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BackgroundT helper (Th) cell subsets primarily assist B cells in differentiating into plasma cells in the germinal center. The mechanism of malignant transformation of plasma cells is an important target for the clinical treatment of MM; however, the mechanism remains unclear.MethodsWe collected the peripheral blood (PB) and bone marrow (BM) samples of 33 patients with MM. In addition, the PB was also collected from 25 normal healthy controls (HCs). We analyzed the percentages of Th cell subsets in the PB and BM samples of patients with MM.ResultsTfh/CD4+ were positively correlated with the proportion of myeloma cells in the BM and PB samples (r = 0.592, P = 0.002 and r = 0.510, P = 0.010 respectively), and showed a strong correlation between the BM and PB samples (r = 0.6559, P = 0.0095). In the PB samples, the percentages of Th2/CD4+ and Tfh2/Tfh cells were significantly lower in patients with MM than in HCs (P = 0.00013 and P = 0.0004, respectively), whereas the percentage of Th17/CD4+ and Tfh17/Tfh was significantly higher in newly diagnosed patients with MM than in HCs (P = 0.0037 and P = 0.03, respectively), and all these cells showed a good predictive value for MM (area under the curve [AUC] 0.781, = 0.792, = 0.837, and 0.723 respectively). In the PB samples, all subsets of PD-1+ICOS- Tfh showed a noticeable downward trend in MM from newly diagnosed to non-remission and remission groups. In contrast, all subsets of PD-1-ICOS+ Tfh increased gradually.ConclusionTh cell subsets play an important role in the occurrence and development of MM and may provide a fundamental basis for identifying new immunotherapy targets and prognosis.

Abstract Numerous Earth system models exhibit excessive aerosol effective forcing at the top of the atmosphere (TOA), including the Department of Energy's Energy Exascale Earth System Model (E3SM). Here, in the context of the E3SM version 3 effort, the predicted particle property (P3) stratiform cloud microphysics scheme and an enhanced deep convection parameterization suite (ZM_plus) are implemented into E3SM. The ZM_plus includes a convective cloud microphysics scheme, a multi‐scale coherent structure parameterization for mesoscale convective systems, and a revised cloud base mass flux formulation considering impacts of the large‐scale environment. The P3 scheme improved cloud and radiation particularly over the Northern Hemisphere and the frequency of heavy precipitation over the tropics, and the ZM_plus improved clouds in the tropics. P3 decreases aerosol effective forcing by 0.15 W m−2, while the ZM_plus increases it by 0.27 W m−2, resulting from excessive direct (0.31 W m−2) and indirect forcing (−1.79 W m−2). The excessive aerosol forcings are due to aerosol overestimation associated with insufficient aerosol wet removal. By improving the physical treatments in the aerosol wet removal, we effectively mitigate anthropogenic aerosol overestimation and thus attenuate direct (0.09 W m−2) and indirect aerosol forcing (−1.52 W m−2). Adjustment to primary organic matter hygroscopicity reduces direct and indirect forcing to more reasonable values: −0.13 W m−2 and −1.31 W m−2, respectively. On climatology, improved aerosol treatments mitigate overestimation of aerosol optical depth.

