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Tissue macrophages arise during embryogenesis from yolk-sac (YS) progenitors that give rise to primitive YS macrophages. Until recently, it has been impossible to isolate or derive sufficient numbers of YS-derived macrophages for further study, but data now suggest that induced pluripotent stem cells (iPSCs) can be driven to undergo a process reminiscent of YS-hematopoiesis in vitro. We asked whether iPSC-derived primitive macrophages (iMacs) can terminally differentiate into specialized macrophages with the help of growth factors and organ-specific cues. Co-culturing human or murine iMacs with iPSC-derived neurons promoted differentiation into microglia-like cells in vitro. Furthermore, murine iMacs differentiated in vivo into microglia after injection into the brain and into functional alveolar macrophages after engraftment in the lung. Finally, iPSCs from a patient with familial Mediterranean fever differentiated into iMacs with pro-inflammatory characteristics, mimicking the disease phenotype. Altogether, iMacs constitute a source of tissue-resident macrophage precursors that can be used for biological, pathophysiological, and therapeutic studies.

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We have searched for intermediate-scale anisotropy in the arrival directions of ultrahigh-energy cosmic rays with energies above 57 EeV in the northern sky using data collected over a 5 yr period by the surface detector of the Telescope Array experiment. We report on a cluster of events that we call the hotspot, found by oversampling using 20 • radius circles. The hotspot has a Li-Ma statistical significance of 5.1σ , and is centered at R.A. = 146. • 7, decl. = 43. • 2. The position of the hotspot is about 19 • off of the supergalactic plane. The probability of a cluster of events of 5.1σ significance, appearing by chance in an isotropic cosmic-ray sky, is estimated to be 3.7 × 10 −4 (3.4σ).

The Telescope Array (TA) collaboration has measured the energy spectrum of ultra-high energy cosmic rays (UHECRs) with primary energies above 1.6 × 10 18 eV. This measurement is based upon four years of observation by the surface detector component of TA. The spectrum shows a dip at an energy of 4.6 × 10 18 eV and a steepening at 5.4 × 10 19 eV which is consistent with the expectation from the GZK cutoff. We present the results of a technique, new to the analysis of UHECR surface detector data, that involves generating a complete simulation of UHECRs striking the TA surface detector. The procedure starts with shower simulations using the CORSIKA Monte Carlo program where we have solved the problems caused by use of the "thinning" approximation. This simulation method allows us to make an accurate calculation of the acceptance of the detector for the energies concerned.