In chemical kinetics research, kinetic models containing hundreds of species and tens of thousands of elementary reactions are commonly used to understand and predict the behavior of reactive chemical systems. Reaction Mechanism Generator (RMG) is a software suite developed to automatically generate such models by incorporating and extrapolating from a database of known thermochemical and kinetic parameters.Here, we present the recent version 3 release of RMG and highlight improvements since the previously published description of RMG v1.0. One important change is that RMG v3.0 is now Python 3 compatible, which supports the most up-to-date versions of cheminformatics and machine learning packages that RMG depends on. Additionally, RMG can now generate heterogeneous catalysis models, in addition to the previously available gas-and liquid-phase capabilities. For model analysis, new methods for local and global uncertainty analysis have been implemented to supplement first-order sensitivity analysis. The RMG database of thermochemical and kinetic parameters has been significantly expanded to cover more types of chemistry. The present release also includes parallelization for reaction generation and on-the-fly quantum calculations, and a new molecule isomorphism approach to improve computational performance. Overall, RMG v3.0 includes many changes which improve the accuracy of the generated chemical mechanisms and allow for exploration of a wider range of chemical systems.

This perspective gives our views on general aspects and future directions of gasphase atmospheric chemical kinetic mechanism development, emphasizing on the work needed for the sustainable development of chemically detailed mechanisms that reflect current kinetic, mechanistic, and theoretical knowledge. Current and future mechanism development efforts and research needs are discussed, including software-aided autogeneration and maintenance of kinetic models as a future-proof approach for atmospheric model development. There is an overarching need for the evaluation and extension of structure-activity relationships (SARs) that predict the properties and reactions of the many multifunctionalized compounds in the atmosphere that are at the core of detailed mechanisms, but for which no direct chemical data are available. Here, we discuss the experimental and theoretical data needed to support the development of mechanisms and SARs, the types of SARs relevant to atmospheric chemistry, the current status and limitations of SARs for various types of atmospheric reactions, the status of thermochemical estimates needed for mechanism development, and our outlook for the future. The authors have recently formed a SAR evaluation working group to address these issues. C

Continuous manufacturing (CM) is an emerging technology in the pharmaceutical manufacturing sector, and the understanding of the impact on product quality is currently evolving. As the final purification and isolation step, crystallization has a significant impact on the final physicochemical properties of drug substance and is considered a critical process step in achieving the continuous manufacturing of drug substances. Although many publications previously focused on various innovative techniques to continuously make crystals with desired properties, engineering difficulties such as system design, automation, and integration with process analytical technology (PAT) tools have not been thoroughly discussed. Here, we focus on how to develop a continuous crystallization system, from the perspective of process engineering, and the related risk considerations on product quality. Specifically, we designed and built an automated two-stage mixed suspension mixed product removal (MSMPR) crystallization platform for a model compound (carbamazepine, CBZ) that exhibits multiple polymorphs. The crystallization process includes the integration of PAT tools (online Raman microscopy and focused beam reflectance microscopy, FBRM) for real-time monitoring. A series of case studies were done to evaluate the performance of the continuous system and PAT tools. Specifically, the drawing schemes, slurry transport, and variations on process variables are considered as the three key risk areas for continuous crystallization process development. Our proof-of-concept continuous crystallization system uses feedback/feedforward controls to achieve constant levels in crystallizers, a centralized automation program coded in LabVIEW, and PAT monitoring for polymorphs and particle size distribution (Raman and FBRM). To the best of our knowledge, this is also the first study on continuous crystallization of carbamazepine for form III and its polymorphic transition (between form II and form III).

Computed tomographic (CT) scans of 34 cases of abdominal fatty masses were reviewed retrospectively in order to establish criteria for distinguishing benign conditions from malignant tumors. By evaluating location, attenuation, internal consistency, and margination, it is possible not only to make this distinction but frequently to suggest a specific diagnosis. Abdominal fatty masses that are sharply marginated, homogeneous, and that show CT numbers less than or equal to the patient's normal fat can be considered benign. Malignancy should be suspected when an extrarenal abdominal fatty mass displays one or more of the following characteristics: inhomogeneity, infiltration or poor margination, CT numbers greater than the patient's normal fat, or contrast enhancement. Criteria for distinguishing between angiomyolipoma and liposarcoma are also discussed.

Enzyme encapsulation is a simple, gentle, and general method for immobilizing enzyme, but it often suffers from one or more problems regarding enzyme loading efficiency, enzyme leakage, mechanical stability, and recyclability. Here we report a novel, simple, and efficient method for enzyme encapsulation to overcome these problems by forming stable organic-inorganic hybrid capsules. A new, facile, one-step, and template-free synthesis of organic-inorganic capsules in aqueous phase were developed based on PEI-induced simultaneous interfacial self-assembly of Fmoc-FF and polycondensation of silicate. Addition of an aqueous solution of Fmoc-FF and sodium silicate into an aqueous solution of PEI gave a new class of organic-inorganic hybrid capsules (FPSi) with multi-layered structure in high yield. The capsules are mechanically stable due to the incorporation of inorganic silica. Direct encapsulation of enzyme such as epoxide hydrolase SpEH and BSA along with the formation of the organic-inorganic capsules gave high yield of enzyme-containing capsules (∼1.2 mm in diameter), >90% enzyme loading efficiency, high specific enzyme loading (158 mg protein g(-1) carrier), and low enzyme leakage (<3% after 48 h incubation). FPSi-SpEH capsules catalyzed the hydrolysis of cyclohexene oxide to give (1R, 2R)-cyclohexane-1,2-diol in high yield and concentration, with high specific activity (6.94 U mg(-1) protein) and the same high enantioselectivity as the free enzyme. The immobilized SpEH demonstrated also excellent operational stability and recyclability: retaining 87% productivity after 20 cycles with a total reaction time of 80 h. The new enzyme encapsulation method is efficient, practical, and also better than other reported encapsulation methods.