Outward transport of plasma in the inner and middle magnetospheres of gas giants results from an interplay between mass loading from the inner dominant mass sources (volcanic moons), flux tube ...interchange in the centrifugally unstable magnetospheric plasma disk, turbulent heating of the plasma, and coupling between the equatorial plasma and the planetary upper atmosphere through magnetic field‐aligned current loops and/or Alfvén waves. We present a new analytical formalism describing large scale transport in gas giant systems, combining two historical approaches: radial diffusion of mass and energy through flux tube interchange, and angular momentum transport through corotation enforcement. Under the hypotheses of axisymmetry, steady‐state, and multi‐fluid plasma, we provide transport equations for total contents of flux tubes. They feature new transport parameters accounting for the latitudinal extent of the disk, and self‐consistently include field‐aligned potential drops in the magnetosphere‐ionosphere coupling. Our general formalism has a wealth of applications, two of which are presented, corresponding to the cases of the two gas giants: the effect of interhemispheric asymmetries in the resistive and magnetic properties between the northern and southern ionospheres on the transport of angular momentum at Jupiter, and the influence of the plasma disk thickness on transport at Saturn. We apply our formalism to derive ionospheric parameters and reproduce the Juno and Cassini data. Further work will allow for more complete numerical solutions of our equations, with the aim of capturing the broad complexity of fast rotating magnetospheric systems which can be found inside and outside the Solar System.
Plain Language Summary
Jupiter and Saturn, the two gas giant systems of the Solar System, are characterized by strong magnetic fields, fast rotation, and the presence of embedded (cryo)volcanic moons feeding their systems with gas and dust. Once produced, the gas is ionized and “picked‐up” by the rotating magnetic field, resulting in a global plasma outflow from the inner to the outer regions forming an elongated disk along the centrifugal equator. This outward transport of plasma involves complex interactions between neutral gas, plasma, magnetic field, and the planet’s upper atmosphere. In this work, we present a new unified formalism combining the description of angular momentum, mass, and energy transport in gas giant magnetospheres. This formalism is valid in their inner and middle magnetospheric regions where the system is approximately axisymmetrical. Assuming a steady‐state flow, we self‐consistently account for the impact of particle acceleration along field lines and the latitudinal distribution of the plasma disk on the global dynamics of the system. We provide simple numerical applications at Jupiter and Saturn which illustrate the influences of coupling of the plasma disk to the upper atmosphere of the planet and of the thickness of the disk, using the cases of Jupiter and Saturn.
Key Points
We develop a new self‐consistent model of transport for the mass, angular momentum, and energy contents in gas giant magnetospheres
We explore the two end‐members of disk thickness cases, using Jupiter and Saturn as examples of thin and extended disks
We explicitly describe the effects of inter‐hemispheric asymmetries of neutral winds and ionospheric conductances on the rotation curve
Since its inception in 2000, metronomic chemotherapy has undergone major advances as an antiangiogenic therapy. The discovery of the pro-immune properties of chemotherapy and its direct effects on ...cancer cells has established the intrinsic multitargeted nature of this therapeutic approach. The past 10 years have seen a marked rise in clinical trials of metronomic chemotherapy, and it is increasingly combined in the clinic with conventional treatments, such as maximum-tolerated dose chemotherapy and radiotherapy, as well as with novel therapeutic strategies, such as drug repositioning, targeted agents and immunotherapy. We review the latest advances in understanding the complex mechanisms of action of metronomic chemotherapy, and the recently identified factors associated with disease resistance. We comprehensively discuss the latest clinical data obtained from studies performed in both adult and paediatric populations, and highlight ongoing clinical trials. In this Review, we foresee the future developments of metronomic chemotherapy and specifically its potential role in the era of personalized medicine.
Tumor angiogenesis is recognized as a major therapeutic target in the fight against cancer. The key involvement of angiogenesis in tumor growth and metastasis has started to redefine chemotherapy and ...new protocols have emerged. Metronomic chemotherapy, which is intended to prevent tumor angiogenesis, is based on more frequent and low-dose drug administrations compared with conventional chemotherapy. The potential of metronomic chemotherapy was revealed in animal models a decade ago and the efficacy of this approach has been confirmed in the clinic. In the past 5 years, multiple clinical trials have investigated the safety and efficacy of metronomic chemotherapy in a variety of human cancers. While the results have been variable, clinical studies have shown that these new treatment protocols represent an interesting alternative for either primary systemic therapy or maintenance therapy. We review the latest clinical trials of metronomic chemotherapy in adult and pediatric cancer patients. Accumulating evidence suggests that the efficacy of such treatment may not only rely on anti-angiogenic activity. Potential new mechanisms of action, such as restoration of anticancer immune response and induction of tumor dormancy are discussed. Finally, we highlight the research efforts that need to be made to facilitate the optimal development of metronomic chemotherapy.
We report two cases of pediatric mammary‐analog secretory carcinoma (MASC), a male operated on at age 8 and a female operated on at 12, who are in remission 2 years after surgery. The diagnosis of ...MASC was challenging and established by identifying the ETV6::NTRK3 fusion transcript in both cases. Given the excellent results of TRK inhibitor treatments in adult MASC and pediatric tumors expressing an ETV6::NTRK3 fusion, they should probably be prescribed as first‐line treatment in cases requiring surgery with foreseeable serious sequelae or metastatic disease.
Transmigration and activation of neutrophils in the lung reflect key steps in the progression of acute lung injury (ALI). It is known that hydrogen sulfide (H
S) can limit neutrophil activation, but ...the respective mechanisms remain elusive. Here, we aimed to examine the underlying pathways in pulmonary inflammation. In vivo, C57BL/6N mice received the H
S slow releasing compound GYY4137 prior to lipopolysaccharide (LPS) inhalation. LPS challenge led to pulmonary injury, inflammation, and neutrophil transmigration that were inhibited in response to H
S pretreatment. Moreover, H
S reduced mRNA expression of macrophage inflammatory protein-2 (MIP-2) and its receptor in lung tissue, as well as the accumulation of MIP-2 and interleukin-1β in the alveolar space. In vitro, GYY4137 did not exert toxic effects on Hoxb8 neutrophils, but prevented their transmigration through an endothelial barrier in the presence and absence of MIP-2. In addition, the release of MIP-2 and reactive oxygen species from LPS-stimulated Hoxb8 neutrophils were directly inhibited by H
S. Taken together, we provide first evidence that H
S limits lung neutrophil sequestration upon LPS challenge. As proposed underlying mechanisms, H
S prevents neutrophil transmigration through the inflamed endothelium and directly inhibits pro-inflammatory as well as oxidative signalling in neutrophils. Subsequently, H
S pretreatment ameliorates LPS-induced ALI.