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The enhancement of immune effector functions has been proposed as a potential strategy for increasing the efficacy of therapeutic antibodies. Here, we show that removing fucose from trastuzumab (Herceptin) increased its binding to FcγRIIIa, enhanced antibody-dependent cell-mediated cytotoxicity, and more than doubled the median progression-free survival when compared with conventional trastuzumab in treating preclinical models of HER2-amplified breast cancer. Our results show that afucosylated trastuzumab has superior efficacy in treating in vivo models of HER2-amplified breast cancer and support the development of effector function-enhanced antibodies for solid tumor therapy.

Accurate snowfall measurements are critical for a wide variety of research fields, including snowpack monitoring, climate variability, and hydrological applications. It has been recognized that systematic errors in snowfall measurements are often observed as a result of the gauge geometry and the weather conditions. The goal of this study is to understand better the scatter in the snowfall precipitation rate measured by a gauge. To address this issue, field observations and numerical simulations were carried out. First, a theoretical study using finite-element modeling was used to simulate the flow around the gauge. The snowflake trajectories were investigated using a Lagrangian model, and the derived flow field was used to compute a theoretical collection efficiency for different types of snowflakes. Second, field observations were undertaken to determine how different types, shapes, and sizes of snowflakes are collected inside a Geonor, Inc., precipitation gauge. The results show that the collection efficiency is influenced by the type of snowflakes as well as by their size distribution. Different types of snowflakes, which fall at different terminal velocities, interact differently with the airflow around the gauge. Fast-falling snowflakes are more efficiently collected by the gauge than slow-falling ones. The correction factor used to correct the data for the wind speed is improved by adding a parameter for each type of snowflake. The results show that accurate measure of snow depends on the wind speed as well as the type of snowflake observed during a snowstorm.

Recent studies have used numerical models to estimate the collection efficiency of solid precipitation gauges when exposed to the wind in both shielded and unshielded configurations. The models used computational fluid dynamics (CFD) simulations of the airflow pattern generated by the aerodynamic response to the gauge-shield geometry. These are used as initial conditions to perform Lagrangian tracking of solid precipitation particles. Validation of the results against field observations yielded similarities in the overall behavior, but the model output only approximately reproduced the dependence of the experimental collection efficiency on wind speed. This paper presents an improved snowflake trajectory modeling scheme due to the inclusion of a dynamically determined drag coefficient. The drag coefficient was estimated using the local Reynolds number as derived from CFD simulations within a time-independent Reynoldsaveraged Navier-Stokes approach. The proposed dynamic model greatly improves the consistency of results with the field observations recently obtained at the Marshall Field winter precipitation test bed in Boulder, Colorado.

The use of windshields to reduce the impact of wind on snow measurements is common. This paper investigates the catching performance of shielded and unshielded gauges using numerical simulations. In Part II, the role of the windshield and gauge aerodynamics, as well as the varying flow field due to the turbulence generated by the shield-gauge configuration, in reducing the catch efficiency is investigated. This builds on the computational fluid dynamics results obtained in Part I, where the airflow patterns in the proximity of an unshielded and single Alter shielded Geonor T-200B gauge are obtained using both time-independent [Reynolds-averaged Navier-Stokes (RANS)] and time-dependent [large-eddy simulation (LES)] approaches. A Lagrangian trajectory model is used to track different types of snowflakes (wet and dry snow) and to assess the variation of the resulting gauge catching performance with the wind speed. The collection efficiency obtained with the LES approach is generally lower than the one obtained with the RANS approach. This is because of the impact of the LES-resolved turbulence above the gauge orifice rim. The comparison between the collection efficiency values obtained in case of shielded and unshielded gauge validates the choice of installing a single Alter shield in a windy environment. However, time-dependent simulations show that the propagating turbulent structures produced by the aerodynamic response of the upwind single Alter blades have an impact on the collection efficiency. Comparison with field observations provides the validation background for the model results.