Brown University

About: Brown University is a education organization based out in Providence, Rhode Island, United States. It is known for research contribution in the topics: Population & Poison control. The organization has 35778 authors who have published 90896 publications receiving 4471489 citations. The organization is also known as: brown.edu & Brown.

Haploinsufficiency of CBFA2 causes familial thrombocytopenia with propensity to develop acute myelogenous leukaemia

Abstract: Familial platelet disorder with predisposition to acute myelogenous leukaemia (FPD/AML, MIM 601399) is an autosomal dominant disorder characterized by qualitative and quantitative platelet defects, and propensity to develop acute myelogenous leukaemia (AML). Informative recombination events in 6 FPD/AML pedigrees with evidence of linkage to markers on chromosome 21q identified an 880-kb interval containing the disease gene. Mutational analysis of regional candidate genes showed nonsense mutations or intragenic deletion of one allele of the haematopoietic transcription factor CBFA2 (formerly AML1) that co-segregated with the disease in four FPD/AML pedigrees. We identified heterozygous CBFA2 missense mutations that co-segregated with the disease in the remaining two FPD/AML pedigrees at phylogenetically conserved amino acids R166 and R201, respectively. Analysis of bone marrow or peripheral blood cells from affected FPD/AML individuals showed a decrement in megakaryocyte colony formation, demonstrating that CBFA2 dosage affects megakaryopoiesis. Our findings support a model for FPD/AML in which haploinsufficiency of CBFA2 causes an autosomal dominant congenital platelet defect and predisposes to the acquisition of additional mutations that cause leukaemia.

The gravitational settling of aerosol particles in homogeneous turbulence and random flow fields

Abstract: The average settling velocity in homogeneous turbulence of a small rigid spherical particle, subject to a Stokes drag force, is shown to depend on the particle inertia and the free-fall terminal velocity in still fluid. With no inertia the particle settles on average at the same rate as in still fluid, assuming there is no mean flow. Particle inertia produces a bias in each trajectory towards regions of high strain rate or low vorticity, which affects the mean settling velocity. Results from a Gaussian random velocity field show that this produces an increased settling velocity.

Family of crack-tip fields characterized by a triaxiality parameter—I. Structure of fields

Abstract: Central to the J-based fracture mechanics approach is the existence of a HRR near-tip field which dominates the actual field over size scales comparable to those over which the micro-separation processes are active. There is now general agreement that the applicability of the J-approach is limited to so-called high-constraint crack geometries. We review the J-annulus concept and then develop the idea of a J-Q annulus. Within the J-Q annulus, the full range of high- and low-triaxiality fields are shown to be members of a family of solutions parameterized by Q when distances are measured in terms of J σ 0 , where σ0 is the yield stress. The stress distribution and the maximum stress depend on Q alone while J sets the size scale over which large stresses and strains develop. Full-field solutions show that the Q-family of fields exists near the crack tip of different crack geometries at large-scale yielding. The Q-family provides a framework for quantifying the evolution of constraint as plastic flow progresses from small-scale yielding to fully yielded conditions, and the limiting (steady-state) constraint when it exist. The Q value of a crack geometry can be used to rank its constraint, thus giving a precise meaning to the term crack-tip constraints, a term which is widely used in the fracture literature but has heretofore been unquantified. A two-parameter fracture mechanics approach for tensile mode crack tip states in which the fracture toughness and the resistance curve depend on Q, i. JC(Q) and JR(Δa, Q), is proposed.

The Surviving Sepsis Campaign Bundle: 2018 update

Abstract: INTRODUCTIONThe “sepsis bundle” has been central to the implementation of the Surviving Sepsis Campaign (SSC) from the first publication of its evidence-based guidelines in 2004 through subsequent editions (1–6). Developed separately from the guidelines publication by the SSC, the bundles have been