Free-energy barrier to melting of single-chain polymer crystallite

We report Monte Carlo simulations of the melting of a single-polymer crystallite. We find that, unlike most atomic and molecular crystals, such crystallites can be heated appreciably above their melting temperature before they transform to the disordered "coil" state. The surface of the superheated crystallite is found to be disordered. The thickness of the disordered layer increases with superheating. However, the order-disorder transition is not gradual but sudden. Free-energy calculations reveal the presence of a large free-energy barrier to melting.Comment: AMS-Latex, 4 pages with 5 figures, submitted to Phys. Rev. Let

Lattice model study of the thermodynamic interplay of polymer crystallization and liquid-liquid demixing

We report Monte Carlo simulations of a lattice-polymer model that can account for both polymer crystallization and liquid-liquid demixing in solutions of semiflexible homopolymers. In our model, neighboring polymer segments can have isotropic interactions that affect demixing, and anisotropic interactions that are responsible for freezing. However, our simulations show that the isotropic interactions also have a noticeable effect on the freezing curve, as do the anisotropic interactions on demixing. As the relative strength of the isotropic interactions is reduced, the liquid-liquid demixing transition disappears below the freezing curve. A simple, extended Flory-Huggins theory accounts quite well for the phase behavior observed in the simulations.Comment: Revtex, 7 pages, the content accepted by J. Chem. Phy

State of Utah v. Marie S. McKinnon : Brief of Appellee

BRIEF OF APPELLEE APPEAL FROM THE DISMISSAL OF A CHARGE OF FALSE NOTARIAL CERTIFICATION, A CLASS B MISDEMEANOR, IN THE FIRST JUDICIAL DISTRICT COURT, BOX ELDER COUNTY, THE HONORABLE BEN H. HADFIELD PRESIDIN

<i>GRIN2A</i>-related disorders:genotype and functional consequence predict phenotype

Alterations of the N-methyl-d-aspartate receptor (NMDAR) subunit GluN2A, encoded by GRIN2A, have been associated with a spectrum of neurodevelopmental disorders with prominent speech-related features, and epilepsy. We performed a comprehensive assessment of phenotypes with a standardized questionnaire in 92 previously unreported individuals with GRIN2A-related disorders. Applying the criteria of the American College of Medical Genetics and Genomics to all published variants yielded 156 additional cases with pathogenic or likely pathogenic variants in GRIN2A, resulting in a total of 248 individuals. The phenotypic spectrum ranged from normal or near-normal development with mild epilepsy and speech delay/apraxia to severe developmental and epileptic encephalopathy, often within the epilepsy-aphasia spectrum. We found that pathogenic missense variants in transmembrane and linker domains (misTMD+Linker) were associated with severe developmental phenotypes, whereas missense variants within amino terminal or ligand-binding domains (misATD+LBD) and null variants led to less severe developmental phenotypes, which we confirmed in a discovery (P = 10-6) as well as validation cohort (P = 0.0003). Other phenotypes such as MRI abnormalities and epilepsy types were also significantly different between the two groups. Notably, this was paralleled by electrophysiology data, where misTMD+Linker predominantly led to NMDAR gain-of-function, while misATD+LBD exclusively caused NMDAR loss-of-function. With respect to null variants, we show that Grin2a+/- cortical rat neurons also had reduced NMDAR function and there was no evidence of previously postulated compensatory overexpression of GluN2B. We demonstrate that null variants and misATD+LBD of GRIN2A do not only share the same clinical spectrum (i.e. milder phenotypes), but also result in similar electrophysiological consequences (loss-of-function) opposing those of misTMD+Linker (severe phenotypes; predominantly gain-of-function). This new pathomechanistic model may ultimately help in predicting phenotype severity as well as eligibility for potential precision medicine approaches in GRIN2A-related disorders

Upscaling of the hot-melt extrusion process: Comparison between laboratory scale and pilot scale production of solid dispersions with miconazole and Kollicoat IR

Since only limited amount of drug is available in early development stages, the extruder design has evolved towards smaller batch sizes, with a more simple design. An in dept study about the consequences of the differences in design is mandatory and little can be found in literature. Miconazole and Kollicoat IR were used as model drug and carrier for this study. Two series of solid dispersions were made with a laboratory scale (internal circulation-simple screw design) and a pilot scale extruder (continuous throughput-modular screw design). Efforts were made to match the operating parameters as close as possible (residence time, extrusion temperature and screw speed). The samples were analyzed with modulated DSC straight after production and after exact 24h and 15 days storage at -26 °C. The kinetic miscibility of the samples prepared with the laboratory scale extruder was slightly higher than the samples prepared with the pilot scale extruder. As the solid dispersions with high drug load were unstable over time, demixing occurred, slightly faster for the samples prepared with the laboratory scale extruder. After 15 days, the levels of molecular mixing were comparable, pointing to the predictive value of samples prepared on laboratory scale.status: publishe

The Morphological Response of Semicrystalline Polymers to Small Oscillatory Temperature Perturbations

status: publishe