181 research outputs found

    Identifying Systems with Symmetries using Equivariant Autoregressive Reservoir Computers

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    The investigation reported in this document focuses on identifying systems with symmetries using equivariant autoregressive reservoir computers. General results in structured matrix approximation theory are presented, exploring a two-fold approach. Firstly, a comprehensive examination of generic symmetry-preserving nonlinear time delay embedding is conducted. This involves analyzing time series data sampled from an equivariant system under study. Secondly, sparse least-squares methods are applied to discern approximate representations of the output coupling matrices. These matrices play a pivotal role in determining the nonlinear autoregressive representation of an equivariant system. The structural characteristics of these matrices are dictated by the set of symmetries inherent in the system. The document outlines prototypical algorithms derived from the described techniques, offering insight into their practical applications. Emphasis is placed on their effectiveness in the identification and predictive simulation of equivariant nonlinear systems, regardless of whether such systems exhibit chaotic behavior.Comment: The views expressed in the article do not necessarily represent the views of the National Commission of Banks and Insurance Companies of Hondura

    Dynamic financial processes identification using sparse regressive reservoir computers

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    In this document, we present key findings in structured matrix approximation theory, with applications to the regressive representation of dynamic financial processes. Initially, we explore a comprehensive approach involving generic nonlinear time delay embedding for time series data extracted from a financial or economic system under examination. Subsequently, we employ sparse least-squares and structured matrix approximation methods to discern approximate representations of the output coupling matrices. These representations play a pivotal role in establishing the regressive models corresponding to the recursive structures inherent in a given financial system. The document further introduces prototypical algorithms that leverage the aforementioned techniques. These algorithms are demonstrated through applications in approximate identification and predictive simulation of dynamic financial and economic processes, encompassing scenarios that may or may not exhibit chaotic behavior.Comment: The content of this publication represents the opinion of the researchers affiliated with the Department of Statistics and Research, but not the official opinion of the CNB

    LRRK2-phosphorylated Rab10 sequesters Myosin Va with RILPL2 during ciliogenesis blockade

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    Activating mutations in LRRK2 kinase causes Parkinson’s disease. Pathogenic LRRK2 phosphorylates a subset of Rab GTPases and blocks ciliogenesis. Thus, defining novel phospho-Rab interacting partners is critical to our understanding of the molecular basis of LRRK2 pathogenesis. RILPL2 binds with strong preference to LRRK2-phosphorylated Rab8A and Rab10. RILPL2 is a binding partner of the motor protein and Rab effector, Myosin Va. We show here that the globular tail domain of Myosin Va also contains a high affinity binding site for LRRK2-phosphorylated Rab10. In the presence of pathogenic LRRK2, RILPL2 and MyoVa relocalize to the peri-centriolar region in a phosphoRab10-dependent manner. PhosphoRab10 retains Myosin Va over pericentriolar membranes as determined by fluorescence loss in photobleaching microscopy. Without pathogenic LRRK2, RILPL2 is not essential for ciliogenesis but RILPL2 over-expression blocks ciliogenesis in RPE cells independent of tau tubulin kinase recruitment to the mother centriole. These experiments show that LRRK2 generated-phosphoRab10 dramatically redistributes a significant fraction of Myosin Va and RILPL2 to the mother centriole in a manner that likely interferes with Myosin Va’s role in ciliogenesis

    Nonlinear software sensor for monitoring genetic regulation processes with noise and modeling errors

