32 research outputs found
Topology of molecular machines of the endoplasmic reticulum: a compilation of proteomics and cytological data
The endoplasmic reticulum (ER) is a key organelle of the secretion pathway involved in the synthesis of both proteins and lipids destined for multiple sites within and without the cell. The ER functions to both co- and post-translationally modify newly synthesized proteins and lipids and sort them for housekeeping within the ER and for transport to their sites of function away from the ER. In addition, the ER is involved in the metabolism and degradation of specific xenobiotics and endogenous biosynthetic products. A variety of proteomics studies have been reported on different subcompartments of the ER providing an ER protein dictionary with new data being made available on many protein complexes of relevance to the biology of the ER including the ribosome, the translocon, coatomer proteins, cytoskeletal proteins, folding proteins, the antigen-processing machinery, signaling proteins and proteins involved in membrane traffic. This review examines proteomics and cytological data in support of the presence of specific molecular machines at specific sites or subcompartments of the ER
Performance of the CMS High Granularity Calorimeter prototype to charged pion beams of 20300 GeV/c
The upgrade of the CMS experiment for the high luminosity operation of the
LHC comprises the replacement of the current endcap calorimeter by a high
granularity sampling calorimeter (HGCAL). The electromagnetic section of the
HGCAL is based on silicon sensors interspersed between lead and copper (or
copper tungsten) absorbers. The hadronic section uses layers of stainless steel
as an absorbing medium and silicon sensors as an active medium in the regions
of high radiation exposure, and scintillator tiles directly readout by silicon
photomultipliers in the remaining regions. As part of the development of the
detector and its readout electronic components, a section of a silicon-based
HGCAL prototype detector along with a section of the CALICE AHCAL prototype was
exposed to muons, electrons and charged pions in beam test experiments at the
H2 beamline at the CERN SPS in October 2018. The AHCAL uses the same technology
as foreseen for the HGCAL but with much finer longitudinal segmentation. The
performance of the calorimeters in terms of energy response and resolution,
longitudinal and transverse shower profiles is studied using negatively charged
pions, and is compared to GEANT4 predictions. This is the first report
summarizing results of hadronic showers measured by the HGCAL prototype using
beam test data.Comment: To be submitted to JINS
Defining the causes of sporadic Parkinson’s disease in the global Parkinson’s genetics program (GP2)
\ua9 2023, Springer Nature Limited. The Global Parkinson’s Genetics Program (GP2) will genotype over 150,000 participants from around the world, and integrate genetic and clinical data for use in large-scale analyses to dramatically expand our understanding of the genetic architecture of PD. This report details the workflow for cohort integration into the complex arm of GP2, and together with our outline of the monogenic hub in a companion paper, provides a generalizable blueprint for establishing large scale collaborative research consortia
Multi-ancestry genome-wide association meta-analysis of Parkinson’s disease
\ua9 2023, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply. Although over 90 independent risk variants have been identified for Parkinson’s disease using genome-wide association studies, most studies have been performed in just one population at a time. Here we performed a large-scale multi-ancestry meta-analysis of Parkinson’s disease with 49,049 cases, 18,785 proxy cases and 2,458,063 controls including individuals of European, East Asian, Latin American and African ancestry. In a meta-analysis, we identified 78 independent genome-wide significant loci, including 12 potentially novel loci (MTF2, PIK3CA, ADD1, SYBU, IRS2, USP8, PIGL, FASN, MYLK2, USP25, EP300 and PPP6R2) and fine-mapped 6 putative causal variants at 6 known PD loci. By combining our results with publicly available eQTL data, we identified 25 putative risk genes in these novel loci whose expression is associated with PD risk. This work lays the groundwork for future efforts aimed at identifying PD loci in non-European populations
Defining the causes of sporadic Parkinson’s disease in the global Parkinson’s genetics program (GP2)
The Global Parkinson’s Genetics Program (GP2) will genotype over 150,000 participants from around the world, and integrate genetic and clinical data for use in large-scale analyses to dramatically expand our understanding of the genetic architecture of PD. This report details the workflow for cohort integration into the complex arm of GP2, and together with our outline of the monogenic hub in a companion paper, provides a generalizable blueprint for establishing large scale collaborative research consortia
Author Correction: Elucidating causative gene variants in hereditary Parkinson’s disease in the Global Parkinson’s Genetics Program (GP2)
Correction to: s41531-023-00526-9 npj Parkinson’s Disease, published online 27 June 2023 In this article the Global Parkinson’s Genetics Program (GP2) members names and affiliations were missing in the main author list of the Original article which are listed in the below
Multi-ancestry genome-wide association meta-analysis of Parkinson?s disease
Although over 90 independent risk variants have been identified for Parkinson’s disease using genome-wide association studies, most studies have been performed in just one population at a time. Here we performed a large-scale multi-ancestry meta-analysis of Parkinson’s disease with 49,049 cases, 18,785 proxy cases and 2,458,063 controls including individuals of European, East Asian, Latin American and African ancestry. In a meta-analysis, we identified 78 independent genome-wide significant loci, including 12 potentially novel loci (MTF2, PIK3CA, ADD1, SYBU, IRS2, USP8, PIGL, FASN, MYLK2, USP25, EP300 and PPP6R2) and fine-mapped 6 putative causal variants at 6 known PD loci. By combining our results with publicly available eQTL data, we identified 25 putative risk genes in these novel loci whose expression is associated with PD risk. This work lays the groundwork for future efforts aimed at identifying PD loci in non-European populations
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The impact of multiplexing on the dynamic requirements of analog-to-digital converters
In data acquisition applications where the signals being digitized are produced in a time-division multiplexed system, the required dynamic performance of the analog-to-digital converter (ADC) is no longer bound by the conditions set forth in the Sampling Theorem. This results from the introduction of very high frequency information by the multiplexing process which, while not necessarily containing information of interest, must be processed by the input circuitry of the ADC. In this situation, signal bandwidths and slew rates can greatly exceed those produced in a Nyquist limited system and can surpass the capability of the ADC, thus degrading overall system performance. This paper will examine two common multiplexing schemes and their impact on ADC dynamic requirements. First, we will examine a simple voltage multiplexing scheme typically found in state-ofhealth or data-logging applications and develop the necessary equations to show how the ADC dynamic requirements are affected. Then, the analysis will then be extended to a multiplexed photodiode array readout to see how this application further challenges the dynamic performance of the ADC. Finally, the issues associated with developing dynamic test methodologies for assessing ADC performance in multiplexed systems will be discussed