Novel metaheuristic for parameter estimation in nonlinear dynamic biological systems

BACKGROUND: We consider the problem of parameter estimation (model calibration) in nonlinear dynamic models of biological systems. Due to the frequent ill-conditioning and multi-modality of many of these problems, traditional local methods usually fail (unless initialized with very good guesses of the parameter vector). In order to surmount these difficulties, global optimization (GO) methods have been suggested as robust alternatives. Currently, deterministic GO methods can not solve problems of realistic size within this class in reasonable computation times. In contrast, certain types of stochastic GO methods have shown promising results, although the computational cost remains large. Rodriguez-Fernandez and coworkers have presented hybrid stochastic-deterministic GO methods which could reduce computation time by one order of magnitude while guaranteeing robustness. Our goal here was to further reduce the computational effort without loosing robustness. RESULTS: We have developed a new procedure based on the scatter search methodology for nonlinear optimization of dynamic models of arbitrary (or even unknown) structure (i.e. black-box models). In this contribution, we describe and apply this novel metaheuristic, inspired by recent developments in the field of operations research, to a set of complex identification problems and we make a critical comparison with respect to the previous (above mentioned) successful methods. CONCLUSION: Robust and efficient methods for parameter estimation are of key importance in systems biology and related areas. The new metaheuristic presented in this paper aims to ensure the proper solution of these problems by adopting a global optimization approach, while keeping the computational effort under reasonable values. This new metaheuristic was applied to a set of three challenging parameter estimation problems of nonlinear dynamic biological systems, outperforming very significantly all the methods previously used for these benchmark problems

Innovating Language Education: An NMC Horizon Project Strategic Brief

The NMC is a leading educational technology organization. A main outcome of the collaboration between the Language Flagship Technology Innovation Center and the NMC was this publication, which highlights recommendations that emerged from discussions of major trends, challenges, and technology developments by experts and practitioners in language technologies in higher education. Innovating Language Education identifies main trends and areas of interest and constitutes a rich resource that includes key definitions and proofs of concept

Acousto-optic signature analysis for inspection of the orbiter thermal protection tile bonds

The goal of this research is to develop a viable NDE technique for the inspection of orbiter thermal protection system (TPS) tile bonds. Phase 2, discussed here, concentrated on developing an empirical understanding of the bonded and unbonded vibration signatures of acreage tiles. Controlled experiments in the laboratory have provided useful information on the dynamic response of TPS tiles. It has been shown that several signatures are common to all the pedigree tiles. This degree of consistency in the tile-SIP (strain isolation pad) dynamic response proves that an unbond can be detected for a known tile and establish the basis for extending the analysis capability to arbitrary tiles for which there are no historical data. The field tests of the noncontacting laser acoustic sensor system, conducted at the Kennedy Space Center (KSC), investigated the vibrational environment of the Orbiter Processing Facility (OPF) and its effect on the measurement and analysis techniques being developed. The data collected showed that for orbiter locations, such as the body flap and elevon, the data analysis scheme, and/or the sensor, will require modification to accommodate the ambient motion. Several methods were identified for accomplishing this, and a solution is seen as readily achievable. It was established that the tile response was similar to that observed in the laboratory. Of most importance, however, is that the field environment will not affect the physics of the dynamic response that is related to bond condition. All of this information is fundamental to any future design and development of a prototype system

Logic-Based Models for the Analysis of Cell Signaling Networks

Computational models are increasingly used to analyze the operation of complex biochemical networks, including those involved in cell signaling networks. Here we review recent advances in applying logic-based modeling to mammalian cell biology. Logic-based models represent biomolecular networks in a simple and intuitive manner without describing the detailed biochemistry of each interaction. A brief description of several logic-based modeling methods is followed by six case studies that demonstrate biological questions recently addressed using logic-based models and point to potential advances in model formalisms and training procedures that promise to enhance the utility of logic-based methods for studying the relationship between environmental inputs and phenotypic or signaling state outputs of complex signaling networks.National Institutes of Health (U.S.) (Grant P50- GM68762)National Institutes of Health (U.S.) (Grant U54-CA112967)United States. Dept. of Defense (Institute for Collaborative Biotechnologies

DOT: A flexible multi-objective optimization framework for transferring features across single-cell and spatial omics

Single-cell RNA sequencing (scRNA-seq) and spatially-resolved imaging/sequencing technologies have revolutionized biomedical research. On one hand, scRNA-seq provides information about a large portion of the transcriptome for individual cells, but lacks the spatial context. On the other hand, spatially-resolved measurements come with a trade-off between resolution and gene coverage. Combining scRNA-seq with different spatially-resolved technologies can thus provide a more complete map of tissues with enhanced cellular resolution and gene coverage. Here, we propose DOT, a novel multi-objective optimization framework for transferring cellular features across these data modalities. DOT is flexible and can be used to infer categorical (cell type or cell state) or continuous features (gene expression) in different types of spatial omics. Our optimization model combines practical aspects related to tissue composition, technical effects, and integration of prior knowledge, thereby providing flexibility to combine scRNA-seq and both low- and high-resolution spatial data. Our fast implementation based on the Frank-Wolfe algorithm achieves state-of-the-art or improved performance in localizing cell features in high- and low-resolution spatial data and estimating the expression of unmeasured genes in low-coverage spatial data across different tissues. DOT is freely available and can be deployed efficiently without large computational resources; typical cases-studies can be run on a laptop, facilitating its use.Comment: 36 pages, 6 figure

Unconventional OFF–ON Response of a Mono(calix[4]arene)-Substituted BODIPY Sensor for Hg2+ through Dimerization Reversion

