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The scale-aware convective parameterization for high resolution global climate models must satisfy the requirement that the parameterized subgrid convective transport diminishes as the model resolution increases to convection-resolving resolutions. A major assumption in current scale-aware convection schemes is that the differences between convective cloud properties and their environmental counterparts are independent of cloud fraction. This study examines convective cloud vertical velocity, moist static energy (MSE), moisture, and the vertical eddy transport of MSE and moisture for different averaging subdomain sizes and fractional convective cloudiness using a cloud resolving model simulation of a midlatitude mesoscale convective system. Results show that convective cloud fraction, mass flux, and vertical transport of MSE and moisture increase with decreasing subdomain size. The differences between convective cloud properties in both updrafts and downdrafts and their environment depend on both cloud fraction and the averaging subdomain size. For a given subdomain size, the differences increase with cloud fraction, in contrast to the assumption used in current scale-aware convection parameterization schemes. A consequence of this is that the parameterized convective eddy transport reaches maximum at a higher cloud fraction than believed in previous studies. This has implications on how fast the subgrid convective transport should diminish as GCM resolution increases. [ABSTRACT FROM AUTHOR]

Cocrystals are of much interest in industrial application as well as academic research, and screening of suitable coformers for active pharmaceutical ingredients is the most crucial and challenging step in cocrystal development. Recently, machine learning techniques are attracting researchers in many fields including pharmaceutical research such as quantitative structure-activity/property relationship. In this paper, we develop machine learning models to predict cocrystal formation. We extract descriptor values from simplified molecular-input line-entry system (SMILES) of compounds and compare the machine learning models by experiments with our collected data of 1476 instances. As a result, we found that artificial neural network shows great potential as it has the best accuracy, sensitivity, and F1 score. We also found that the model achieved comparable performance with about half of the descriptors chosen by feature selection algorithms. We believe that this will contribute to faster and more accurate cocrystal development. [ABSTRACT FROM AUTHOR]

This study estimates entrainment rate and investigates its relationships with cloud properties in 156 deep convective clouds based on in-situ aircraft observations during the TOGA-COARE (Tropical Ocean Global Atmosphere Coupled Ocean Atmosphere Response Experiment) field campaign over the western Pacific. To the authors' knowledge, this is the first study on the probability density function of entrainment rate, the relationships between entrainment rate and cloud microphysics, and the effects of dry air sources on the calculated entrainment rate in deep convection from an observational perspective. Results show that the probability density function of entrainment rate can be well fitted by lognormal, gamma or Weibull distribution, with coefficients of determination being 0.82, 0.85 and 0.80, respectively. Entrainment tends to reduce temperature, water vapor content and moist static energy in cloud due to evaporative cooling and dilution. Inspection of the relationships between entrainment rate and microphysical properties reveals a negative correlation between volume-mean radius and entrainment rate, suggesting the potential dominance of homogeneous mechanism in the clouds examined. In addition, entrainment rate and environmental water vapor content show similar tendencies of variation with the distance of the assumed environmental air to the cloud edges. Their variation tendencies are non-monotonic due to the relatively short distance between adjacent clouds. [ABSTRACT FROM AUTHOR]

In recent research on the formulation prediction of oral dissolving drugs, deep learning models with significantly improved performance compared to machine learning models were proposed. However, the performance degradation due to limitations of an imbalanced dataset with a small size and inefficient neural network structure has still not been resolved. Therefore, we propose new deep learning-based prediction models that maximize the prediction performance for disintegration time of oral fast disintegrating films (OFDF) and cumulative dissolution profiles of sustained-release matrix tablets (SRMT). In the case of OFDF, we use principal component analysis (PCA) to reduce the dimensionality of the dataset, thereby improving the prediction performance and reducing the training time. In the case of SRMT, the Wasserstein generative adversarial network (WGAN), a neural network-based generative model, is used to overcome the limitation of performance improvement due to the lack of experimental data. To the best of our knowledge, this is the first work that utilizes WGAN for pharmaceutical formulation prediction. Experimental results show that the proposed methods have superior performance than the existing methods for all the performance metrics considered. [ABSTRACT FROM AUTHOR]

