Single-cell multi-omics identifies chronic inflammation as a driver of TP53-mutant leukemic evolution

Understanding the genetic and nongenetic determinants of tumor protein 53 (TP53)-mutation-driven clonal evolution and subsequent transformation is a crucial step toward the design of rational therapeutic strategies. Here we carry out allelic resolution single-cell multi-omic analysis of hematopoietic stem/progenitor cells (HSPCs) from patients with a myeloproliferative neoplasm who transform to TP53-mutant secondary acute myeloid leukemia (sAML). All patients showed dominant TP53 ‘multihit’ HSPC clones at transformation, with a leukemia stem cell transcriptional signature strongly predictive of adverse outcomes in independent cohorts, across both TP53-mutant and wild-type (WT) AML. Through analysis of serial samples, antecedent TP53-heterozygous clones and in vivo perturbations, we demonstrate a hitherto unrecognized effect of chronic inflammation, which suppressed TP53 WT HSPCs while enhancing the fitness advantage of TP53-mutant cells and promoted genetic evolution. Our findings will facilitate the development of risk-stratification, early detection and treatment strategies for TP53-mutant leukemia, and are of broad relevance to other cancer types

Report (U.S. Atomic Energy Commission)

Startup and initial operation of the APPR-1 and summary of the results of the test program on the reactor

Shielding Requirements for the Army Package Power Reactor

The design, selection, and calculation of the Army Package Power Reactor shielding are described. The APPR-1, a prototype of a package reactor for remote locations, has a primary shield of Fe and water. This shield has been adopted to permit fast erection and to provide low transported weight. Economically, including transportation cost, the Fe--water shield is better thnn a Pb--water shield and is competitive with a concrete shield for a remote site. Because of its location at Fort Belvoir, Va., the shielding requirements for the APPR-1 are considerably more stringent than those for a reactor at a remote base. Since the secondary shielding which surrounds the entire primary system must provide protection for personnel at any location outside the vapor container, concrete is provided for this need. (auth

Atomic Energy Commission Report APAE-MEMO-68

As described in this report, the APPR-1 will be operated with Rods A and B full out and with the other five rods ganged

A nuclear plate camera for fast neutron spectroscopy at the bulk shielding facility /

Work performed at the Oak Ridge National Laboratory."This report is based on ORNL-1046.""Date Declassified: November 1, 1951.""September 14, 1951."Mode of access: Internet

A standard gamma ray ionization chamber for shielding measurements /

"July 9, 1951."Includes bibliographical references.Mode of access: Internet

Hazards summary report on the zero power experiments for the army package power reactor /

At head of title: United States Atomic Energy Commission."Contract no. AT (11-1)-318.""January 27, 1956.""APAE-5 and suppl. ; Reactors-Power."Mode of access: Internet.This bibliographic record is available under the Creative Commons CC0 public domain dedication. The University of Florida Libraries, as creator of this bibliographic record, has waived all rights to it worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law

Reactivity measurements with the bulk shielding reactor /

Work performed at the Oak Ridge National Laboratory."Operated by Carbide and Carbon Chemicals Company for the U.S. Atomic Energy Commission under Contract No. W-7405-eng-26."--P. ii."November 19, 1954."Cover title.Includes bibliographical references (p. 79).Mode of access: Internet.This bibliographic record is available under the Creative Commons CC0 public domain dedication. The University of Florida Libraries, as creator of this bibliographic record, has waived all rights to it worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law

Determination of the power of the bulk shielding reactor :

"March 11, 1954."Bibliographical references: p. 80.Operated by Carbide and Carbon Chemicals CompanyMode of access: Internet

Cherchez la femme: Looking for lesbian femininities in literature, 1850-1928

Cherchez la femme: Looking for lesbian femininities in literature, 1850-192