12 research outputs found
New insights into the genetic etiology of Alzheimer's disease and related dementias
Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele
Proteogenomic analysis of Candida glabrata using high resolution mass spectrometry.
Item does not contain fulltextCandida glabrata is a common opportunistic human pathogen leading to significant mortality in immunosuppressed and immunodeficient individuals. We carried out proteomic analysis of C. glabrata using high resolution Fourier transform mass spectrometry with MS resolution of 60,000 and MS/MS resolution of 7500. On the basis of 32,453 unique peptides identified from 118,815 peptide-spectrum matches, we validated 4421 of the 5283 predicted protein-coding genes (83%) in the C. glabrata genome. Further, searching the tandem mass spectra against a six frame translated genome database of C. glabrata resulted in identification of 11 novel protein coding genes and correction of gene boundaries for 14 predicted gene models. A subset of novel protein-coding genes and corrected gene models were validated at the transcript level by RT-PCR and sequencing. Our study illustrates how proteogenomic analysis enabled by high resolution mass spectrometry can enrich genome annotation and should be an integral part of ongoing genome sequencing and annotation efforts
Development and implementation of control of stand‐alone PMSG‐based distributed energy system with variation in input and output parameters
Evaluation of planar silicon pixel sensors with the RD53A readout chip for the Phase-2 Upgrade of the CMS Inner Tracker
The Large Hadron Collider (LHC) at CERN will undergo an upgrade in order to increase its luminosity to cms. The increased luminosity during this High-Luminosity running phase\\
(HL-LHC), starting around 2029, means a higher rate of proton-proton interactions, hence a larger ionizing dose and particle fluence for the detectors.
The current tracking system of the CMS experiment will be fully replaced in order to cope with the new operating conditions. Prototype planar pixel sensors for the CMS Inner Tracker with square m m and rectangular m m pixels read out by the RD53A chip were characterized in the lab and at the DESY-II testbeam facility in order to identify designs that meet the requirements of CMS at the HL-LHC. A spatial resolution of approximately 3.4m (2m) is obtained using the modules with m m (m m) pixels at the optimal angle of incidence before irradiation. After irradiation to a 1 MeV neutron equivalent fluence of cm, a resolution of 9.4m is achieved at a bias voltage of 800 V using a module with m m pixel size. All modules retain a hit efficiency in excess of 99\% after irradiation to fluences up to cm.
Further studies of the electrical properties of the modules, especially crosstalk, are also presented in this paper.The Large Hadron Collider at CERN will undergo an upgrade inorder to increase its luminosity to7.5 × 10 cms. The increased luminosityduring this High-Luminosity running phase, starting around 2029,means a higher rate of proton-proton interactions, hence a largerionizing dose and particle fluence for the detectors. The currenttracking system of the CMS experiment will be fully replaced inorder to cope with the new operating conditions. Prototype planarpixel sensors for the CMS Inner Tracker with square50 μm × 50 μm and rectangular100 μm × 25 μm pixels read out by theRD53A chip were characterized in the lab and at the DESY-II testbeamfacility in order to identify designs that meet the requirements ofCMS during the High-Luminosity running phase. A spatial resolutionof approximately 3.4 μm (2 μm) is obtained using themodules with 50 μm × 50 μm(100 μm × 25 μm) pixels at the optimalangle of incidence before irradiation. After irradiation to a 1 MeVneutron equivalent fluence ofΦ = 5.3 × 10 cm, a resolution of9.4 μm is achieved at a bias voltage of 800 V using a modulewith 50 μm × 50 μm pixel size. All modulesretain a hit efficiency in excess of 99% after irradiation tofluences up to 2.1 × 10 cm. Further studies ofthe electrical properties of the modules, especially crosstalk, arealso presented in this paper.The Large Hadron Collider (LHC) at CERN will undergo an upgrade in order to increase its luminosity to cms. The increased luminosity during this High-Luminosity running phase (HL-LHC), starting around 2029, means a higher rate of proton-proton interactions, hence a larger ionizing dose