Fission of 1 A GeV 238^{238}U-ions on a hydrogen-target

PACSThe production cross sections and the kinematical properties of fission fragment residues have been studied in the reaction $^{238}$U(1 A.GeV) + p. Isotopic distributions were measured for all elements from O(Z=8) to Gd(Z=64). The distribution of fission velocities and of production cross sections as function of Z of the fragments, provide relevant informations on the intermediate fissioning nucle

Distribution of nuclides produced in the collision of 1 AGeV 238^{238}U-ions on p

PACSProduction cross sections and kinematical properties of the complete set of fission fragment residues from the reaction $^{238}$U(1 A.GeV)+p have been obtained. Isotopic distributions are measured for all elements from O(Z=8) to W(Z=74). Fission velocities and production cross sections are shown as a function of Z, the charge and N, the number of neutrons of the fragments. The very asymmetric pairs of fragments can be attributed to excited fissioning parent nuclei of charge Z, 8

Genome-wide association analysis of dementia and its clinical endophenotypes reveal novel loci associated with Alzheimer's disease and three causality networks: The GR@ACE project

INTRODUCTION: Large variability among Alzheimer's disease (AD) cases might impact genetic discoveries and complicate dissection of underlying biological pathways. METHODS: Genome Research at Fundacio ACE (GR@ACE) is a genome-wide study of dementia and its clinical endophenotypes, defined based on AD's clinical certainty and vascular burden. We assessed the impact of known AD loci across endophenotypes to generate loci categories. We incorporated gene coexpression data and conducted pathway analysis per category. Finally, to evaluate the effect of heterogeneity in genetic studies, GR@ACE series were meta-analyzed with additional genome-wide association study data sets. RESULTS: We classified known AD loci into three categories, which might reflect the disease clinical heterogeneity. Vascular processes were only detected as a causal mechanism in probable AD. The meta-analysis strategy revealed the ANKRD31-rs4704171 and NDUFAF6-rs10098778 and confirmed SCIMP-rs7225151 and CD33-rs3865444. DISCUSSION: The regulation of vasculature is a prominent causal component of probable AD. GR@ACE meta-analysis revealed novel AD genetic signals, strongly driven by the presence of clinical heterogeneity in the AD series

Genome-wide association analysis of dementia and its clinical endophenotypes reveal novel loci associated with Alzheimer's disease and three causality networks : The GR@ACE project

Introduction: Large variability among Alzheimer's disease (AD) cases might impact genetic discoveries and complicate dissection of underlying biological pathways. Methods: Genome Research at Fundacio ACE (GR@ACE) is a genome-wide study of dementia and its clinical endophenotypes, defined based on AD's clinical certainty and vascular burden. We assessed the impact of known AD loci across endophenotypes to generate loci categories. We incorporated gene coexpression data and conducted pathway analysis per category. Finally, to evaluate the effect of heterogeneity in genetic studies, GR@ACE series were meta-analyzed with additional genome-wide association study data sets. Results: We classified known AD loci into three categories, which might reflect the disease clinical heterogeneity. Vascular processes were only detected as a causal mechanism in probable AD. The meta-analysis strategy revealed the ANKRD31-rs4704171 and NDUFAF6-rs10098778 and confirmed SCIMP-rs7225151 and CD33-rs3865444. Discussion: The regulation of vasculature is a prominent causal component of probable AD. GR@ACE meta-analysis revealed novel AD genetic signals, strongly driven by the presence of clinical heterogeneity in the AD series

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

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Complete survey of nuclides produced in spallation of 238^{238}U+p at 1GeV

PAC

Study of the spallation of 136Xe in collision with 1H and 12C at 1 GeV per nucleon

International audienceThe collision of 136Xe with a proton and with 12C at 1 GeV per nucleon has been studied in inverse kinematics with the SPALADIN setup at GSI. The detection in coincidence of the final state fragments (projectile residues, neutrons and Z ⩾ 2 charged fragments) with a large geometrical efficiency is provided by the inverse kinematics combined with a large-aperture dipole magnet and large detectors. Such a coincidence, measured on an event basis, allows us to select the excitation energy of the prefragment formed after the nuclear cascade and study its different de-excitation channels such as evaporation of light particles, asymmetric binary decay or multifragmentation. After a short summary of spallation reactions modeling, followed by the description of the setup, some preliminary results will be shown including the cross-sections of the reaction on the proton, compared in particular to other measurements as well as the cross-sections for the various fragment multiplicities. In the last section, we explain our method for the selection of the prefragment excitation energy and give a hint of the variables available in our experiment to study the excitation energy dependence of the prefragment de-excitation mechanism for both reactions