Наблюдатель изменений в лесах кратчайших путей на динамических графах транспортных сетей

The purpose of the work is the development of basic data structures, speed-efficient and memoryefficient algorithms for tracking changes in predefined decisions about sets of shortest paths on transport networks, notifications about which are received by autonomous coordinated transport agents with centralized or collective control. A characteristic feature of transport operations is the independence and asynchrony of the emergence of perturbations of optimal solutions, as well as the lack of global influence of individual perturbations on the set of all processes on the network. This clearly determines the feasibility of realizing the idea of reoptimizing existing solutions in real time as information is received about disturbances in the structure and parameters of the transport network, various restrictions on the use of existing shortest paths. In contrast to the classical problems of finding shortest paths on static or dynamic graphs, it is proposed to supplement the set of situations controlled by the observer by taking into account the associations of shortest path trees with agents that actually use such paths. This will improve the responsiveness of agent notification processes for timely switching to a new path. The space of search states is a dynamically generated bipartite sparse graph of the transport network, represented by a list of arcs. The basic algorithm for finding the shortest paths uses Dijkstra's scheme, but implements a bootstrapping method to generate the search result. The compactness of the representation of the observed forest of shortest paths is achieved by mapping individual trees of such a forest onto the projection of tree vertices in memory, where the position of each vertex corresponds to the distance from the tree root. The proposed version of the construction of the search procedure is based on the mechanisms existing in database management systems for creating different relational representations of the physical data model. This eliminates the need to solve technological problems of complexing heterogeneous models of dynamic transport networks, memory allocation. As a result, the specification of various rules for the logistics of transport operations is simplified, since such operations in terms of object-oriented models are easily determined by polymorphic classes of transitions between nodes of the transport network.Цель работы – разработка базовых структур данных и эффективных по быстродействию и памяти алгоритмов слежения за изменениями предопределенных решений о множествах кратчайших путей на транспортных сетях, уведомления о которых получают автономные координируемые транспортные агенты с централизованным или коллективным управлением. Характерная особенность транспортных операций – независимость и асинхронность появления возмущений оптимальных решений, а также отсутствие глобального влияния отдельных возмущений на множество всех процессов на сети. Тем самым, очевидно, определяется целесообразность реализации идеи реоптимизации существующих решений в реальном времени по мере поступления информации о возмущениях структуры и параметров транспортной сети, различных ограничений на использование существующих кратчайших путей. В отличие от классических задач поиска кратчайших путей на статических или динамических графах, набор контролируемых наблюдателем ситуаций предлагается дополнить учетом ассоциаций деревьев кратчайших путей с фактически использующими такие пути агентами. Это позволит улучшить реактивность процессов уведомления агентов для своевременного переключения на новый путь. Пространство состояний поиска – динамически формируемый двудольный разреженный граф транспортной сети, представленный списком дуг. Базовый алгоритм поиска кратчайших путей использует схему Дейкстры, но реализует для формирования результата поиска метод бутстрэппинга. Компактность представления наблюдаемого леса кратчайших путей достигается отображением отдельных деревьев такого леса на проекцию вершин дерева в памяти, где позиция каждой вершины соответствует расстоянию от корня дерева. Предложенная версия построения процедуры поиска опирается на существующие в системах управления базами данных механизмы создания разных реляционных представлений физической модели данных. Это избавляет от необходимости решения технологических задач комплексирования гетерогенных моделей динамических транспортных сетей, распределения памяти. В результате спецификация различных правил логистики транспортных операций упрощается, так как такие операции в терминах объектно-ориентированных моделей легко определяются полиморфными классами переходов между узлами транспортной сети

