a scenario in which homotypic interactions of a putative Hh target molecule at the cell surface are converted into a mechanical force. Such a scenario could explain why the mechanical output of Hh signaling appears to be confined to the compartment boundary, despite the longer range of the Hh molecule itself. Our study is the first to couple a cellular vertex model describing mechanical properties of cells in a growing tissue, to an explicit model of an entire signaling pathway, including a freely diffusible component. We discuss potential applications and challenges of such an approach

Validation of a 40-Gene Expression Profile Test to Predict Metastatic Risk in Localized High-Risk Cutaneous Squamous Cell Carcinoma

Background: Current staging systems for cutaneous squamous cell carcinoma (cSCC) have limited positive predictive value (PPV) for identifying patients who will experience metastasis. Objective: To develop and validate a gene expression profile (GEP) test for predicting risk for metastasis in localized, high-risk cSCC with the goal of improving risk-directed patient management. Methods: Archival formalin-fixed paraffin-embedded primary cSCC tissue and clinicopathologic data (n=586) were collected from 23 independent centers in a prospectively designed study. A GEP signature was developed using a discovery cohort (n=202) and validated in a separate, non-overlaping, independent cohort (n=324). Results: A prognostic, 40-gene expression profile (40-GEP) test was developed and validated, stratifying high-risk cSCC patients into classes based on metastasis risk: Class 1 (low-risk), Class 2A (high-risk), and Class 2B (highest-risk). For the validation cohort, 3-year metastasis-free survival (MFS) rates were 91.4%, 80.6%, and 44.0%, respectively. A PPV of 60% was achieved for the highest-risk group (Class 2B), an improvement over staging systems; while negative predictive value, sensitivity, and specificity were comparable to staging systems. Limitations: Potential understaging of cases could affect metastasis rate accuracy.Conclusion: The 40-GEP test is an independent predictor of metastatic risk that can complement current staging systems for patients with high-risk cSCC

N2L 3G1 Large-Strain Axisymmetric Deformation of Cylindrical Shells

Introduction Much of the research on axisymmetric deformation of shells of revolution is based on sets of equations, such as those of This paper develops energy-form, large-strain constitutive equations for the axisymmetric deformation of thin, cylindrical shells made of Mooney-Rivlin materials. No limitations are placed on the magnitude of strains. It is only required that a relaxed form of the Kirchhoff hypothesis apply; i.e., fibers remain straight and normal to the middle surface during deformation, but may change in length. A variational principle is used to find the deformed configuration. Numerical implementation of the equations circumvents the need to restrict strains and rotations. The axisymmetric behavior of a cylindrical shell of length I, radius a, and thickness h, which is clamped at one end and loaded with either a radial load Q or an edge moment Mat the other is then investigated (se