A 40-week phase 2B randomized, multicenter, double-blind, placebo-controlled study evaluating the safety and efficacy of memantine in amyotrophic lateral sclerosis.

Introduction: Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disease with no known cure, limited treatment options with minimal benefits, and significant unmet need for disease modifying therapies.

Aims: This study investigated memantine's impact on ALS progression, with an additional focus on the effects of memantine on cognitive and behavioral changes associated with the disease.

Methods: A randomized, double-blind, placebo-controlled clinical trial was conducted from December 2018 to September 2020.

Identification of 5-HT receptor signaling pathways associated with psychedelic potential.

Serotonergic psychedelics possess considerable therapeutic potential. Although 5-HT receptor activation mediates psychedelic effects, prototypical psychedelics activate both 5-HT-Gq/11 and β-arrestin2 transducers, making their respective roles unclear. To elucidate this, we develop a series of 5-HT-selective ligands with varying Gq efficacies, including β-arrestin-biased ligands.

Identification of 5-HT Receptor Signaling Pathways Responsible for Psychedelic Potential.

Serotonergic psychedelics possess considerable therapeutic potential. Although 5-HT receptor activation mediates psychedelic effects, prototypical psychedelics activate both 5-HT-Gq/11 and β-arrestin2 signaling, making their respective roles unclear. To elucidate this, we developed a series of 5-HT-selective ligands with varying Gq efficacies, including β-arrestin-biased ligands.

Phase 2 trial in acetylcholine receptor antibody-positive myasthenia gravis of transition from intravenous to subcutaneous immunoglobulin: The MGSCIg study.

Background And Purpose: Data on maintenance therapy with subcutaneous immunoglobulin (SCIg) in myasthenia gravis (MG) are limited. We report on transitioning acetylcholine receptor (AChR) antibody-positive (Ab+) MG patients on stable intravenous immunoglobulin (IVIg) regimens as part of routine clinical care to SCIg 1:1.2.

Methotrexate Polyglutamation in a Myasthenia Gravis Clinical Trial.

Introduction: Methotrexate (MTX) is an immunosuppressive and anti-inflammatory drug used to treat rheumatoid arthritis (RA) and other autoimmune conditions. MTX is transported into cells, where glutamate moieties are added and is retained as methotrexate polyglutamates (MTXPGs). In the RA literature, it has been reported that the degree of polyglutamation correlates with the anti-inflammatory effect of MTX in RA.

A Randomized, Double-Blinded, Placebo-Controlled, Cross Over Study Evaluating the Efficacy and Safety of Timolol Ophthalmic Solution as an Acute Treatment of Migraine.

Introduction: Daily oral beta-adrenoreceptor antagonist has been shown to be effective in preventing migraine headaches. Timolol 0.5% ophthalmic solution is a non-selective beta-adrenoreceptor antagonist, where the primary use is for glaucoma.

Improving homology modeling of G-protein coupled receptors through multiple-template derived conserved inter-residue interactions.

Evidenced by the three-rounds of G-protein coupled receptors (GPCR) Dock competitions, improving homology modeling methods of helical transmembrane proteins including the GPCRs, based on templates of low sequence identity, remains an eminent challenge. Current approaches addressing this challenge adopt the philosophy of "modeling first, refinement next". In the present work, we developed an alternative modeling approach through the novel application of available multiple templates.

Developing a high-quality scoring function for membrane protein structures based on specific inter-residue interactions.

Membrane proteins are of particular biological and pharmaceutical importance, and computational modeling and structure prediction approaches play an important role in studies of membrane proteins. Developing an accurate model quality assessment program is of significance to the structure prediction of membrane proteins. Few such programs are proposed that can be applied to a broad range of membrane protein classes and perform with high accuracy.

Molecular dynamics simulations of detonation instability.

After making modifications to the reactive empirical bond-order potential for molecular dynamics (MD) of Brenner et al. [Phys. Rev.

Interaction potential for atomic simulations of conventional high explosives.

In an effort to develop a chemically reactive interaction potential suitable for application to the study of conventional, organic explosives, we have modified the diatomic AB potential of Brenner et al. [Phys. Rev.

Influence of interatomic bonding potentials on detonation properties.

The dependences of the macroscopic detonation properties of a two-dimensional (2D) diatomic (AB) molecular system on the fundamental molecular properties were investigated. This includes examining the detonation velocity, reaction zone thickness, and critical width as functions of the exothermicity (Q) of the gas-phase reaction [AB --> (1/2)(A(2) + B(2))] and the gas-phase dissociation energy (D(e)(AB)) for AB --> A + B . Following previous work, molecular dynamics (MD) simulations with a reactive empirical bond-order potential were used to characterize the shock-induced response of a diatomic AB molecular solid, which exothermically reacts to produce A2 and B2 gaseous products.