2,902 research outputs found
ETV6 germline mutations cause HDAC3/NCOR2 mislocalization and upregulation of interferon response genes
ETV6 is an ETS family transcription factor that plays a key role in hematopoiesis and megakaryocyte development. Our group and others have identified germline mutations in ETV6 resulting in autosomal dominant thrombocytopenia and predisposition to malignancy; however, molecular mechanisms defining the role of ETV6 in megakaryocyte development have not been well established. Using a combination of molecular, biochemical, and sequencing approaches in patient-derived PBMCs, we demonstrate abnormal cytoplasmic localization of ETV6 and the HDAC3/NCOR2 repressor complex that led to overexpression of HDAC3-regulated interferon response genes. This transcriptional dysregulation was also reflected in patient-derived platelet transcripts and drove aberrant proplatelet formation in megakaryocytes. Our results suggest that aberrant transcription may predispose patients with ETV6 mutations to bone marrow inflammation, dysplasia, and megakaryocyte dysfunction
Silicon CMOS photonics platform for enabling high-speed DQPSK transceivers
In this work we review the results obtained under the framework of FP7-HELIOS project for integrated DQPSK transceivers in silicon photonics. A differential DQPSK receiver with balanced zero biased Germanium photodiodes has been demonstrated at 10Gbit/s with an error floor around 10(-15). Furthermore, DPSK modulation up to 10Gbit/s with a bit error rate below 10(-9) is also demonstrated using a silicon push-pull operated dual-drive Mach-Zehnder modulator (MZM) based on carrier depletion. The results indicate the potential of the silicon CMOS photonics platform for boosting next-generation optical networks based on advanced modulation formats
The Ets dominant repressor En/Erm enhances intestinal epithelial tumorigenesis in ApcMin mice
<p>Abstract</p> <p>Background</p> <p>Ets transcription factors have been widely implicated in the control of tumorigenesis, with most studies suggesting tumor-promoting roles. However, few studies have examined Ets tumorigenesis-modifying functions <it>in vivo </it>using model genetic systems.</p> <p>Methods</p> <p>Using mice expressing a previously characterized Ets dominant repressor transgene in the intestinal epithelium (Villin-En/Erm), we examined the consequences of blocking endogenous Ets-mediated transcriptional activation on tumorigenesis in the Apc<sup>Min </sup>model of intestinal carcinoma.</p> <p>Results</p> <p>En/Erm expression in the intestine, at levels not associated with overt crypt-villus dysmorphogenesis, results in a marked increase in tumor number in Apc<sup>Min </sup>animals. Moreover, when examined histologically, tumors from En/Erm-expressing animals show a trend toward greater stromal invasiveness. Detailed analysis of crypt-villus homeostasis in these En/Erm transgenic animals suggests increased epithelial turnover as one possible mechanism for the enhanced tumorigenesis.</p> <p>Conclusion</p> <p>Our findings provide <it>in vivo </it>evidence for a tumor-restricting function of endogenous Ets factors in the intestinal epithelium.</p
Promoter hypomethylation, especially around the E26 transformation-specific motif, and increased expression of poly (ADP-ribose) polymerase 1 in BRCA-mutated serous ovarian cancer
Differential branching fraction and angular analysis of the decay B0→K∗0μ+μ−
The angular distribution and differential branching fraction of the decay B 0→ K ∗0 μ + μ − are studied using a data sample, collected by the LHCb experiment in pp collisions at s√=7 TeV, corresponding to an integrated luminosity of 1.0 fb−1. Several angular observables are measured in bins of the dimuon invariant mass squared, q 2. A first measurement of the zero-crossing point of the forward-backward asymmetry of the dimuon system is also presented. The zero-crossing point is measured to be q20=4.9±0.9GeV2/c4 , where the uncertainty is the sum of statistical and systematic uncertainties. The results are consistent with the Standard Model predictions
Measurement of the relative rate of prompt χc0, χc1 and χc2 production at √s=7TeV
Prompt production of charmonium χc0, χc1 and χc2 mesons is studied using proton-proton collisions at the LHC at a centre-of-mass energy of √s=7TeV. The χc mesons are identified through their decay to J/ψγ, with J/ψ→μ+mu− using photons that converted in the detector. A data sample, corresponding to an integrated luminosity of 1.0fb−1 collected by the LHCb detector, is used to measure the relative prompt production rate of χc1 and χc2 in the rapidity range 2.0<y<4.5 as a function of the J/ψ transverse momentum from 3 to 20 GeV/c. First evidence for χc0 meson production at a hadron collider is also presented
Observation of the decay
The decay is observed for the first
time, using proton-proton collisions collected with the LHCb detector
corresponding to an integrated luminosity of 3fb. A signal yield of
decays is reported with a significance of 6.2 standard deviations.
The ratio of the branching fraction of \B_c \rightarrow J/\psi K^+ K^- \pi^+
decays to that of decays is measured to be
, where the first uncertainty is statistical and the
second is systematic.Comment: 18 pages, 2 figure
Opposite-side flavour tagging of B mesons at the LHCb experiment
The calibration and performance of the oppositeside
flavour tagging algorithms used for the measurements
of time-dependent asymmetries at the LHCb experiment
are described. The algorithms have been developed using
simulated events and optimized and calibrated with
B
+ →J/ψK
+, B0 →J/ψK
∗0 and B0 →D
∗−
μ
+
νμ decay
modes with 0.37 fb−1 of data collected in pp collisions
at
√
s = 7 TeV during the 2011 physics run. The oppositeside
tagging power is determined in the B
+ → J/ψK
+
channel to be (2.10 ± 0.08 ± 0.24) %, where the first uncertainty
is statistical and the second is systematic
Measurement of the ratio of branching fractions BR(B0 -> K*0 gamma)/BR(Bs0 -> phi gamma)
The ratio of branching fractions of the radiative B decays B0 -> K*0 gamma
and Bs0 -> phi gamma has been measured using 0.37 fb-1 of pp collisions at a
centre of mass energy of sqrt(s) = 7 TeV, collected by the LHCb experiment. The
value obtained is BR(B0 -> K*0 gamma)/BR(Bs0 -> phi gamma) = 1.12 +/- 0.08
^{+0.06}_{-0.04} ^{+0.09}_{-0.08}, where the first uncertainty is statistical,
the second systematic and the third is associated to the ratio of fragmentation
fractions fs/fd. Using the world average for BR(B0 -> K*0 gamma) = (4.33 +/-
0.15) x 10^{-5}, the branching fraction BR(Bs0 -> phi gamma) is measured to be
(3.9 +/- 0.5) x 10^{-5}, which is the most precise measurement to date.Comment: 15 pages, 1 figure, 2 table
Observation of associated production of a boson with a meson in the~forward region
A search for associated production of a boson with an open charm meson is
presented using a data sample, corresponding to an integrated luminosity of
of proton--proton collisions at a centre-of-mass energy
of 7\,TeV, collected by the LHCb experiment. %% Seven candidate events for
associated production of a boson with a meson and four candidate
events for a boson with a meson are observed with a combined
significance of 5.1standard deviations. The production cross-sections in the
forward region are measured to be where the first uncertainty is statistical and the
second systematic.Comment: 18 pages, 2 figure
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