Simplified Characterization of Anisotropic Yield Criteria for an Injection-Molded Polymer Material.

Injection-molded polyethylene plates exhibit highly anisotropic mechanical behavior due to, e.g., the uneven orientation of the polymer chains during the molding process and the differential cooling, especially in the thickness direction. Elastoplastic finite element modeling of these plates in particular is used with isotropic yield criteria like von Mises, trading off accuracy in favor of simpler constitutive characterization and faster solution. This article studies three different anisotropic yield criteria, namely, Hill 1948, Barlat Yld91, and Barlat Yld2004-18P, for the finite element modeling of low-density polyethylene (LDPE) at large uniaxial tensile deformation and compares the accuracy and computation time with von Mises. A simplified calibration technique is investigated to identify the constitutive parameters of the studied Barlat group yield criteria. The calibration process is simplified in the sense that only uniaxial tensile tests with digital image correlation measurements are used for the calibration of all the yield criteria studied in this article, although a standard calibration procedure for the Barlat group yield criteria requires additional material testing using more demanding test setups. It is concluded that both Barlat Yld91 and Barlat Yld2004-18P yield criteria can be calibrated with only a few tensile tests and still capture anisotropy in deformation-stress-strain at different levels of accuracy.

Longitudinal alterations in mRNA expression of the BDNF neurotrophin signaling cascade in blood correlate with changes in depression scores in patients undergoing electroconvulsive therapy.

Electroconvulsive therapy (ECT) appears to be the most effective treatment for severe depression. However, its mechanisms of action are incompletely understood. Evidence suggests ECT enhances neuroplasticity and neurogenesis. While studies on ECT-induced neuroplasticity focused on brain-derived neurotrophic factor (BDNF), other factors of the BDNF/TrkB signaling cascade remain underinvestigated. We assessed longitudinal changes in depression scores, serum BDNF protein levels, and mRNA expression of BDNF/TrkB related genes (BDNF, AKT1, ERK1, CREB), NR3C1 and IGF1 in peripheral blood in 19 treatment-resistant depressed patients undergoing ECT. We also analysed DNA methylation patterns at various timepoints to explore possible epigenetic regulation of mRNA expression. Using multilevel regression, we found a negative association between depression scores and blood-based mRNA expression of BDNF/TrkB related genes and NR3C1. Expression of BDNF, ERK1 and NR3C1 increased significantly over time (BDNF: ß = 0.0295, p = 0.003; ERK1: ß = 0.0170, p = 0.034; NR3C1: ß = 0.0035, p = 0.050). For these three genes changes in mRNA expression were highly correlated (R = 0.59 - 0.88) with changes in DNA methylation for multiple CpG sites in the respective genes. Also, serum BDNF protein levels increased across the study period (ß = 0.11, p = 0.001). Our findings show that the antidepressant effects of ECT are associated with changes in expression of BDNF and its signaling molecules and that these molecular markers can be detected in peripheral blood. Alterations in DNA methylation could be a key mechanism whereby ECT influences gene expression.

The impact of electroconvulsive therapy on the tryptophan-kynurenine metabolic pathway.

BACKGROUND: There is still limited knowledge about the mechanism of action of electroconvulsive therapy (ECT) in the treatment of depression. Substantial evidence suggests a role for the immune-moderated tryptophan (TRP)-kynurenine (KYN) pathway in depression; i.e. a depression-associated disturbance in the balance between the TRP-KYN metabolites towards a neurotoxic process. We, therefore, aimed to investigate the impact of ECT treatment on the TRP-KYN pathway, in association with ECT-related alterations in depressive symptoms. METHOD: Twenty-three patients with unipolar or bipolar depression, treated with bilateral ECT twice a week were recruited. Blood serum samples, and depression scores using the Hamilton Depression Rating Scale-17 items (HDRS) as well as the Beck Depression Inventory (BDI) were collected repeatedly during the period of ECT and until 6 weeks after the last ECT session. TRP and KYN metabolites were analyzed in serum using the High Performance Liquid Chromatography. Four patients could not complete the study; thereby yielding data of 19 patients. Analyses were performed using multilevel linear regression analysis. RESULTS: There was an increase in kynurenic acid (KYNA) (B=0.04, p=0.001), KYN/TRP ratio (B=0.14, p=0.001), KYNA/KYN ratio (B=0.07, p<0.0001), and KYNA/3-hydroxykynurenine ratio (B=0.01, p=0.008) over time during the study period. KYN (B=-0.02, p=0.003) and KYN/TRP (B=-0.19, p=0.003) were negatively associated with total HDRS over time. Baseline TRP metabolite concentrations did not predict time to ECT response. CONCLUSION: Our findings show that ECT influences the TRP-KYN pathway, with a shift in TRP-KYN metabolites balance towards molecules with neuroprotective properties correlating with antidepressant effects of ECT; thereby providing a first line of evidence that the mechanism of action of ECT is (co)mediated by the TRP-KYN pathway.

Effects on neurite outgrowth and cell survival of a secreted fibroblast growth factor binding protein upregulated during spinal cord injury.

The fibroblast growth factor binding protein (FGF-BP; GenBank accession no. NP_005121) is a secreted protein that mobilizes FGFs from the extracellular matrix, protects them from degradation, and enhances their biological activity. Several previous studies reported that FGF-BP is an early response gene upregulated during tissue repair processes including wound healing and atherogenesis. In this study we analyzed whether FGF-BP expression was impacted by spinal cord injury and could have an effect on neuronal cell viability. Immunohistochemical and in situ hybridization studies revealed a dramatic upregulation of FGF-BP protein and mRNA levels following unilateral hemisection and contusion injury of adult rat spinal cord. In spinal cord sections of laminectomized rats, increased FGF-BP expression was observed in the fibers and cell bodies ipsilateral to the lesion site but was absent in the uninjured spinal cord tissue contralateral to the lesion. Increased expression of FGF-BP was observed at all postinjury time points, examined with peak levels occurring at day 4, a time when injury-induced increased levels of FGF2 have also been reported to be maximal. Moreover, using PC12 cells as a neuronal model, we observed that exogenous FGF-BP increased the capacity of FGF2 to stimulate neurite outgrowth and to increase cell survival. At the molecular level, FGF-BP enhanced FGF2-induced protein tyrosine phosphorylation and AKT/PKB activation. Collectively, these results suggest that FGF-BP is an early response gene after spinal cord injury and that its upregulation in regenerating spinal cord tissue may provide a molecular mechanism for enhancing the initial FGF2-mediated neurotrophic effects occurring after such tissue damage.