Observations of discrete harmonics emerging from equatorial noise

A number of modes of oscillations of particles and fields can exist in space plasmas. Since the early 1970s, space missions have observed noise-like plasma waves near the geomagnetic equator known as ‘equatorial noise’. Several theories were suggested, but clear observational evidence supported by realistic modelling has not been provided. Here we report on observations by the Cluster mission that clearly show the highly structured and periodic pattern of these waves. Very narrow-banded emissions at frequencies corresponding to exact multiples of the proton gyrofrequency (frequency of gyration around the field line) from the 17th up to the 30th harmonic are observed, indicating that these waves are generated by the proton distributions. Simultaneously with these coherent periodic structures in waves, the Cluster spacecraft observes ‘ring’ distributions of protons in velocity space that provide the free energy for the waves. Calculated wave growth based on ion distributions shows a very similar pattern to the observations

HER2-Mediated Internalization of Cytotoxic Agents in ERBB2 Amplified or Mutant Lung Cancers

Amplification and oncogenic mutations of ERBB2, the gene encoding the HER2 receptor tyrosine kinase, promote receptor hyperactivation and tumor growth. Here we demonstrate that HER2 ubiquitination and internalization, rather than its overexpression, are key mechanisms underlying endocytosis and consequent efficacy of the anti-HER2 antibody-drug conjugates (ADCs) ado-trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (T-DXd) in lung cancer cell lines and patient-derived xenograft models. These data translated into a 51% response rate in a clinical trial of T-DM1 in 49 patients with ERBB2/HER2-amplified or mutant lung cancers. We show that co-treatment with irreversible pan-HER inhibitors enhances receptor ubiquitination and consequent ADC internalization and efficacy. We also demonstrate that ADC switching to T-DXd, which harbors a different cytotoxic payload, achieves durable responses in a patient with lung cancer and corresponding xenograft model developing resistance to T-DM1. Our findings may help guide future clinical trials and expand the field of ADC as cancer therapy