Everolimus in Combination with Cyclosporin A as Pre- and Posttransplantation Immunosuppressive Therapy in Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation

Everolimus (RAD001) is an mTOR inhibitor that has been successfully used as an immunosuppressant in solid-organ transplantation. Data in allogeneic hematopoietic stem cell transplantation (HSCT) is limited. This study aimed to investigate pharmacokinetics, safety, and efficacy of RAD001 in a canine allogeneic HSCT model. First, pharmacokinetics of RAD001 were performed in healthy dogs in order to determine the appropriate dosing. Doses of 0.25 mg RAD001 twice daily in combination with 15 mg/kg cyclosporin A (CsA) twice daily were identified as appropriate starting doses to achieve the targeted range of RAD001 (3-8 μg/L) when orally administered. Subsequently, 10 dogs were transplanted using 2 Gy total body irradiation (TBI) for conditioning and 0.25 mg RAD001 twice daily plus 15 mg/kg CsA twice daily for pre- and posttransplantation immunosuppression. Seven of the 10 transplanted dogs were maintained at the starting RAD001 dose throughout the study. For the remaining 3 dogs, dose adjustments were necessary. RAD001 accumulation over time did not occur. All dogs initially engrafted. Five dogs eventually rejected the graft (weeks 10, 10, 13, 27, and 56). Two dogs died of pneumonia (weeks 8 and 72) but were chimeric until then. Total cholesterol rose from median 4.1 mmol/L (3.5-5.7 mmol/L) before HSCT to 6.0 mmol/l (5.0-8.5 mmol/l) at day 21 after HSCT, but remained always within normal range. Changes in creatinine and triglyceride values were not observed. Long-term engraftment rates were inferior to sirolimus/CsA and mycophenolate mofetil (MMF)/CsA regimen, respectively. RAD001/CsA caused a more pronounced reduction of platelet counts to median 2 × 109/L (range: 0-21 × 109/L) and longer time to platelet recovery of 21 days (range: 14-24 days) compared with MMF/CsA. CsA c2h levels were significantly enhanced in the RAD001/CsA regimen, but c0h and area under the curve from 0 to 12 hours (AUC0-12h) values did not differ compared with an MMF/CsA immunosuppression. In summary, immunosuppression consisting of RAD001 and CsA is well tolerated but not as efficient as with other established immunosuppressants in a canine nonmyeloablative HSCT regimen. Hence, our study does not support the application of RAD001/CsA as standard practice in this setting

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Challenges and performance of the frontier technology applied to an ATLAS Phase-I calorimeter trigger board dedicated to the jet identification

The 'Phase-I' upgrade of the Large Hadron Collider (LHC), scheduled to be completed in 2021, will lead to an enhanced collision luminosity of 2.5x10e34cm-2s-1. To cope with the new and challenging accelerator conditions, all the CERN experiments have planned a major detector upgrade to be installed during the associated experimental shutdown period. One of the physics goals of the ATLAS experiment is to maintain sensitivity to electroweak processes despite the increased number of interactions per LHC bunch crossing. To this end, the component of the first level hardware trigger based on calorimeter data will be upgraded to exploit fine-granularity readout using a new system of Feature EXtractors (FEXs), which each uses different physics objects for trigger selection. There will be three FEX systems in total, with this contribution focusing on the first prototype of the jet FEX (jFEX). This system identifies jets and large area tau candidates while also calculating global variables such as transverse energy sums and missing transverse energy. The jFEX prototype is characterised by four large Xilinx Ultrascale Field Programmable Gate Arrays (FPGAs), XCVU190FLGA2577, so far the largest available on the market, capable of handling a data volume of more than 3 TB/s of input bandwidth. The choice of such large devices was driven by the requirement for large input bandwidth and processing power. This comes from the need to exploit high granularity calorimeter information and also run several jet identification algorithms within the few hundred nanoseconds latency budget (~350 ns). This presentation will report on the hardware design challenges and adopted solutions to preserve signal integrity within a densely populated high signal speed ATCA board. The parallel simulation activity that supported and validated the board design will also be presented. Particular emphasis will be given to the large FPGA power consumption effects on the boards. This was assessed via dedicated thermal simulation and cross-checked with a campaign of measurements. Preliminary results will also be presented from tests both at CERN and Mainz, based on the first jFEX prototype from December 2016

