Pathogenic Huntingtin Repeat Expansions in Patients with Frontotemporal Dementia and Amyotrophic Lateral Sclerosis.

We examined the role of repeat expansions in the pathogenesis of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) by analyzing whole-genome sequence data from 2,442 FTD/ALS patients, 2,599 Lewy body dementia (LBD) patients, and 3,158 neurologically healthy subjects. Pathogenic expansions (range, 40-64 CAG repeats) in the huntingtin (HTT) gene were found in three (0.12%) patients diagnosed with pure FTD/ALS syndromes but were not present in the LBD or healthy cohorts. We replicated our findings in an independent collection of 3,674 FTD/ALS patients. Postmortem evaluations of two patients revealed the classical TDP-43 pathology of FTD/ALS, as well as huntingtin-positive, ubiquitin-positive aggregates in the frontal cortex. The neostriatal atrophy that pathologically defines Huntington's disease was absent in both cases. Our findings reveal an etiological relationship between HTT repeat expansions and FTD/ALS syndromes and indicate that genetic screening of FTD/ALS patients for HTT repeat expansions should be considered

Dijet Resonance Search with Weak Supervision Using root S=13 TeV pp Collisions in the ATLAS Detector

This Letter describes a search for narrowly resonant new physics using a machine-learning anomaly detection procedure that does not rely on signal simulations for developing the analysis selection. Weakly supervised learning is used to train classifiers directly on data to enhance potential signals. The targeted topology is dijet events and the features used for machine learning are the masses of the two jets. The resulting analysis is essentially a three-dimensional search A → BC, for mA ∼ OðTeVÞ, mB; mC ∼ Oð100 GeVÞ and B, C are reconstructed as large-radius jets, without paying a penalty associated with a large trials factor in the scan of the masses of the two jets. The full run 2 ffiffi s p ¼ 13 TeV pp collision dataset of 139 fb−1 recorded by the ATLAS detector at the Large Hadron Collider is used for the search. There is no significant evidence of a localized excess in the dijet invariant mass spectrum between 1.8 and 8.2 TeV. Cross-section limits for narrow-width A, B, and C particles vary with mA, mB, and mC. For example, when mA ¼ 3 TeV and mB ≳ 200 GeV, a production cross section between 1 and 5 fb is excluded at 95% confidence level, depending on mC. For certain masses, these limits are up to 10 times more sensitive than those obtained by the inclusive dijet search. These results are complementary to the dedicated searches for the case that B and C are standard model boson

Numerical Study of the Influence of Opaque External Trees with Pyramidal Shape on the Thermal Behaviour of a School Building in Summer Conditions

This paper describes a numerical study of the influence of opaque external trees with pyramidal shape on the thermal behaviour of a school building in Summer conditions. The software used simulates the thermal response of buildings with complex topology under transient conditions. This software has previously been validated by real studies both in Summer and Winter conditions. The school building considered is localised in the South of Portugal. It has three levels divided into 97 rooms or spaces, 1277 main structures and 211 windows with plain transparent glass. In the model, the building is shaded by 49 "opaque'' trees of pyramidal shape growing in front of the windows on one side of each building considered. The simulation considered a typical Summer school day with clear sky and with 800 occupants in the building. Two situations with the same configuration were analysed. In the first one, the trees (located in front of the windows) were placed to the West and South-West of the buildings, while in the second one, after a 180 degrees building rotation, they were to the East and North-East. Both situations were studied with and without the presence of trees. Temperatures in the building and the occupant's thermal comfort conditions were calculated