Will California\u27s One Strike Law Stop Sexual Predators, or is a Civil Commitment System Needed?

This Comment urges California and other jurisdictions to enact sexual predator laws to civilly commit dangerous, mentally ill sex offenders who are nearing release from prison and are a credible threat to re-offend. The author propounds a Model Sexual Predators Act, which is argued to be narrowly tailored to achieve the state goal, as required by the Constitution. The author also argues that this Model Act surmounts substantive and procedural due process concerns, increases the safety of the public, and safeguards the accused individual\u27s interest in liberty

Novel Nanomolar Allosteric Modulators of AMPA Receptor of Bis(pyrimidine) Series: Synthesis, Biotesting and SAR Analysis

Positive allosteric modulators (PAMs) of AMPA receptors represent attractive candidates for the development of drugs for the treatment of cognitive and neurodegenerative disorders. Dimeric molecules have been reported to have an especially potent modulating effect, due to the U-shaped form of the AMPA receptor’s allosteric binding site. In the present work, novel bis(pyrimidines) were studied as AMPA receptor modulators. A convenient and flexible preparative approach to bis(pyrimidines) containing a hydroquinone linker was elaborated, and a series of derivatives with varied substituents was obtained. The compounds were examined in the patch clamp experiments for their influence on the kainate-induced currents, and 10 of them were found to have potentiating properties. The best potency was found for 2-methyl-4-(4-((2-methyl-5,6,7,8-tetrahydroquinazolin-4-yl)oxy)phenoxy)-6,7,8,9-tetrahydro-5H-cyclohepta[d]pyrimidine, which potentiated the kainate-induced currents by up to 77% in all tested concentrations (10−12–10−6 M). The results were rationalized via the modeling of modulator complexes with the dimeric ligand binding domain of the GluA2 AMPA receptor, using molecular docking and molecular dynamics simulation. The prediction of ADMET, physicochemical, and PAINS properties of the studied bis(pyrimidines) confirmed that PAMs of this type may act as the potential lead compounds for the development of neuroprotective drugs

A reflection on adaptability, achievement motivation and success of Central and Eastern European students in one English university

This article focuses Central and Eastern European (CEE) students’ adaptability and achievement in one English post-1992 university. There are few studies that discuss values, beliefs, attitudes and needs as well as achievement (and factors contributing to it) between CEE and other learners. Since the expansion of the European Union, CEE students’ presence in British higher education has become more pronounced. CEE learners are treated as home students and yet they come from a distinctively different socio-historical background and pedagogic tradition, which is, to a certain extent, common in CEE countries as a result of the sovietisation of education systems within post communistic countries of Central and Eastern Europe. In the British higher education sector there is a move in curriculum delivery towards more personalised learning, which underlines that effective teaching and learning starts with understanding the individual student. Therefore, it is important that universities with a high proportion of EU students attempt to understand where CEE students come from and what their aspirations might be. This article attempts to provide some insights into CEE learners’ values, attitudes and motivations to learn and looks for possible reasons for their success

A Facile Approach to Bis(isoxazoles), Promising Ligands of the AMPA Receptor

A convenient synthetic approach to novel functionalized bis(isoxazoles), the promising bivalent ligands of the AMPA receptor, was elaborated. It was based on the heterocyclization reactions of readily available electrophilic alkenes with the tetranitromethane-triethylamine complex. The structural diversity of the synthesized compounds was demonstrated. In the electrophysiological experiments using the patch clamp technique on Purkinje neurons, the compound 1,4-phenylenedi(methylene)bis(5-aminoisoxazole-3-carboxylate) was shown to be highly potent positive modulator of the AMPA receptor, potentiating kainate-induced currents up to 70% at 10−11 M

New Adamantane-Containing Edaravone Conjugates as Potential Neuroprotective Agents for ALS Treatments

Currently, there are no effective drugs for the treatment of amyotrophic lateral sclerosis (ALS). Only two drugs—edaravone and riluzole—have been approved, but they have very limited efficacy. The aim of this work was to modify the structural core of the Edaravone—phenylpyrazolone moiety and combine it with aminoadamantane pharmacophore in order to expand the spectrum of its action to a number of processes involved in the pathogenesis of ALS. New conjugates of edaravone derivatives with 1-aminoadamantanes combined with alkylene or hydroxypropylene spacers were synthesized, and their biological activity was investigated. Compounds were found that could inhibit lipid peroxidation and calcium-related mitochondrial permeability, block fast sodium currents of CNS neurons, and reduce aggregation of the mutated form of the FUS-protein typical to ALS. So, the proposed modification of the edaravone molecule has allowed the obtaining of new original structures that combine some prospective therapeutic mechanisms against key chains of the pathogenesis of ALS. The identified lead compounds can be used for further optimization and development of new promising drugs on this basis for the treatment of ALS