and particle fluence for the detectors. The current tracking system of the CMS experiment will be fully replaced in order to cope with the new operating conditions. Prototype planar pixel sensors for the CMS Inner Tracker with square m m and rectangular m m pixels read out by the RD53A chip were characterized in the lab and at the DESY-II testbeam facility in order to identify designs that meet the requirements of CMS at the HL-LHC. A spatial resolution of approximately 3.4m (2m) is obtained using the modules with m m (m m) pixels at the optimal angle of incidence before irradiation. After irradiation to a 1 MeV neutron equivalent fluence of cm, a resolution of 9.4m is achieved at a bias voltage of 800 V using a module with m m pixel size. All modules retain a hit efficiency in excess of 99% after irradiation to fluences up to cm. Further studies of the electrical properties of the modules, especially crosstalk, are also presented in this paper
Beam Test Performance Studies of CMS Phase-2 Outer Tracker Module Prototypes
International audienceA new tracking detector will be installed as part of the Phase-2 upgrade of the CMS detector for the high-luminosity LHC era. This tracking detector includes the Inner Tracker, equipped with silicon pixel sensor modules, and the Outer Tracker, consisting of modules with two parallel stacked silicon sensors. The Outer Tracker front-end ASICs will be able to correlate hits from charged particles in these two sensors to perform on-module discrimination of transverse momenta . The information is generated at a frequency of 40 MHz and will be used in the Level-1 trigger decision of CMS. Prototypes of the so-called 2S modules were tested at the Test Beam Facility at DESY Hamburg between 2019 and 2020. These modules use the final front-end ASIC, the CMS Binary Chip (CBC), and for the first time the Concentrator Integrated Circuit (CIC), optical readout and on-module power conversion. In total, seven modules were tested, one of which was assembled with sensors irradiated with protons. An important aspect was to show that it is possible to read out modules synchronously. A cluster hit efficiency of about 99.75% was achieved for all modules. The CBC discrimination mechanism has been verified to work together with the CIC and optical readout. The measured module performance meets the requirements for operation in the upgraded CMS tracking detector
Evaluation of HPK - planar pixel sensors for the CMS Phase-2 upgrade
International audienceTo cope with the challenging environment of the planned high luminosity upgrade of the Large Hadron Collider (HL-LHC), sched-uled to start operation in 2029, CMS will replace its entire tracking system. The requirements for the tracker are largely determinedby the long operation time of 10 years with an instantaneous peak luminosity of up to 7.5 × 1034 cm−2 s−1 in the ultimate perfor-mance scenario. Depending on the radial distance from the interaction point, the silicon sensors will receive a particle fluencecorresponding to a non-ionizing energy loss of up to Φeq = 3.5 × 1016 cm−2. This paper focuses on planar pixel sensor design andqualification up to a fluence of Φeq = 1.4 × 1016 cm−2.For the development of appropriate planar pixel sensors an R&D program was initiated, which includes n+-p sensors on 150 mm(6”) wafers with an active thickness of 150 μm with pixel sizes of 100 × 25 μm2 and 50 × 50 μm2 manufactured by Hamamatsu.Single chip modules with ROC4Sens and RD53A readout chips were made. Irradiation with protons and neutrons, as well was anextensive test beam campaign at DESY were carried out. This paper presents the investigation of various assemblies mainly withROC4Sens readout chips. It demonstrates that multiple designs fulfill the requirements in terms of breakdown voltage, leakagecurrent and efficiency. The single point resolution for 50 × 50 μm2 pixels is measured as 4.0 μm for non-irradiated samples, and6.3 μm after irradiation to Φeq = 7.2 × 1015 cm−2
Evaluation of HPK - planar pixel sensors for the CMS Phase-2 upgrade
To cope with the challenging environment of the planned high luminosity upgrade
of the Large Hadron Collider (HL-LHC), scheduled to start operation in 2029, CMS will replace its entire tracking system. The requirements for the tracker are largely determined by the long operation time of 10~years with an instantaneous peak luminosity of up to
~cms in the ultimate performance scenario.
