Full-circle Eulerian cradle for low temperature neutron investigations

A full-circle Eulerian cradle has been developed for single crystal neutron diffraction investigations at low temperatures (2 K < T < 300 K). The device including two stepping motors is mounted completely inside the sample room of a helium cryostat. One step of the chi- and phi-motors is equivalent to a rotation of 0.005° in chi and 0.01° in phi, permitting a positioning within 0.01° in chi and 0.02° in phi with a reproducibility in the same range.Un berceau Eulérien à cercle entier a été développé pour des études de diffraction neutronique par des monocristaux à basses températures (2 K < T < 300 K). L'appareil avec deux moteurs pas à pas est monté complètement dans un cryostat d'hélium. Un pas pour l'angle chi est équivalent à une rotation de 0,005° et pour l'angle phi à une rotation de 0,01°, ce qui permet un positionnement de 0,01° en chi et 0,02° en phi avec une reproductibilité du même ordre

Efficacy and Determinants of Response to HER Kinase Inhibition in <i>HER2</i>-Mutant Metastatic Breast Cancer

mutations define a subset of metastatic breast cancers with a unique mechanism of oncogenic addiction to HER2 signaling. We explored activity of the irreversible pan-HER kinase inhibitor neratinib, alone or with fulvestrant, in 81 patients with -mutant metastatic breast cancer. Overall response rate was similar with or without estrogen receptor (ER) blockade. By comparison, progression-free survival and duration of response appeared longer in ER patients receiving combination therapy, although the study was not designed for direct comparison. Preexistent concurrent activating or alterations were associated with poor treatment outcome. Similarly, acquisition of multiple -activating events, as well as gatekeeper alterations, were observed at disease progression in a high proportion of patients deriving clinical benefit from neratinib. Collectively, these data define mutations as a therapeutic target in breast cancer and suggest that coexistence of additional HER signaling alterations may promote both and acquired resistance to neratinib. SIGNIFICANCE: mutations define a targetable breast cancer subset, although sensitivity to irreversible HER kinase inhibition appears to be modified by the presence of concurrent activating genomic events in the pathway. These findings have implications for potential future combinatorial approaches and broader therapeutic development for this genomically defined subset of breast cancer.