Method for Constructing Periodic Solutions of a Controlled Dynamic System with a Cylindrical Phase Space

Journal of Computer and Systems Sciences International - We consider a controlled mechanical system with one degree of freedom described by an angular coordinate. The system is under the action of...     

A Dual Inhibitor of DYRK1A and GSK3β for β-Cell Proliferation: Aminopyrazine Derivative GNF4877

Loss of β-cell mass and function can lead to insufficient insulin levels and ultimately to hyperglycemia and diabetes mellitus. The mainstream treatment approach involves regulation of insulin levels; however, approaches intended to increase β-cell mass are less developed. Promoting β-cell proliferation with low-molecular-weight inhibitors of dual-specificity tyrosine-regulated kinase 1A (DYRK1A) offers the potential to treat diabetes with oral therapies by restoring β-cell mass, insulin content and glycemic control. GNF4877, a potent dual inhibitor of DYRK1A and glycogen synthase kinase 3β (GSK3β) was previously reported to induce primary human β-cell proliferation in vitro and in vivo. Herein, we describe the lead optimization that lead to the identification of GNF4877 from an aminopyrazine hit identified in a phenotypic high-throughput screening campaign measuring β-cell proliferation.     

Towards Diastereomeric Pure Salts with Antisolvent Methods

Chiral molecules, especially enantiomers and diastereomers of purity > 99 %, present a significant market share within the chemical, pharmaceutical, and flavor industries. Antisolvent precipitations, both batch and semicontinuous operations to serve the current trends in flow chemistry were demonstrated to be environmentally benign and efficient tools in achieving high optical purities. Although salts are known to be insoluble in supercritical CO₂, instabilities of the nascent salts were detected and applied for increasing efficiency. Diastereomeric excess values of the crystalline products exceeded 99 % in maximum of three consecutive steps both by repeated resolution with half molar equivalent of the amine to the acid and by direct recrystallization of the salts.     

A simple model for the semicontinuous heterophase polymerization: Ethyl methacrylate as a case example

A simple but comprehensive model considering homogeneous and micellar nucleation, coagulation, entry of radicals to particles and to micelles and radicals' exit from particles, is presented. The model is validated, in a starved semicontinuous heterophase polymerization of ethyl methacrylate, at three monomer addition rates. The model accurately describes the overall and instantaneous conversion, the average particle density and diameter, and the number and weight average molar masses evolutions over time. It is found that even though the average number of radicals is much smaller than 0.5, the system is not 0-1. An empirical function was used to describe the gel effect. The homogeneous nucleation was the prevailing mechanism for particle formation and large exit rates of radicals were observed. POLYM. ENG. SCI., 60: 223–232, 2019. © 2019 Society of Plastics Engineers     

One-Pot Methods for the Protection and Assembly of Sugars

In recent years, there has been rapid expansion of glycan synthesis, fueled by the recognition that the structural complexity of sugars translates to a myriad of biological functions. Such chemical syntheses involve many challenges, mostly due to the regio- and stereochemical aspects of glycosidic bond formation. One-pot strategies were developed to assist in attaining faster and more economical access to the glycan constructs. In this front, achievements in protecting group manipulation, glycosylation, and combinations of these have been reported. Protecting group manipulations in one pot take advantage of the reaction compatibility of commonly used transformations, many of which occur in high regioselectivity. Sequential glycosylations, on the other hand, rely on leaving group orthogonalities and reactivity tuning, as well as the preactivation technique. Altogether, these approaches offer attractive means to the much needed glycan structures and, consequently, help usher in advances in glycoscience.     

Apparent power-law distributions in animal movements can arise from intraspecific interactions

Lévy flights have gained prominence for analysis of animal movement. In a Lévy flight, step-lengths are drawn from a heavy-tailed distribution such as a power law (PL), and a large number of empirical demonstrations have been published. Others, however, have suggested that animal movement is ill fit by PL distributions or contend a state-switching process better explains apparent Lévy flight movement patterns. We used a mix of direct behavioural observations and GPS tracking to understand step-length patterns in females of two related butterflies. We initially found movement in one species (Euphydryas editha taylori) was best fit by a bounded PL, evidence of a Lévy flight, while the other (Euphydryas phaeton) was best fit by an exponential distribution. Subsequent analyses introduced additional candidate models and used behavioural observations to sort steps based on intraspecific interactions (interactions were rare in E. phaeton but common in E. e. taylori). These analyses showed a mixed-exponential is favoured over the bounded PL for E. e. taylori and that when step-lengths were sorted into states based on the influence of harassing conspecific males, both states were best fit by simple exponential distributions. The direct behavioural observations allowed us to infer the underlying behavioural mechanism is a state-switching process driven by intraspecific interactions rather than a Lévy flight.