Long Non-Coding RNA Profile in Mantle Cell Lymphoma Identifies a Functional lncRNA ROR1-AS1 Associated With EZH2/PRC2 Complex.

Mantle cell lymphoma (MCL) is an aggressive B-cell lymphoma characterized by rapid disease progression. The needs for new therapeutic strategies for MCL patients call for further understanding on the molecular mechanisms of pathogenesis of MCL. Recently, long noncoding RNAs (lncRNAs) have been recognized as key regulators of gene expression and disease development, however, the role of lncRNAs in non-Hodgkin lymphoma and specifically in MCL is still unknown. Next generation RNA-sequencing was carried out on MCL patient samples along with normal controls and data was analyzed. As a result, several novel lncRNAs were found significantly overexpressed in the MCL samples with lncRNA ROR1-AS1 the most significant one. We cloned the ROR1-AS1 lncRNA in expression vector and ectopically transfected in MCL cell lines. Results showed that overexpression of ROR1-AS1 lncRNA promoted growth of MCL cells while decreased sensitivity to the treatment with drugs ibrutinib and dexamethasone. ROR-AS1 overexpression also decreased the mRNA expression of P16 (P = 0.21), and SOX11 (p = 0.017), without much effect on P53, ATM and P14 mRNA. RNA-immunoprecipitation assays demonstrated high affinity binding of lncRNA ROR1-AS1 with EZH2 and SUZ12 proteins of the polycomb repressive complex-2 (PRC2). Suppressing EZH2 activity with pharmacological inhibitor GSK343 abolished binding of ROR1-AS1 with EZH2. Taken together, this study identified a functional lncRNA ROR-AS1 involved with regulation of gene transcription via associating with PRC2 complex, and may serve as a novel biomarker in MCL patients

Deregulation of Polycomb Repressive Complex-2 in Mantle Cell Lymphoma Confers Growth Advantage by Epigenetic Suppression of

The polycomb repressive complex 2 (PRC2) maintains the transcriptional repression of target genes through its catalytic component enhancer of zeste homolog 2 (EZH2). Through modulating critical gene expression, EZH2 also plays a role in cancer development and progression by promoting cancer cell survival and invasion. Mutations in EZH2 are prevalent in certain B-cell lymphoma subtypes such as diffuse large cell lymphoma and follicular lymphoma; while no EZH2 mutation has been reported in the mantle cell lymphoma (MCL). Here we demonstrate that the PRC2 components EZH2, EED and SUZ12 are upregulated in the MCL cells as compared to normal B-cells. Moreover, stably transfected cells with wild-type EZH2 or-EED showed increased cell growth and H3K27-trimehtylation. However, unlike wild-type EZH2, ectopic expression of a deletion construct of EZH2 (EZH

A 5 Gb/s Radiation Tolerant Laser Driver

A laser driver for data transmission at 5 Gb/s has been developed as a part of the Giga Bit Transceiver (GBT) project. The Giga Bit Laser Driver (GBLD) targets High Energy Physics (HEP) applications for which radiation tolerance is mandatory. The GBLD ASIC can drive both VCSELs and some types of edge emitting lasers. It is essentially composed of two drivers capable of sinking up to 12 mA each from the load at a maximum data rate of 5 Gb/s, and of a current sink for the laser bias current. The laser driver include also pre-emphasis and duty cycle control capabilities

Single event upset studies for the ATLAS SCT and pixel optical links

Optical data transmission has been chosen for the ATLAS Pixel and SemiConductor Tracker to deliver both timing and control information to the detector modules and transmit tracking data to the remote computer room. Radiation hardness of individuals optical components and their ASICs drivers have been reported in previous papers. We will report here the Single Event Upset studies carried out on a customised optopackage using a high-energy pion beam. It will be shown that the system is sufficiently robust to SEU at the ATLAS SCT level

A Fully Bidirectional Optical Network With Latency Monitoring Capability for the Distribution of Timing-Trigger and Control Signals in High-Energy Physics Experiments

The present paper discusses recent advances on a Passive Optical Network inspired Timing-Trigger and Control scheme for the future upgrade of the TTC system installed in the LHC experiments' and more specifically the currently known as TTCex to TTCrx link. The timing PON is implemented with commercially available FPGAs and 1-Gigabit Ethernet PON transceivers and provides a fixed latency gigabit downlink that can carry level-1 trigger accept decisions and commands as well as an upstream link for feedback from the front-end electronics

FPGA-based Bit-Error-Rate Tester for SEU-hardened Optical Links

The next generation of optical links for future High-Energy Physics experiments will require components qualified for use in radiation-hard environments. To cope with radiation induced single-event upsets, the physical layer protocol will include Forward Error Correction (FEC). Bit-Error-Rate (BER) testing is a widely used method to characterize digital transmission systems. In order to measure the BER with and without the proposed FEC, simultaneously on several devices, a multi-channel BER tester has been developed. This paper describes the architecture of the tester, its implementation in a Xilinx Virtex-5 FPGA device and discusses the experimental results

Passive Optical Networks for the Distribution of Timed Signals in Particle Physics Experiments

A passive optical network for timing distribution applications based on FPGAs has been successfully demonstrated. Deterministic latency was achieved in the critical downstream direction where triggers are distributed while a burst mode receiver was successfully implemented in the upstream direction. Finally, a simple and efficient protocol was introduced for the communication between the OLT and the ONUs in the network that maximizes bandwidth utilization

Prototype ATLAS IBL Modules using the FE-I4A Front-End Readout Chip

The ATLAS Collaboration will upgrade its semiconductor pixel tracking detector with a new Insertable B-layer (IBL) between the existing pixel detector and the vacuum pipe of the Large Hadron Collider. The extreme operating conditions at this location have necessitated the development of new radiation hard pixel sensor technologies and a new front-end readout chip, called the FE-I4. Planar pixel sensors and 3D pixel sensors have been investigated to equip this new pixel layer, and prototype modules using the FE-I4A have been fabricated and characterized using 120 GeV pions at the CERN SPS and 4 GeV positrons at DESY, before and after module irradiation. Beam test results are presented, including charge collection efficiency, tracking efficiency and charge sharing.Comment: 45 pages, 30 figures, submitted to JINS