Latest Frontier Technology and Design of the ATLAS Calorimeter Trigger Board Dedicated to Jet Identification for the LHC Run 3

To cope with the enhanced luminosity of the beam delivered by the Large Hadron Collider (LHC) in 2020, the A Thoroidal LHC ApparatuS (ATLAS) experiment has planned a major upgrade. As part of this, the trigger at Level-I based on calorimeter data, will be upgraded to exploit fine-granularity readout using a new system of Feature Extractors, which differ in the physics objects for the trigger selection. The presentation is focused on the jet Feature EXtractor (jFEX) prototype, one of the three Feature Extractors. In few hundreds nanoseconds latency budget, up to 2 TB/s have to be processed to provide jet identification (even large area jets) and measurements of global variables. This requires the use of large Field Programmable Gate Array (FPGA) with the largest Multi Giga Transceiver available on the market. The jFEX board prototype hosts four large FPGAs from the Xilinx Ultrascale family with 120 Multi Giga Transceivers each, connected to 24 opto-electrical devices, resulting in a densely populated high speed signals board. For the 24 layers jFEX board stack-up, the MEGTRON6 material was chosen for its property of low transmission loss with high frequency signals (GHz range) and to further preserve the signal integrity, special care has been put into the design accompanied by simulation to optimise the voltage drop and minimise the current density over the power planes. An integrated test has been installed at the ATLAS test facility to perform numerous tests and measurements with the JFEX prototype

Development of the jet Feature EXtractor (jFEX) for the ATLAS Level 1 calorimeter trigger upgrade at the LHC

To cope with the enhanced luminosity delivered by the Large Hadron Collider from 2021 onwards, the ATLAS experiment has planned several upgrades. The first level trigger based on calorimeter data will be upgraded to exploit fine-granularity readout using a new system of Feature EXtractors (FEXs, FPGA-based trigger boards), each optimized to trigger on different physics objects. This contribution is focused on the jet FEX. The main challenges of such a board are the input bandwidth of up to 3.1 Tbps, dense routing of high-speed signals and power consumption. The design, PCB simulations and results of integrated tests of a prototype are shown in this document

Design and testing of the high speed signal densely populated ATLAS calorimeter trigger board dedicate to jet identification

Abstract—The ATLAS experiment has planned a major upgrade in view of the enhanced luminosity of the beam delivered by the Large Hadron Collider (LHC) in 2021. As part of this, the trigger at Level-1 based on calorimeter data will be upgraded to exploit fine-granularity readout using a new system of Feature Extractors (three in total), which each uses different physics objects for the trigger selection. The contribution focusses on the jet Feature EXtractor (jFEX) prototype. Up to a data volume of 2 TB/s has to be processed to provide jet identification (including large area jets) and measurements of global variables within few hundred nanoseconds latency budget. Such requirements translate into the use of large Field Programmable Gate Array (FPGA) with the largest number of Multi Gigabit Transceivers (MGTs) available on the market. The jFEX board prototype hosts four large FPGAs from the Xilinx Ultrascale family with 120 MGTs each, connected to 24 opto-electrical devices, resulting in a densely populated high speed signal board. MEGTRON6 was chosen as the material for the 24 layers jFEX board stackup because of its property of low transmission loss with high frequency signals (GHz range) and to further preserve the signal integrity special care has been put into the design accompanied by simulation to optimise the voltage drop and minimise the current density over the power planes. The jFEX prototype was delivered at the beginning of December and the preliminary results on the design validation and board characterisation will be reported

Latest Frontier Technology and Design of the ATLAS Calorimeter Trigger Board Dedicated to Jet Identification

