421 research outputs found
Common variable immunodeficiency, impaired neurological development and reduced numbers of T regulatory cells in a 10-year-old boy with a STAT1 gain-of-function mutation
Recently, gain-of-function (GOF) mutations in the gene encoding signal transducer and activator of transcription 1 (STAT1) have been associated with chronic mucocutaneous candidiasis (CMC). This case report describes a 10-year-old boy presenting with signs of common variable immunodeficiency (CVID), failure to thrive, impaired neurological development, and a history of recurrent mucocutaneous Candida infections. Sequencing of the STAT1 gene identified a heterozygous missense mutation in exon 7 encoding the STAT1 coiled-coil domain (c.514T > C, p.Phe172Leu). In addition to hypogammaglobulinemia with B-cell deficiency, and a low percentage of Th17 cells, immunological analysis of the patient revealed a marked depletion of forkhead-box P3+-expressing regulatory T cells (Tregs). In vitro stimulation of T cells from the patient with interferon-α (IFNα) and/or IFNɣ resulted in a significantly increased expression of STAT1-regulated target genes such as MIG1, IRF1, MX1, MCP1/CCL2, IFI-56K, and CXCL10 as compared to IFN-treated cells from a healthy control, while no IFNα/ɣ-mediated up-regulation of the FOXP3 gene was found. These data demonstrate that the STAT1 GOF mutation F172L, which results in impaired stability of the antiparallel STAT1 dimer conformation, is associated with inhibited Treg cell development and neurological symptoms
Earth system modeling with endogenous and dynamic human societies: the copan:CORE open World-Earth modeling framework
Analysis of Earth system dynamics in the Anthropocene requires explicitly taking into account the increasing magnitude of processes operating in human societies, their cultures, economies and technosphere and their growing feedback entanglement with those in the physical, chemical and biological systems of the planet. However, current state-of-the-art Earth system models do not represent dynamic human societies and their feedback interactions with the biogeophysical Earth system and macroeconomic integrated assessment models typically do so only with limited scope. This paper (i) proposes design principles for constructing world-Earth models (WEMs) for Earth system analysis of the Anthropocene, i.e., models of social (world)-ecological (Earth) coevolution on up to planetary scales, and (ii) presents the copan:CORE open simulation modeling framework for developing, composing and analyzing such WEMs based on the proposed principles. The framework provides a modular structure to flexibly construct and study WEMs. These can contain biophysical (e.g., carbon cycle dynamics), socio-metabolic or economic (e.g., economic growth or energy system changes), and sociocultural processes (e.g., voting on climate policies or changing social norms) and their feedback interactions, and they are based on elementary entity types, e.g., grid cells and social systems. Thereby, copan:CORE enables the epistemic flexibility needed for contributions towards Earth system analysis of the Anthropocene given the large diversity of competing theories and methodologies used for describing socio-metabolic or economic and sociocultural processes in the Earth system by various fields and schools of thought. To illustrate the capabilities of the framework, we present an exemplary and highly stylized WEM implemented in copan:CORE that illustrates how endogenizing sociocultural processes and feedbacks such as voting on climate policies based on socially learned environmental awareness could fundamentally change macroscopic model outcomes
Measurement of the proton electric to magnetic form factor ratio from \vec ^1H(\vec e, e'p)
We report the first precision measurement of the proton electric to magnetic
form factor ratio from spin-dependent elastic scattering of longitudinally
polarized electrons from a polarized hydrogen internal gas target. The
measurement was performed at the MIT-Bates South Hall Ring over a range of
four-momentum transfer squared from 0.15 to 0.65 (GeV/c).
Significantly improved results on the proton electric and magnetic form factors
are obtained in combination with previous cross-section data on elastic
electron-proton scattering in the same region.Comment: 4 pages, 2 figures, submitted to PR
The Charge Form Factor of the Neutron at Low Momentum Transfer from the Reaction
We report new measurements of the neutron charge form factor at low momentum
transfer using quasielastic electrodisintegration of the deuteron.
Longitudinally polarized electrons at an energy of 850 MeV were scattered from
an isotopically pure, highly polarized deuterium gas target. The scattered
electrons and coincident neutrons were measured by the Bates Large Acceptance
Spectrometer Toroid (BLAST) detector. The neutron form factor ratio
was extracted from the beam-target vector asymmetry
at four-momentum transfers , 0.20, 0.29 and 0.42
(GeV/c).Comment: 5 pages, 3 figures, submitted to Phys. Rev. Let
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