Rapid diffusion of electrons in GaMnAs

We report ultrafast transient-grating measurements, above and below the Curie temperature, of the dilute ferromagnetic semiconductor (Ga,Mn)As containing 6% Mn. At 80 K (15 K), we observe that photoexcited electrons in the conduction band have a lifetime of 8 ps (5 ps) and diffuse at about 70 cm2/s (60 cm2/s). Such rapid diffusion requires either an electronic mobility exceeding 7,700 cm2/Vs or a conduction-band effective mass less than half the GaAs value. Our data suggest that neither the scattering rate nor the effective mass of the (Ga,Mn)As conduction band differs significantly from that of GaAs.Comment: 5 pages, 3 figures. Differs from the previous version in incorporating additional data and changes made during the review process. Differs from the published version in including section headings and in omitting AIP copy-edits. No substantial differences in scientific conclusions from either versio

A geochronological review of magmatism along the external margin of Columbia and in the Grenville-age orogens forming the core of Rodinia

A total of 4344 magmatic U-Pb ages in the range 2300 to 800 Ma have been compiled from the Great Proterozoic Accretionary Orogen along the margin of the Columbia / Nuna supercontinent and from the subsequent Grenvillian collisional orogens forming the core of Rodinia. The age data are derived from Laurentia (North America and Greenland, n = 1212), Baltica (NE Europe, n = 1922), Amazonia (central South America, n = 625), Kalahari (southern Africa and Dronning Maud Land in East Antarctica, n = 386), and western Australia (n = 199). Laurentia, Baltica, and Amazonia (and possibly other cratons) most likely formed a ca. 10 000-km-long external active continental margin of Columbia from its assembly at ca. 1800 Ma until its dispersal at ca. 1260 Ma, after which all cratons studied were involved in the Rodinia-forming Grenvillian orogeny. However, the magmatic record is not smooth and even but highly irregular, with marked peaks and troughs, both for individual cratons and the combined data set. Magmatic peaks typically range in duration from a few tens of million years up to around hundred million years, with intervening troughs of comparable length. Some magmatic peaks are observed on multiple cratons, either by coincidence or because of paleogeographic proximity and common tectonic setting, while others are not. The best overall correlation, 0.617, is observed between Baltica and Amazonia, consistent with (but not definitive proof of) their being close neighbours in a SAMBA-like configuration at least in Columbia, and perhaps having shared the same peri-Columbian subduction system for a considerable time. Correlation factors between Laurentia and Baltica, or Laurentia and Amazonia, are below 0.14. Comparison between the Grenville Province in northeastern Laurentia and the Sveconorwegian Province in southwestern Fennoscandia (Baltica) shows some striking similarities, especially in the Mesoproterozoic, but also exhibits differences in the timing of events, especially during the final Grenville-Sveconorwegian collision, when the Sveconorwegian evolution seems to lag behind by some tens of million years. Between the other cratons, the evolution before and during the final Grenvillian collision is also largely diachronous. After 900 Ma, magmatic activity had ceased in all areas investigated, attesting to the position of most of them within the stable interior of Rodinia.publishedVersio

A geochronological review of magmatism along the external margin of Columbia and in the Grenville-age orogens forming the core of Rodinia