Rationales, design and recruitment of the Taizhou Longitudinal Study

<p/> <p>Background</p> <p>Rapid economic growth in China in the past decades has been accompanied by dramatic changes in lifestyle and environmental exposures. The burdens of non-communicable diseases, such as cardiovascular diseases, diabetes and cancer, have also increased substantially.</p> <p>Methods/design</p> <p>We initiated a large prospective cohort–the Taizhou Longitudinal Study–in Taizhou (a medium-size city in China) to explore the environmental and genetic risk factors for common non-communicable diseases. The sample size of the cohort will be at least 100,000 adults aged 30–80 years drawn from the general residents of the districts of Hailin, Gaogang, and Taixing (sample frame, 1.8 million) of Taizhou. A three-stage stratified sampling method will be applied. Baseline investigations include interviewer-administered questionnaire, anthropometric measurements, and collection of buccal mucosal cells and blood specimens. DNA will be extracted for genetic studies and serum samples will be used for biochemical examinations. A follow-up survey will be conducted every three years to obtain information on disease occurrence and information on selected lifestyle exposures. Study participants will be followed-up indefinitely by using a chronic disease register system for morbidity and cause-specific mortality. Information on non-fatal events will be obtained for certain major categories of disease (e.g., cancer, stroke, myocardial infarction) through established registry systems.</p> <p>Discussion</p> <p>The Taizhou Longitudinal Study will provide a good basis for exploring the roles of many important environmental factors (especially those concomitant with the economic transformation in China) for common chronic diseases, solely or via interaction with genetic factors.</p

Динамическая асимметричная задача о назначении в открытых многоагентных системах

The purpose of the work is to develop models and algorithms for optimizing matching in dynamically generated graphs of asymmetric relations in coordinated open systems of interacting agents with centralized and collective control. The dynamic asymmetric matching optimization problem arises here as a result of a compromise approximation of the mapping of the dynamic programming method onto a stream of known open assignment problems or several traveling salesmen. However, the branching alternatives presented in this way for independent tasks do not take into account the interdependence of real relationships between agents and their tasks, including their relationship to time. Ignoring the dependence of branching alternatives leads to a delay in the moment or to a loss in the quality of assignment of tasks to coordinated agents. The main idea of the proposed implementation of the principle known for effective control is to postpone the moment the final decision is made to the latest moment, taking into account the susceptibility of the system to local changes in state variables. The interdependence of states is revealed on the basis of the analysis of the correspondence of the graph of the current matching with the optimal solution on the subgraph of perfect matching. The transition between states is implemented by the incremental version of the reoptimization algorithm for solving linear problems of assigning the shortest replenishing path using the method. The space of search states is a dynamically generated bipartite sparse graph of alternatives for a combination of agents and tasks, represented by a list of arcs. To highlight the sets of changed arcs, it is proposed to supplement the weight of the arcs with the boundaries of the stability intervals of the solution, optionally formed in the background. By default, the weight of the modified arc matches the boundary of the stability interval. On each correction cycle of the lists of agents, tasks, and their associations, subsets of elements are selected for which reconsideration of matching is required. An enhanced condition for the selection of such elements is to go beyond the boundaries of the stability interval. In this case, the asymmetry of the assignment problem is taken into account by choosing the adjacency structure for the fraction of the graph with a minimum of vertices. As a result, the reaction time of procedures for solving the assignment problem is reduced by an order of magnitude.Цель работы – разработка моделей и алгоритмов оптимизации паросочетаний в динамически формируемых графах асимметричных отношений в координируемых открытых системах взаимодействующих агентов с централизованным и коллективным управлением. Динамическая асимметричная задача оптимизации паросочетаний здесь возникает как результат компромиссной аппроксимации отображения метода динамического программирования на поток известных открытых задач о назначении или нескольких странствующих коммивояжёров. Однако представленные таким образом альтернативы ветвления на независимых задачах не учитывают взаимозависимость реальных отношений между агентами и их заданиями, включая их привязку ко времени. Игнорирование зависимости альтернатив ветвления приводит к задержке момента или потере качества назначения заданий координируемым агентам. Основная идея предлагаемой реализации известного для эффективного управления принципа – откладывание момента принятия окончательного решения на наиболее поздний момент, учет восприимчивости системы к локальным изменениям переменных состояния. Взаимозависимость состояний выявляется на основе анализа соответствия графа текущего паросочетания оптимальному решению на подграфе совершенного паросочетания. Переход между состояниями реализуется инкрементальной версией алгоритма реоптимизации решения линейных задач о назначении методом кратчайшего пополняющего пути. Пространство состояний поиска – динамически формируемый двудольный разреженный граф альтернатив сочетания агентов и задач, представленный списком дуг. Для выделения множеств изменившихся дуг предложено дополнить веса дуг границами интервалов устойчивости решения, факультативно формируемых в фоновом режиме. По умолчанию вес измененной дуги совпадает с границей интервала устойчивости. На каждом цикле коррекции списков агентов, задач и их ассоциаций выделяются подмножества элементов, для которых требуется пересмотр паросочетания. Усиленное условие отбора таких элементов – выход за границы интервала устойчивости. При этом асимметрия задачи назначения учитывается выбором структуры смежности для доли графа с минимумом вершин. В результате время реакции процедур решения задачи назначения сокращается на порядок