Key Points The editors thank the 2023 peer reviewers

Abstract The vertical distribution of biomass burning aerosol (BBA) is important in regulating their impacts on weather and climate. The plume‐rise process affects the injection height of BBA and interacts with the air parcel lifting and cloud processes. However, these processes are not represented in most global climate models. In this study, we replaced the fixed vertical profiles of monthly BBA emissions in the Department of Energy's Energy Exascale Earth System Model version 1 (E3SMv1) with an interactive fire plume‐rise model. The vertical distribution of BBA emissions was calculated as a function of ambient thermodynamic conditions from the host E3SMv1, with distributions of fire sizes and sensible heat fluxes derived from the observations. The maximum fire radiative power (FRP) technique was used to determine the fire size. Scaling‐FRP technique is used to calculate the wildfire heat release. Daily BBA emission, superimposed with a fire diurnal cycle retrieved from the satellite observation, was included in model simulations. The model shows improved agreement with satellite retrievals and in situ measurement during the National Oceanic and Atmospheric Administration Wildfire Experiment for Cloud chemistry, Aerosol absorption, and Nitrogen campaign. The model‐observation comparison demonstrates the importance of the plume‐rise model and fire diurnal cycle assumption in determining the BBA fields. We also find that E3SMv1 with new features produces a larger carbonaceous aerosol burden, leading to 0.13 W m−2 warming at the top of atmosphere compared to the default E3SMv1. This highlights the importance of accurately representing the BBA injection height and indicates a no‐linear nature in the BBA‐induced radiative effect.

Abstract The editors of Journal of Advances in Modeling Earth Systems thank the 702 reviewers who provided 1362 reviews during 2022. Their hard work and insights, typically done anonymously, benefits authors, readers, and the broader science community.

Abstract The mission of AGU's Journal of Advances in Modeling Earth Systems (JAMES) is to publish original research papers that advance the science underlying Earth system models and emerging from their use. JAMES' scope encompasses the outer envelope of the Earth system including the atmosphere, oceans, land surface, and cryosphere. It publishes papers that expand capabilities to model, understand, and predict the Earth system and the physical, chemical, and biological processes shaping it. In this editorial, we present general principles as well as specific notions that guide the strategy of JAMES' editors in realizing the journal's mission. This document serves as an update to Griffies et al. (2021), https://doi.org/10.1029/2021MS002567.

Tornadoes pose a risk of catastrophic economic loss and casualty in the United States. Modification of land use by urbanization alters the meteorological conditions that may impact tornado formation and intensification processes. Here we explored the simulated impact of Kansas City urbanization on the tornado potential of a supercell storm. In this studied case, we found that urbanization might enhance tornado potential by a) strengthening the low-level streamwise vorticity in the storm inflow region, thus forming stronger rotating updrafts; and b) intensifying near-surface horizontal vorticity near the boundary of the forward-flank cold pool which increases the ingestion, tilting, and stretching of streamwise horizontal vorticity into vertical vorticity. The former results from the stronger east-to-west pressure perturbation gradient due to the faster, stronger outflow boundary, and the latter is mainly a result of stronger cold fronts and a better alignment of storm-relative inflow with the horizontal vorticity vector. We emphasize that our conclusions only represent one possibility of how urbanization would affect tornado potential, and a more systematic examination is needed to achieve a more general conclusion.