Vonoprazan (VPZ) is the first-in-class potassium-competitive acid blocker (P-CAB), and has many advantages over proton pump inhibitors (PPIs). It is administered as a fumarate salt for the treatment of acid-related diseases, including reflux esophagitis, gastric ulcer, and duodenal ulcer, and for eradication of Helicobacter pylori. To discover novel cocrystals of VPZ, we adopted an artificial neural network (ANN)-based machine learning model as a virtual screening tool that can guide selection of the most promising coformers for VPZ cocrystals. Experimental screening by liquid-assisted grinding (LAG) confirmed that 8 of 19 coformers selected by the ANN model were likely to create new solid forms with VPZ. Structurally similar benzenediols and benzenetriols, i.e., catechol (CAT), resorcinol (RES), hydroquinone (HYQ), and pyrogallol (GAL), were used as coformers to obtain phase pure cocrystals with VPZ by reaction crystallization. We successfully prepared and characterized three novel cocrystals: VPZ–RES, VPZ–CAT, and VPZ–GAL. VPZ–RES had the highest solubility among the novel cocrystals studied here, and was even more soluble than the commercially available fumarate salt of VPZ in solution at pH 6.8. In addition, novel VPZ cocrystals had superior stability in aqueous media than VPZ fumarates, demonstrating their potential for improved pharmaceutical performance. [ABSTRACT FROM AUTHOR]

Malaria remains by far one of the most threatening and dangerous illnesses caused by the plasmodium falciparum parasite. Chloroquine (CQ) and first-line artemisinin-based combination treatment (ACT) have long been the drug of choice for the treatment and controlling of malaria; however, the emergence of CQ-resistant and artemisinin resistance parasites is now present in most areas where malaria is endemic. In this work, we developed five machine learning models to predict antimalarial bioactivities of a drug against plasmodium falciparum from the features (i.e., molecular descriptors values) obtained from PaDEL software from SMILES of compounds and compare the machine learning models by experiments with our collected data of 4794 instances. As a consequence, we found that three models amongst the five, namely artificial neural network (ANN), extreme gradient boost (XGB), and random forest (RF), outperform the others in terms of accuracy while observing that, using roughly a quarter of the promising descriptors picked by the feature selection algorithm, the five models achieved equivalent and comparable performance. Nevertheless, the contribution of all molecular descriptors in the models was investigated through the comparison of their rank values by the feature selection algorithm and found that the most potent and relevant descriptors which come from the 'Autocorrelation' module contributed more while the 'Atom type electrotopological state' contributed the least to the model. [ABSTRACT FROM AUTHOR]

Even with ever-increasing societal interest in tornado activities engendering catastrophes of loss of life and property damage, the long-term change in the geographic location and environment of tornado activity centers over the last six decades (1954–2018), and its relationship with climate warming in the U.S., is still unknown or not robustly proved scientifically. Utilizing discriminant analysis, we show a statistically significant geographic shift of U.S. tornado activity center (i.e., Tornado Alley) under warming conditions, and we identify five major areas of tornado activity in the new Tornado Alley that were not identified previously. By contrasting warm versus cold years, we demonstrate that the shift of relative warm centers is coupled with the shifts in low pressure and tornado activity centers. The warm and moist air carried by low-level flow from the Gulf of Mexico combined with upward motion acts to fuel convection over the tornado activity centers. Employing composite analyses using high resolution reanalysis data, we further demonstrate that high tornado activities in the U.S. are associated with stronger cyclonic circulation and baroclinicity than low tornado activities, and the high tornado activities are coupled with stronger low-level wind shear, stronger upward motion, and higher convective available potential energy (CAPE) than low tornado activities. The composite differences between high-event and low-event years of tornado activity are identified for the first time in terms of wind shear, upward motion, CAPE, cyclonic circulation and baroclinicity, although some of these environmental variables favorable for tornado development have been discussed in previous studies. [ABSTRACT FROM AUTHOR]