A total of 4344 magmatic U-Pb ages in the range 2300 to 800 Ma have been compiled from the Great Proterozoic Accretionary Orogen along the margin of the Columbia / Nuna supercontinent and from the subsequent Grenvillian collisional orogens forming the core of Rodinia. The age data are derived from Laurentia (North America and Greenland, n = 1212), Baltica (NE Europe, n = 1922), Amazonia (central South America, n = 625), Kalahari (southern Africa and Dronning Maud Land in East Antarctica, n = 386), and western Australia (n = 199). Laurentia, Baltica, and Amazonia (and possibly other cratons) most likely formed a ca. 10 000-km-long external active continental margin of Columbia from its assembly at ca. 1800 Ma until its dispersal at ca. 1260 Ma, after which all cratons studied were involved in the Rodinia-forming Grenvillian orogeny. However, the magmatic record is not smooth and even but highly irregular, with marked peaks and troughs, both for individual cratons and the combined data set. Magmatic peaks typically range in duration from a few tens of million years up to around hundred million years, with intervening troughs of comparable length. Some magmatic peaks are observed on multiple cratons, either by coincidence or because of paleogeographic proximity and common tectonic setting, while others are not. The best overall correlation, 0.617, is observed between Baltica and Amazonia, consistent with (but not definitive proof of) their being close neighbours in a SAMBA-like configuration at least in Columbia, and perhaps having shared the same peri-Columbian subduction system for a considerable time. Correlation factors between Laurentia and Baltica, or Laurentia and Amazonia, are below 0.14. Comparison between the Grenville Province in northeastern Laurentia and the Sveconorwegian Province in southwestern Fennoscandia (Baltica) shows some striking similarities, especially in the Mesoproterozoic, but also exhibits differences in the timing of events, especially during the final Grenville-Sveconorwegian collision, when the Sveconorwegian evolution seems to lag behind by some tens of million years. Between the other cratons, the evolution before and during the final Grenvillian collision is also largely diachronous. After 900 Ma, magmatic activity had ceased in all areas investigated, attesting to the position of most of them within the stable interior of Rodinia.

Activating Inducible T-cell Costimulator Yields Antitumor Activity Alone and in Combination with Anti-PD-1 Checkpoint Blockade

Unlabelled: In recent years, there has been considerable interest in mAb-based induction of costimulatory receptor signaling as an approach to combat cancer. However, promising nonclinical data have yet to translate to a meaningful clinical benefit. Inducible T-cell costimulator (ICOS) is a costimulatory receptor important for immune responses. Using a novel clinical-stage anti-ICOS immunoglobulin G4 mAb (feladilimab), which induces but does not deplete ICOS+ T cells and their rodent analogs, we provide an end-to-end evaluation of the antitumor potential of antibody-mediated ICOS costimulation alone and in combination with programmed cell death protein 1 (PD-1) blockade. We demonstrate, consistently, that ICOS is expressed in a range of cancers, and its induction can stimulate growth of antitumor reactive T cells. Furthermore, feladilimab, alone and with a PD-1 inhibitor, induced antitumor activity in mouse and humanized tumor models. In addition to nonclinical evaluation, we present three patient case studies from a first-time-in-human, phase I, open-label, dose-escalation and dose-expansion clinical trial (INDUCE-1; ClinicalTrials.gov: NCT02723955), evaluating feladilimab alone and in combination with pembrolizumab in patients with advanced solid tumors. Preliminary data showing clinical benefit in patients with cancer treated with feladilimab alone or in combination with pembrolizumab was reported previously; with example cases described here. Additional work is needed to further validate the translation to the clinic, which includes identifying select patient populations that will benefit from this therapeutic approach, and randomized data with survival endpoints to illustrate its potential, similar to that shown with CTLA-4 and PD-1 blocking antibodies. Significance: Stimulation of the T-cell activation marker ICOS with the anti-ICOS agonist mAb feladilimab, alone and in combination with PD-1 inhibition, induces antitumor activity across nonclinical models as well as select patients with advanced solid tumors

Supplementary Figure 7 from Activating Inducible T cell Co-stimulator (ICOS) yields anti-tumor activity alone and in combination with anti-PD-1 checkpoint blockade

Healthy human donor CD4+ T cells were pre-activated with antiCD3/CD28 for 48 hours and then re-stimulated with plate-bound anti-CD3 in the presence of increasing concentrations of soluble or plate-bound feladilimab or isotype control for 72 hours. IFNg levels were then assessed from cell-free supernatants using Meso Scale Discovery (MSD)-based detection.</p

Supplementary Table 6 from Activating Inducible T cell Co-stimulator (ICOS) yields anti-tumor activity alone and in combination with anti-PD-1 checkpoint blockade

Example TIL marker expression phenotypes from clinical patient case studies of feladilimab monotherapy and in combination with pembrolizumab.</p

Supplementary Figure 12 from Activating Inducible T cell Co-stimulator (ICOS) yields anti-tumor activity alone and in combination with anti-PD-1 checkpoint blockade

Clinical case studies of feladilimab monotherapy and in combination with pembrolizumab.</p