Depending on the radial distance from the interaction point, the silicon sensors will receive a particle fluence corresponding to a non-ionizing energy loss of up to ~cm. This paper focuses on planar pixel sensor design and qualification up to a fluence of ~cm.
For the development of appropriate planar pixel
sensors an R\&D program was initiated, which includes - sensors on
150 mm (6'')
wafers with an active thickness of 150~m with pixel sizes of
~m and
~m manufactured by Hamamatsu Photonics K.K.\ (HPK). Single chip
modules with ROC4Sens and RD53A readout chips were made. Irradiation with protons and neutrons, as well was an extensive test beam campaign at DESY were carried out.
This paper presents the investigation of various assemblies mainly with ROC4Sens readout chips.
It demonstrates that
multiple designs fulfill the requirements
in terms of breakdown voltage, leakage current and efficiency. The single
point resolution for ~m pixels
is measured as 4.0~m for non-irradiated samples,
and 6.3~m after irradiation to ~cm.To cope with the challenging environment of the planned high luminosity upgrade of the Large Hadron Collider (HL-LHC), sched-
uled to start operation in 2029, CMS will replace its entire tracking system. The requirements for the tracker are largely determined
by the long operation time of 10 years with an instantaneous peak luminosity of up to 7.5 × 1034 cm−2 s−1 in the ultimate perfor-
mance scenario. Depending on the radial distance from the interaction point, the silicon sensors will receive a particle fluence
corresponding to a non-ionizing energy loss of up to Φeq = 3.5 × 1016 cm−2. This paper focuses on planar pixel sensor design and
qualification up to a fluence of Φeq = 1.4 × 1016 cm−2.
For the development of appropriate planar pixel sensors an R&D program was initiated, which includes n+-p sensors on 150 mm
(6”) wafers with an active thickness of 150 μm with pixel sizes of 100 × 25 μm2 and 50 × 50 μm2 manufactured by Hamamatsu.
Single chip modules with ROC4Sens and RD53A readout chips were made. Irradiation with protons and neutrons, as well was an
extensive test beam campaign at DESY were carried out. This paper presents the investigation of various assemblies mainly with
ROC4Sens readout chips. It demonstrates that multiple designs fulfill the requirements in terms of breakdown voltage, leakage
current and efficiency. The single point resolution for 50 × 50 μm2 pixels is measured as 4.0 μm for non-irradiated samples, and
6.3 μm after irradiation to Φeq = 7.2 × 1015 cm−2.To cope with the challenging environment of the planned high luminosity upgrade of the Large Hadron Collider (HL-LHC), scheduled to start operation in 2029, CMS will replace its entire tracking system. The requirements for the tracker are largely determined by the long operation time of 10 years with an instantaneous peak luminosity of up to 7.5 × 1034cm−2s−1 in the ultimate performance scenario. Depending on the radial distance from the interaction point, the silicon sensors will receive a particle fluence corresponding to a non-ionising energy loss of up to Φeq= 3.5 × 1016cm−2. This paper focuses on planar pixel sensor design and qualification up to a fluence of Φeq = 1.4 × 1016cm−2. For the development of appropriate planar pixel sensors an R&D program was initiated, which includes n+-p sensors on 150mm (6”) wafers with an active thickness of 150µm with pixel sizes of 100×25 µm2 and 50×50 µm2 manufactured by Hamamatsu Photonics K.K. (HPK). Single chip modules with ROC4Sens and RD53A readout chips were made. Irradiation with protons and neutrons, as well was an extensive test beam campaign at DESY were carried out. This paper presents the investigation of various assemblies mainly with ROC4Sens readout chips. It demonstrates that multiple designs fulfil the requirements in terms of breakdown voltage, leakage current and efficiency. The single point resolution for 50×50 µm2 pixels is measured as 4.0µm for non-irradiated samples, and 6.3µm after irradiation to Φeq = 7.2 × 1015cm−2