PECTORAL FROM TOVSTA MOHYLA AS A REMINISCENCE OF THE SHIELD OF ACHILLES: SEARCHING THE ORIGIN OF IDEA

Pectorals in form of breast decoration of a moon-like shape were not peculiar for the Scythian culture. Many ideas on manufacturing the pectoral, which was found by B. Mozolevsky in 1971 during the Tovsta Mohyla excavations, were borrowed by the craftsman from the other culture environment. By the opinion of many researchers, the influence of different traditions of the ancient Greek art is easy-to-see in the pectoral’s composition. Besides, it is inheriting in frieze forming similarelly to sculptural compositions fronton of the Parthenon, borrowing motives of floral ornaments, coin plots etc. But the creative work of the author of pectoral could have been influenced not only by decorative art but the literary monument too. To the latter the Homer’s «Iliad» can be named, especially its 18th playsong, which describes Hephaestus manufacturing the Shield of Achilles. It is interesting that the Pectoral from Tovsta Mohyla was compared with the Shield of Achilles by many researchers (I. V. Yatsenko, L. A. Lelekov and D. S. Rayevsky, V. Y. Mukhaylin). As at its core both Shield of Achilles and the pectoral are pieces of art of high artistic merit, which represent world cosmologic pictures with the help of the opposite action areas made with high relief figures. The breast collars, which are widely known by the findings of Thrace and Macedonia, could lead to generation of ideas that influenced the pectoral’s invention. Such breast collars actually were small hanging shields, which protected in battle the warrior’s weakest spot. By their form and functions they are close to peltes — light skin shields of a moon-like shape. Such peltes were not only well known by toreuts who worked on the Scythians’ orders, but also were recreated by them in battle-pieces on the comb from Soloha and on the calathus from Vylyka Blysnytsya. So it can be considered that the pectoral’s conception was based on the different but connected ideas, borrowed by the craftsman from the military sphere. As a result of the composed transformation of the association chain the Shield of Achilles — Peltes shield — breast collars (or vise versa) and synthesis of several ideas, there was formed a general vision of the pectoral with the corresponding shape, composition structure and separate ornamental patterns.

Pediatric Irritability and Disruptive Behaviors

This chapter describes adaptations made to the Unified Protocol for Transdiagnostic Treatment of Children (UP-C) when treating youth with chronic irritability and/or disruptive behaviors. Despite increased recognition of the clinical importance of pediatric irritability as a transdiagnostic symptom dimension, there is a lack of evidence-based treatments for this population that simultaneously and equitably address both child and contextual (e.g., parental) factors implicated in the development and maintenance of emotional and behavioral difficulties. In this chapter, the authors summarize current treatments available for this patient population, highlighting the advantages of using the UP-C, as it supports the parent–child dyad in addressing coercive interpersonal processes through use of opposite action strategies. A detailed description of how to adapt the UP-C for irritability is provided, including guidance on effective use of frustration exposures to develop mastery of treatment strategies. The chapter concludes with a case example to further illustrate this treatment approach.

Incentive-based extinction of safety behaviors: Positive outcomes competing with aversive events reduce safety behaviors and prevent protection from fear extinction

Maladaptive safety behavior maintains fear and anxiety by prohibiting inhibitory learning about the non-occurrence of feared outcomes (known as protection from extinction). Not engaging in safety behavior, however, requires to act opposite to fear-motivated behavioral tendencies. The initiation of such fear-opposite action by positive outcomes, which were in conflict with safety behavior, was tested. Following fear acquisition to a warning signal (CS+), participants acquired safety behavior to prevent the aversive outcome (N=98). Next, safety behavior also prevented gaining rewards. In a control group, neutral outcomes were presented to control for novelty effects of the second outcome. Subsequently, no aversive outcome occurred anymore. Phases with safety behavior were intermitted by phases without safety behavior to examine cognitive and physiological indicators of fear and anxiety. Without competing positive outcomes, safety behavior was frequently executed, persisted in absence of the aversive outcome, and prohibited extinction learning. Positive outcomes clearly reduced safety behavior despite equal levels of acquired fear. This enabled fear extinction as soon as the aversive outcome was absent. Importantly, this extinction learning resulted in attenuated fear and anxiety responses when safety behavior became unavailable. Post-hoc findings indicated that the mere anticipation of positive outcomes slightly reduced safety behavior. Thus, competing positive outcomes triggered fear-opposite action that prevented persistent safety behavior and protection from extinction.

