Activin signaling as an emerging target for therapeutic interventions

After the initial discovery of activins as important regulators of reproduction, novel and diverse roles have been unraveled for them. Activins are expressed in various tissues and have a broad range of activities including the regulation of gonadal function, hormonal homeostasis, growth and differentiation of musculoskeletal tissues, regulation of growth and metastasis of cancer cells, proliferation and differentiation of embryonic stem cells, and even higher brain functions. Activins signal through a combination of type I and II transmembrane serine/threonine kinase receptors. Activin receptors are shared by multiple transforming growth factor-β (TGF-β) ligands such as myostatin, growth and differentiation factor-11 and nodal. Thus, although the activity of each ligand is distinct, they are also redundant, both physiologically and pathologically in vivo. Activin receptors activated by ligands phosphorylate the receptor-regulated Smads for TGF-β, Smad2 and 3. The Smad proteins then undergo multimerization with the co-mediator Smad4, and translocate into the nucleus to regulate the transcription of target genes in cooperation with nuclear cofactors. Signaling through receptors and Smads is controlled by multiple mechanisms including phosphorylation and other posttranslational modifications such as sumoylation, which affect potein localization, stability and transcriptional activity. Non-Smad signaling also plays an important role in activin signaling. Extracellularly, follistatin and related proteins bind to activins and related TGF-β ligands, and control the signaling and availability of ligands

Strength prediction for bi-axial braided composites by a multi-scale modelling approach

The final publication is available at Springer via http://dx.doi.org/10.1007/s10853-016-9901-z.Braided textile-reinforced composites have become increasingly attractive as protection materials thanks to their unique inter-weaving structures and excellent energy-absorption capacity. However, development of adequate models for simulation of failure processes in them remains a challenge. In this study, tensile strength and progressive damage behaviour of braided textile composites are predicted by a multi-scale modelling approach. First, a micro-scale model with hexagonal arrays of fibres was built to compute effective elastic constants and yarn strength under different loading conditions. Instead of using cited values, the input data for this micro-scale model were obtained experimentally. Subsequently, the results generated by this model were used as input for a meso-scale model. At meso-scale, Hashin’s 3D with Stassi’s failure criteria and a modified Murakami-type stiffness-degradation scheme was employed in a user-defined subroutine developed in the general-purpose finite-element software Abaqus/Standard. An overall stress–strain curve of a meso-scale representative unit cell was verified with the experimental data. Numerical studies show that bias yarns suffer continuous damage during an axial tension test. The magnitudes of ultimate strengths and Young’s moduli of the studied braided composites decreased with an increase in the braiding angle

Monitoring of acoustic emission damage during tensile loading of 3D woven carbon/epoxy composites

Registration of acoustic emission (AE) events during tensile loading of fiber-reinforced composites allows the damage caused by these events to be defined and monitored, including damage initiation and progression thresholds. It also provides frequency-based recognition of different types of damage and comparison of its intensity in materials with different reinforcement architectures. The paper reports results of AE registration for 3D non-crimp orthogonal woven (3DNCOW) carbon/epoxy composites. The observed repeatability and spatial distribution of AE events confirm that damage initiation and development are uniform over the tensile sample. The damage characterization by AE is compared with the morphology of damage observed on the specimen cross-sections at characteristic stages of the damage development. The main parameter distinguishing damage mode obtained from the AE registration is the AE energy. It has however been found that the peak frequency of the AE events does not correlate directly with the sequence of the observed damage modes. AE events of high peak frequency, assumed to be related to fiber fracture, suggest that it starts at a later stage than predicted by the Weibull statistics of fiber strength.status: publishe

Internal geometry evaluation of non-crimp 3D orthogonal woven carbon fabric composite

Measurements of the internal geometry of a carbon fiber non-crimp 3D orthogonal woven composite are presented, including: waviness of the yarns, cross sections of the yarns, dimensions of the yarn cross sections, and local fiber volume fraction. The measured waviness of warp and fill yarns are well below 0.1%, which shows that the fabric termed here ‘‘non-crimp” has nearly straight in-plane fibers as-produced, and this feature is maintained after going through all steps of fabric handling and composite manufacturing. The variability of dimensions of the yarns is in the range of 4–8% for warp and fill directions, while the variability of the yarn spacing is in the range of 3–4%. These variability parameters are lower than respective ranges of variability of the yarn waviness and the cross-sectional dimensions in typical carbon 2D weave and 3D interlock weave composites, which are also illustrated in this work for comparison.status: publishe