16 research outputs found
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
<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