Relationship of Change in Plasma Clozapine/N-desmethylclozapine Ratio with Cognitive Performance in Patients with Schizophrenia

Objective The clozapine/N-desmethylclozapine (NDMC) ratio is proposed to be used as a predictor of cognitive performance in clozapine-treated patients, as its principal metabolite, NDMC, has an opposite action with clozapine on the cholinergic system. The aim of this study is to determine whether clozapine has influence on cognitive performance in accordance with changes in the clozapine/NDMC in patients with schizophrenia.Methods The data of fifteen patients with schizophrenia, who had initial and follow-up assessments after starting clozapine treatment, were retrospectively collected. The assessments included clinical scale, cognitive battery, and pharmacological data including plasma concentrations of clozapine and NDMC. The data were analyzed with Pearson correlation and stepwise multiple regression analyses.Results ΔAttention/vigilance, Δsocial cognition, and Δcomposite score had a significant correlation with Δclozapine/NDMC ratio, while ΔWorking memory had correlation with Δclozapine concentration and ΔNDMC concentration, and Δsocial cognition had association with Δclozapine concentration. Multiple regression analysis showed that Δattention/vigilance had negative association with Δclozapine/NDMC ratio, Δworking memory had negative relation with Δclozapine concentration, and that Δsocial cognition had negative association with Δclozapine concentration.Conclusion This finding implicates that lowering the clozapine/NDMC ratio could enhance cognition in patients with schizophrenia treated with clozapine.

Recent Approaches to Chiral 1,4-Dihydropyridines and their Fused Analogues

The purpose of this review is to highlight recent developments in the synthesis of chiral 1,4-dihydropyridines and their fused analogues. 1,4-Dihydropyridines are among the most active calcium antagonists that are used for the treatment of hypertension. Enantiomers of unsymmetrical 1,4-dihydropyridines often show different biological activities and may have even an opposite action profile. Hantzsch synthesis usually produces racemic mixtures of unsymmetrical 1,4-dihydropyridines. Therefore, the development of stereoselective synthesis of 1,4-dihydropyridines is one of the priorities of medicinal chemistry. Over the years, numerous methodologies have been developed for the production of enantiopure 1,4-dihydropyridines, such as stereoselective synthesis using chiral auxiliaries and chiral cyclocondensation partners, chromatographical methods, resolution of diastereomeric 1,4-dihydropyridine salts, enzyme catalysed kinetic resolution, or asymmetrisation of ester groups of 1,4-dihydropyridines. These approaches have been studied in detail and are relatively well established. The catalytic asymmetric approach holds the greatest promise in delivering the most practical and widely applicable methods. Substantial progress has been made toward the development of enantioselective organocatalytic methods for the construction of the chiral dihydropyridines. However, most of them do not provide a convenient way to pharmacologically important 1,4-dihydropyridine-3,5-dicarboxylates. Organocatalytic enantioselective desymmetrisation of prochiral 1,4-dihydropyridine-3,5-dicarbaldehydes also has great promise in the synthesis of pharmacologically important 1,4-dihydropyridine-3,5-dicarboxylates.

The Chemistry of Love and Strife

Empedocles managed to reconcile the antinomies between the Heraclitean becoming (the constant change) and the Parmenidean Being (the constancy) by introducing four unchangeable primary substances of matter: earth, water, air, and fire, later called elements, and two types of forces, love and strife. Change was produced when the opposite action of the forces mixed and separated the unchangeable elements in many different ways, an idea in basic agreement with modern chemistry or, more fundamentally, with the standard model of particle physics. Everlasting cosmological cycles, described in his unique cosmology, could have addressed successfully the deceptively simple question, Why is the sky dark at night? (known as Olbers’s paradox), before the cosmology of the big bang had it figured out in the twentieth century. Four primary substances of matter for Empedocles, but infinitely many for the mind of Anaxagoras, and everything is in everything.

TspanC8 tetraspanins differentially regulate ADAM10 endocytosis and half-life

ADAM10 is a transmembrane metalloprotease that is essential for development and tissue homeostasis. It cleaves the ectodomain of many proteins, including amyloid precursor protein, and plays an essential role in Notch signaling. ADAM10 associates with six members of the tetraspanin superfamily referred to as TspanC8 (Tspan5, Tspan10, Tspan14, Tspan15, Tspan17, and Tspan33), which regulate its exit from the endoplasmic reticulum and its substrate selectivity. We now show that ADAM10, Tspan5, and Tspan15 influence each other’s expression level. Notably, ADAM10 undergoes faster endocytosis in the presence of Tspan5 than in the presence of Tspan15, and Tspan15 stabilizes ADAM10 at the cell surface yielding high expression levels. Reciprocally, ADAM10 stabilizes Tspan15 at the cell surface, indicating that it is the Tspan15/ADAM10 complex that is retained at the plasma membrane. Chimeric molecules indicate that the cytoplasmic domains of these tetraspanins contribute to their opposite action on ADAM10 trafficking and Notch signaling. In contrast, an unusual palmitoylation site at the end of Tspan15 C-terminus is dispensable. Together, these findings uncover a new level of ADAM10 regulation by TspanC8 tetraspanins.