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    Nonlinear control techniques by means of a software sensor that are commonly used in chemical engineering could be also applied to genetic regulation processes. We provide here a realistic formulation of this procedure by introducing an additive white Gaussian noise, which is usually found in experimental data. Besides, we include model errors, meaning that we assume we do not know the nonlinear regulation function of the process. In order to illustrate this procedure, we employ the Goodwin dynamics of the concentrations [B.C. Goodwin, Temporal Oscillations in Cells, (Academic Press, New York, 1963)] in the simple form recently applied to single gene systems and some operon cases [H. De Jong, J. Comp. Biol. 9, 67 (2002)], which involves the dynamics of the mRNA, given protein, and metabolite concentrations. Further, we present results for a three gene case in co-regulated sets of transcription units as they occur in prokaryotes. However, instead of considering their full dynamics, we use only the data of the metabolites and a designed software sensor. We also show, more generally, that it is possible to rebuild the complete set of nonmeasured concentrations despite the uncertainties in the regulation function or, even more, in the case of not knowing the mRNA dynamics. In addition, the rebuilding of concentrations is not affected by the perturbation due to the additive white Gaussian noise and also we managed to filter the noisy output of the biological systemComment: 21 pages, 7 figures; also selected in vjbio of August 2005; this version corrects a misorder in the last three references of the published versio

    Programming gene expression with combinatorial promoters

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    Promoters control the expression of genes in response to one or more transcription factors (TFs). The architecture of a promoter is the arrangement and type of binding sites within it. To understand natural genetic circuits and to design promoters for synthetic biology, it is essential to understand the relationship between promoter function and architecture. We constructed a combinatorial library of random promoter architectures. We characterized 288 promoters in Escherichia coli, each containing up to three inputs from four different TFs. The library design allowed for multiple −10 and −35 boxes, and we observed varied promoter strength over five decades. To further analyze the functional repertoire, we defined a representation of promoter function in terms of regulatory range, logic type, and symmetry. Using these results, we identified heuristic rules for programming gene expression with combinatorial promoters

    A feed-forward pathway drives LRRK2 kinase membrane recruitment and activation

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    Activating mutations in the leucine-rich repeat kinase 2 (LRRK2) cause Parkinson’s disease, and previously we showed that activated LRRK2 phosphorylates a subset of Rab GTPases (Steger et al., 2017). Moreover, Golgi-associated Rab29 can recruit LRRK2 to the surface of the Golgi and activate it there for both auto- and Rab substrate phosphorylation. Here, we define the precise Rab29 binding region of the LRRK2 Armadillo domain between residues 360–450 and show that this domain, termed ‘site #1,’ can also bind additional LRRK2 substrates, Rab8A and Rab10. Moreover, we identify a distinct, N-terminal, higher-affinity interaction interface between LRRK2 phosphorylated Rab8 and Rab10 termed ‘site #2’ that can retain LRRK2 on membranes in cells to catalyze multiple, subsequent phosphorylation events. Kinase inhibitor washout experiments demonstrate that rapid recovery of kinase activity in cells depends on the ability of LRRK2 to associate with phosphorylated Rab proteins, and phosphorylated Rab8A stimulates LRRK2 phosphorylation of Rab10 in vitro. Reconstitution of purified LRRK2 recruitment onto planar lipid bilayers decorated with Rab10 protein demonstrates cooperative association of only active LRRK2 with phospho-Rab10-containing membrane surfaces. These experiments reveal a feed-forward pathway that provides spatial control and membrane activation of LRRK2 kinase activity

