Dopamine D_2-receptor activation elicits akinesia, rigidity, catalepsy, and tremor in mice expressing hypersensitive 4 nicotinic receptors via a cholinergic-dependent mechanism

Recent studies suggest that high-affinity neuronal nicotinic acetylcholine receptors (nAChRs) containing α4 and β2 subunits (α4β2*) functionally interact with G-protein-coupled dopamine (DA) D_2 receptors in basal ganglia. We hypothesized that if a functional interaction between these receptors exists, then mice expressing an M2 point mutation (Leu9'Ala) rendering 4 nAChRs hypersensitive to ACh may exhibit altered sensitivity to a D_2-receptor agonist. When challenged with the D_(2)R agonist, quinpirole (0.5–10 mg/kg), Leu9'Ala mice, but not wild-type (WT) littermates, developed severe, reversible motor impairment characterized by rigidity, catalepsy, akinesia, and tremor. While striatal DA tissue content, baseline release, and quinpirole-induced DA depletion did not differ between Leu9'Ala and WT mice, quinpirole dramatically increased activity of cholinergic striatal interneurons only in mutant animals, as measured by increased c-Fos expression in choline acetyltransferase (ChAT)-positive interneurons. Highlighting the importance of the cholinergic system in this mouse model, inhibiting the effects of ACh by blocking muscarinic receptors, or by selectively activating hypersensitive nAChRs with nicotine, rescued motor symptoms. This novel mouse model mimics the imbalance between striatal DA/ACh function associated with severe motor impairment in disorders such as Parkinson’s disease, and the data suggest that a D_(2)R–α4*-nAChR functional interaction regulates cholinergic interneuron activity.—Zhao-Shea, R., Cohen, B. N., Just, H., McClure-Begley, T., Whiteaker, P., Grady, S. R., Salminen, O., Gardner, P. D., Lester, H. A., Tapper, A. R. Dopamine D2-receptor activation elicits akinesia, rigidity, catalepsy, and tremor in mice expressing hypersensitive α4 nicotinic receptors via a cholinergic-dependent mechanism

Opioid prescriptions are associated with hepatic encephalopathy in a national cohort of patients with compensated cirrhosis

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154367/1/apt15639_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154367/2/apt15639.pd

Letter: are opioid prescriptions associated with hepatic encephalopathy in patients with compensated cirrhosis? Authors’ reply

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154393/1/apt15669.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154393/2/apt15669_am.pd

First results on the performance of the CMS global calorimeter trigger

The CMS Global Calorimeter Trigger (GCT) uses data from the CMS calorimeters to compute a number kinematical quantities which characterize the LHC event. The GTC output is used by the Global Trigger (GT) along with data from the Global Muon Trigger (GMT) to produce the Level-1 Accept (L1A) decision. The design for the current GCT system commenced early in 2006. After a rapid development phase all the different GCT components have been produced and a large fraction of them have been installed at the CMS electronics cavern (USC-55). There the GCT system has been under test since March 2007. This paper reports results from tests which took place at the USC-55. Initial tests aimed to test the integrity of the GCT data and establish that the proper synchronization had been achieved both internally within GCT as well as with the Regional Calorimeter Trigger (RCT) which provides the GCT input data and with GT which receives the GCT results. After synchronization and data integrity had been established, Monte Carlo Events with electrons in the final state were injected at the GCT inputs and were propagated to the GCT outputs. The GCT output was compared with the predictions of the GCT emulator model in the CMS Monte Carlo and were found to be identical

Revised CMS Global Calorimeter Trigger Functionality & Algorithms

The Global Calorimeter Trigger (GCT) is a device which uses data from the CMS calorimeters to search for jets, produce isolated and non-isolated electron lists and compute all the transverse and missing transverse energy sums used for the Level-1 trigger decision (L1A). GCT performs these functions by receiving and processing the data from the Regional Calorimeter Trigger (RCT) and transmitting a summary to the Global Trigger (GT) which computes the L1A decision. The GCT must also transmit a copy of the RCT and GCT data to the CMS DAQ. The vast amount of data received by the GCT (230 Gb/s) as well as the necessity for data sharing required by the jet finder impose severe constrains on the GCT design. This paper presents an overview of the revised design, in particular, the algorithms, data flow and associated latency within the revised GCT

The design, construction and performance of the MICE scintillating fibre trackers

This is the Pre-print version of the Article. The official published version can be accessed from the link below - Copyright @ 2011 ElsevierCharged-particle tracking in the international Muon Ionisation Cooling Experiment (MICE) will be performed using two solenoidal spectrometers, each instrumented with a tracking detector based on diameter scintillating fibres. The design and construction of the trackers is described along with the quality-assurance procedures, photon-detection system, readout electronics, reconstruction and simulation software and the data-acquisition system. Finally, the performance of the MICE tracker, determined using cosmic rays, is presented.This work was supported by the Science and Technology Facilities Council under grant numbers PP/E003214/1, PP/E000479/1, PP/E000509/1, PP/E000444/1, and through SLAs with STFC-supported laboratories. This work was also supportedby the Fermi National Accelerator Laboratory, which is operated by the Fermi Research Alliance, under contract No. DE-AC02-76CH03000 with the U.S. Department of Energy, and by the U.S. National Science Foundation under grants PHY-0301737,PHY-0521313, PHY-0758173 and PHY-0630052. The authors also acknowledge the support of the World Premier International Research Center Initiative (WPI Initiative), MEXT, Japan

Run 2 Upgrades to the CMS Level-1 Calorimeter Trigger

The CMS Level-1 calorimeter trigger is being upgraded in two stages to maintain performance as the LHC increases pile-up and instantaneous luminosity in its second run. In the first stage, improved algorithms including event-by-event pile-up corrections are used. New algorithms for heavy ion running have also been developed. In the second stage, higher granularity inputs and a time-multiplexed approach allow for improved position and energy resolution. Data processing in both stages of the upgrade is performed with new, Xilinx Virtex-7 based AMC cards.Comment: 10 pages, 7 figure

Performance of the CMS Global Calorimeter Trigger

The CMS Global Calorimeter Trigger system performs a wide-variety of calorimeter data processing functions required by the CMS Level-1 trigger. It is responsible for finding and classifying jets and tau-jets, calculating total and missing transverse energy, total transverse energy identified within jets, sorting e/$\gamma$ candidates, and calculating several quantities based on forward calorimetry for minimum-bias triggers. The system is based on high-speed serial optical links and large FPGAs. The system has provided CMS with calorimeter triggers during commissioning and cosmic runs throughout 2008. The performance of the system in validation tests and cosmic runs is presented here