Characterization of IGH locus breakpoints in multiple myeloma indicates a subset of translocations appear to occur in pregerminal center B cells.

Translocations in myeloma are thought to occur solely in mature B cells in the germinal center through class switch recombination (CSR). We used a targeted captured technique followed by massively parallel sequencing to determine the exact breakpoints in both the immunoglobulin heavy chain (IGH) locus and the partner chromosome in 61 presentation multiple myeloma samples. The majority of samples (62%) have a breakpoint within the switch regions upstream of the IGH constant genes and are generated through CSR in a mature B cell. However, the proportion of CSR translocations is not consistent between cytogenetic subgroups. We find that 100% of t(4;14) are CSR-mediated; however, 21% of t(11;14) and 25% of t(14;20) are generated through DH-JH recombination activation gene-mediated mechanisms, indicating they occur earlier in B-cell development at the pro-B-cell stage in the bone marrow. These 2 groups also generate translocations through receptor revision, as determined by the breakpoints and mutation status of the segments used in 10% and 50% of t(11;14) and t(14;20) samples, respectively. The study indicates that in a significant number of cases the translocation-based etiological events underlying myeloma may arise at the pro-B-cell hematological progenitor cell level, much earlier in B-cell development than was previously thought.

Modelling the crush behaviour of thermoplastic composites

Thermoplastic composites are likely to emerge as the preferred solution for meeting the high-volume production demands of passenger road vehicles. Substantial effort is currently being directed towards the development of new modelling techniques to reduce the extent of costly and time consuming physical testing. Developing a high-fidelity numerical model to predict the crush behaviour of composite laminates is dependent on the accurate measurement of material properties as well as a thorough understanding of damage mechanisms associated with crush events. This paper details the manufacture, testing and modelling of self-supporting corrugated-shaped thermoplastic composite specimens for crashworthiness assessment. These specimens demonstrated a 57.3% higher specific energy absorption compared to identical specimen made from thermoset composites. The corresponding damage mechanisms were investigated in-situ using digital microscopy and post analysed using Scanning Electron Microscopy (SEM). Splaying and fragmentation modes were the 2 primary failure modes involving fibre breakage, matrix cracking and delamination. A mesoscale composite damage model, with new non-linear shear constitutive laws, which combines a range of novel techniques to accurately capture the material response under crushing, is presented. The force-displacement curves, damage parameter maps and dissipated energy, obtained from the numerical analysis, are shown to be in a good qualitative and quantitative agreement with experimental results. The proposed approach could significantly reduce the extent of physical testing required in the development of crashworthy structures.