Multiple ITS Copies Reveal Extensive Hybridization within Rheum (Polygonaceae), a Genus That Has Undergone Rapid Radiation

During adaptive radiation events, characters can arise multiple times due to parallel evolution, but transfer of traits through hybridization provides an alternative explanation for the same character appearing in apparently non-sister lineages. The signature of hybridization can be detected in incongruence between phylogenies derived from different markers, or from the presence of two divergent versions of a nuclear marker such as ITS within one individual.In this study, we cloned and sequenced ITS regions for 30 species of the genus Rheum, and compared them with a cpDNA phylogeny. Seven species contained two divergent copies of ITS that resolved in different clades from one another in each case, indicating hybridization events too recent for concerted evolution to have homogenised the ITS sequences. Hybridization was also indicated in at least two further species via incongruence in their position between ITS and cpDNA phylogenies. None of the ITS sequences present in these nine species matched those detected in any other species, which provides tentative evidence against recent introgression as an explanation. Rheum globulosum, previously indicated by cpDNA to represent an independent origin of decumbent habit, is indicated by ITS to be part of clade of decumbent species, which acquired cpDNA of another clade via hybridization. However decumbent and glasshouse morphology are confirmed to have arisen three and two times, respectively.These findings suggested that hybridization among QTP species of Rheum has been extensive, and that a role of hybridization in diversification of Rheum requires investigation

Antitumor activity and mechanisms of action of total glycosides from aerial part of Cimicifuga dahurica targeted against hepatoma

<p>Abstract</p> <p>Background</p> <p>Medicinal plant is a main source of cancer drug development. Some of the cycloartane triterpenoids isolated from the aerial part of <it>Cimicifuga dahurica </it>showed cytotoxicity in several cancer cell lines. It is of great interest to examine the antiproliferative activity and mechanisms of total triterpenoid glycosides of <it>C. dahurica </it>and therefore might eventually be useful in the prevention or treatment of Hepatoma.</p> <p>Methods</p> <p>The total glycosides from the aerial part (TGA) was extracted and its cytotoxicity was evaluated in HepG2 cells and primary cultured normal mouse hepatocytes by an MTT assay. Morphology observation, Annexin V-FITC/PI staining, cell cycle analysis and western blot were used to further elucidate the cytotoxic mechanism of TGA. Implanted mouse H₂₂hepatoma model was used to demonstrate the tumor growth inhibitory activity of TGA <it>in vivo</it>.</p> <p>Results</p> <p>The IC₅₀values of TGA in HepG2 and primary cultured normal mouse hepatocytes were 21 and 105 μg/ml, respectively. TGA induced G₀/G₁cell cycle arrest at lower concentration (25 μg/ml), and triggered G₂/M arrest and apoptosis at higher concentrations (50 and 100 μg/ml respectively). An increase in the ratio of Bax/Bcl-2 was implicated in TGA-induced apoptosis. In addition, TGA inhibited the growth of the implanted mouse H₂₂tumor in a dose-dependent manner.</p> <p>Conclusion</p> <p>TGA may potentially find use as a new therapy for the treatment of hepatoma.</p

Comparative transcriptome sequencing of germline and somatic tissues of the Ascaris suum gonad

