Predicting the corona for the 21 August 2017 total solar eclipse

D.H.M. thanks both the UK STFC and the Leverhulme Trust for their financial support.The total solar eclipse that occurred on 21 August 2017 across the United States provided an opportunity to test a magnetohydrodynamic model of the solar corona driven by measured magnetic fields. We used a new heating model based on the dissipation of Alfvén waves, and a new energization mechanism to twist the magnetic field in filament channels. We predicted what the corona would look like one week before the eclipse. Here, we describe how this prediction was accomplished, and show that it compared favourably with observations of the eclipse in white light and extreme ultraviolet. The model allows us to understand the relationship of observed features, including streamers, coronal holes, prominences, polar plumes and thin rays, to the magnetic field. We show that the discrepancies between the model and observations arise from limitations in our ability to observe the Sun’s magnetic field. Predictions of this kind provide opportunities to improve the models, forging the path to improved space weather prediction.PostprintPeer reviewe

Predicting the corona for the 21 August 2017 total solar eclipse

The total solar eclipse that occurred on 21 August 2017 across the United States provided an opportunity to test a magnetohydrodynamic model of the solar corona driven by measured magnetic fields. We used a new heating model based on the dissipation of Alfvén waves, and a new energization mechanism to twist the magnetic field in filament channels. We predicted what the corona would look like one week before the eclipse. Here, we describe how this prediction was accomplished, and show that it compared favourably with observations of the eclipse in white light and extreme ultraviolet. The model allows us to understand the relationship of observed features, including streamers, coronal holes, prominences, polar plumes and thin rays, to the magnetic field. We show that the discrepancies between the model and observations arise from limitations in our ability to observe the Sun’s magnetic field. Predictions of this kind provide opportunities to improve the models, forging the path to improved space weather prediction

Granulocyte-macrophage colony-stimulating factor (GM-CSF)–secreting cellular immunotherapy in combination with autologous stem cell transplantation (ASCT) as postremission therapy for acute myeloid leukemia (AML)

Preclinical models have demonstrated the efficacy of granulocyte-macrophage colony-stimulating factor-secreting cancer immunotherapies (GVAX platform) accompanied by immunotherapy-primed lymphocytes after autologous stem cell transplantation in hematologic malignancies. We conducted a phase 2 study of this combination in adult patients with acute myeloid leukemia. Immunotherapy consisted of autologous leukemia cells admixed with granulocyte-macrophage colony-stimulating factor-secreting K562 cells. “Primed” lymphocytes were collected after a single pretransplantation dose of immunotherapy and reinfused with the stem cell graft. Fifty-four subjects were enrolled; 46 (85%) achieved a complete remission, and 28 (52%) received the pretransplantation immunotherapy. For all patients who achieved complete remission, the 3-year relapse-free survival (RFS) rate was 47.4% and overall survival was 57.4%. For the 28 immunotherapy-treated patients, the RFS and overall survival rates were 61.8% and 73.4%, respectively. Posttreatment induction of delayed-type hypersensitivity reactions to autologous leukemia cells was associated with longer 3-year RFS rate (100% vs 48%). Minimal residual disease was monitored by quantitative analysis of Wilms tumor-1 (WT1), a leukemia-associated gene. A decrease in WT1 transcripts in blood was noted in 69% of patients after the first immunotherapy dose and was also associated with longer 3-year RFS (61% vs 0%). In conclusion, immunotherapy in combination with primed lymphocytes and autologous stem cell transplantation shows encouraging signals of potential activity in acute myeloid leukemia (ClinicalTrials.gov: NCT00116467)

Loss of the neural-specific BAF subunit ACTL6B relieves repression of early response genes and causes recessive autism.

Synaptic activity in neurons leads to the rapid activation of genes involved in mammalian behavior. ATP-dependent chromatin remodelers such as the BAF complex contribute to these responses and are generally thought to activate transcription. However, the mechanisms keeping such "early activation" genes silent have been a mystery. In the course of investigating Mendelian recessive autism, we identified six families with segregating loss-of-function mutations in the neuronal BAF (nBAF) subunit ACTL6B (originally named BAF53b). Accordingly, ACTL6B was the most significantly mutated gene in the Simons Recessive Autism Cohort. At least 14 subunits of the nBAF complex are mutated in autism, collectively making it a major contributor to autism spectrum disorder (ASD). Patient mutations destabilized ACTL6B protein in neurons and rerouted dendrites to the wrong glomerulus in the fly olfactory system. Humans and mice lacking ACTL6B showed corpus callosum hypoplasia, indicating a conserved role for ACTL6B in facilitating neural connectivity. Actl6b knockout mice on two genetic backgrounds exhibited ASD-related behaviors, including social and memory impairments, repetitive behaviors, and hyperactivity. Surprisingly, mutation of Actl6b relieved repression of early response genes including AP1 transcription factors (Fos, Fosl2, Fosb, and Junb), increased chromatin accessibility at AP1 binding sites, and transcriptional changes in late response genes associated with early response transcription factor activity. ACTL6B loss is thus an important cause of recessive ASD, with impaired neuron-specific chromatin repression indicated as a potential mechanism