Rare and low-frequency coding variants alter human adult height

Height is a highly heritable, classic polygenic trait with ~700 common associated variants identified so far through genome - wide association studies . Here , we report 83 height - associated coding variants with lower minor allele frequenc ies ( range of 0.1 - 4.8% ) and effects of up to 2 16 cm /allele ( e.g. in IHH , STC2 , AR and CRISPLD2 ) , >10 times the average effect of common variants . In functional follow - up studies, rare height - increasing alleles of STC2 (+1 - 2 cm/allele) compromise d proteolytic inhibition of PAPP - A and increased cleavage of IGFBP - 4 in vitro , resulting in higher bioavailability of insulin - like growth factors . The se 83 height - associated variants overlap genes mutated in monogenic growth disorders and highlight new biological candidates ( e.g. ADAMTS3, IL11RA, NOX4 ) and pathways ( e.g . proteoglycan/ glycosaminoglycan synthesis ) involved in growth . Our results demonstrate that sufficiently large sample sizes can uncover rare and low - frequency variants of moderate to large effect associated with polygenic human phenotypes , and that these variants implicate relevant genes and pathways

Modeling the dynamics of soil erosion and size-selective sediment transport over nonuniform topography in flume-scale experiments

Soil erosion and the associated nutrient fluxes can lead to severe degradation of surface waters. Given that both sediment transport and nutrient sorption are size selective, it is important to predict the particle size distribution (PSD) as well as the total amount of sediment being eroded. In this paper, a finite volume implementation of the Hairsine-Rose soil erosion model is used to simulate flume-scale experiments with detailed observations of soil erosion and sediment transport dynamics. The numerical implementation allows us to account for the effects of soil surface microtopography (measured using close range photogrammetry) on soil erosion. An in-depth discussion of the model parameters and the constraints is presented. The model reproduces the dynamics of sediment concentration and PSD well, although some discrepancies can be observed. The calibrated parameters are also consistent with independent data in the literature and physical reason. Spatial variations in the suspended and deposited sediment and an analysis of model sensitivity highlight the value of collecting distributed data for a more robust validation of the model and to enhance parametric determinacy. The related issues of spatial resolution and scale in erosion prediction are briefly discussed

Influence of sediment settling velocity on mechanistic soil erosion modeling

We report on a series of soil erosion experiments performed on the 2-m × 6-m EPFL erosion flume. Total sediment concentrations and the concentrations of seven size fractions (1000 μm) were measured during 14 high-intensity (47.5–52.5 mm/h) rainfall experiments on three different slopes (2.2–12.4%). The short-time and long-time analytical solutions for the Hairsine-Rose erosion model were rewritten to account for infiltration. The newly collected data were used to test the model under conditions that had not been explored before (steeper slopes, infiltration, more realistic soil composition). The analytical solutions could predict the observed total sediment concentration well. However, the observed sediment concentrations for the individual size classes could be predicted only when adjusted settling velocities were used. The adjusted settling velocities were estimated through manual optimization. The optimized settling velocities for the smallest and midsize particles (315 μm) were smaller than measured. The effective settling velocities could also be calculated from the calculated amount of material in the shield of each size class at the end of the experiments. This calculated settling velocity distribution agreed very well with the optimized settling velocities. This study moves the Hairsine-Rose model another step closer to an operational soil erosion model for field applications

Mechanism of Laccase¿TEMPO-Catalyzed Oxidation of Benzyl Alcoho

The oxidation of benzyl alcohol by air, catalyzed by the organocatalyst TEMPO and the enzyme laccase has been investigated. To establish the kinetically significant pathways and corresponding kinetic parameters, a series of experiments is conducted with synthesized stable oxidized and reduced forms of the organocatalyst, the oxoammonium cation, and hydroxylamine. The time course of TEMPO and its oxidized and reduced derivatives is monitored off line by a combination of GC analysis, UV/Vis spectroscopy, EPR spectroscopy, and FTIR spectroscopy. TEMPO is found to be regenerated through noncatalyzed comproportionation of the oxoammonium cation with hydroxylamine. A kinetic model is presented based on the experimentally determined kinetically significant pathways. The time dependences of the concentrations of the three redox states of TEMPO and benzyl alcohol are adequately described by the model. The results provide new leads for the development of a practical process for a combined laccase–TEMPO-catalyzed selective oxidation of alcohol

Effect of raindrop splash and transversal width on soil erosion: laboratory flume experiments and analysis with the Hairsine–Rose model

The parameter consistency of the one-dimensional Hairsine–Rose (H–R) erosion model under conditions of significant rainfall splash was examined. To account for the splash characteristic length scale and its interaction with the transverse erosion width, experiments were carried out using erosion flumes of the same length (6 m), but different widths, with sediment concentrations measured at the flume exits. Total sediment concentration and the concentration of seven size fractions (1000 μm) were measured at high rainfall intensity (60 mm h−1) and with a gentle slope (2.2%). The conditions employed ensured that erosion was predominantly precipitation-driven. The experimental results showed that raindrop splash affected particularly the sediment breakthrough from the wider flumes (flumes 1 and 2, 1- and 0.5-m wide, respectively). However, the raindrop splash effect was less significant in observed sediment concentrations from the narrower flumes (flumes 3 and 4, both 0.25-m wide). For these flumes, the detached sediment was affected by the transversal width of the flume in that an amount of detached sediment adhered to the barriers instead of being removed in the overland flow. The one-dimensional H–R model was fitted to the experimental results and good agreement was found, in particular for the finer size classes. The data for the coarser grain sizes were more scattered, suggesting sediment motion by mechanisms other than suspension in the overland flow (e.g., rolling along the soil surface). The optimized parameters indicated that the shield layers (where the shield consists of re-deposited eroded sediment) of the wider flumes (1 and 2) developed within 5–10 min from the start of the experiment, whereas in the narrower flumes (3 and 4) they never fully developed. The optimized detachment rates were consistent with previous findings, but the estimated thickness of the deposited layer was too small to provide complete protection of the original soil against raindrop detachment, indicating that the shield was not uniform. The experimental design allowed us to investigate directly the effect of flow non-uniformity on soil erosion by inclusion of an offset drainage point in flume 4. The observations taken during and after the experiment, as well as surface elevation data, confirmed the noticeable impact of non-uniform flow on the erosion process