Background: Tacrolimus (TAC) and mycophenolic acid (MPA) are commonly used immunosuppressive therapies after renal transplant. Our objective was to quantify TAC and MPA concentrations in peripheral blood mononuclear cells (PBMCs) using liquid chromatography tandem mass spectrometry (LC-MS/MS) and to evaluate and validate the performance of the methodology. A prospective follow-up cohort study was conducted to determine whether intracellular concentrations were associated with adverse outcomes in renal transplants. Methods: PBMCs were prepared using the Ficoll separation technique and purified with erythrocyte lysis. The cells were counted using Sysmex XN-3100 and then packaged and frozen according to a 50 µL volume containing 1.0 × 106 cells. TAC and MPA were extracted using MagnaBeads and quantified using an LC-MS/MS platform. The chromatography was run on a reversed-phase Waters Acquity UPLC BEH C18 column (1.7 µm, 50 mm × 2.1 mm) for gradient elution separation with a total run time of 4.5 min and a flow rate of 0.3 mL/min. Mobile phases A and B were water and methanol, respectively, each containing 2 mM ammonium acetate and 0.1% formic acid. Renal transplant recipients receiving TAC and MPA in combination were selected for clinical validation and divided into two groups: a stable group and an adverse outcome group. The concentrations were dynamically monitored at 5, 7, 14, and 21 days (D5, D7, D14, and D21) and 1, 2, 3, and 6 months (M1, M2, M3, and M6) after operation. Results: Method performance validation was performed according to Food and Drug Administration guidelines, showing high specificity and sensitivity. The TAC and MPA calibration curves were linear (r2 = 0.9988 and r2 = 0.9990, respectively). Both intra-day and inter-day imprecision and inaccuracy were less than 15%. Matrix effects and recoveries were satisfactory. The TAC and MPA concentrations in 304 “real” PBMC samples from 47 renal transplant recipients were within the calibration curve range (0.12 to 16.40 ng/mL and 0.20 to 4.72 ng/mL, respectively). There was a weak correlation between PBMC-C0TAC and WB-C0TAC (p < 0.05), but no correlation was found for MPA. The level of immunosuppressive intra-patient variation (IPV) was higher in PBMC at 77.47% (55.06, 97.76%) than in WB at 34.61% (21.90, 49.85%). During the dynamic change in C0TAC, PBMC-C0TAC was in a fluctuating state, and no stable period was found. PBMC-C0TAC did not show a significant difference between the stable and adverse outcome group, but the level of the adverse outcome group was generally higher than that of the stable group. Conclusions: Compared with conventional therapeutic drug monitoring, the proposed rapid and sensitive method can provide more clinically reliable information on drug concentration at an active site, which has the potential to be applied to the clinical monitoring of intracellular immunosuppressive concentration in organ transplantation. However, the application of PBMC-C0TAC in adverse outcomes of renal transplant should be studied further.

Nanofibers show promise as bone tissue engineering scaffolds (BTESs). In this study, electrospun poly (lactic-co-glycolic acid) (PLGA)/silicon nitride (Si3N4) composite nanofiber membranes were formed and the osteogenesis capability of mesenchymal stem cells (MSC) from the scaffold marrow was investigated. By modifying the different properties of Si3N4 in the PLGA, two hybrid scaffolds were successfully prepared, including the PLGA/Si3N4 (1 wt.%) nanofiber scaffold and PLGA/Si3N4 (2 wt.%) nanofiber scaffold. The diameter of the fiber nanofiber scaffold PLGA/Si3N4 was decreased and the mechanical strength was increased compared to PLGA. In vitro studies showed better cell adhesion and proliferation on the PLGA/Si3N4 nanofiber scaffold compared to the PLGA nanofiber scaffold. The integration of Si3N4 promoted osteogenesis capacity by increasing the gene expression of bone-related proteins (BMP2, ALP, OPN, COL1a1, Runx2, and OCN), calcium deposits, and support of ALP activity compared to those for the PLGA nanofiber scaffold. Similarly, the PLGA/Si3N4 (2 wt.%) nanofiber scaffold showed better mechanics and biological activity compared to the PLGA/Si3N4 (1 wt.%) nanofiber scaffold. Overall, the PLGA/Si3N4 nanofiber scaffold showed potential as a promising hybrid scaffold for bone regeneration.

Abstract Hailstones and extreme precipitation generate substantial economic losses across the United States (US) and the globe. Their strong association with short‐lived, intense convective storms poses a great challenge in predicting their future changes. Here, we conducted model simulations at 1.2 km grid spacing for severe convective storms with large hail and heavy precipitation that occurred in two typical types of synoptic‐scale environments in spring seasons over the central US under both current and future climate conditions. We find that the responses of large hail (diameters >2.5 cm) to anthropogenic climate change (ACC) are markedly different between the hailstorms developed in the two types of synoptic‐scale environments, with over 110% increase in large hail occurrences for the frontal systems, whereas less than 30% increase for the Great Plains low‐level jet (GPLLJ) systems. This is explained by the larger increase in convective intensity and updraft width and a smaller increase in warm cloud depth in the frontal storms compared with the GPLLJ storms. Interestingly, the occurrences and intensity of heavy precipitation (rain rate >20 mm hr−1) in both types of systems are similarly sensitive to ACC (e.g., 40% and 33% increases in the occurrences for the frontal and GPLLJ systems, respectively). These results advance our knowledge of hail projection and have important implications for managing risks for future hail.

