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BRD4 is a BET family protein that binds acetylated histones and regulates transcription. BET/BRD4 inhibitors block blood cancer growth and inflammation and serve as a new therapeutic strategy. However, the biological role of BRD4 in normal hematopoiesis and inflammation is not fully understood. Analysis of Brd4 conditional knockout (KO) mice showed that BRD4 is required for hematopoietic stem cell expansion and progenitor development. Nevertheless, BRD4 played limited roles in macrophage development and inflammatory response to LPS. ChIP‐seq analysis showed that despite its limited importance, BRD4 broadly occupied the macrophage genome and participated in super‐enhancer (SE) formation. Although BRD4 is critical for SE formation in cancer, BRD4 was not required for macrophage SEs, as KO macrophages created alternate, BRD4‐less SEs that compensated BRD4 loss. This and additional mechanisms led to the retention of inflammatory responses in macrophages. Our results illustrate a context‐dependent role of BRD4 and plasticity of epigenetic regulation.

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ABSTRACT. The effective and efficient delivery of children's health care depends on the pediatrician workforce. The number, composition, and distribution of pediatricians necessary to deliver this care have been the subject of long-standing policy and professional debate. This technical report reviews current characteristics and recent trends in the pediatric workforce and couples the workforce to a conceptual model of improvement in children's health and well-being. Important recent changes in the workforce include (1)

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Negative views of managed care are widespread among medical students, residents, faculty members, and medical school deans.

With a projected increase in the number of female pediatricians and a decline in international medical graduates, our study suggests that pediatrics may continue to shift toward an increased proportion of general pediatricians. Lifestyle issues are a major factor influencing job choice and must be addressed.

We present a new parametric lens model for the massive galaxy cluster Abell 2744 based on new ultra-deep JWST imaging taken in the framework of the UNCOVER program. These observations constitute the deepest JWST images of a lensing cluster to date, adding to existing deep Hubble Space Telescope (HST) images and the recent JWST ERS and DDT data taken for this field. The wide field-of-view of UNCOVER (∼45 arcmin2) extends beyond the cluster’s well-studied central core and reveals a spectacular wealth of prominent lensed features around two massive cluster sub-structures in the north and north-west, where no multiple images were previously known. We identify 75 new multiple images and candidates of 17 sources, 43 of which allow us, for the first time, to constrain the lensing properties and total mass distribution around these extended cluster structures using strong lensing (SL). Our model yields an effective Einstein radius of θE, main = 23.2″ ± 2.3″ for the main cluster core (for zs = 2), enclosing a mass of M( < θE, main) = (7.7 ± 1.1) × 1013 M⊙, and θE, NW = 13.1″ ± 1.3″ for the newly discovered north-western SL structure enclosing M( < θE, NW) = (2.2 ± 0.3) × 1013 M⊙. The northern clump is somewhat less massive with θE, N = 7.4″ ± 0.7″ enclosing M( < θE, N) = (0.8 ± 0.1) × 1013 M⊙. We find the northern sub-structures of Abell 2744 to broadly agree with the findings from weak lensing (WL) analyses and align with the filamentary structure found by these previous studies. Our model in particular reveals a large area of high magnification values between the various cluster structures, which will be paramount for lensed galaxy studies in the UNCOVER field. The model is made publicly available to accompany the first UNCOVER data release.