Improving solar wind modeling at Mercury: Incorporating transient solar phenomena into the WSA‐ENLIL model with the Cone extension

Coronal mass ejections (CMEs) and other transient solar phenomena play important roles in magnetospheric and exospheric dynamics. Although a planet may interact only occasionally with the interplanetary consequences of these events, such transient phenomena can result in departures from the background solar wind that often involve more than an order of magnitude greater ram pressure and interplanetary electric field applied to the planetary magnetosphere. For Mercury, an order of magnitude greater ram pressure combined with high Alfvén speeds and reconnection rates can push the magnetopause essentially to the planet's surface, exposing the surface directly to the solar wind flow. In order to understand how the solar wind interacts with Mercury's magnetosphere and exosphere, previous studies have used the Wang‐Sheeley‐Arge (WSA)‐ENLIL solar wind modeling tool to calculate basic and composite solar wind parameters at Mercury's orbital location. This model forecasts only the background solar wind, however, and does not include major transient events. The Cone extension permits the inclusion of CMEs and related solar wind perturbations and thus enables characterization of the effects of strong solar wind disturbances on the Mercury system. The Cone extension is predicated on the assumption of constant angular and radial velocities of CMEs to integrate these phenomena into the WSA‐ENLIL coupled model. Comparisons of the model results with observations by the MESSENGER spacecraft indicate that the WSA‐ENLIL+Cone model more accurately forecasts total solar wind conditions at Mercury and has greater predictive power for magnetospheric and exospheric processes than the WSA‐ENLIL model alone

Carbohydrate and Amino Acid Metabolism as Hallmarks for Innate Immune Cell Activation and Function

Immune activation is now understood to be fundamentally linked to intrinsic and/or extrinsic metabolic processes which are essential for immune cells to survive, proliferate, and perform their effector functions. Moreover, disruption or dysregulation of these pathways can result in detrimental outcomes and underly a number of pathologies in both communicable and non-communicable diseases. In this review, we discuss how the metabolism of carbohydrates and amino acids in particular can modulate innate immunity and how perturbations in these pathways can result in failure of these immune cells to properly function or induce unfavorable phenotypes

Serum-free Erythroid Differentiation for Efficient Genetic Modification and High-Level Adult Hemoglobin Production

In vitro erythroid differentiation from primary human cells is valuable to develop genetic strategies for hemoglobin disorders. However, current erythroid differentiation methods are encumbered by modest transduction rates and high baseline fetal hemoglobin production. In this study, we sought to improve both genetic modification and hemoglobin production among human erythroid cells in vitro. To model therapeutic strategies, we transduced human CD34+ cells and peripheral blood mononuclear cells (PBMCs) with lentiviral vectors and compared erythropoietin-based erythroid differentiation using fetal-bovine-serum-containing media and serum-free media. We observed more efficient transduction (85%–93%) in serum-free media than serum-containing media (20%–69%), whereas the addition of knockout serum replacement (KSR) was required for serum-free media to promote efficient erythroid differentiation (96%). High-level adult hemoglobin production detectable by electrophoresis was achieved using serum-free media similar to serum-containing media. Importantly, low fetal hemoglobin production was observed in the optimized serum-free media. Using KSR-containing, serum-free erythroid differentiation media, therapeutic adult hemoglobin production was detected at protein levels with β-globin lentiviral transduction in both CD34+ cells and PBMCs from sickle cell disease subjects. Our in vitro erythroid differentiation system provides a practical evaluation platform for adult hemoglobin production among human erythroid cells following genetic manipulation. Keywords: lentiviral vector, hematopoietic stem cells, erythroid cells, erythroid differentiation, adult hemoglobin, gene therapy, genome editin