A Multi-telescope Campaign on FRB 121102: Implications for the FRB Population

We present results of the coordinated observing campaign that made the first subarcsecond localization of a Fast Radio Burst, FRB 121102. During this campaign, we made the first simultaneous detection of an FRB burst by multiple telescopes: the VLA at 3 GHz and the Arecibo Observatory at 1.4 GHz. Of the nine bursts detected by the Very Large Array at 3 GHz, four had simultaneous observing coverage at other observatories. We use multi-observatory constraints and modeling of bursts seen only at 3 GHz to confirm earlier results showing that burst spectra are not well modeled by a power law. We find that burst spectra are characterized by a ~500 MHz envelope and apparent radio energy as high as $10^{40}$ erg. We measure significant changes in the apparent dispersion between bursts that can be attributed to frequency-dependent profiles or some other intrinsic burst structure that adds a systematic error to the estimate of DM by up to 1%. We use FRB 121102 as a prototype of the FRB class to estimate a volumetric birth rate of FRB sources $R_{FRB} \approx 5x10^{-5}/N_r$ Mpc$^{-3}$ yr$^{-1}$, where $N_r$ is the number of bursts per source over its lifetime. This rate is broadly consistent with models of FRBs from young pulsars or magnetars born in superluminous supernovae or long gamma-ray bursts, if the typical FRB repeats on the order of thousands of times during its lifetime.Comment: 17 pages, 7 figures. Submitted to AAS Journal

Rapid generation of human B-cell lymphomas via combined expression of Myc and Bcl2 and their use as a preclinical model for biological therapies

Although numerous mouse models of B-cell malignancy have been developed via the enforced expression of defined oncogenic lesions, the feasibility of generating lineage-defined human B-cell malignancies using mice reconstituted with modified human hematopoietic stem cells (HSCs) remains unclear. In fact, whether human cells can be transformed as readily as murine cells by simple oncogene combinations is a subject of considerable debate. Here, we describe the development of humanized mouse model of MYC/BCL2-driven ‘double-hit’ lymphoma. By engrafting human HSCs transduced with the oncogene combination into immunodeficient mice, we generate a fatal B malignancy with complete penetrance. This humanized-MYC/BCL2-model (hMB) accurately recapitulates the histopathological and clinical aspects of steroid-, chemotherapy- and rituximab-resistant human ‘double-hit’ lymphomas that involve the MYC and BCL2 loci. Notably, this model can serve as a platform for the evaluation of antibody-based therapeutics. As a proof of principle, we used this model to show that the anti-CD52 antibody alemtuzumab effectively eliminates lymphoma cells from the spleen, liver and peripheral blood, but not from the brain. The hMB humanized mouse model underscores the synergy of MYC and BCL2 in ‘double-hit’ lymphomas in human patients. Additionally, our findings highlight the utility of humanized mouse models in interrogating therapeutic approaches, particularly human-specific monoclonal antibodies.Kathy and Curt Marble Cancer Research FundSingapore-MIT Alliance for Research and TechnologyNational Institutes of Health (U.S.) (Grant R01-CA128803)Virginia and Daniel K. Ludwig Graduate FellowshipNational Institute of General Medical Sciences (U.S.) (Medical Scientist Training Program Grant T32GM007753)MIT School of Science (Cancer Research Fellowship

Transformation of Human Mesenchymal Cells and Skin Fibroblasts into Hematopoietic Cells

Patients with prolonged myelosuppression require frequent platelet and occasional granulocyte transfusions. Multi-donor transfusions induce alloimmunization, thereby increasing morbidity and mortality. Therefore, an autologous or HLA-matched allogeneic source of platelets and granulocytes is needed. To determine whether nonhematopoietic cells can be reprogrammed into hematopoietic cells, human mesenchymal stromal cells (MSCs) and skin fibroblasts were incubated with the demethylating agent 5-azacytidine (Aza) and the growth factors (GF) granulocyte-macrophage colony-stimulating factor and stem cell factor. This treatment transformed MSCs to round, non-adherent cells expressing T-, B-, myeloid-, or stem/progenitor-cell markers. The transformed cells engrafted as hematopoietic cells in bone marrow of immunodeficient mice. DNA methylation and mRNA array analysis suggested that Aza and GF treatment demethylated and activated HOXB genes. Indeed, transfection of MSCs or skin fibroblasts with HOXB4, HOXB5, and HOXB2 genes transformed them into hematopoietic cells. Further studies are needed to determine whether transformed MSCs or skin fibroblasts are suitable for therapy

