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CONTEXT: It is important to identify patients at highest risk of fractures. OBJECTIVE: To compare the separate and combined performances of bone-related genetic risk scores (GRSs) for prediction of forearm, hip and vertebral fractures separately, as well as of trabecular and cortical bone microstructure parameters separately. DESIGN, SETTING, AND PARTICIPANTS: Using 1103 single nucleotide polymorp

Transposable elements (TEs) are dynamically expressed at high levels in multiple human tissues, but the function of TE-derived transcripts remains largely unknown. In this study, we identify numerous TE-derived microRNAs (miRNAs) by conducting Argonaute2 RNA immunoprecipitation followed by small RNA sequencing (AGO2 RIP-seq) on human brain tissue. Many of these miRNAs originated from LINE-2 (L2) e

The aggregates of the Ab peptide associated with Alzheimer's disease are able to both grow in size aswell as generate, through secondary nucleation, new small oligomeric species, that are major cytotoxins associated with neuronal death. Despite the importance of these amyloid fibril-dependent processes, their structural and molecular underpinnings have remained challenging to elucidate. Here, we c

Unforeseen ground conditions are risk factors often leading to delays and significant additional costs in conjunction with underground infrastructure construction work. There are two main geological hazards that are important to identify, manage, or possibly avoid, for safe and efficient underground construction. The first is unstable rock and the second is large groundwater inflow. The latter exi

Background: Atherosclerotic plaque ruptures, triggered by blood flow–associated biomechanical forces, cause most myocardial infarctions and strokes. Objectives: This study aims to investigate the exact location and underlying mechanisms of atherosclerotic plaque ruptures, identifying therapeutic targets against cardiovascular events. Methods: Histology, electron microscopy, bulk and spatial RNA se

Covalent inhibitors of Bruton tyrosine kinase (BTK) have transformed the therapy of chronic lymphocytic leukemia (CLL), but continuous therapy has been complicated by the development of resistance. The most common resistance mechanism in patients whose disease progresses on covalent BTK inhibitors (BTKis) is a mutation in the BTK 481 cysteine residue to which the inhibitors bind covalently. Pirtob

Mapping of the spatial and temporal motion of particles inside an optical field is critical for understanding and further improvement of the 3D spatio-temporal control over their optical trapping dynamics. However, it is not trivial to capture the 3D motion, and most imaging systems only capture a 2D projection of the 3D motion, in which the information about the axial movement is not directly ava

Comparative cognitive and behavior research aims to investigate cognitive evolution by comparing performance in different species to understand how these abilities have evolved. Ideally, this requires large and diversesamples; however, these can be difficult to obtain by single labs or institutions, leading to potential reproducibility and generalization issues with small, less representative samp

The global nature of businesses has increased the geographical dispersion of operations and has made the location decision an important strategic perspective for manufacturing firms. The consensus view is that three major plant location factors must be kept in mind: (1) access to low-cost manufacturing, (2) proximity to market, and (3) access to development competences. Two options for changing th

Policy intervention schemes for increased deployment of solar photovoltaics (PV) have been launched in several countries, with varying success. In order to ensure an efficient deployment of the technology, thorough knowledge is needed about relevant present actors and institutions, and about how a desirable actor base and institutional setup should look like; mere cost reductions are not enough to

Where and how new industrial paths emerge are much debated questions in economic geography, especially in light of the recent evolutionary turn. This article contributes to the ongoing debate on path creation with a new analytical framework that specifies the formation of generic resources in embryonic industries. It suggests that path creation processes are not only conditioned by preexisting reg

Plant cells have two main modes of growth generating anisotropic structures. Diffuse growth where whole cell walls extend in specific directions, guided by anisotropically positioned cellulose fibers, and tip growth, with inhomogeneous addition of new cell wall material at the tip of the structure. Cells are known to regulate these processes via molecular signals and the cytoskeleton. Mechanical s