English peasants and agrarian policy of the Tudors and the first Stuarts: legislation and peasant mentality through social conflict communication (1550-1640-s)= Английские крестьяне и аграрная политика Тюдоров и первых Стюартов: законодательство и крестьянская психология через социальные конфликты (1550-1640 гг.)

The article focuses on the essence of social conflicts involving peasants in the period of 1550-1640-s and the constituents of these conflicts = В статье отмечается сущность социальных конфликтов, в которых участвовали крестьяне в период 1550-1640 гг., их составные компоненты в контексте междициплинарного подход

English peasants and agrarian policy of the Tudors and the first Stuarts: outlines of enclosure legislation = Английские крестьяне и аграрная политика Тюдоров и первых Стюартов: основы законодательства об огораживаниях

In the article considers the legislation of the Tudors and the first Stuarts related to the existent process of ploughland enclosure in the kingdom of England in the second half of the 16th - first half of the 17th century. The article researches into the origins of a number of agrarian statutes in Parliament and provides analysis of the contents of their separate articles referring to the peasants and the new gentr

Библиотека, которую «и организовал, и создал»: дело всей жизни Н.И. Драницына

The Nizhny Novgorod Regional Archive Academic Committee’s library collection formation long-term activities of N. Dranitsyn, who was the organizer of study of the local history and library science, is revealed in the paper. New archival materials are used. For realization of the purpose N. Dranitsyn managed to attract S. Platonov, the outstanding scientist-historian, the honorary member of the commission.С привлечением новых архивных материалов раскрывается многолетняя деятельность крупного организатора краеведения и библиотечного дела Н.И. Драницына по формированию фондов библиотеки Нижегородской губернской ученой архивной комиссии. Для реализации своей цели ему удалось привлечь выдающегося ученого-историка, почетного члена комиссии С.Ф. Платонова

Predictive Approach Identifies Molecular Targets and Interventions to Restore Angiogenesis in Wounds With Delayed Healing

Impaired angiogenesis is a hallmark of wounds with delayed healing, and currently used therapies to restore angiogenesis have limited efficacy. Here, we employ a computational simulation-based approach to identify influential molecular and cellular processes, as well as protein targets, whose modulation may stimulate angiogenesis in wounds. We developed a mathematical model that captures the time courses for platelets, 9 cell types, 29 proteins, and oxygen, which are involved in inflammation, proliferation, and angiogenesis during wound healing. We validated our model using previously published experimental data. By performing global sensitivity analysis on thousands of simulated wound-healing scenarios, we identified six processes (among the 133 modeled in total) whose modulation may improve angiogenesis in wounds. By simulating knockouts of 25 modeled proteins and by simulating different wound-oxygenation levels, we identified four proteins [namely, transforming growth factor (TGF)-β, vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF-2), and angiopoietin-2 (ANG-2)], as well as oxygen, as therapeutic targets for stimulating angiogenesis in wounds. Our modeling results indicated that simultaneous inhibition of TGF-β and supplementation of either FGF-2 or ANG-2 could be more effective in stimulating wound angiogenesis than the modulation of either protein alone. Our findings suggest experimentally testable intervention strategies to restore angiogenesis in wounds with delayed healing

Kinetic model facilitates analysis of fibrin generation and its modulation by clotting factors: implications for hemostasis-enhancing therapies

We developed a computational model that accounts for essential kinetic features of thrombin generation, fibrin formation, and fibrinolysis in diverse in vitro systems. We applied it to characterize strategies to improve hemostasis

Positive Autoregulation Shapes Response Timing and Intensity in Two-component Signal Transduction Systems

Positive feedback loops are regulatory elements that can modulate expression output, kinetics and noise in genetic circuits. Transcriptional regulators participating in such loops are often expressed from two promoters, one constitutive and one autoregulated. Here, we investigate the interplay of promoter strengths and the intensity of the stimulus activating the transcriptional regulator in defining the output of a positively autoregulated genetic circuit. Using a mathematical model of twocomponent regulatory systems, which are present in all domains of life, we establish that positive feedback strongly affects the steady-state output levels at both low and high levels of stimulus if the constitutive promoter of the regulator is weak. By contrast, the effect of positive feedback is negligible when the constitutive promoter is sufficiently strong, unless the stimulus intensity is very high. Furthermore, we determine that positive feedback can affect both transient and steady state output levels even in the simplest genetic regulatory systems. We tested our modeling predictions by abolishing the positive feedback loop in the two-component regulatory system PhoP/PhoQ of Salmonella enterica, which resulted in diminished induction of PhoP-activated genes

Evolution and Dynamics of Regulatory Architectures Controlling Polymyxin B Resistance in Enteric Bacteria

Complex genetic networks consist of structural modules that determine the levels and timing of a cellular response. While the functional properties of the regulatory architectures that make up these modules have been extensively studied, the evolutionary history of regulatory architectures has remained largely unexplored. Here, we investigate the transition between direct and indirect regulatory pathways governing inducible resistance to the antibiotic polymyxin B in enteric bacteria. We identify a novel regulatory architecture—designated feedforward connector loop—that relies on a regulatory protein that connects signal transduction systems post-translationally, allowing one system to respond to a signal activating another system. The feedforward connector loop is characterized by rapid activation, slow deactivation, and elevated mRNA expression levels in comparison with the direct regulation circuit. Our results suggest that, both functionally and evolutionarily, the feedforward connector loop is the transitional stage between direct transcriptional control and indirect regulation

Noisy Monte Carlo: Convergence of Markov chains with approximate transition kernels

Monte Carlo algorithms often aim to draw from a distribution $\pi$ by simulating a Markov chain with transition kernel $P$ such that $\pi$ is invariant under $P$. However, there are many situations for which it is impractical or impossible to draw from the transition kernel $P$. For instance, this is the case with massive datasets, where is it prohibitively expensive to calculate the likelihood and is also the case for intractable likelihood models arising from, for example, Gibbs random fields, such as those found in spatial statistics and network analysis. A natural approach in these cases is to replace $P$ by an approximation $\hat{P}$. Using theory from the stability of Markov chains we explore a variety of situations where it is possible to quantify how 'close' the chain given by the transition kernel $\hat{P}$ is to the chain given by $P$. We apply these results to several examples from spatial statistics and network analysis.Comment: This version: results extended to non-uniformly ergodic Markov chain