Cardiac fibrosis results from both the differentiation of cardiac fibroblasts and excessive accumulation of extracellular matrix (ECM), leading to myocardial stiffness and reduced compliance of the ventricular wall. The conversion of cardiac fibroblasts to myofibroblasts is the most important initiating step in the process of this pathological cardiac remodeling. It occurs during the progression of many cardiovascular diseases, adversely influencing both the clinical course and outcome of the disease. The pathogenesis is complex and there is no effective treatment. Exosomes are extracellular vesicles that mediate intercellular communication through delivering specific cargoes of functional nucleic acids and proteins derived from particular cell types. Recent studies have found that exosomes play an important role in the diagnosis and treatment of cardiac fibrosis, and is a potential biotherapeutics and drug delivery vectors for the treatment of cardiac fibrosis. The present review aimed to summarize the current knowledge of exosome-related mechanisms underlying cardiac fibrosis and to suggest potential therapy that could be used to treat the condition.

Key Point The editors thank the 2021 peer reviewers

Lymphocyte subsets significantly change during childhood; thus, age-matched reference values derived from healthy children are crucial. We established reference values for lymphocyte subsets, including T cells (CD3+), CD4 T cells (CD3 + CD4+), CD8 T cells (CD3 + CD8+), double negative T (DNT) cells (CD3 + CD4-CD8-), B cells (CD3-CD19+), NK cells (CD3-CD56+), and NKT-like cells (CD3 + CD56+) in the peripheral blood of 813 healthy children. We used the method of the international standard document (Clinical Laboratory Standard Institute C28-A3) to establish reference intervals with a single platform. First, we used the Skewness and Kurtosis test to analyze the normality of the data. The nonnormally distributed data was transformed into approximately normal distribution by the Box-Cox transformation. Second, we used the Tukey’s method to eliminate outliers. Further, all the subjects were grouped into subgroups according to sex (male and female) and age (0–1 month, 2–12 months, 1–3 years, 4–6 years, and 7–18 years). We used the standard normal deviation test (Z-test) to evaluate whether age and sex were possible grouping factors. The analyses indicated age to be an important factor associated with changes in lymphocyte subsets. The absolute number of lymphocyte subsets and total number of lymphocytes, T cells, CD4 T cells, CD8 T cells, and B cells gradually increase from birth to 12 months and then gradually decrease with age. Furthermore, CD4 T cells and the ratio of CD4+/CD8+ gradually decrease with age. In contrast, CD8 T and DNT cells gradually increase with age. The percentage and number of NK and NKT-like cells gradually increase with age and remain stable between 1 and 18 years of age. In conclusion, the age-related reference intervals established in healthy children in this study can aid in monitoring and assessing the changes in immune levels in diseased conditions.

Abstract Mesoscale convective systems (MCSs) are a major source of precipitation in many regions of the world. Traditional global climate models (GCMs) do not have adequate parameterizations to represent MCSs. In contrast, the Multiscalex Modeling Framework (MMF), which explicitly resolves convection within the cloud‐resolving model embedded in each GCM column, has been shown to be a promising tool for simulating MCSs, particularly over the Tropics. In this work, we use ground‐based radar‐observed precipitation, North American Regional Reanalysis data, and a high‐resolution Weather Research and Forecasting simulation to evaluate in detail the MCS‐associated precipitation over the central United States predicted by a prototype MMF simulation that has a 2° host‐GCM grid. We show that the prototype MMF with nudged winds fails to capture the convective initiation in three out of four major MCS events during May 201x1 and underpredicts the precipitation rates for the remaining event, because the model cannot resolve the mesoscale drylines/fronts that are important drivers for initiating convection over the Southern Great Plains region. By reducing the host‐GCM grid spacing to 0.25° in the MMF and nudging the winds, the simulation is able to better capture the mesoscale dynamics, which drastically improves the model performance. We also show that the MMF model performs better than the traditional GCM in capturing the precipitation intensity. Our results suggest that increasing resolution plays a dominant role in improving the simulation of precipitation in the MMF, and the cloud‐resolving model embedded in each GCM column further helps to boost precipitation rate.

