Simultaneous Global Ionospheric Disturbances Associated With Penetration Electric Fields During Intense and Minor Solar and Geomagnetic Disturbances

A new observational phenomenon, named Simultaneous Global Ionospheric Density Disturbance (SGD), is identified in GNSS total electron content (TEC) data during periods of three typical geospace disturbances: a Coronal Mass Ejection-driven severe disturbance event, a high-speed stream event, and a minor disturbance day with a maximum Kp of 4. SGDs occur frequently on dayside and dawn sectors, with a ∼1% TEC increase. Notably, SGDs can occur under minor solar-geomagnetic disturbances. SGDs are likely caused by penetration electric fields (PEFs) of solar-geomagnetic origin, as they are associated with Bz southward, increased auroral AL/AU, and solar wind pressure enhancements. These findings offer new insights into the nature of PEFs and their ionospheric impact while confirming some key earlier results obtained through alternative methods. Importantly, the accessibility of extensive GNSS networks, with at least 6,000 globally distributed receivers for ionospheric research, means that rich PEF information can be acquired, offering researchers numerous opportunities to investigate geospace electrodynamics

Turbulence Around Auroral Arcs

The spectacular visual displays from the aurora come from curtains of excited atoms and molecules, impacted by energetic charged particles. These particles are accelerated from great distances in Earth's magnetotail, causing them to precipitate into the ionosphere. Energetic particle precipitation is associated with currents that generate electric fields, and the end result is a dissipation of the hundreds of gigawatts to terrawatts of energy injected into Earth's atmosphere during geomagnetic storms. While much is known about how the aurora dissipates energy through Joule heating, little is known about how it does so via small‐scale plasma turbulence. Here we show the first set of combined radar and optical images that track the position of this turbulence, relative to particle precipitation, with high spatial precision. During two geomagnetic storms occurring in 2021, we unambiguously show that small‐scale turbulence (several meters) is preferentially created on the edges of auroral forms. We find that turbulence appears both poleward and equatorward of auroral forms, as well as being nestled between auroral forms in the north‐south direction. These measurements make it clear that small scale auroral plasma turbulence is an integral part of the electrical current system created by the aurora, in the sense that turbulent transport around auroral forms enhances ionospheric energy deposition through Joule heating while at the same time reducing the average strength of the electric field

Fabrication of Pt/Ru Nanoparticle Pair Arrays with Controlled Separation and their Electrocatalytic Properties

Aiming at the investigation of spillover and transport effects in electrocatalytic reactions on bimetallic catalyst electrodes, we have prepared novel, nanostructured electrodes consisting of arrays of homogeneously distributed pairs of Pt and Ru nanodisks of uniform size and with controlled separation on planar glassy carbon substrates. The nanodisk arrays (disk diameter approximate to 60 nm) were fabricated by hole-mask colloidal lithography; the separation between pairs of Pt and Ru disks was varied from -25 nm (overlapping) via +25 nm to +50 nm. Morphology and (surface) composition of the Pt/Ru nanodisk arrays Were characterized by scanning electron microscopy, energy dispersive X-ray analysis, and X-ray Photoelectron spectroscopy, the electrochemical/electrocatalytic properties were explored by cyclic voltammetry, COad monolayer oxidation ("COad stripping"), and potentiodynamic hydrogen oxidation. Detailed analysis of the 2 COad oxidation peaks revealed that on all bimetallic pairs these cannot be reproduced by superposition of the peaks obtained on electrodes with Pt/Pt or Ru/Ru pairs, pointing to effective Pt-Ru interactions even between rather distant pairs (50 nm). Possible reasons for this observation and its relevance for the understanding of previous reports of highly active catalysts with separate Pt and Ru nanoparticles are discussed. The results clearly demonstrate that this preparation method is perfectly suited for fabrication of planar model electrodes with well-defined arrays of bimetallic nanodisk pairs, which opens up new possibilities for model studies of electrochemical/electrocatalytic reactions

