Optical probes of intradiskal processes in rod photoreceptors. II: Light-scattering study of ATP-dependent light reactions.

Rod outer segment (ROS) disks, either stacked or freely floating, respond to flash illumination to yield a specific, ATP-dependent, light-scattering signal AL. In broken ROS AL signals occur only when AD signals (see Part I) have preceded them, The degree to which the preceding AD signal has been completed determines the amplitude of the following AL signal. However, in freshly detached ROS from dark-adapted frogs AL signals with maximal size can be obtained without pre-incubation with exogenous ATP. The energized state, which is restored in broken ROS with the help of ATP, appears to prevail in the living retina and must therefore be considered to be “physiological”. AL signals require structurally intact disks. Neither peripheral ROS proteins nor connecting filaments between adjacent disks are necessary. Their structural origin is the same as that of the preceding AD signal, i.e. osmotic disk swelling. AL signals consist of a single slow kinetic component (half-life 10 s at room temperature) and multiphase fast kinetic component (70 ms). The slow phase corresponds to a light-stimulated resumption of ATPase activity (this has been dealt with in a previous paper) whereas the fast component reflects an immediate response of the energized disk to the metarhodopsin I to metarhodopsin II transition. The latter effect is the subject of this paper. A variety of experiments, using different ATPase inhibitors, ionophores and membrane-permeable salts, have been carried out; they are all consistent with the notion that AL originates in the disk interior and probes the existence of a proton electrochemical potential difference Δμ(H+) across the disk membrane. A model is presented which can explain all given properties of AL satisfactorily. According to this model the photolysis of rhodopsin causes a proton release in the disk lumen. This, in turn, results in osmotic swelling of the disks, provided that the internal buffer sites have been (at least partially) titrated with protons prior to the flash. Such conditions, i.e. a low internal pH, are provided by the proton transport across the disk membrane, which presumably takes place during the course of the preceding AD signal

Optical probes of intradiskal processes in rod photoreceptors I: Light-scattering study of ATP-dependent dark reactions.

ATP can cause dramatic structural changes in the outer segment of rod photoreceptors. These changes can be visualized by means of a concomitant light-scattering signal AD, a decrease in scattered light intensity of over 20%. The large size of the signal suggests that the major structural changes occur. The underlying molecular events may reflect an important, yet still unknown, part of the photoreceptor machinery. AD signals reflect ATPase-driven transmembrane events which occur in and at the disk membrane. Their only structural prerequisite is the structural integrity of the disk compartment. The angular dependence of AD, which can be mimicked by an osmotically-induced disk-swelling, suggests that the disk compartment swells during the production of the AD signal. AD signals proceed with first-order kinetics (half-life = 1 min at 20 °C and ATP concentrations of greater than 100 /gmM) and are accompanied by the hydrolysis of approximately 4 mol ATP (mol rhodopsin)−1. The AD signal is inhibited by a number of transport ATPase inhibitors (quercetin, NBD·Cl, vanadate, DCCD), but not by oligomycin, azide and ouabain. The sensitivity to DCCD, together with the fact that except magnesium no other cation has to be present, points to a proton translocation. This proton transport appears to be electrogenic, since AD signals require the presence of a permeant anion. In physiological saline this is chloride, and the chloride flux is facilitated by a DIDS-sensitive anion transport unit in the disk membrane

Long-term planning and its role as a tool of fiscal security of the economy

Актуальность исследования определяется тем, что обеспечение бюджетно-финансовой безопасности в России связано с проведением исполнительными органами государственной власти бюджетно-финансового планирования, основанного на принципах законности, плановости и открытости, прописанных в Бюджетном кодексе РФ. Все это рождает острую необходимость принятия базового документа (Долгосрочной бюджетной стратегии). Цель работы: провести анализ бюджетно-финансового планирования в его историческом, межстрановом и правовом аспектах, дать характеристику современного состояния бюджетно-финансового планирования в России. Методы исследования: моделирование, обобщение зарубежного опыта использования долгосрочного планирования, сопоставление и контент-анализ, который позволил выявить принципы долгосрочного планирования в бюджетной сфере, а также острую необходимость принятия Долгосрочной бюджетной стратегии на современном этапе в России. Результаты. Проведенное исследование отражает генезис бюджетного планирования в России в 1917-2017 гг. Анализ применения такого планирования в развитых странах (США, Германия, Великобритания, Франция и др.) определил основные принципы, которые могут быть заложены в основу Долгосрочной бюджетной стратегии в России на федеральном и региональном уровнях. Как основной базовый документ бюджетно-финансового планирования текущего периода утвержденная Долгосрочная бюджетная стратегия позволит предопределить результаты долгосрочного развития и обеспечить достаточный уровень экономической безопасности бюджетно- финансовой сферы.The relevance of this research is determined by the fact that ensuring fiscal security in Russia is connected with the Executive bodies of state power, budget and financial planning based on the principles of legality, planning and openness spelled out in the Budget code of the Russian Federation. All this creates an urgent need of adoption of the core document (Long-term budget strategy). The aim of the work is to analyze the budget and financial planning in its historical, interstate and legal aspects, State of fiscal planning in Russia. Research methods: modeling, generalization of foreign experience in using long-term planning. Comparison and content analysis, which allowed revealing the principles of long-term planning in the budgetary sphere and urgent need to adopt a Long-term budget strategy at the present stage in Russia. Results. The study reflects the Genesis of budget planning in Russia in 1917-2017. Analysis of application of such planning in developed countries (USA, Germany, UK, France, etc.) helped identify basic principles that can be the base of Long-term budget strategy in Russia at Federal and regional levels. The approved Long-term budget strategy, as the base document for budget and financial planning of the current period, will enable to predetermine the outcome of long-term development and to ensure a sufficient level of economic security fiscal sphere

