Principal manifolds and graphs in practice: from molecular biology to dynamical systems

We present several applications of non-linear data modeling, using principal manifolds and principal graphs constructed using the metaphor of elasticity (elastic principal graph approach). These approaches are generalizations of the Kohonen's self-organizing maps, a class of artificial neural networks. On several examples we show advantages of using non-linear objects for data approximation in comparison to the linear ones. We propose four numerical criteria for comparing linear and non-linear mappings of datasets into the spaces of lower dimension. The examples are taken from comparative political science, from analysis of high-throughput data in molecular biology, from analysis of dynamical systems.Comment: 12 pages, 9 figure

Late Pleistocene insects from the Dubrovino site at Ob River (West Siberia, Russia) and their paleoenvironmental significance

A blue-grey clay loam lens with plant and insect remains was found in an expo-sure of the Ob River, 2 km upper Dubrovino village in Novosibirskaya Oblast of Russia.Conventional radiocarbon dating of the Dubrovino deposit is ca 19,444±159 14C BP(23,234±338 cal yr BP) and coincides with Sartan glaciation period (MIS 2). Ninety-twoColeoptera species, dominated by fragments of Curculionidae and Carabidae are rep-resented in the Dubrovino deposit. Species of the tundra-steppe fauna are dominant,followed by meadow-dwelling taxa and coniferous forest taxa. A comparison of theDubrovino assemblage with the previously studied late Pleistocene Kalistratikha andBunkovo fossil assemblages showed that tundra-steppe landscapes with coniferousgroves and sparse meadow vegetation were typical for this area from the end of Kargininterglacial (MIS 3) through the end of the Sartan glaciation (MIS 2)

Комплексы жесткокрылых из четвертичных отложений р. Кизиха - самые южные позднеплейстоценовые насекомые Западно-Сибирской равнины

Two sites with insect remains were found in an exposure on the bank of Kizikha river, in the Rubtsovskii District of the Altaiskii Krai of Russia, Kizikha-1 with radiocarbon age 13455±150 14C BP (SPb-1347), and Kizikha-2 with the age 26094±400 14C BP (SPb-1418). This period is coincides with Sartan stadial and Kargin interstadial (MIS 2 and MIS 3). This is the southernmost late Pleistocene insect bearing deposit found in West Siberia. The fragments in both sites are represented mainly by Coleoptera. Beetle fauna from the site Kizikha-1 is represented by 34 species from 9 families. The majority of fragments belong to weevils and ground beetles. 28 species from 8 families are found in Kizikha-2 site, the majority of fragments belong to Carabidae. 7 species found in the sites, Dyschiriodes rufimanus, Cymindis cf. rostowtzowi (Carabidae), Cidnopus cf. parallelus, Pristilophus punctatissimus (Elateridae), Hemitrichapion alexsandri (Brentidae), Paophilus albilaterus and Otiorhynchus sushkini (Curculionidae), are recorded in Pleistocene deposits for the first time. Sub-fossil insect assemblages of the two sites coincides with the late Pleistocene “Otiorhynchus-type” sub-fossil insect fauna from southeastern part of West-Siberian Plain (Zinovyev, 2011; Legalov et al., 2016) with characteristics as follows: dominance of steppe species, presence of halophile species, lack of forest species. Most of these species are absent in the contemporary regional fauna. The complex of eastern species and presence of endemics of Altai-Sayan Mountain system is also characteristic to the both studied sites. Specifics of the deposit assemblages in comparison with the other late Pleistocene fauna of West Siberian Plain is in high share of meadow species that could be explained by taphonomic condition of sedimentation or microclimatic conditions caused by close location to Altai mountains. Analysis of sub-fossil insect fragments showed that open landscapes with zonal steppe and sparse meadow vegetation near rivers and in depressions were typical for this area. In comparison to contemporary conditions climate was dry and cold, but Kizikha-2 (end of MIS 3) was formed in more mild climate conditions than Kizikha-1 (end of MIS 2). Results gained from Kizikha-1 and Kizikha-2 sites are complementing data on latitudinal-zonal distribution of beetles found in late Pleistocene deposits in West Siberian Plain