A DHODH inhibitor increases p53 synthesis and enhances tumor cell killing by p53 degradation blockage

ML, CD, IvL, GP, TM, SD, MS, APF, CT, DL, MAH, KL and SL: project grants from the Swedish Research Council, the Swedish Cancer Society and the Swedish Childhood Cancer Foundation. MHi and JC: Cancer Research UK (C8/A6613). MC, EP and WE: Wellcome Trust (073915). MN and BV: projects MEYS-NPS-LO1413 and GACR P206/12/G151. EMC, MP, MMS, ZF and PG: Norwegian Cancer Society (182735, 732200) and Helse Vest (911884, 911789). RB and SC: NIH (R01 CA95684), the Leukemia and Lymphoma Society and the Waxman Foundation. NW, AH, Ad’H: Cancer Research UK (C21383/A6950) and Engineering and Physical Sciences Research Council Doctoral Training Program. JL and YZ: Cancer Research UK (C240/A15751). MH and BW: SARomics Biostructures ABUY, KF: DDDP SciLife, Sweden. LJ, MHa, RS and A-LG: CBCS, Sweden. VP: SciLife fellowship. AT: Breast Cancer Research Scotland.The development of non-genotoxic therapies that activate wild-type p53 in tumors is of great interest since the discovery of p53 as a tumor suppressor. Here we report the identification of over 100 small-molecules activating p53 in cells. We elucidate the mechanism of action of a chiral tetrahydroindazole (HZ00), and through target deconvolution, we deduce that its active enantiomer (R)-HZ00, inhibits dihydroorotate dehydrogenase (DHODH). The chiral specificity of HZ05, a more potent analog, is revealed by the crystal structure of the (R)-HZ05/DHODH complex. Twelve other DHODH inhibitor chemotypes are detailed among the p53 activators, which identifies DHODH as a frequent target for structurally diverse compounds. We observe that HZ compounds accumulate cancer cells in S-phase, increase p53 synthesis, and synergize with an inhibitor of p53 degradation to reduce tumor growth in vivo. We, therefore, propose a strategy to promote cancer cell killing by p53 instead of its reversible cell cycle arresting effect.Publisher PDFPeer reviewe

Publisher Correction: A DHODH inhibitor increases p53 synthesis and enhances tumor cell killing by p53 degradation blockage

Correction to: Nature Communications, published online 16 March 2018 This Article contains an error in Fig. 6. The submitted and peer reviewed versions of this article contain distinct distributions of sub-G1 cells in Fig 6 d, however, one of those distributions was inadvertently duplicated during the production process. Additionally, one of the distributions in Fig 6 d was omitted during the production process. The correct version of Fig 6 is: (Figure presented.) which replaces the previous incorrect version of Fig. 6. The error has been corrected in the PDF or HTML version of the Article.</p

A DHODH inhibitor increases p53 synthesis and enhances tumor cell killing by p53 degradation blockage

The development of non-genotoxic therapies that activate wild-type p53 in tumors is of great interest since the discovery of p53 as a tumor suppressor. Here we report the identification of over 100 small-molecules activating p53 in cells. We elucidate the mechanism of action of a chiral tetrahydroindazole (HZ00), and through target deconvolution, we deduce that its active enantiomer (R)-HZ00, inhibits dihydroorotate dehydrogenase (DHODH). The chiral specificity of HZ05, a more potent analog, is revealed by the crystal structure of the (R)-HZ05/DHODH complex. Twelve other DHODH inhibitor chemotypes are detailed among the p53 activators, which identifies DHODH as a frequent target for structurally diverse compounds. We observe that HZ compounds accumulate cancer cells in S-phase, increase p53 synthesis, and synergize with an inhibitor of p53 degradation to reduce tumor growth in vivo. We, therefore, propose a strategy to promote cancer cell killing by p53 instead of its reversible cell cycle arresting effect