<p>Abstract</p> <p>Background</p> <p><it>Ascaris suum </it>(large roundworm of pigs) is a parasitic nematode that causes substantial losses to the meat industry. This nematode is suitable for biochemical studies because, unlike <it>C. elegans</it>, homogeneous tissue samples can be obtained by dissection. It has large sperm, produced in great numbers that permit biochemical studies of sperm motility. Widespread study of <it>A. suum </it>would be facilitated by more comprehensive genome resources and, to this end, we have produced a gonad transcriptome of <it>A. suum</it>.</p> <p>Results</p> <p>Two 454 pyrosequencing runs generated 572,982 and 588,651 reads for germline (TES) and somatic (VAS) tissues of the <it>A. suum </it>gonad, respectively. 86% of the high-quality (HQ) reads were assembled into 9,955 contigs and 69,791 HQ reads remained as singletons. 2.4 million bp of unique sequences were obtained with a coverage that reached 16.1-fold. 4,877 contigs and 14,339 singletons were annotated according to the <it>C. elegans </it>protein and the Kyoto Encyclopedia of Genes and Genomes (KEGG) protein databases. Comparison of TES and VAS transcriptomes demonstrated that genes participating in DNA replication, RNA transcription and ubiquitin-proteasome pathways are expressed at significantly higher levels in TES tissues than in VAS tissues. Comparison of the <it>A. suum </it>TES transcriptome with the <it>C. elegans </it>microarray dataset identified 165 <it>A. suum </it>germline-enriched genes (83% are spermatogenesis-enriched). Many of these genes encode serine/threonine kinases and phosphatases (KPs) as well as tyrosine KPs. Immunoblot analysis further suggested a critical role of phosphorylation in both testis development and spermatogenesis. A total of 2,681 <it>A. suum </it>genes were identified to have associated RNAi phenotypes in <it>C. elegans</it>, the majority of which display embryonic lethality, slow growth, larval arrest or sterility.</p> <p>Conclusions</p> <p>Using deep sequencing technology, this study has produced a gonad transcriptome of <it>A. suum</it>. By comparison with <it>C. elegans </it>datasets, we identified sets of genes associated with spermatogenesis and gonad development in <it>A. suum</it>. The newly identified genes encoding KPs may help determine signaling pathways that operate during spermatogenesis. A large portion of <it>A. suum </it>gonadal genes have related RNAi phenotypes in <it>C. elegans </it>and, thus, might be RNAi targets for parasite control.</p

Organic and Third Phase in HNO3/TBP/n-Dodecane System: No Reverse Micelles

The composition and speciation of the organic and third phases in the system HNO3/TBP (tri-n-butyl phosphate)/n-dodecane have been examined by a combination of gravimetric, Karl Fischer analysis, chemical analysis, FTIR, and 31P NMR spectroscopy, with particular emphasis on the transition from the two-phase to the three-phase region. Phase densities indicate that third-phase formation takes place for initial aqueous HNO3 concentrations above 15 M, while the results from the stoichiometric analysis imply that the organic and third phases are characterized by two distinct species, namely the mono-solvate TBP⋅HNO3 and the hemi-solvate TBP⋅2HNO3, respectively. Furthermore, the 31P NMR spectra of organic and third phase show no significant chemical differences at the phosphorus centers, suggesting that the second HNO3 molecule in the third phase is bound to HNO3 rather than TBP. The third-phase FTIR spectra reveal stronger vibrational absorption bands at 1028, 1310, 1653, and 3200–3500 cm−1, reflecting higher concentrations of H2O, HNO3, and TBP. The molecular dynamics simulation data predict structures in accord with the spectroscopically identified speciation, indicating inequivalent HNO3 molecules in the third phase. The predicted structures of the organic and third phases are more akin to microemulsion networks rather than the distinct, reverse micelles assumed in previous studies. H2O appears to be present as a disordered hydrogen-bonded solvate stabilizing the polar TBP/HNO3 aggregates in the organic matrix, and not as a strongly bound hydrate species in aggregates with defined stoichiometry

Pyrosequencing of the Camptotheca acuminata transcriptome reveals putative genes involved in camptothecin biosynthesis and transport

