Electron-Electron Interactions in Transfer and Excitation in F⁸⁺ →₂ Collisions

We have measured projectile Auger electrons emitted after collisions of H-like F with H2. The cross sections for emission of KLL, KLM, KLN, and KLO Auger electrons show maxima as a function of the projectile energy. One maximum in the KLL emission cross section is due to resonant transfer and excitation. A second maximum in the cross section for KLL emission as well as the maxima in the emission cross section for the higher-n Auger electrons are attributed to a new transfer and excitation process. This involves excitation of a projectile electron by one target electron accompanied by the capture of a second target electron

Projectile Energy Loss in Multiply Ionizing Ion-Atom Collisions

The projectile energy loss for 7.5--25-MeV C6+,5+ and F6+ ions was measured for single collisions with He, Ne, Ar, and Kr as a function of the recoil-ion charge state and the projectile scattering. This energy loss was measured for collisions in which the projectile captured an electron and for those involving just direct ionization. We investigated and found a large average energy transfer (100--250 eV/electron) to the continuum electrons. A strong increase of the scattering angle with recoil-ion charge state was observed for both capture and direct ionization. The results imply that, for smaller impact parameters, higher recoil-ion charge states are produced and that higher energy losses are obtained. We observed a weak target-Z dependence of the energy loss. The results are compared with n-body classical-trajectory Monte Carlo calculations by Olson, semiclassical-approximation calculations by Schuch et al. [Nucl. Instrum. Methods Phys. Res. Sect. B 42, 566 (1989)], and the energy-deposition model

Population of Highly Excited Intermediate Resonance States by Electron Transfer and Excitation

Coincidences between two sulfur K x rays were detected from collisions of hydrogenlike S ions with H2 gas in the projectile energy range between 150 and 225 MeV. These K x rays are emitted in the decay of doubly excited states formed in the collisions via transfer and excitation. The excitation function for two coincident Kβ transitions peaks at about 175 MeV, slightly above the expected KMM resonance energy for resonant transfer and excitation (RTE). This demonstrates the occurrence of ΔN≥2 transitions (i.e., KMM and higher resonances) in the RTE process. The cross sections for the population of the very highly excited states are higher than those predicted by theoretical calculations that use dielectronic recombination rates folded with the Compton profile for the bound electrons

Resonant Dielectronic and Direct Excitation in Crystal Channels

We have observed dielectronic and direct excitation of H-like S15+ and Ca19+ and He-like Ti20+ ions in silicon channels caused by collision with weakly bound target electrons which behave as a free-electron gas. As in vacuo, relaxation of the doubly excited states can occur radiatively leading to ions of decreased charge, but in a crystal channel collisional effects can cause double ionization. The effects are seen in both the x-ray yields and charge-state fractions, and, in the case of Ti20+, in charge-state x-ray coincidences

Differential regulation of myeloid leukemias by the bone marrow microenvironment

Like their normal hematopoietic stem cell counterparts, leukemia stem cells (LSC) in chronic myelogenous leukemia (CML) and acute myeloid leukemia (AML) are presumed to reside in specific niches in the bone marrow microenvironment (BMM)1, and may be the cause of relapse following chemotherapy.2 Targeting the niche is a novel strategy to eliminate persistent and drug-resistant LSC. CD443,4 and IL-65 have been implicated previously in the LSC niche. Transforming growth factor (TGF)-β1 is released during bone remodeling6 and plays a role in maintenance of CML LSCs7, but a role for TGF-β1 from the BMM has not been defined. Here, we show that alteration of the BMM by osteoblastic cell-specific activation of the parathyroid hormone (PTH) receptor8,9 attenuates BCR-ABL1-induced CML-like myeloproliferative neoplasia (MPN)10 but enhances MLL-AF9-induced AML11 in mouse transplantation models, possibly through opposing effects of increased TGF-β1 on the respective LSC. PTH treatment caused a 15-fold decrease in LSCs in wildtype mice with CML-like MPN, and reduced engraftment of immune deficient mice with primary human CML cells. These results demonstrate that LSC niches in chronic and acute myeloid leukemias are distinct, and suggest that modulation of the BMM by PTH may be a feasible strategy to reduce LSC, a prerequisite for the cure of CML

Autism as a disorder of neural information processing: directions for research and targets for therapy

The broad variation in phenotypes and severities within autism spectrum disorders suggests the involvement of multiple predisposing factors, interacting in complex ways with normal developmental courses and gradients. Identification of these factors, and the common developmental path into which theyfeed, is hampered bythe large degrees of convergence from causal factors to altered brain development, and divergence from abnormal brain development into altered cognition and behaviour. Genetic, neurochemical, neuroimaging and behavioural findings on autism, as well as studies of normal development and of genetic syndromes that share symptoms with autism, offer hypotheses as to the nature of causal factors and their possible effects on the structure and dynamics of neural systems. Such alterations in neural properties may in turn perturb activity-dependent development, giving rise to a complex behavioural syndrome many steps removed from the root causes. Animal models based on genetic, neurochemical, neurophysiological, and behavioural manipulations offer the possibility of exploring these developmental processes in detail, as do human studies addressing endophenotypes beyond the diagnosis itself

Evaluation of presumably disease causing SCN1A variants in a cohort of common epilepsy syndromes

Objective: The SCN1A gene, coding for the voltage-gated Na+ channel alpha subunit NaV1.1, is the clinically most relevant epilepsy gene. With the advent of high-throughput next-generation sequencing, clinical laboratories are generating an ever-increasing catalogue of SCN1A variants. Variants are more likely to be classified as pathogenic if they have already been identified previously in a patient with epilepsy. Here, we critically re-evaluate the pathogenicity of this class of variants in a cohort of patients with common epilepsy syndromes and subsequently ask whether a significant fraction of benign variants have been misclassified as pathogenic. Methods: We screened a discovery cohort of 448 patients with a broad range of common genetic epilepsies and 734 controls for previously reported SCN1A mutations that were assumed to be disease causing. We re-evaluated the evidence for pathogenicity of the identified variants using in silico predictions, segregation, original reports, available functional data and assessment of allele frequencies in healthy individuals as well as in a follow up cohort of 777 patients. Results and Interpretation: We identified 8 known missense mutations, previously reported as path

Barrier Tissue Macrophages: Functional Adaptation to Environmental Challenges

Macrophages are found throughout the body, where they have crucial roles in tissue development, homeostasis and remodeling, as well as being sentinels of the innate immune system that can contribute to protective immunity and inflammation. Barrier tissues, such as the intestine, lung, skin and liver, are exposed constantly to the outside world, which places special demands on resident cell populations such as macrophages. Here we review the mounting evidence that although macrophages in different barrier tissues may be derived from distinct progenitors, their highly specific properties are shaped by the local environment, which allows them to adapt precisely to the needs of their anatomical niche. We discuss the properties of macrophages in steady-state barrier tissues, outline the factors that shape their differentiation and behavior and describe how macrophages change during protective immunity and inflammation

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure