Mixed Valence {Ni²⁺Ni¹⁺} Clusters as Models of Acetyl Coenzyme ASynthase Intermediates

Acetyl coenzyme A synthase (ACS) catalyzes the formation and deconstruction of the key biological metabolite, acetyl coenzyme A (acetyl-CoA). The active site of ACS features a {NiNi} cluster bridged to a [Fe4S4]n+ cubane known as the A-cluster. The mechanism by which the A-cluster functions is debated, with few model complexes able to replicate the oxidation states, coordination features, or reactivity proposed in the catalytic cycle. In this work, we isolate the first bimetallic models of two hypothesized intermediates on the paramagnetic pathway of the ACS function. The heteroligated {Ni2+Ni1+} cluster, [K(12-crown-4)2][1], effectively replicates the coordination number and oxidation state of the proposed “Ared” state of the A-cluster. Addition of carbon monoxide to [1]− allows for isolation of a dinuclear {Ni2+Ni1+(CO)} complex, [K(12-crown-2)n][2] (n = 1–2), which bears similarity to the “ANiFeC” enzyme intermediate. Structural and electronic properties of each cluster are elucidated by X-ray diffraction, nuclear magnetic resonance, cyclic voltammetry, and UV/vis and electron paramagnetic resonance spectroscopies, which are supplemented by density functional theory (DFT) calculations. Calculations indicate that the pseudo-T-shaped geometry of the three-coordinate nickel in [1]– is more stable than the Y-conformation by 22 kcal mol–1, and that binding of CO to Ni1+ is barrierless and exergonic by 6 kcal mol–1. UV/vis absorption spectroscopy on [2]− in conjunction with time-dependent DFT calculations indicates that the square-planar nickel site is involved in electron transfer to the CO π*-orbital. Further, we demonstrate that [2]− promotes thioester synthesis in a reaction analogous to the production of acetyl coenzyme A by ACS

Методология синтеза архитектуры программно-технического комплекса автоматизированной системы мониторинга обстановки

Предложен подход к проектированию архитектуры программно-технического комплекса автоматизированной системы мониторинга обстановки в реальном времени, основанный на классификации решаемых функциональных задач на основе методов кластерного анализа и выбранного множества признаков подобия. Разработанный подход позволяет из множества функций системы выделить подобные (по определенным признакам) и объединить их в архитектурные компоненты (унифицированные функциональные модули).Запропоновано підхід до проектування архітектури центру обробки інформації автоматизованої системи моніторингу середовища в реальному часі, що заснований на класифікації функціональних задач на підставі методів кластерного аналізу і обраної множини ознак схожості. Розроблений підхід дозволяє вибрати із множини функцій системи схожі (за певними ознаками) і поєднати їх в архітектурні компоненти (уніфіковані функціональні модулі).The approach to designing architecture of the information processing complex of the automated real time conditions monitoring system based on classification of functional tasks on the basis of methods of cluster analysis and the chosen set of similarity attributes is offered. The developed approach allows to allocate from a set of functions the systems similar (on certain attributes) and to unite them in architectural components (unified functional modules)

Avaliação da retroversão da cabeça do úmero em jogadores de handebol Evaluation of humeral head retroversion in handball players

OBJETIVOS: Avaliar a retroversão da cabeça do úmero em jogadores de handebol e sua relação com a movimentação do ombro. MATERIAIS E MÉTODOS: Foram avaliados 17 jogadores profissionais por meio de exame físico e avaliação radiográfica, para se determinar o ângulo de retroversão e, sua relação com o arco de movimento. O mesmo foi realizado num grupo controle. RESULTADOS: A diferença entre a média do ângulo de retroversão da cabeça do úmero do membro dominante e não dominante foi de 3,06°. Entre eles, aqueles que tiveram um início de treino antes dos 10 anos, apresentaram uma média desse ângulo de 36,29°, enquanto que aqueles que iniciaram acima dessa idade tinham uma média de 26,6° (p< 0,05). A média da rotação lateral do membro dominante, cujo ângulo de retroversão era maior que 30°, foi 112,27°, e naqueles, em que o ângulo era inferior ou igual a 30°, a média foi 95,10° (p<0,05). CONCLUSÃO: Houve uma diferença estatística na retroversão quando comparamos os ombros dominantes e não dominantes. Os atletas que começaram a jogar antes dos 10 anos apresentaram, estatisticamente, uma maior retroversão. Há uma relação estatística entre o aumento da retroversão com o aumento da rotação lateral.<br>OBJECTIVES: To evaluate the humeral head retroversion of handball players and its relationship to shoulder's range of motion. MATERIALS AND METHODS: Seventeen professional players were evaluated by physical examination and X-ray images to determine the humeral head retroversion and its relationship to the range of motion. A control group was also submitted to the same evaluations. RESULTS: The difference between the average of the humeral head retroversion of the dominant and non dominant shoulders was 3.06°. The mean value for this angle between the athletes who had started training as early as 10 years old was 36.29°, compared to those who had started later in life, which was 26.6° (p<0.05). The average of the external rotation of the players whose retroversion angle was bigger than 30° was 112.27°, and for those whose angle was smaller or equal to 30°, it was 95.10° (p<0.05). CONCLUSION: There was a significant difference in the retroversion angle when comparing dominant and non-dominant shoulders. The athletes who started to play before the age of 10 presented, statistically, an increased retroversion. There is a statistical relationship between retroversion increase and shoulder's external rotation gain

Selenium and Vitamin E for Prostate Cancer: Post-SELECT (Selenium and Vitamin E Cancer Prevention Trial) Status

Various formulations of selenium and vitamin E, both essential human dietary components, have been shown to possess a therapeutic and preventive effect against prostate cancer. Fortuitous results of clinical trials also implied a risk-reduction effect of selenium and vitamin E supplements. The Selenium and Vitamin E Cancer Prevention Trial (SELECT), using oral selenium and vitamin E supplementation in disease-free volunteers, was designed to test a prostate cancer chemoprevention hypothesis. SELECT was terminated early because of both safety concerns and negative data for the formulations and doses given. Here, we review and discuss the studies done before and since the inception of SELECT, as well as the parameters of the trial itself. We believe that there is a lack of appropriate in vivo preclinical studies on selenium and vitamin E despite many promising in vitro studies on these agents. It seems that the most effective doses and formulations of these agents for prostate cancer chemoprevention have yet to be tested. Also, improved understanding of selenium and vitamin E biology may facilitate the discovery of these doses and formulations