Reactive Petri Nets for Workflow Modeling

Petri nets are widely used for modeling and analyzing workflows

J. Exp. Med.

The cross talk between host and pathogen starts with recognition of bacterial signatures through pattern recognition receptors (PRRs), which mobilize downstream signaling cascades. We investigated the role of the cytosolic adaptor caspase recruitment domain family, member 9 (CARD9) in tuberculosis. This adaptor was critical for full activation of innate immunity by converging signals downstream of multiple PRRs. Card9(-/-) mice succumbed early after aerosol infection, with higher mycobacterial burden, pyogranulomatous pneumonia, accelerated granulocyte recruitment, and higher abundance of proinflammatory cytokines and granulocyte colony-stimulating factor (G-CSF) in serum and lung. Neutralization of G-CSF and neutrophil depletion significantly prolonged survival, indicating that an exacerbated systemic inflammatory disease triggered lethality of Card9(-/-) mice. CARD9 deficiency had no apparent effect on T cell responses, but a marked impact on the hematopoietic compartment. Card9(-/-) ranulocytes failed to produce IL-10 after Mycobaterium tuberculosis infection, suggesting that an absent antiinflammatory feedback loop accounted for granulocyte-dominated pathology, uncontrolled bacterial replication, and, ultimately, death of infected Card9(-/-) mice. Our data provide evidence that deregulated innate responses trigger excessive lung inflammation and demonstrate a pivotal role of CARD9 signaling in autonomous innate host defense against tuberculosis

The 4C spectrum of fundamental behavioral relations for concurrent systems

The design of concurrent software systems, in particular process-aware information systems, involves behavioral modeling at various stages. Recently, approaches to behavioral analysis of such systems have been based on declarative abstractions defined as sets of behavioral relations. However, these relations are typically defined in an ad-hoc manner. In this paper, we address the lack of a systematic exploration of the fundamental relations that can be used to capture the behavior of concurrent systems, i.e., co-occurrence, conflict, causality, and concurrency. Besides the definition of the spectrum of behavioral relations, which we refer to as the 4C spectrum, we also show that our relations give rise to implication lattices. We further provide operationalizations of the proposed relations, starting by proposing techniques for computing relations in unlabeled systems, which are then lifted to become applicable in the context of labeled systems, i.e., systems in which state transitions have semantic annotations. Finally, we report on experimental results on efficiency of the proposed computations

Comparing Petri Net and Activity Diagram Variants for Workflow Modelling:A Quest for Reactive Petri Nets

Petri net variants are widely used as a workflow modelling technique. Recently, UMLa ctivity diagrams have been used for the same purpose, even though the syntax and semantics of activity diagrams has not been yet fully worked out. Nevertheless, activity diagrams seem very similar to Petri nets and on the surface, one may think that they are variants of each other. To substantiate or deny this claim, we need to formalise the intended semantics of activity diagrams and then compare this with various Petri net semantics. In previous papers we have defined two formal semantics for UMLact ivity diagrams that are intended for workflow modelling. In this paper, we discuss the design choices that underlie these two semantics and investigate whether these design choices can be met in low-level and high-level Petri net semantics. We argue that the main difference between the Petri net semantics and our semantics of UML act ivity diagrams is that the Petri net semantics models resource usage of closed, active systems that are non-reactive, whereas our semantics of UMLact ivity diagrams models open, reactive systems. Since workflow systems are open, reactive systems, we conclude that Petri nets cannot model workflows accurately, unless they are extended with a syntax and semantics for reactivity