A new state in 6He following the 7Li(γ,p)6He reaction

A broad excited state was observed in 6He with energy Ex=5+-1 MeV and width Gamma=3+-1 MeV, following the reaction 7Li(γ,p)6He. The state is consistent with a number of broad resonances predicted by recent cluster model calculations. The well-established reaction mechanism, combined with a simple and transparent analysis procedure confers considerable validity to this observation

The Mars Environmental Dynamics Analyzer, MEDA: a suite of environmental sensors for the Mars 2020 mission

This is a post-peer-review, pre-copyedit version of an article published in Space science reviews. The final authenticated version is available online at: http://dx.doi.org/10.1007/s11214-021-00816-9NASA’s Mars 2020 (M2020) rover mission includes a suite of sensors to monitor current environmental conditions near the surface of Mars and to constrain bulk aerosol properties from changes in atmospheric radiation at the surface. The Mars Environmental Dynamics Analyzer (MEDA) consists of a set of meteorological sensors including wind sensor, a barometer, a relative humidity sensor, a set of 5 thermocouples to measure atmospheric temperature at ~1.5 m and ~0.5 m above the surface, a set of thermopiles to characterize the thermal IR brightness temperatures of the surface and the lower atmosphere. MEDA adds a radiation and dust sensor to monitor the optical atmospheric properties that can be used to infer bulk aerosol physical properties such as particle size distribution, non-sphericity, and concentration. The MEDA package and its scientific purpose are described in this document as well as how it responded to the calibration tests and how it helps prepare for the human exploration of Mars. A comparison is also presented to previous environmental monitoring payloads landed on Mars on the Viking, Pathfinder, Phoenix, MSL, and InSight spacecraft.Peer ReviewedPostprint (published version

Yersinia effectors target mammalian signalling pathways

Animals have an immune system to fight off challenges from both viruses and bacteria. The first line of defence is innate immunity, which is composed of cells that engulf pathogens as well as cells that release potent signalling molecules to activate an inflammatory response and the adaptive immune system. Pathogenic bacteria have evolved a set of weapons, or effectors, to ensure survival in the host. Yersinia spp. use a type III secretion system to translocate these effector proteins, called Yops, into the host. This report outlines how Yops thwart the signalling machinery of the host immune system.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73466/1/j.1462-5822.2002.00182.x.pd

THEMIS: A Parameter Estimation Framework for the Event Horizon Telescope

The Event Horizon Telescope (EHT) provides the unprecedented ability to directly resolve the structure and dynamics of black hole emission regions on scales smaller than their horizons. This has the potential to critically probe the mechanisms by which black holes accrete and launch outflows, and the structure of supermassive black hole spacetimes. However, accessing this information is a formidable analysis challenge for two reasons. First, the EHT natively produces a variety of data types that encode information about the image structure in nontrivial ways; these are subject to a variety of systematic effects associated with very long baseline interferometry and are supplemented by a wide variety of auxiliary data on the primary EHT targets from decades of other observations. Second, models of the emission regions and their interaction with the black hole are complex, highly uncertain, and computationally expensive to construct. As a result, the scientific utilization of EHT observations requires a flexible, extensible, and powerful analysis framework. We present such a framework, Themis, which defines a set of interfaces between models, data, and sampling algorithms that facilitates future development. We describe the design and currently existing components of Themis, how Themis has been validated thus far, and present additional analyses made possible by Themis that illustrate its capabilities. Importantly, we demonstrate that Themis is able to reproduce prior EHT analyses, extend these, and do so in a computationally efficient manner that can efficiently exploit modern high-performance computing facilities. Themis has already been used extensively in the scientific analysis and interpretation of the first EHT observations of M87

