176 research outputs found
Nonlinear stability of solitons against strong external perturbations
We study soliton stability under the action of strong external perturbations. Limits on the weak perturbation approach are established with the help of average Lagrangian methods and full simulations. We found that for the same relative perturbation, larger amplitude solitons develop instability earlier than weaker amplitude solitons.F. B. Rizzato, G. I. de Oliveira, and A. C.-L. Chia
Caracterização das exigĂȘncias nutricionais de mudas de Pfaffia glomerata em Argissolo Vermelho distrĂłfico arĂȘnico pela tĂ©cnica do nutriente faltante
CorrelaçÔes do Ăndice de ĂĄrea do cladĂłdio com caracterĂsticas morfogĂȘnicas e produtivas da palma forrageira
Passage kinetics of digesta in horses fed with coastcross hay ground to different degrees
SOIL ORGANIC CARBON, CARBON STOCK AND THEIR RELATIONSHIPS TO PHYSICAL ATTRIBUTES UNDER FOREST SOILS IN CENTRAL AMAZONIA
Fontes de silĂcio no desenvolvimento de plĂąntulas de bananeira 'Maçã' micropropagadas
Genetic heterogeneity and actionable mutations in HER2-positive primary breast cancers and their brain metastases
Brain metastases constitute a challenge in the management of patients with HER2- positive breast cancer treated with anti-HER2 systemic therapies. Here we sought to define the repertoire of mutations private to or enriched for in HER2-positive brain metastases. Massively parallel sequencing targeting all exons of 254 genes frequently mutated in breast cancers and/or related to DNA repair was used to characterize the spatial and temporal heterogeneity of HER2-positive breast cancers and their brain metastases in six patients. Data were analyzed with state-of-the-art bioinformatics algorithms and selected mutations were validated with orthogonal methods. Spatial and temporal inter-lesion genetic heterogeneity was observed in the HER2-positive brain metastases from an index patient subjected to a rapid autopsy. Genetic alterations restricted to the brain metastases included mutations in cancer genes FGFR2, PIK3CA and ATR, homozygous deletion in CDKN2A and amplification in KRAS. Shifts in clonal composition and the acquisition of additional mutations in the progression from primary HER2-positive breast cancer to brain metastases following anti-HER2 therapy were investigated in additional five patients. Likely pathogenic mutations private to or enriched in the brain lesions affected cancer and clinically actionable genes, including ATR, BRAF, FGFR2, MAP2K4, PIK3CA, RAF1 and TP53. Changes in clonal composition and the acquisition of additional mutations in brain metastases may affect potentially actionable genes in HER2-positive breast cancers. Our observations have potential clinical implications, given that treatment decisions for patients with brain metastatic disease are still mainly based on biomarkers assessed in the primary tumor
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