Clouds play an important role in weather and climate. In addition to their key role in the hydrologic cycle, clouds scatter incoming solar radiation and trap infrared radiation from the surface and lower atmosphere. Despite their importance, feedbacks involving clouds remain as one of the largest sources of uncertainty in climate models. To better simulate cloud processes requires better characterization of cloud microphysical processes, which can affect the spatial extent, optical depth and lifetime of clouds. To this end, we developed a new parameterization to be used in numerical models that describes the variation of ice nuclei (IN) number concentrations active to form ice crystals in mixed-phase (water droplets and ice crystals co-existing) cloud conditions as these depend on existing aerosol properties and temperature. The parameterization is based on data collected using the Colorado State University continuous flow diffusion chamber in aircraft and ground-based campaigns over a 14-year period, including data from the DOE-supported Mixed-Phase Arctic Cloud Experiment. The resulting relationship is shown to more accurately represent the variability of ice nuclei distributions in the atmosphere compared to currently used parameterizations based on temperature alone. When implemented in one global climate model, the new parameterization predicted more realistic annually averaged cloud water and ice distributions, and cloud radiative properties, especially for sensitive higher latitude mixed-phase cloud regions. As a test of the new global IN scheme, it was compared to independent data collected during the 2008 DOE-sponsored Indirect and Semi-Direct Aerosol Campaign (ISDAC). Good agreement with this new data set suggests the broad applicability of the new scheme for describing general (non-chemically specific) aerosol influences on IN number concentrations feeding mixed-phase Arctic stratus clouds. Finally, the parameterization was implemented into a regional cloud-resolving model to compare predictions of ice crystal concentrations and other cloud properties to those observed in two intensive case studies of Arctic stratus during ISDAC. Our implementation included development of a prognostic scheme of ice activation using the IN parameterization so that the most realistic treatment of ice nuclei, including their budget (gains and losses), was achieved. Many cloud microphysical properties and cloud persistence were faithfully reproduced, despite a tendency to under-predict (by a few to several times) ice crystal number concentrations and cloud ice mass, in agreement with some other studies. This work serves generally as the basis for improving predictive schemes for cloud ice crystal activation in cloud and climate models, and more specifically as the basis for such a scheme to be used in a Multi-scale Modeling Format (MMF) that utilizes a connected system of cloud-resolving models on a global grid in an effort to better resolve cloud processes and their influence on climate.