Abstract Mesoscale convective systems (MCSs) are one of the most climatically significant forms of convection because of their large role in water and energy cycles. The mesoscale features associated with MCS are difficult to represent in climate models because the relevant dynamics and physics are absent or poorly represented with coarse model resolution (∼100 km). Using a regionally refined model (RRM) with 0.25° grid spacing embedded in the Energy Exascale Earth System Model (E3SM), we explore the impact of cloud microphysics parameterizations on the simulation of precipitation, particularly MCS precipitation over the contiguous United States. The Predicted Particle Properties (P3) cloud microphysics scheme has been modified and implemented into E3SM to overcome the limitations of the default Morrison and Gettelman (MG2) scheme in which rimed precipitating ice particles (graupel/hail) are absent and frozen particles are artificially partitioned into cloud ice and snow. We show that P3 improves the simulation of precipitation statistics including frequency distribution compared with MG2 with a limited effect on the diurnal cycle. P3 predicts higher hourly rain rates, resulting in 20% more MCSs and a higher total MCS precipitation (4.4%) compared to MG2, agreeing better with observations. The improvements with P3 mainly result from improved representations of ice microphysics, which not only produces higher rain rates through melting but also leads to a stronger large‐scale ascending motion by releasing more latent heating. This study suggests that improving microphysics parameterization is important for simulating MCS precipitation as future climate model resolutions continue to increase.

Abstract In this editorial, we present general principles as well as specific notions that guide the strategy of JAMES′ editors in realizing the journal's mission.

Abstract The net radiative effects of tropical clouds are determined by the evolution of thick, freshly detrained anvil clouds into thin anvil clouds. Thick anvil clouds reduce Earth's energy balance and cool the climate, while thin anvil clouds warm the climate. To determine role of these clouds in climate change we need to understand how interactions of their microphysical and macrophysical properties control their radiative properties. We explore anvil cloud evolution using a cloud‐resolving model in three‐simulation setups of increasing complexity to disentangle the impacts of the various components of diabatic heating and their interaction with cloud‐scale motions. The first phase of evolution and rapid cloud spreading is dominated by latent heating within convective updrafts. After the convective detrainment stops, most of the spreading and thinning of the anvil cloud is driven by cloud radiative processes and latent heating. The combination of radiative cooling at cloud top, latent cooling due to sublimation at cloud base, latent heating due to deposition and radiative heating in between leads to a sandwich‐like, cooling‐heating‐cooling structure. The heating sandwich promotes the development of two within‐anvil convective layers and a double cell circulation, dominated by strong outflow at 12‐km altitude with inflow above and below. Our study reveals how small‐scale processes including convective, microphysical processes, latent and radiative heating interact within the anvil cloud system. The absence or a different representation of only one component results in a significantly different cloud evolution with large impacts on cloud radiative effects.

It remains unclear how urban emissions influence the formation of secondary organic aerosols (SOA), including in the Amazon forest. Here, the authors simulate the formation of SOAs in the Amazon using a high-resolution regional chemical transport model. They find that urban emissions of NOx from Manaus enhance the production of biogenic SOA by 60–200%.