To cope with the enhanced luminosity of the beam delivered by the Large Hadron Collider (LHC) in 2020, the A Thoroidal LHC ApparatuS (ATLAS) experiment has planned a major upgrade. As part of this, the trigger at Level-I based on calorimeter data, will be upgraded to exploit fine-granularity readout using a new system of Feature Extractors, which differ in the physics objects for the trigger selection. The presentation is focused on the jet Feature EXtractor (jFEX) prototype, one of the three Feature Extractors. In few hundreds nanoseconds latency budget, up to 2 TB/s have to be processed to provide jet identification (even large area jets) and measurements of global variables. This requires the use of large Field Programmable Gate Array (FPGA) with the largest Multi Giga Transceiver available on the market. The jFEX board prototype hosts four large FPGAs from the Xilinx Ultrascale family with 120 Multi Giga Transceivers each, connected to 24 opto-electrical devices, resulting in a densely populated high speed signals board. For the 24 layers jFEX board stack-up, the MEGTRON6 material was chosen for its property of low transmission loss with high frequency signals (GHz range) and to further preserve the signal integrity, special care has been put into the design accompanied by simulation to optimise the voltage drop and minimise the current density over the power planes. An integrated test has been installed at the ATLAS test facility to perform numerous tests and measurements with the JFEX prototype

Challenges and performance of the frontier technology applied to an ATLAS Phase-I calorimeter trigger board dedicated to the jet identification

The 'Phase-I' upgrade of the Large Hadron Collider (LHC), scheduled to be completed in 2021, will lead to an enhanced collision luminosity of 2.5x10e34cm-2s-1. To cope with the new and challenging accelerator conditions, all the CERN experiments have planned a major detector upgrade to be installed during the associated experimental shutdown period. One of the physics goals of the ATLAS experiment is to maintain sensitivity to electroweak processes despite the increased number of interactions per LHC bunch crossing. To this end, the component of the first level hardware trigger based on calorimeter data will be upgraded to exploit fine-granularity readout using a new system of Feature EXtractors (FEXs), which each uses different physics objects for trigger selection. There will be three FEX systems in total, with this contribution focusing on the first prototype of the jet FEX (jFEX). This system identifies jets and large area tau candidates while also calculating global variables such as transverse energy sums and missing transverse energy. The jFEX prototype is characterised by four large Xilinx Ultrascale Field Programmable Gate Arrays (FPGAs), XCVU190FLGA2577, so far the largest available on the market, capable of handling a data volume of more than 3 TB/s of input bandwidth. The choice of such large devices was driven by the requirement for large input bandwidth and processing power. This comes from the need to exploit high granularity calorimeter information and also run several jet identification algorithms within the few hundred nanoseconds latency budget (~350 ns). This presentation will report on the hardware design challenges and adopted solutions to preserve signal integrity within a densely populated high signal speed ATCA board. The parallel simulation activity that supported and validated the board design will also be presented. Particular emphasis will be given to the large FPGA power consumption effects on the boards. This was assessed via dedicated thermal simulation and cross-checked with a campaign of measurements. Preliminary results will also be presented from tests both at CERN and Mainz, based on the first jFEX prototype from December 2016

Ultrascale+ for the new ATLAS calorimeter trigger board dedicated to jet identification

To cope with the expected increase in luminosity at the Large Hadron Collider in 2021, the ATLAS collaboration is planning a major detector upgrade to be installed during Long Shutdown 2. As a part of this, the Level-1 trigger, based on calorimeter data, will be upgraded to exploit the fine granularity readout using a new system of Feature EXtractors (FEXs), which each reconstruct different physics objects for the trigger selection. The Jet FEX (jFEX) is one of three FEXs and has been conceived to identify small/large area jets, large area tau leptons, missing transverse energy and the total sum of the transverse energy. The use of the latest generation Xilinx Field Programmable Gate Array (FPGA), the Ultrascale+, was dictated by the physics requirements which include substantial processing power and large input bandwidth, up to $\sim$ 3Tb/s, within a tight latency budget $<$ 390 ns. The modular design of the jFEX board allowed for an optimal routing of a large number of high speed signals within the limited space of an ATCA board. To guarantee the signal integrity, the board design has been accompanied by simulation of the power, current and thermal distribution. The printed circuit board has a 24-layer stack-up and uses the MEGTRON6 material, commonly used for signal transmission above 10 Gb/s. The jFEX system, consisting of 6 boards, will be produced by end of 2018 to allow the installation and commissioning of the full system in time for the LHC restart at the beginning of 2021