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

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

Higgs Physics at the CLIC Electron-Positron Linear Collider

The Compact Linear Collider (CLIC) is an option for a future e+e- collider operating at centre-of-mass energies up to 3 TeV, providing sensitivity to a wide range of new physics phenomena and precision physics measurements at the energy frontier. This paper is the first comprehensive presentation of the Higgs physics reach of CLIC operating at three energy stages: sqrt(s) = 350 GeV, 1.4 TeV and 3 TeV. The initial stage of operation allows the study of Higgs boson production in Higgsstrahlung (e+e- -> ZH) and WW-fusion (e+e- -> Hnunu), resulting in precise measurements of the production cross sections, the Higgs total decay width Gamma_H, and model-independent determinations of the Higgs couplings. Operation at sqrt(s) > 1 TeV provides high-statistics samples of Higgs bosons produced through WW-fusion, enabling tight constraints on the Higgs boson couplings. Studies of the rarer processes e+e- -> ttH and e+e- -> HHnunu allow measurements of the top Yukawa coupling and the Higgs boson self-coupling. This paper presents detailed studies of the precision achievable with Higgs measurements at CLIC and describes the interpretation of these measurements in a global fit.The Compact Linear Collider (CLIC) is an option for a future ${\mathrm{e}^{+}}{\mathrm{e}^{-}}$ collider operating at centre-of-mass energies up to $3\,\text {TeV}$ , providing sensitivity to a wide range of new physics phenomena and precision physics measurements at the energy frontier. This paper is the first comprehensive presentation of the Higgs physics reach of CLIC operating at three energy stages: $\sqrt{s} = 350\,\text {GeV}$ , 1.4 and $3\,\text {TeV}$ . The initial stage of operation allows the study of Higgs boson production in Higgsstrahlung ( ${\mathrm{e}^{+}}{\mathrm{e}^{-}} \rightarrow {\mathrm{Z}} {\mathrm{H}}$ ) and ${\mathrm{W}} {\mathrm{W}}$ -fusion ( ${\mathrm{e}^{+}}{\mathrm{e}^{-}} \rightarrow {\mathrm{H}} {{\nu }}_{\!\mathrm{e}} {\bar{{\nu }}}_{\!\mathrm{e}}$ ), resulting in precise measurements of the production cross sections, the Higgs total decay width $\varGamma _{{\mathrm{H}}}$ , and model-independent determinations of the Higgs couplings. Operation at $\sqrt{s} > 1\,\text {TeV}$ provides high-statistics samples of Higgs bosons produced through ${\mathrm{W}} {\mathrm{W}}$ -fusion, enabling tight constraints on the Higgs boson couplings. Studies of the rarer processes ${\mathrm{e}^{+}}{\mathrm{e}^{-}} \rightarrow \mathrm{t} {\bar{\mathrm{t}}} {\mathrm{H}}$ and ${\mathrm{e}^{+}}{\mathrm{e}^{-}} \rightarrow {\mathrm{H}} {\mathrm{H}} {{\nu }}_{\!\mathrm{e}} {\bar{{\nu }}}_{\!\mathrm{e}}$ allow measurements of the top Yukawa coupling and the Higgs boson self-coupling. This paper presents detailed studies of the precision achievable with Higgs measurements at CLIC and describes the interpretation of these measurements in a global fit

Genome-wide haplotype association study identifies the FRMD4A gene as a risk locus for Alzheimer's disease

Recently, several genome-wide association studies (GWASs) have led to the discovery of nine new loci of genetic susceptibility in Alzheimer's disease (AD). However, the landscape of the AD genetic susceptibility is far away to be complete and in addition to single-SNP (single-nucleotide polymorphism) analyses as performed in conventional GWAS, complementary strategies need to be applied to overcome limitations inherent to this type of approaches. We performed a genome-wide haplotype association (GWHA) study in the EADI1 study (n=2025 AD cases and 5328 controls) by applying a sliding-windows approach. After exclusion of loci already known to be involved in AD (APOE, BIN1 and CR1), 91 regions with suggestive haplotype effects were identified. In a second step, we attempted to replicate the best suggestive haplotype associations in the GERAD1 consortium (2820 AD cases and 6356 controls) and observed that 9 of them showed nominal association. In a third step, we tested relevant haplotype associations in a combined analysis of five additional case-control studies (5093 AD cases and 4061 controls). We consistently replicated the association of a haplotype within FRMD4A on Chr.10p13 in all the data set analyzed (OR: 1.68; 95% CI: (1.43-1.96); P=1.1 × 10 -10). We finally searched for association between SNPs within the FRMD4A locus and Aβ plasma concentrations in three independent non-demented populations (n=2579). We reported that polymorphisms were associated with plasma Aβ42/Aβ40 ratio (best signal, P=5.4 × 10 -7). In conclusion, combining both GWHA study and a conservative three-stage replication approach, we characterised FRMD4A as a new genetic risk factor of AD