High-grade B-Cell lymphoma with MYC and BCL6 rearrangements associated with Richter transformation of chronic lymphocytic leukemia

Richter transformation (RT), or Richter syndrome, is defined as the transformation of chronic lymphocytic leukemia (CLL) to an aggressive B-cell lymphoma. The vast majority, up to 99%, transform into diffuse large B-cell lymphoma (DLBCL), with a small subset (<1%) becoming classical Hodgkin lymphoma. Approximately half of RT cases progress through a pathway involving dysregulation of C-MYC. High-grade B-cell lymphoma (HGBL) is a recent diagnostic category of aggressive B-cell lymphomas set forth in the updated 2017 WHO Classification of Hematopoietic and Lymphoid Tissues. HGBL with MYC and BCL2 and/or BCL6 rearrangements, formerly “double-hit” and “triple-hit” lymphomas, comprise the majority of HGBL cases. Patients with HGBL have a worse prognosis than those with diffuse large B-cell lymphoma. We present a case of RT with rearrangements of MYC and BCL6. To our knowledge, there are no reported cases of RT with a “double-hit” lymphoma genotype

Measurements of the Diffuse Ultraviolet Background and the Terrestrial Airglow with the Space Telescope Imaging Spectrograph

Far-UV observations in and near the Hubble Deep Fields demonstrate that the Space Telescope Imaging Spectrograph (STIS) can potentially obtain unique and precise measurements of the diffuse far-ultraviolet background. Although STIS is not the ideal instrument for such measurements, high-resolution images allow Galactic and extragalactic objects to be masked to very faint magnitudes, thus ensuring a measurement of the truly diffuse UV signal. The programs we have analyzed were not designed for this scientific purpose, but would be sufficient to obtain a very sensitive measurement if it were not for a weak but larger-than-expected signal from airglow in the STIS 1450-1900 A bandpass. Our analysis shows that STIS far-UV crystal quartz observations taken near the limb during orbital day can detect a faint airglow signal, most likely from NI\1493, that is comparable to the dark rate and inseparable from the far-UV background. Discarding all but the night data from these datasets gives a diffuse far-ultraviolet background measurement of 501 +/- 103 ph/cm2/sec/ster/A, along a line of sight with very low Galactic neutral hydrogen column (N_HI = 1.5E20 cm-2) and extinction (E(B-V)=0.01 mag). This result is in good agreement with earlier measurements of the far-UV background, and should not include any significant contribution from airglow. We present our findings as a warning to other groups who may use the STIS far-UV camera to observe faint extended targets, and to demonstrate how this measurement may be properly obtained with STIS.Comment: 7 pages, Latex. 4 figures. Uses corrected version of emulateapj.sty and apjfonts.sty (included). Accepted for publication in A

A Comprehensive Survey of Hydrogen Chloride in the Galaxy

We report new observations of the fundamental $J=1-0$ transition of HCl (at 625.918GHz) toward a sample of 25 galactic star-forming regions, molecular clouds, and evolved stars, carried out using the Caltech Submillimeter Observatory. Fourteen sources in the sample are also observed in the corresponding H\tscl\ $J=1-0$ transition (at 624.978GHz). We have obtained clear detections in all but four of the targets, often in emission. Absorptions against bright background continuum sources are also seen in nine cases, usually involving a delicate balance between emission and absorption features. From RADEX modeling, we derive gas densities and HCl column densities for sources with HCl emission. HCl is found in a wide range of environments, with gas densities ranging from $10^5$ to $10^7$~cm$^{-3}$. The HCl abundance relative to H$_2$ is in the range of $(3-30)\times10^{-10}$. Comparing with the chlorine abundance in the solar neighborhood, this corresponds to a chlorine depletion factor of up to $\sim$400, assuming that HCl accounts for one third of the total chlorine in the gas phase. The [\tfcl]/[\tscl] isotopic ratio is rather varied, from unity to $\sim$5, mostly lower than the terrestrial value of 3.1. Such variation is highly localized, and could be generated by the nucleosynthesis in supernovae, which predicts a \tscl\ deficiency in most models. The lower ratios seen in W3IRS4 and W3IRS5 likely confine the progenitors of the supernovae to stars with relatively large mass (\ga25M_\sun) and high metallicity (Z$\sim$0.02).Comment: 11 pages, 5 figures, accepted by Ap

