Acylindrically hyperbolic groups with exotic properties

We prove that every countable family of countable acylindrically hyperbolic groups has a common finitely generated acylindrically hyperbolic quotient. As an application, we obtain an acylindrically hyperbolic group $Q$ with strong fixed point properties: $Q$ has property $FL^p$ for all $p\in [1, +\infty)$, and every action of $Q$ on a finite dimensional contractible topological space has a fixed point. In addition, $Q$ has other properties which are rather unusual for groups exhibiting "hyperbolic-like" behaviour. E.g., $Q$ is not uniformly non-amenable and has finite generating sets with arbitrary large balls consisting of torsion elements

Synthetic Approaches to Novel Pyridine and Indole Derivatives as Potential Agents for the Treatment of Neurodegenerative Disorders

Alzheimer’s Disease (AD), Parkinson’s Disease (PD) and Lewy Body Disease (LBD) are some of the many neurodegenerative disorders associated with dementia, for which there is no ultimate cure. It is widely accepted that central nervous system (CNS) nicotinic acetylcholine receptors (nAChRs) may be strongly implicated in the pathology of these devastating disorders, and that stimulation of nAChRs can enhance cognitive behaviour in animals and humans. Nicotine and other nicotinic receptor binding compounds have, over many years, been explored as potential therapies for disorders such as AD and PD. This thesis describes the preparation and pharmacological investigation of a series of 3- substituted and 3,5-disubstitued pyridine derivatives as potential novel and selective nictotinic receptor agonists. Chapter Two details the synthesis of targeted compounds using the generation of [(pyridin-3-yl)methyl]lithium and [(5-methylpyridin-3- yl)methyl]lithium, respectively and subsequent reaction with various electrophiles. Unsuccessful attempts at the synthesis of enantiomerically pure 4-substituted arylpyridin-3-yl-ethanol derivatives by reduction of prochiral 4-substituted arylpyridin-3-yl-ethanone derivatives were made using both catalytic and enzymatic approaches; however, a pair of enantiomerically pure alcohols were isolated via the resolution of diastereomeric esters (prepared by reaction with (S)-O-acetyl mandelic acid) and subsequent hydrolysis. iv Chapter Three explores the synthesis of targeted compounds using halogen-lithium exchange reactions of 3-bromopyridine using n-BuLi and ring-opening by the resultant pyridin-3-yllithium of 4-substituted aryl epoxides. As an extension, Sonogashira cross-coupling of 3- bromopyridine and 4-substituted arylacetylenes and subsequent hydration as an approach to 4-substituted pyridin-3-yl-ethanone derivatives is described. A series of indole derivatives were synthesised using identical approaches. Using methodology developed in previous Chapters, Chapter Four describes approaches to symmetrical and asymmetrical 3,5- bis(arylethynyl)pyridine derivatives, the corresponding bis(ketones), alcohols and 3,5-disubstituted keto-alcohol products. Chapter Five details preliminary pharmacological data (binding and functional assays) performed by our collaborators at Institut de Recherches Servier

Sex-Specific Effects of a Wartime-Like Radiation Exposure on Cognitive Function.

Evaluating the risk for central nervous system (CNS) effects after whole-body or partial-body irradiation presents challenges due in part to the varied exposure scenarios in the context of occupational, accidental or wartime releases. Risk estimations are further complicated by the fact that robust changes in brain function are unlikely to manifest until significantly late post exposure times. Collectively, the current data regarding CNS radiation risk are conflicting in humans and a survey of the animal model data shows that it is similarly inconsistent. Due to the sparseness of such data, the current study was conducted using male and female mice to evaluate the brain for the delayed effects of a 2 Gy whole-body exposure to c rays starting six months postirradiation. Behavioral testing indicated sex-specific differences in the induction of anxiety-like behaviors and in the ability to abolish fear memories. Molecular analyses showed alterations in post-synaptic protein levels that might affect synaptic plasticity and increased levels of global DNA methylation, suggesting a potential epigenetic mechanism that might contribute to radiation-induced cognitive dysfunction. These data add to the understanding of the CNS response to whole-body irradiation and may lead to improved risk assessment and provide guidance in the development of effective radiation countermeasures to protect military personnel and civilians alike

Social guarantees of the status of disabled in constitutional texts of the CIS countries

In the article, based on the analysis of constitutional texts of CIS countries to reflect the social guarantees of persons with disabilities in them, the socially-guaranteeing and social-status models of such consolidation are identifie

Logical classification of legal procedural restrictions

This paper on the basis of analytical and synthesis research of a wide range of sources presents an approach to the classification of legal procedural restrictions, based on the division of the object by the modification of the feature at the basis of such divisio

Ampk regulates IgD expression but not energy stress with B cell activation.

Ampk is an energy gatekeeper that responds to decreases in ATP by inhibiting energy-consuming anabolic processes and promoting energy-generating catabolic processes. Recently, we showed that Lkb1, an understudied kinase in B lymphocytes and a major upstream kinase for Ampk, had critical and unexpected roles in activating naïve B cells and in germinal center formation. Therefore, we examined whether Lkb1 activities during B cell activation depend on Ampk and report surprising Ampk activation with in vitro B cell stimulation in the absence of energy stress, coupled to rapid biomass accumulation. Despite Ampk activation and a controlling role for Lkb1 in B cell activation, Ampk knockout did not significantly affect B cell activation, differentiation, nutrient dynamics, gene expression, or humoral immune responses. Instead, Ampk loss specifically repressed the transcriptional expression of IgD and its regulator, Zfp318. Results also reveal that early activation of Ampk by phenformin treatment impairs germinal center formation but does not significantly alter antibody responses. Combined, the data show an unexpectedly specific role for Ampk in the regulation of IgD expression during B cell activation

Automorphisms of Partially Commutative Groups II: Combinatorial Subgroups

We define several "standard" subgroups of the automorphism group Aut(G) of a partially commutative (right-angled Artin) group and use these standard subgroups to describe decompositions of Aut(G). If C is the commutation graph of G, we show how Aut(G) decomposes in terms of the connected components of C: obtaining a particularly clear decomposition theorem in the special case where C has no isolated vertices. If C has no vertices of a type we call dominated then we give a semi-direct decompostion of Aut(G) into a subgroup of locally conjugating automorphisms by the subgroup stabilising a certain lattice of "admissible subsets" of the vertices of C. We then characterise those graphs for which Aut(G) is a product (not necessarily semi-direct) of two such subgroups.Comment: 7 figures, 63 pages. Notation and definitions clarified and typos corrected. 2 new figures added. Appendix containing details of presentation and proof of a theorem adde

Legal form of action: the issues of content and methodology

Based on the examination of a wide range of sources, this paper presents the author’s opinion on certain essential characteristics of the legal form of action in the context of the general theory of law and the state. This work outlines and systematically studies procedural proceedings, procedural stages, and procedural regime as the fundamental components, which are essential for the knowledge of the content of the legal form of actio