Chemical Reaction Dynamics at Surfaces

Contains reports on three research projects.Joint Services Electronics Program Contract DAAL03-89-C-0001Joint Services Electronics Program Contract DAAL03-92-C-0001National Science Foundation Grant CHE 90-2062

Chemical Reaction Dynamics at Surfaces

Contains reports on three research projects.Joint Services Electronics Program Contract DAAL03-92-C-0001National Science Foundation Grant CHE 90-20623U.S. Department of Energy Grant DE-FG02-89-ER1403

Sheared Solid Materials

We present a time-dependent Ginzburg-Landau model of nonlinear elasticity in solid materials. We assume that the elastic energy density is a periodic function of the shear and tetragonal strains owing to the underlying lattice structure. With this new ingredient, solving the equations yields formation of dislocation dipoles or slips. In plastic flow high-density dislocations emerge at large strains to accumulate and grow into shear bands where the strains are localized. In addition to the elastic displacement, we also introduce the local free volume {\it m}. For very small $m$ the defect structures are metastable and long-lived where the dislocations are pinned by the Peierls potential barrier. However, if the shear modulus decreases with increasing {\it m}, accumulation of {\it m} around dislocation cores eventually breaks the Peierls potential leading to slow relaxations in the stress and the free energy (aging). As another application of our scheme, we also study dislocation formation in two-phase alloys (coherency loss) under shear strains, where dislocations glide preferentially in the softer regions and are trapped at the interfaces.Comment: 16pages, 11figure

A Phase I Dose Escalation Study of the Triple Angiokinase Inhibitor Nintedanib Combined with Low-Dose Cytarabine in Elderly Patients with Acute Myeloid Leukemia

Nintedanib (BIBF 1120), a potent multikinase inhibitor of VEGFR-1/-2/-3, FGFR-1/-2/-3 and PDGFR-α/-β, exerts growth inhibitory and pro-apoptotic effects in myeloid leukemic cells, especially when used in combination with cytarabine. This phase I study evaluated nintedanib in combination with low-dose cytarabine (LDAC) in elderly patients with untreated or relapsed/refractory acute myeloid leukemia (AML) ineligible for intensive chemotherapy in a 3+3 design. Nintedanib (dose levels 100, 150, and 200 mg orally twice daily) and LDAC (20 mg subcutaneous injection twice daily for 10 days) were administered in 28-day cycles. Dose-limiting toxicity (DLT) was defined as non-hematological severe adverse reaction CTC grade ≥ 4 with possible or definite relationship to nintedanib. Between April 2012 and October 2013, 13 patients (median age 73 [range: 62–86] years) were enrolled. One patient did not receive study medication and was replaced. Nine (69%) patients had relapsed or refractory disease and 6 (46%) patients had unfavorable cytogenetics. The most frequently reported treatment-related adverse events (AE) were gastrointestinal events. Twelve SAEs irrespective of relatedness were reported. Two SUSARs were observed, one fatal hypercalcemia and one fatal gastrointestinal infection. Two patients (17%) with relapsed AML achieved a complete remission (one CR, one CRi) and bone marrow blast reductions without fulfilling PR criteria were observed in 3 patients (25%). One-year overall survival was 33%. Nintedanib combined with LDAC shows an adequate safety profile and survival data are promising in a difficult-to-treat patient population. Continuation of this trial with a phase II recommended dose of 2 x 200 mg nintedanib in a randomized, placebo-controlled phase II study is planned. The trial is registered to EudraCT as 2011-001086-41

Plastic Flow in Two-Dimensional Solids

A time-dependent Ginzburg-Landau model of plastic deformation in two-dimensional solids is presented. The fundamental dynamic variables are the displacement field \bi u and the lattice velocity {\bi v}=\p {\bi u}/\p t. Damping is assumed to arise from the shear viscosity in the momentum equation. The elastic energy density is a periodic function of the shear and tetragonal strains, which enables formation of slips at large strains. In this work we neglect defects such as vacancies, interstitials, or grain boundaries. The simplest slip consists of two edge dislocations with opposite Burgers vectors. The formation energy of a slip is minimized if its orientation is parallel or perpendicular to the flow in simple shear deformation and if it makes angles of $\pm \pi/4$ with respect to the stretched direction in uniaxial stretching. High-density dislocations produced in plastic flow do not disappear even if the flow is stopped. Thus large applied strains give rise to metastable, structurally disordered states. We divide the elastic energy into an elastic part due to affine deformation and a defect part. The latter represents degree of disorder and is nearly constant in plastic flow under cyclic straining.Comment: 16pages, Figures can be obtained at http://stat.scphys.kyoto-u.ac.jp/index-e.htm