Abstract Regional climate simulations over the continental United States were conducted for the 2011 warm season using the Weather Research and Forecasting model at convection‐permitting resolution (4 km) with two commonly used microphysics parameterizations (Thompson and Morrison). Sensitivities of the simulated mesoscale convective system (MCS) properties and feedbacks to large‐scale environments are systematically examined against high‐resolution geostationary satellite and 3‐D mosaic radar observations. MCS precipitation including precipitation amount, diurnal cycle, and distribution of hourly precipitation intensity are reasonably captured by the two simulations despite significant differences in their simulated MCS properties. In general, the Thompson simulation produces better agreement with observations for MCS upper level cloud shield and precipitation area, convective feature horizontal and vertical extents, and partitioning between convective and stratiform precipitation. More importantly, Thompson simulates more stratiform rainfall, which agrees better with observations and results in top‐heavier heating profiles from robust MCSs compared to Morrison. A stronger dynamical feedback to the large‐scale environment is therefore seen in Thompson, wherein an enhanced mesoscale vortex behind the MCS strengthens the synoptic‐scale trough and promotes advection of cool and dry air into the rear of the MCS region. The latter prolongs the MCS lifetimes in the Thompson relative to the Morrison simulations. Hence, different treatment of cloud microphysics not only alters MCS convective‐scale dynamics but also has significant impacts on their macrophysical properties such as lifetime and precipitation. As long‐lived MCSs produced 2–3 times the amount of rainfall compared to short‐lived ones, cloud microphysics parameterizations have profound impact in simulating extreme precipitation and the hydrologic cycle.

Abstract Modeling the aerosol lifecycle in traditional global climate models (GCM) is challenging for a variety of reasons, not the least of which is the coarse grid. The multiscale modeling framework (MMF), in which a cloud resolving model replaces conventional parameterizations of cloud processes within each GCM grid column, provides a promising framework to address this challenge. Here we develop a new version of MMF that for the first time treats aerosol processes at cloud scale to improve the aerosol‐cloud interaction representation in the model. We demonstrate that the model with the explicit aerosol treatments shows significant improvements of many aspects of the simulated aerosols compared to the previous version of MMF with aerosols parameterized at the GCM grid scale. The explicit aerosol treatments produce a significant increase of the column burdens of black carbon (BC), primary organic aerosol, and sulfate by up to 40% in many remote regions, a decrease of the sea‐salt aerosol burdens by 40% in remote regions. These differences are caused by the differences in aerosol convective transport and wet removal between these two models. The new model also shows reduced bias of BC surface concentration in North America and BC vertical profiles in the high latitudes. However, the biased‐high BC concentrations in the upper troposphere over the remote Pacific regions remain, requiring further improvements on other process representations (e.g., secondary activation neglected in the model).

Aerosol particles can affect cloud microphysical properties by serving as ice nuclei (IN). Large uncertainties exist in the ice nucleation parameterizations (INPs) used in current climate models. In this Part II paper, to examine the sensitivity of the model predictions to different heterogeneous INPs, WRF-CAM5 simulation using the INP of Niemand et al. (N12) [1] is conducted over East Asia for two full years, 2006 and 2011, and compared with simulation using the INP of Meyers et al. (M92) [2], which is the original INP used in CAM5. M92 calculates the nucleated ice particle concentration as a function of ice supersaturation, while N12 represents the nucleated ice particle concentration as a function of temperature and the number concentrations and surface areas of dust particles. Compared to M92, the WRF-CAM5 simulation with N12 produces significantly higher nucleated ice crystal number concentrations (ICNCs) in the northern domain where dust sources are located, leading to significantly higher cloud ice number and mass concentrations and ice water path, but the opposite is true in the southern domain where temperatures and moistures play a more important role in ice formation. Overall, the simulation with N12 gives lower downward shortwave radiation but higher downward longwave radiation, cloud liquid water path, cloud droplet number concentrations, and cloud optical depth. The increase in cloud optical depth and the decrease in downward solar flux result in a stronger shortwave and longwave cloud forcing, and decreases temperature at 2-m and precipitation. Changes in temperature and radiation lower surface concentrations of OH, O3, SO42−, and PM2.5, but increase surface concentrations of CO, NO2, and SO2 over most of the domain. By acting as cloud condensation nuclei (CCN) and IN, dust particles have different impacts on cloud water and ice number concentrations, radiation, and temperature at 2-m and precipitation depending on whether the dominant role of dust is CCN or IN. These results indicate the importance of the heterogeneous ice nucleation treatments and dust emissions in accurately simulating regional climate and air quality.