In this study, a WRF (Weather Research and Forecasting) model is used as a cloud-resolving model to simulate a squall line observed on 20 May 2011 in the Southern Great Plains (SGP) of the United States. The model output is then used to examine the relationships between convective precipitation and coarse-grained variables averaged over a range of subdomain sizes equivalent to various global climate model horizontal resolutions. The objective is to determine to what extent convection within the subdomains can be related to these "large-scale" variables, thus that they can potentially serve as closure in convective parameterization. Results show that convective precipitation is well correlated with the vertical velocity at 500 hPa, column integrated moisture convergence and CAPE change due to large-scale advective forcing (dCAPE) for various subdomain sizes, but the correlation decreases with decreasing subdomain size. dCAPE leads convective precipitation for all subdomain sizes examined; however, the lead time decreases with decreasing subdomain size. Moisture convergence leads convective precipitation for subdomain sizes greater than 32 km but has no lead time for smaller subdomain sizes. Mid-tropospheric vertical velocity has no lead time or slightly lags convective precipitation. The lead/lag composite analysis with respect to maximum precipitation time indicates that peaks of large-scale variables increase with decreasing subdomain size. The peaks of 500 hPa vertical velocity and column integrated moisture convergence occur at the same time as maximum precipitation, but maximum dCAPE leads maximum precipitation by twelve minutes. [ABSTRACT FROM AUTHOR]

Background: The genetic background of Toll-like receptor 4 (TLR4) proved to be important in the induction of immune protection against Bordetella pertussis infection in humans. Currently, the evaluation of the acellular pertussis (aP) vaccine depends largely on using different mouse strains, while the TLR4 genotype of different mouse strains in response to pertussis toxin (PT) is not carefully determined. The current study was designed to determine the differences in TLR4 genotype and TLR4 pathway-related cytokines in response to PT stimulation among mouse strains of ICR, NIH, and BALB/c., Method: We first determined the single-nucleotide polymorphisms (SNPs) in the TLR4 gene by using first-generation sequencing. Then, the cellular response, including the TLR4 mRNA expression and TLR4 signaling-related cytokines, of immune cells from different mouse strains after PT stimulation was determined., Result: Three missense mutation sites (rs13489092, rs13489093, rs13489097) of the TLR4 gene were found. ICR mice were homozygous without mutation, NIH mice were partially heterozygous, and BALB/c mice were homozygous with a missense mutation. The expression of TLR4 was repressed while the downstream cytokines were upregulated after PT stimulation differently among mouse strains. The IFN-β cytokine of the TRIF pathway was significantly increased in ICR mice ( p < 0.05). The IL-6 cytokine of the MyD88-dependent pathway was significantly increased in BALB/c mice ( p < 0.05). The identified SNPs of the TLR4 gene in different mouse strains might account for the differences in cytokines levels determined after PT stimulation., Conclusions: Our studies might provide useful referees to reduce the mouse-derived difference in the determination of vaccine titer and increase the comparability of the vaccine from different origins, as different mouse strains were used for vaccine development in different countries.

An empirical model to estimate global solar radiation was developed at Qomolangma Station using observed solar radiation and meteorological parameters. The predicted hourly global solar radiation agrees well with observations at the ground in 2008-2011. This model was used to calculate global solar radiation at the ground and its loss in the atmosphere due to absorbing and scattering substances in 2007-2020. A sensitivity analysis shows that the responses of global solar radiation to changes in water vapor and scattering factors (expressed as water-vapor pressure and the attenuation factor, AF, respectively) are nonlinear, and global solar radiation is more sensitive to changes in scattering than to changes in absorption. Further applying this empirical model, the albedos at the top of the atmosphere (TOA) and the surface in 2007-2020 were computed and are in line with satellite-based retrievals. During 2007-2020, the mean estimated annual global solar radiation increased by 0.22% per year, which was associated with a decrease in AF of 1.46% and an increase in water-vapor pressure of 0.37% per year. The annual mean air temperature increased by about 0.16 °C over the 14 years. Annual mean losses of solar radiation caused by absorbing and scattering substances and total loss were 2.55, 0.64, and 3.19 MJ m -2 , respectively. The annual average absorbing loss was much larger than the scattering loss; their contributions to the total loss were 77.23% and 22.77%, indicating that absorbing substances play significant roles. The annual absorbing loss increased by 0.42% per year, and scattering and total losses decreased by 2.00% and 0.14% per year, respectively. The estimated and satellite-derived annual albedos increased at the TOA and decreased at the surface. This study shows that solar radiation and its interactions with atmospheric absorbing and scattering substances have played key but different roles in regional climate and climate change at the three poles.