    Mapping Colombian Caribbean and Pacific bottom seascapes and marine ecosystems

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    Colombia is recognized as a mega diverse country on the basis of the number of terrestrial animal and plant species occurring within its boundaries (Williams 1997). However, its privileged coasts position on both Caribbean Sea and Pacific Ocean exhibiting distinct geological, oceanographic, and climatic features could perhaps rank the country within the highest marine biological diversity in South America and among the most biodiverse in the world. An inventory of the full variety of physical bottom types or seascapes map of Colombian territorial waters was produced as a response to provide basis to assess how marine protected areas may well capture marine habitats and thus biodiversity. This map is part of a National initiative to generate an official 1:500.000 scale map where terrestrial, marine and coastal natural ecosystems are all shown. It was made using existing data which are recognized as varying in quality and spatial coverage and have problems with compatibility between data sets. Mapping approach is based on a benthic marine classification system conditions using enduring physiographic and recurrent oceanographic features that are known to affect distribution of communities and their component organisms. Seascapes classification system and the methods used were reviewed at expert workshops. Seascape modeling bases on a digital depth model using ground true points obtained from various time and scale bathymetric charts. Data for the benthic realms are assembled and classified in an ecologically meaningful way and then combined (overlaid) to derive bottom seascapes maps. Each benthic seascape is uniquely defined by the combination of bottom geomorphology, sediment types and oceanic climate values or ranges. Throughout expert knowledge undersea features were identified using slope maps, isoclines and 3D visual analysis. Sediment types were obtained from the digitalization and generalization of sedimentary facies charts. Ocean climate was classified using physical and chemical oceanographic records from the World Ocean Atlas 2001. Coastal line, mangrove and coastal lagoons extent was obtained by visual interpretation, region segmentation and unsupervised classification using 3, 4, and 5 bands of Landsat 7 ETM+ dataset. Available ecosystem level information on reef areas and sea grasses was generalized and superimposed to the generated seascapes. A newly set for discussion regionalization of Colombian underwater territory, ranges from Realms, Provinces, Ecozones to Ecorregions and encompass a total of 155 seascapes extending 532.200 km2 of the Caribbean Sea and 360.510 km2 of the Pacific Ocean. Seascapes distribute up to a maximum of 4990 meters depth. Distinctive features of the Caribbean include the Colombia Basin covering 210.000 km2 Magdalena Fan covering an area of about 24.400 km2 in close relation to the river delta. Extensive coral reefs top the mountainous seascapes of the Tayrona Ridge Ecozone NE of the Mesoamerican platform. Malpelo Ridge and Pacific Rise are distinctive features over the Pacific Basin. The Colombia trench, running parallel along the coast is a characteristically very deep and asymmetrical depression of the Pacific sea floor. Upcoming work is pointing to seascape accuracy evaluation and verification. This map serves as a basis for future management proposals, conservation plans and sustainable management planning. (Document has 27 slides

    Tractor_DB (version 2.0): a database of regulatory interactions in gamma-proteobacterial genomes

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    The version 2.0 of Tractor_DB is now accessible at its three international mirrors: , and . This database contains a collection of computationally predicted Transcription Factors' binding sites in gamma-proteobacterial genomes. These data should aid researchers in the design of microarray experiments and the interpretation of their results. They should also facilitate studies of Comparative Genomics of the regulatory networks of this group of organisms. In this paper we describe the main improvements incorporated to the database in the past year and a half which include incorporating information on the regulatory networks of 13—increasing to 30—new gamma-proteobacteria and developing a new computational strategy to complement the putative sites identified by the original weight matrix-based approach. We have also added dynamically generated navigation tabs to the navigation interfaces. Moreover, we developed a new interface that allows users to directly retrieve information on the conservation of regulatory interactions in the 30 genomes included in the database by navigating a map that represents a core of the known Escherichia coli regulatory network

    Automatic reconstruction of a bacterial regulatory network using Natural Language Processing

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    <p>Abstract</p> <p>Background</p> <p>Manual curation of biological databases, an expensive and labor-intensive process, is essential for high quality integrated data. In this paper we report the implementation of a state-of-the-art Natural Language Processing system that creates computer-readable networks of regulatory interactions directly from different collections of abstracts and full-text papers. Our major aim is to understand how automatic annotation using Text-Mining techniques can complement manual curation of biological databases. We implemented a rule-based system to generate networks from different sets of documents dealing with regulation in <it>Escherichia coli </it>K-12.</p> <p>Results</p> <p>Performance evaluation is based on the most comprehensive transcriptional regulation database for any organism, the manually-curated RegulonDB, 45% of which we were able to recreate automatically. From our automated analysis we were also able to find some new interactions from papers not already curated, or that were missed in the manual filtering and review of the literature. We also put forward a novel Regulatory Interaction Markup Language better suited than SBML for simultaneously representing data of interest for biologists and text miners.</p> <p>Conclusion</p> <p>Manual curation of the output of automatic processing of text is a good way to complement a more detailed review of the literature, either for validating the results of what has been already annotated, or for discovering facts and information that might have been overlooked at the triage or curation stages.</p
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