Online-coupled climate and chemistry models are necessary to realistically represent the interactions between climate variables and chemical species and accurately simulate aerosol direct and indirect effects on cloud, precipitation, and radiation. In this Part I of a two-part paper, simulations from the Weather Research and Forecasting model coupled with the physics package of Community Atmosphere Model (WRF-CAM5) are conducted with the default heterogeneous ice nucleation parameterization over East Asia for two full years: 2006 and 2011. A comprehensive model evaluation is performed using satellite and surface observations. The model shows an overall acceptable performance for major meteorological variables at the surface and in the boundary layer, as well as column variables (e.g., precipitation, cloud fraction, precipitating water vapor, downward longwave and shortwave radiation). Moderate to large biases exist for cloud condensation nuclei over oceanic areas, cloud variables (e.g., cloud droplet number concentration, cloud liquid and ice water paths, cloud optical depth, longwave and shortwave cloud forcing). These biases indicate a need to improve the model treatments for cloud processes, especially cloud droplets and ice nucleation, as well as to reduce uncertainty in the satellite retrievals. The model simulates well the column abundances of chemical species except for column SO2 but relatively poor for surface concentrations of several species such as CO, NO2, SO2, PM2.5, and PM10. Several reasons could contribute to the underestimation of major chemical species in East Asia including underestimations of anthropogenic emissions and natural dust emissions, uncertainties in the spatial and vertical distributions of the anthropogenic emissions, as well as biases in meteorological, radiative, and cloud predictions. Despite moderate to large biases in the chemical predictions, the model performance is generally consistent with or even better than that reported for East Asia with only a few exceptions. The model generally reproduces the observed seasonal variations and the difference between 2006 and 2011 for most variables or chemical species. Overall, these results demonstrate promising skills of WRF-CAM5 for long-term simulations at a regional scale and suggest several areas of potential improvements.

An intercomparison of six cloud-resolving and large-eddy simulation models is presented. This case study is based on observations of a persistent mixed-phase boundary layer cloud gathered on 7 May, 1998 from the Surface Heat Budget of Arctic Ocean (SHEBA) and First ISCCP Regional Experiment - Arctic Cloud Experiment (FIRE-ACE). Ice nucleation is constrained in the simulations in a way that holds the ice crystal concentration approximately fixed, with two sets of sensitivity runs in addition to the baseline simulations utilizing different specified ice nucleus (IN) concentrations. All of the baseline and sensitivity simulations group into two distinct quasi-steady states associated with either persistent mixed-phase clouds or all-ice clouds after the first few hours of integration, implying the existence of multiple equilibria. These two states are associated with distinctly different microphysical, thermodynamic, and radiative characteristics. Most but not all of the models produce a persistent mixed-phase cloud qualitatively similar to observations using the baseline IN/crystal concentration, while small increases in the IN/crystal concentration generally lead to rapid glaciation and conversion to the all-ice state. Budget analysis indicates that larger ice deposition rates associated with increased IN/crystal concentrations have a limited direct impact on dissipation of liquid in these simulations. However, the impact of increased ice deposition is greatly enhanced by several interaction pathways that lead to an increased surface precipitation flux, weaker cloud top radiative cooling and cloud dynamics, and reduced vertical mixing, promoting rapid glaciation of the mixed-phase cloud for deposition rates in the cloud layer greater than about 1-2x10-5 g kg-1 s-1. These results indicate the critical importance of precipitation-radiative-dynamical interactions in simulating cloud phase, which have been neglected in previous fixed-dynamical parcel studies of the cloud phase parameter space. Large sensitivity to the IN/crystal concentration also suggests the need for improved understanding of ice nucleation and its parameterization in models.