Background: Camptotheca acuminata is a Nyssaceae plant, often called the "happy tree", which is indigenous in Southern China. C. acuminata produces the terpenoid indole alkaloid, camptothecin (CPT), which exhibits clinical effects in various cancer treatments. Despite its importance, little is known about the transcriptome of C. acuminata and the mechanism of CPT biosynthesis, as only few nucleotide sequences are included in the GenBank database.Results: From a constructed cDNA library of young C. acuminata leaves, a total of 30,358 unigenes, with an average length of 403 bp, were obtained after assembly of 74,858 high quality reads using GS De Novo assembler software. Through functional annotation, a total of 21,213 unigenes were annotated at least once against the NCBI nucleotide (Nt), non-redundant protein (Nr), Uniprot/SwissProt, Kyoto Encyclopedia of Genes and Genomes (KEGG), and Arabidopsis thaliana proteome (TAIR) databases. Further analysis identified 521 ESTs representing 20 enzyme genes that are involved in the backbone of the CPT biosynthetic pathway in the library. Three putative genes in the upstream pathway, including genes for geraniol-10-hydroxylase (CaPG10H), secologanin synthase (CaPSCS), and strictosidine synthase (CaPSTR) were cloned and analyzed. The expression level of the three genes was also detected using qRT-PCR in C. acuminata. With respect to the branch pathway of CPT synthesis, six cytochrome P450s transcripts were selected as candidate transcripts by detection of transcript expression in different tissues using qRT-PCR. In addition, one glucosidase gene was identified that might participate in CPT biosynthesis. For CPT transport, three of 21 transcripts for multidrug resistance protein (MDR) transporters were also screened from the dataset by their annotation result and gene expression analysis.Conclusion: This study produced a large amount of transcriptome data from C. acuminata by 454 pyrosequencing. According to EST annotation, catalytic features prediction, and expression analysis, novel putative transcripts involved in CPT biosynthesis and transport were discovered in C. acuminata. This study will facilitate further identification of key enzymes and transporter genes in C. acuminata

Polysaccharides from the root of Angelica sinensis promotes hematopoiesis and thrombopoiesis through the PI3K/AKT pathway

<p>Abstract</p> <p>Background</p> <p>Dozens of Traditional Chinese Medicine (TCM) formulas have been used for promotion of "blood production" for centuries, and we are interested in developing novel thrombopoietic medicines from these TCMs. Our previous studies have demonstrated the hematopoietic effects of DangGui BuXue Tong (DBT), a formula composed of <it>Radix Angelicae Sinensis </it>and <it>Radix Astragali </it>in animal and cellular models. As a step further to identify and characterize the active chemical components of DBT, we tested the hematopoietic and particularly, thrombopoietic effects of polysaccharide-enriched fractions from the root of <it>Radix Angelicae Sinensis </it>(APS) in this study.</p> <p>Methods</p> <p>A myelosuppression mouse model was treated with APS (10 mg/kg/day). Peripheral blood cells from APS, thrombopoietin and vehicle-treated samples were then counted at different time-points. Using the colony-forming unit (CFU) assays, we determined the effects of APS on the proliferation and differentiation of hematopoietic stem/progenitor cells and megakaryocytic lineages. Using a megakaryocytic cell line M-07e as model, we analyzed the cellular apoptosis progression with and without APS treatment by Annexin V, Mitochondrial Membrane Potential and Caspase 3 assays. Last, the anti-apoptotic effect of APS on cells treated with Ly294002, a Phosphatidylinositol 3-Kinse inhibitor (PI3K) was also tested.</p> <p>Results</p> <p>In animal models, APS significantly enhanced not only the recovery of platelets, other blood cells and their progenitor cells, but also the formation of Colony Forming Unit (CFU). In M-07e cells, we observed the anti-apoptotic effect of APS. Treatment by Ly294002 alone increased the percentage of cells undergoing apoptosis. However, addition of APS to Ly294002-treated cells significantly reduced the percentage of cells undergoing apoptosis.</p> <p>Conclusions</p> <p>APS promotes hematopoiesis and thrombopoiesis in the mouse model. This effect likely resulted from the anti-apoptosis activity of APS and is likely to involve the PI3K/AKT pathway.</p