A Novel t(8;14)(q24;q11) Rearranged Human Cell Line as a Model for Mechanistic and Drug Discovery Studies of NOTCH1-Independent Human T-Cell Leukemia

MYC-translocated T-lineage acute lymphoblastic leukemia (T-ALL) is a rare subgroup of T-ALL associated with CDKN2A/B deletions, PTEN inactivation, and absence of NOTCH1 or FBXW7 mutations. This subtype of T-ALL has been associated with induction failure and aggressive disease. Identification of drug targets and mechanistic insights for this disease are still limited. Here, we established a human NOTCH1-independent MYC-translocated T-ALL cell line that maintains the genetic and phenotypic characteristics of the parental leukemic clone at diagnosis. The University of Padua T-cell acute lymphoblastic leukemia 13 (UP-ALL13) cell line has all the main features of the above described MYC-translocated T-ALL. Interestingly, UP-ALL13 was found to harbor a heterozygous R882H DNMT3A mutation typically found in myeloid leukemia. Chromatin immunoprecipitation coupled with high-throughput sequencing for histone H3 lysine 27 (H3K27) acetylation revealed numerous putative super-enhancers near key transcription factors, including MYC, MYB, and LEF1. Marked cytotoxicity was found following bromodomain-containing protein 4 (BRD4) inhibition with AZD5153, suggesting a strict dependency of this particular subtype of T-ALL on the activity of super-enhancers. Altogether, this cell line may be a useful model system for dissecting the signaling pathways implicated in NOTCH1-independent T-ALL and for the screening of targeted anti-leukemia agents specific for this T-ALL subgroup

The Mira Distance to M101 and a 4% Measurement of H0

The giant spiral galaxy M101 is host to the nearest recent Type Ia Supernova (SN 2011fe) and thus has been extensively monitored in the near-infrared to study the late-time lightcurve of the supernova. Leveraging this existing baseline of observations, we derive the first Mira-based distance to M101 by discovering and classifying a sample of 211 Miras with periods ranging from 240 to 400 days in the supernova field. Combined with new HST WFC3/IR channel observations, our dataset totals 11 epochs of F110W (HST $YJ$) and 13 epochs of F160W (HST $H$) data spanning $\sim$2900 days. We adopt absolute calibrations of the Mira Period-Luminosity Relation based on geometric distances to the Large Magellanic Cloud and the water megamaser host galaxy NGC 4258, and find $\mu_{\rm M101} =$ 29.10 $\pm$ 0.06 mag. This distance is in 1$\sigma$ agreement with most other recent Cepheid and Tip of the Red Giant Branch distance measurements to M101. Including the previous Mira-SNIa host, NGC 1559 and SN 2005df, we determine the fiducial SN Ia peak luminosity, $M^0_B = -19.27 \pm 0.09$ mag. With the Hubble diagram of SNe Ia, we derive $H_0 = 72.37 \pm 2.97$ km s$^{-1}$Mpc$^{-1}$, a $4.1\%$ measurement of $H_0$ using Miras. We find excellent agreement with recent Cepheid distance ladder measurements of $H_0$ and confirm previous indications that the local universe value of $H_0$ is higher than the early-universe value at $\sim$ $95\%$ confidence. Currently, the Mira-based $H_0$ measurement is still dominated by the statistical uncertainty in the SN Ia peak magnitude.Comment: 22 pages, 11 figures, accepted to Ap

Cervical Varices Presenting as Vaginal Bleeding: A Description of Two Cases and A Management Plan

Background: Varicose veins are common in pregnancy. However, potentially life-threatening uterine cervical varices have rarely been reported and there are currently no guidelines for their management. Cases: We present two cases of cervical varices found in the setting of second and third trimester bleeding, report on the clinical outcomes and propose a management plan. Both of our patients were delivered between 38-39 weeks gestation and required interdisciplinary meetings between Obstetrics and Gynecology, Anesthesiology, Neonatology and Interventional Radiology to prepare for delivery. Conclusion: For patients in which varices are found inside the cervix, we recommend consideration of second trimester cerclage followed by serial ultrasound and scheduled cesarean delivery. Vascular embolization should also be considered

Measurements of the magnetic form factor of the proton for timelike momentum transfers

Fermilab experiment E835 has measured the cross section for the reaction p\u304p \u2192 e+e- at s = 11.63, 12.43, 14.40 and 18.22 GeV2. From the analysis of the 66 observed events new high-precision measurements of the proton magnetic form factor are obtained

Measurement of pseudorapidity distributions of charged particles in proton-proton collisions at sqrt(s) = 8 TeV by the CMS and TOTEM experiments

Pseudorapidity ( $\eta$ ) distributions of charged particles produced in proton–proton collisions at a centre-of-mass energy of 8 $~\text {TeV}$ are measured in the ranges $|\eta | < 2.2$ and $5.3 < |\eta | < 6.4$ covered by the CMS and TOTEM detectors, respectively. The data correspond to an integrated luminosity of $\mathcal {L} = 45 \mu {\mathrm {b}}^{-1}$ . Measurements are presented for three event categories. The most inclusive category is sensitive to 91–96 % of the total inelastic proton–proton cross section. The other two categories are disjoint subsets of the inclusive sample that are either enhanced or depleted in single diffractive dissociation events. The data are compared to models used to describe high-energy hadronic interactions. None of the models considered provide a consistent description of the measured distributions