Gray zones around diffuse large B cell lymphoma. Conclusions based on the workshop of the XIV meeting of the European Association for Hematopathology and the Society of Hematopathology in Bordeaux, France

The term “gray-zone” lymphoma has been used to denote a group of lymphomas with overlapping histological, biological, and clinical features between various types of lymphomas. It has been used in the context of Hodgkin lymphomas (HL) and non-Hodgkin lymphomas (NHL), including classical HL (CHL), and primary mediastinal large B cell lymphoma, cases with overlapping features between nodular lymphocyte predominant Hodgkin lymphoma and T-cell/histiocyte-rich large B cell lymphoma, CHL, and Epstein–Barr-virus-positive lymphoproliferative disorders, and peripheral T cell lymphomas simulating CHL. A second group of gray-zone lymphomas includes B cell NHL with intermediate features between diffuse large B cell lymphoma and classical Burkitt lymphoma. In order to review controversial issues in gray-zone lymphomas, a joint Workshop of the European Association for Hematopathology and the Society for Hematopathology was held in Bordeaux, France, in September 2008. The panel members reviewed and discussed 145 submitted cases and reached consensus diagnoses. This Workshop summary is focused on the most controversial aspects of gray-zone lymphomas and describes the panel’s proposals regarding diagnostic criteria, terminology, and new prognostic and diagnostic parameters

A direct localization of a fast radio burst and its host

Fast radio bursts are astronomical radio flashes of unknown physical nature with durations of milliseconds. Their dispersive arrival times suggest an extragalactic origin and imply radio luminosities orders of magnitude larger than any other kind of known short-duration radio transient. Thus far, all FRBs have been detected with large single-dish telescopes with arcminute localizations, and attempts to identify their counterparts (source or host galaxy) have relied on contemporaneous variability of field sources or the presence of peculiar field stars or galaxies. These attempts have not resulted in an unambiguous association with a host or multi-wavelength counterpart. Here we report the sub-arcsecond localization of FRB 121102, the only known repeating burst source, using high-time-resolution radio interferometric observations that directly image the bursts themselves. Our precise localization reveals that FRB 121102 originates within 100 mas of a faint 180 uJy persistent radio source with a continuum spectrum that is consistent with non-thermal emission, and a faint (25th magnitude) optical counterpart. The flux density of the persistent radio source varies by tens of percent on day timescales, and very long baseline radio interferometry yields an angular size less than 1.7 mas. Our observations are inconsistent with the fast radio burst having a Galactic origin or its source being located within a prominent star-forming galaxy. Instead, the source appears to be co-located with a low-luminosity active galactic nucleus or a previously unknown type of extragalactic source. [Truncated] If other fast radio bursts have similarly faint radio and optical counterparts, our findings imply that direct sub-arcsecond localizations of FRBs may be the only way to provide reliable associations.Comment: Nature, published online on 4 Jan 2017, DOI: 10.1038/nature2079

Correlation of Shear to Compression for Progressive Fracture Obliquity

The accompanying shear force at the point of bone opposition is an important factor inherent to tibial fracture stability during axial loading. We determined at which angle of fracture obliquity shearing becomes a dominant force after stabilization with circular external fixation, and how modifications to the external fixator can reduce this effect. We constructed tibial fracture models with a successively increasing fracture angle obliquely (from 0° to 60°) to determine the stability in the classic Ilizarov frame and subsequent frame modifications during axial loading (maximum, 1000 N). Stability was determined by measuring the fracture line displacement for each fracture obliquity model after an applied axial load. Fracture line displacement was recorded as coordinate component changes as measured by an ultrasonic digitizer. We defined construct stability as less than 2 mm of fracture line migration with loading. More than 3500 data points were collected for this study. The classic Ilizarov construct successfully stabilized fractures with up to 30° of fracture obliquity, after which divergent instability occurs. The addition of proximal and distal perpendicular half-pins provides little benefit. Arced wires provided stability up to 40° fracture obliquity. A formal steerage pin construct provided stability for all fracture models (up to 60° of fracture obliquity) with all applied loads (up to 1000-N axial load)