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A high‐fidelity finite element model is proposed for the complete simulation of the time‐harmonic acoustic propagation in wind instruments. The challenge is to meet the extremely high accuracy required by professional musicians, in a complex domain, for all fingerings and over a wide frequency range, within an affordable computational time. Several modelling assumptions are made to limit the numerical complexity of the problem while preserving all relevant physics. A dedicated high‐performance solution strategy is also proposed, based on partitioning, condensation and model order reduction, exploiting the combinatorial nature of wind instrument fingerings. Finally, the proposed approach is applied to the simulation of an alto saxophone. An order of magnitude reduction in memory and computational cost is achieved. [ABSTRACT FROM AUTHOR]

Over a range roughly C5–C6, sopranos usually tune their first vocal tract resonance (R1) to the fundamental frequency (fo) of the note sung: R1:fo tuning. Those who sing well above C6 usually adjust their second vocal tract resonance (R2) and use R2:fo tuning. This study investigated these questions: Can singers quickly learn R2:fo tuning when given suitable feedback? Can they subsequently use this tuning without feedback? And finally, if so, does this assist their singing in the high range? New computer software for the technique of resonance estimation by broadband excitation at the lips was used to provide real-time visual feedback on fo and vocal tract resonances. Eight sopranos participated. In a one-hour session, they practised adjusting R2 whilst miming (i.e. without phonating), and then during singing. Six sopranos learned to tune R2 over a range of several semi-tones, when feedback was present. This achievement did not immediately extend their singing range. When the feedback was removed, two sopranos spontaneously used R2:fo tuning at the top of their range above C6. With only one hour of training, singers can learn to adjust their vocal tract shape for R2:fo tuning when provided with visual feedback. One additional participant who spent considerable time with the software, acquired greater skill at R2:fo tuning and was able to extend her singing range. A simple version of the hardware used can be assembled using basic equipment and the software is available online. [ABSTRACT FROM AUTHOR]

Chronic myeloid leukemia (CML) tumorigenicity is driven by the oncogenic BCR-ABL tyrosine kinase. Specific tyrosine kinase inhibitors (TKI) have been designed and are now used for the treatment of CML. These TKI induce apoptosis in leukemic cells in a BIM-dependent mechanism. We hypothesized that an increase in BIM activity could sensitize CML cells to TKI. We blocked the anti-apoptotic proteins of the Bcl-2 family by using ABT-737, a Bcl-2 and Bcl-XL inhibitor. ABT-737 modified Bcl-2 protein interactions toward a pro-apoptotic phenotype. Its combination with TKI resulted in a strong synergism in CML cell lines. The association also induced a large decrease in X-linked inhibitor of apoptosis (XIAP), followed by caspase-3 activation. This XIAP decrease was due to post-translational events. The mitochondrial serine protease HtrA2/Omi was identified as being responsible for this off-target effect. Then, ABT-737 and TKI cooperate at several levels to induce apoptosis of CML cells lines, and the benefit of this association was also observed in CML hematopoietic progenitors. Interestingly, a lethal effect was also observed in the more immature CD34+CD38− TKI-insensitive population. Combination therapy might by an interesting strategy for the treatment of CML patients. [ABSTRACT FROM AUTHOR]