A new selective fluorogenic chemosensor for Hg2+, which combines a calixarene derivative with a BODIPY core as a fluorescent reporter, is described. The remarkable change in its fluorogenic properties in DMSO and CHCl3 has been analyzed. A study of its spectral properties on dilution, along with molecular modeling studies, allowed us to explain that this behavior involves the formation of a J-dimer, as well as how the sensing mechanism of Hg2+ proceeds

Zebrafish fin immune responses during high mortality infections with viral haemorrhagic septicemia rhabdovirus. A proteomic and transcriptomic approach

<p>Abstract</p> <p>Background</p> <p>Despite rhabdoviral infections being one of the best known fish diseases, the gene expression changes induced at the surface tissues after the natural route of infection (infection-by-immersion) have not been described yet. This work describes the differential infected versus non-infected expression of proteins and immune-related transcripts in fins and organs of zebrafish <it>Danio rerio </it>shortly after infection-by-immersion with viral haemorrhagic septicemia virus (VHSV).</p> <p>Results</p> <p>Two-dimensional differential gel electrophoresis detected variations on the protein levels of the enzymes of the glycolytic pathway and cytoskeleton components but it detected very few immune-related proteins. Differential expression of immune-related gene transcripts estimated by quantitative polymerase chain reaction arrays and hybridization to oligo microarrays showed that while more transcripts increased in fins than in organs (spleen, head kidney and liver), more transcripts decreased in organs than in fins. Increased differential transcript levels in fins detected by both arrays corresponded to previously described infection-related genes such as complement components (<it>c3b, c8 </it>and <it>c9</it>) or class I histocompatibility antigens (<it>mhc1</it>) and to newly described genes such as secreted immunoglobulin domain (<it>sid4</it>), macrophage stimulating factor (<it>mst1</it>) and a cluster differentiation antigen (<it>cd36</it>).</p> <p>Conclusions</p> <p>The genes described would contribute to the knowledge of the earliest molecular events occurring in the fish surfaces at the beginning of natural rhabdoviral infections and/or might be new candidates to be tested as adjuvants for fish vaccines.</p

How Prosecutors and Defense Attorneys Differ in Their Use of Neuroscience Evidence

Much of the public debate surrounding the intersection of neuroscience and criminal law is based on assumptions about how prosecutors and defense attorneys differ in their use of neuroscience evidence. For example, according to some commentators, the defense’s use of neuroscience evidence will abdicate criminals of all responsibility for their offenses. In contrast, the prosecution’s use of that same evidence will unfairly punish the most vulnerable defendants as unfixable future dangers to society. This “double- edged sword” view of neuroscience evidence is important for flagging concerns about the law’s construction of criminal responsibility and punishment: it demonstrates that the same information about the defendant can either be mitigating or aggravating depending on who is raising it. Yet empirical assessments of legal decisions reveal a far more nuanced reality, showing that public beliefs about the impact of neuroscience on the criminal law can often be wrong. This Article takes an evidence-based and multidisciplinary approach to examining how courts respond to neuroscience evidence in capital cases when the defense presents it to argue that the defendant’s mental state at the time of the crime was below the given legal requisite due to some neurologic or cognitive deficiency

Los depósitos de ceniza volcánica del Pleistoceno Superior-Holoceno de la región de Tafí del Valle-Cafayate, noroeste de Argentina

[EN]We identified volcanic ash deposits, whose thickness can exceed sometimes the 4 m, in the southeastern margin of La Puna and neighbouring areas (Provinces of Tucuman and Salta, Argentina). These Late Pleistocene and Holocene deposits show the existence of a highly explosive volcanism only some few thousand years ago, without comparison with any historical volcanic episode in northwestern Argentina. We have characterized the size distribution of ash (laser diffraction), morphology of particles (SEM), mineralogy (XRD) and the geochemistry of major and trace elements in bulk sample using mass spectrometry (HR-ICP-MS). The information provided by these deposits is of great interest to size adequately the geochemical impact models of ashfall in future volcanic eruptions in the Central Volcanic Zone of the Andes, quantifying the contribution of volcanic ash to the regional geochemical balances, both with respect to nutrients (e.g., Ca and Fe) and potentially toxic elements (e.g., As and F), among other elements of interest.[ES] Se han localizado diversos depósitos de ceniza volcánica, cuyos espesores llegan a superar en ocasiones los 4 m al suroeste de La Puna y áreas limítrofes (Provincias de Tucumán y Salta, Argentina). Estos depósitos son de edad Pleistoceno Superior y Holoceno y muestran la existencia hace pocos miles de años de volcanismo altamente explosivo, sin comparación con ningún episodio volcánico histórico en el noroeste de Argentina. Se han caracterizado la distribución granulométrica de la ceniza (difracción laser), la morfología de las partículas (microscopía electrónica de barrido), mineralogía (difracción de rayos X) y la geoquímica de elementos mayores y trazas en muestra total mediante espectrometría de masas (HR-ICP-MS). La información suministrada por estos depósitos tiene gran interés a la hora de dimensionar los modelos de impacto geoquímico de la caída de ceniza de futuras erupciones volcánicas en la Zona Volcánica Central de los Andes, cuantificando la contribución de la ceniza volcánica a los balances geoquímicos regionales, tanto por lo que respecta a nutrientes (p. ej., Ca y Fe), como de elementos potencialmente tóxicos (p. ej., As y F), entre otros elementos de interés.Agradecemos el apoyo técnico del labGEOTOP (infraestructura cofinanciada por FEDER, CSIC08-4E-001) del ICTJA-CSIC; de los Grupos PEGEFA (2009-SGR-972) y GEOVOL y fue financiado por el Proyecto QUECA (CGL2011-23307).Peer reviewe