Elastic principal manifolds and their practical applications

Principal manifolds serve as useful tool for many practical applications. These manifolds are defined as lines or surfaces passing through "the middle" of data distribution. We propose an algorithm for fast construction of grid approximations of principal manifolds with given topology. It is based on analogy of principal manifold and elastic membrane. The first advantage of this method is a form of the functional to be minimized which becomes quadratic at the step of the vertices position refinement. This makes the algorithm very effective, especially for parallel implementations. Another advantage is that the same algorithmic kernel is applied to construct principal manifolds of different dimensions and topologies. We demonstrate how flexibility of the approach allows numerous adaptive strategies like principal graph constructing, etc. The algorithm is implemented as a C++ package elmap and as a part of stand-alone data visualization tool VidaExpert, available on the web. We describe the approach and provide several examples of its application with speed performance characteristics.Comment: 26 pages, 10 figures, edited final versio

In-vivo Studies of Ultrasound-activated Drug-loaded Porous Silicon Nanoparticles for Cancer Therapy Application

It is investigated the therapeutic efficacy of combined action of ultrasound and porous silicon nanoparticles loaded with anticancer drug doxorubicin by using an experimental cancer model of lung Lewis carcinoma in vivo. Time dependences of growth of the primary tumor with introduced nanoparticles and without them, as well as the life span of mice after exposure to therapeutic ultrasound with intensity of 1W/cm2 and frequency of 1 MHz were studied. The obtained results show the effectiveness of inhibiting the growth of primary tumor site, as well as slowing the process of metastasis, in the case of combined action of ultrasound and drug-loaded porous silicon nanoparticles that indicates the prospect of latter as sonosensitizers and nanocontainers for the delivery and controlled release of drugs in sonodynamic therapy of malignant tumors. Keywords: silicon nanoparticles, nanocontainers, medical ultrasound, sonodynamic therapy, sonosensitizer

ОСЛОЖНЕНИЯ ИЗОЛИРОВАННОЙ РЕГИОНАРНОЙ ХИМИОПЕРФУЗИИ КОНЕЧНОСТЕЙ

Currently, the methods of delivering high local doses of chemotherapy to locally-advanced tumors of the extremities, while avoiding systemic toxicity, are actively investigated. Isolated regional limb chemoperfusion is one of these methods. From 2004 to 2014, a total of 70 patients underwent isolated limb perfusion (ILP) for locally-advanced soft tissue sarcoma and transit metastases of extremity melanoma. Complications of ILP, causes of their occurrence and preventive measures were analyzed.В настоящее время активно изучаются методы локального воздействия на местно-диссеминированные опухоли конечностей, позволяющие избежать калечащей операции и сохранить высокое качество жизни больного. Одной из таких методик является изолированная регионарная химиоперфузия конечностей. Мы изучили данные по 70 больным, которым в отделении общей онко логии НИИ онкологии им. Н.Н. Петрова в период с 2004 по 2014  выполнена изолированная химиоперфузия по поводу местно распространенных сарком мягких тканей, а также транзитных метастазов меланомы конечностей. Представлен анализ возможных осложнений ИРП, причины их возникновения и возможные пути профилактики

Mathematical Modelling of Cell-Fate Decision in Response to Death Receptor Engagement

Cytokines such as TNF and FASL can trigger death or survival depending on cell lines and cellular conditions. The mechanistic details of how a cell chooses among these cell fates are still unclear. The understanding of these processes is important since they are altered in many diseases, including cancer and AIDS. Using a discrete modelling formalism, we present a mathematical model of cell fate decision recapitulating and integrating the most consistent facts extracted from the literature. This model provides a generic high-level view of the interplays between NFκB pro-survival pathway, RIP1-dependent necrosis, and the apoptosis pathway in response to death receptor-mediated signals. Wild type simulations demonstrate robust segregation of cellular responses to receptor engagement. Model simulations recapitulate documented phenotypes of protein knockdowns and enable the prediction of the effects of novel knockdowns. In silico experiments simulate the outcomes following ligand removal at different stages, and suggest experimental approaches to further validate and specialise the model for particular cell types. We also propose a reduced conceptual model implementing the logic of the decision process. This analysis gives specific predictions regarding cross-talks between the three pathways, as well as the transient role of RIP1 protein in necrosis, and confirms the phenotypes of novel perturbations. Our wild type and mutant simulations provide novel insights to restore apoptosis in defective cells. The model analysis expands our understanding of how cell fate decision is made. Moreover, our current model can be used to assess contradictory or controversial data from the literature. Ultimately, it constitutes a valuable reasoning tool to delineate novel experiments