Science Requirement Document for the European Solar Telescope

The European Solar Telescope (EST)1 is a research infrastructure for solar physics. It is planned to be an on-axis solar telescope with an aperture of 4m and equipped with an innovative suite of spectro-polarimetric and imaging post-focus instrumentation. The EST project was initiated and is driven by EAST2, the European Association for Solar Telescopes. EAST was founded in 2006 as an association of 14 European countries. Today, as of December 2019, EAST consists of 26 European research institutes from 18 European countries. The Preliminary Design Phase of EST was accomplished between 2008 and 2011. During this phase, in 2010, the first version of the EST Science Requirement Document (SRD)was published. After EST became a project on the ESFRI3 roadmap 2016, the preparatory phase started. This phase is partially supported by EU funding through the PRE-EST H2020 project4. The goal of the preparatory phase is to accomplish a final design for the telescope and the legal governance structure of EST. A major milestone on this path is to revisit and update the Science Requirement Document (SRD). The EST Science Advisory Group (SAG) has been constituted by EAST and the Board of the PRE-EST4 EU project in November 2017 and has been charged with the task of providing with a final statement on the science requirements for EST. Based on the conceptual design, the SRD update takes into account recent technical and scientific developments, to ensure that EST provides significant advancement beyond the current state-of-the-art. The present update of the EST SRD has been developed and discussed during a series of EST SAG meetings: 1st telecon meeting on Nov 5th, 2017 2nd meeting in Freiburg, Nov 24, 2017 3rd telecon meeting, Dec 15, 2017 4th telecon meeting, March 26, 2018 5th meeting in Belfast, April 16 & 17, 2018 6th meeting in Naxos, June 16, 2018 7th telecon meeting, January 14, 2019 8th telecon meeting, October 11, 2019 9th telecon meeting, October 22, 2019 10th telecon meeting, December 3, 2019 The SRD develops the top-level science objectives of EST into individual science cases. Identifying critical science requirements is one of its main goals. Those requirements will define the capabilities of EST and the post-focus instrument suite. The technical requirements for the final design of EST will be derived from the SRD. The science cases presented in Part II (Sects. 1 to 8) are not intended to cover all the science questions to be addressed with EST, but rather to provide a precise overview of the capabilities that will make of EST a competitive state-of-the-art telescope to push the boundaries of our knowledge over the next few decades. The science cases contain detailed observing programmes specifying the type of observations needed to solve specific science problems. An eort is being made to define the parameters of the required observations as accurately as possible, taking into account both present capabilities and technological developments expected in the near future. The tables of the observing programmes corresponding to the science cases are compiled in Sect. 10. The EST science cases represent challenging observations that put strong constraints on the telescope and its instrument suite. Ultimately, they will be translated into Technical Requirement Document (TRD) leading to the final EST design to be implemented during the construction phase. The unique design advantages of the EST concept is presented in Section 11. The eect of the science cases on the EST design are discussed in Section 12 and summarized in Section 13.This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 739 50

Single-cell profiling of myasthenia gravis identifies a pathogenic T cell signature.

Myasthenia gravis (MG) is an autoimmune disease characterized by impaired neuromuscular signaling due to autoantibodies targeting the acetylcholine receptor. Although its auto-antigens and effector mechanisms are well defined, the cellular and molecular drivers underpinning MG remain elusive. Here, we employed high-dimensional single-cell mass and spectral cytometry of blood and thymus samples from MG patients in combination with supervised and unsupervised machine-learning tools to gain insight into the immune dysregulation underlying MG. By creating a comprehensive immune map, we identified two dysregulated subsets of inflammatory circulating memory T helper (Th) cells. These signature ThCD103 and ThGM cells populated the diseased thymus, were reduced in the blood of MG patients, and were inversely correlated with disease severity. Both signature Th subsets rebounded in the blood of MG patients after surgical thymus removal, indicative of their role as cellular markers of disease activity. Together, this in-depth analysis of the immune landscape of MG provides valuable insight into disease pathogenesis, suggests novel biomarkers and identifies new potential therapeutic targets for treatment

Evidences of vortex curvature and anisotropic pinning in superconducting films by quantitative magneto-optics

We present the experimental observation of magnetic field line curvature at the surface of a superconducting film by local quantitative magneto-optics. In addition to the knowledge of the full induction field at the superconductor surface yielding the quantitative observation of the flux line curvature, our analysis method allows also local value measurements of the electrical current density inside the sample. Thus, we study the interplay between the electrodynamic constraints dictated by the film geometry and the pinning properties of the superconductor. In particular, we investigate the anisotropic vortex-pinning, due to columnar defects introduced by heavy ion irradiation, as revealed in the local current density dependence on the vortex curvature during magnetic flux diffusion inside the superconducting film.Comment: 12 pages, 11 figures, to be submitted to Phys. Rev.

Multiwavelength studies of MHD waves in the solar chromosphere: An overview of recent results

The chromosphere is a thin layer of the solar atmosphere that bridges the relatively cool photosphere and the intensely heated transition region and corona. Compressible and incompressible waves propagating through the chromosphere can supply significant amounts of energy to the interface region and corona. In recent years an abundance of high-resolution observations from state-of-the-art facilities have provided new and exciting ways of disentangling the characteristics of oscillatory phenomena propagating through the dynamic chromosphere. Coupled with rapid advancements in magnetohydrodynamic wave theory, we are now in an ideal position to thoroughly investigate the role waves play in supplying energy to sustain chromospheric and coronal heating. Here, we review the recent progress made in characterising, categorising and interpreting oscillations manifesting in the solar chromosphere, with an impetus placed on their intrinsic energetics.Comment: 48 pages, 25 figures, accepted into Space Science Review