Human cytomegalovirus US28 facilitates cell-to-cell viral dissemination

Human cytomegalovirus (HCMV) encodes a number of viral proteins with homology to cellular G protein-coupled receptors (GPCRs). These viral GPCRs, including US27, US28, UL33, and UL78, have been ascribed numerous functions during infection, including activating diverse cellular pathways, binding to immunomodulatory chemokines, and impacting virus dissemination. To investigate the role of US28 during virus infection, two variants of the clinical isolate TB40/E were generated: TB40/E-US28(YFP) expressing a C-terminal yellow fluorescent protein tag, and TB40/E-FLAG(YFP) in which a FLAG-YFP cassette replaces the US28 coding region. The TB40/E-US28(YFP) protein localized as large perinuclear fluorescent structures at late times post-infection in fibroblasts, endothelial, and epithelial cells. Interestingly, US28(YFP) is a non-glycosylated membrane protein throughout the course of infection. US28 appears to impact cell-to-cell spread of virus, as the ΔUS28 virus (TB40/E-FLAG(YFP)) generated a log-greater yield of extracellular progeny whose spread could be significantly neutralized in fibroblasts. Most strikingly, in epithelial cells, where dissemination of virus occurs exclusively by the cell-to-cell route, TB40/E-FLAG(YFP) (ΔUS28) displayed a significant growth defect. The data demonstrates that HCMV US28 may contribute at a late stage of the viral life cycle to cell-to-cell dissemination of virus

Comparison of Robot-Assisted Nephrectomy with Laparoscopic and Hand-Assisted Laparoscopic Nephrectomy

Early experience with robotic assistance for radical and simple nephrectomy offers no significant advantage over traditional laparoscopic or hand-assisted approaches

Direct CP Violation, Branching Ratios and Form Factors B→πB \to \pi, B→KB \to K in BB Decays

The $B \to \pi$ and $B \to K$ transitions involved in hadronic B decays are investigated in a phenomenological way through the framework of QCD factorization. By comparing our results with experimental branching ratios from the BELLE, BABAR and CLEO Collaborations for all the B decays including either a pion or a kaon, we propose boundaries for the transition form factors $B \to \pi$ and $B \to K$ depending on the CKM matrix element parameters $\rho$ and $\eta$. From this analysis, the form factors required to reproduce the experimental data for branching ratios are $F^{B \to \pi}= 0.31 \pm 0.12$ and $F^{B \to K}= 0.37\pm 0.13$. We calculate the direct CP violating asymmetry parameter, $a_{CP}$, for $B \to \pi^{+} \pi^{-} \pi$ and $B \to \pi^{+} \pi^{-} K$ decays, in the case where $\rho-\omega$ mixing effects are taken into account. Based on these results, we find that the direct CP asymmetry for $B^{-} \to \pi^{+} \pi^{-} \pi^{-}$, $\bar{B}^{0} \to \pi^{+} \pi^{-} \pi^{0}$, $B^{-} \to \pi^{+} \pi^{-} K^{-}$, and $\bar{B}^{0} \to \pi^{+} \pi^{-} \bar{K}^{0}$, reaches its maximum when the invariant mass $\pi^{+} \pi^{-}$ is in the vicinity of the $\omega$ meson mass. The inclusion of $\rho-\omega$ mixing provides an opportunity to erase, without ambiguity, the phase uncertainty mod$(\pi)$ in the determination of the CKM angles $\alpha$ in case of $b\to u$ and $\gamma$ in case of $b \to s$.Comment: 74 pages, 15 figures, 8 tables. A few misprints corrected, two references adde

A Mathematical Framework for Agent Based Models of Complex Biological Networks

Agent-based modeling and simulation is a useful method to study biological phenomena in a wide range of fields, from molecular biology to ecology. Since there is currently no agreed-upon standard way to specify such models it is not always easy to use published models. Also, since model descriptions are not usually given in mathematical terms, it is difficult to bring mathematical analysis tools to bear, so that models are typically studied through simulation. In order to address this issue, Grimm et al. proposed a protocol for model specification, the so-called ODD protocol, which provides a standard way to describe models. This paper proposes an addition to the ODD protocol which allows the description of an agent-based model as a dynamical system, which provides access to computational and theoretical tools for its analysis. The mathematical framework is that of algebraic models, that is, time-discrete dynamical systems with algebraic structure. It is shown by way of several examples how this mathematical specification can help with model analysis.Comment: To appear in Bulletin of Mathematical Biolog